Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy - Yohannes, Indra; Hild, Sebastian; Vasiliniuc, Stefan; Langner, Oliver; Graeff, Christian; Bert, Christoph (Medical Physics, 2016)
Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated.Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93 MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated.Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively.The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy.
EVALuna2:18348

Temozolomide-induced liver damage. A case report - Becker, F.; Hecht, Markus; Schmidtner, J.; Semrau, S.; Fietkau, Rainer (Strahlentherapie und Onkologie, 2014)
Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed each year. Therefore, all severe side effects of TMZ, even those rarely observed, are relevant to radiotherapists.We report a case of severe drug-induced toxic hepatitis that developed during chemoradiotherapy with TMZ in a patient with glioblastoma multiforme.Transaminase elevation was observed after 5 weeks of TMZ treatment, followed by severe jaundice symptoms which only subsided 2 months later. These findings were consistent with diagnosis of the mixed hepatic/cholestatic type of drug-induced toxic hepatitis. Due to the early termination of treatment, no life-threatening complications occurred in our patient. However, rare reports of encephalopathy and fatality as complications of TMZ therapy can be found in the literature.When using TMZ for treatment of glioblastoma, monitoring of liver enzyme levels should be performed twice weekly to prevent fatal toxic hepatitis. In the case of any drug-induced hepatitis, TMZ must be discontinued immediately.
EVALuna2:18198

Temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine - Stritzelberger, Jenny; Distel, T.; Fietkau, Rainer; Putz, Florian (2016)
EVALuna2:18332

Temporarily increased TGFβ following radon spa correlates with reduced pain while serum IL-18 is a general predictive marker for pain sensitivity - Kullmann, Miriam; Rühle, Paul-Friedrich; Harrer, Alexandra; Donaubauer, Anna-Jasmina; Becker, Ina; Sieber, Renate; Klein, Gerhart; Fournier, Claudia; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (Radiation and Environmental Biophysics, 2019)
Sustained pain relief following radon spa therapy in patients suffering from chronic painful diseases has been well described. But still, the underlying mechanisms are not fully understood. We conducted the prospective and explorative RAD-ON01 study which included 103 patients who suffered from chronic painful musculoskeletal disorders of the spine and/or joints and present here the data of the examination of pro- and anti-inflammatory cytokines in the serum of the patients before and at weeks 6, 12 and 30 after therapy. While TNFα, IL-1β, IFNγ, IL-1Ra and IL-10 were not altered, TGFβ was temporarily significantly (p = 0.013) elevated 6 weeks after therapy. Importantly, this elevation positively correlated with lowered pain sensitivity (r = 0.41). Further, the amount of IL-18 in the serum positively correlated with lowered pain sensitivity. Therefore, IL-18 can be considered as predictive marker for pain sensitivity of radon spa patients. We conclude that alterations in TGFβ and general IL-18 levels in serum have prognostic and predictive value in situations of lowered pain by exposure of patients to very low-doses of radiation as it is the case in radon spa.
EVALuna2:36449

The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma - Cathomas, Richard; Lorch, Anja; Bruins, Harman M.; Compérat, Eva M.; Cowan, Nigel C.; Efstathiou, Jason A.; Fietkau, Rainer; Gakis, Georgios; Hernández, Virginia; Espinós, Estefania Linares; Neuzillet, Yann; Ribal, Maria J.; et al. (European Urology, 2022)
Context: Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. Objective: This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. Evidence acquisition: A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. Evidence synthesis: Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. Conclusions: This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. Patient summary: In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients.
CRIS-Team Scopus Importer:2021-12-24
Keywords: Bladder cancer; European Association of Urology; Guidelines; Immunotherapy; Metastatic; Systemic therapy; Urothelial carcinoma

The 3rd ESTRO-EFOMP core curriculum for medical physics experts in radiotherapy - Garibaldi, Cristina; Essers, Marion; Heijmen, Ben; Bertholet, Jenny; Koutsouveli, Efi; Schwarz, Marco; Bert, Christoph; Bodale, Marin; Casares-Magaz, Oscar; Gerskevitch, Eduard; Koniarova, Irena; Korreman, Stine; et al. (Radiotherapy and Oncology, 2022)
Purpose: To update the 2011 ESTRO-EFOMP core curriculum (CC) for education and training of medical physics experts (MPE)s working in radiotherapy (RT), in line with recent EU guidelines, and to provide a framework for European countries to develop their own curriculum. Material and methods: Since September 2019, 27 European MPEs representing ESTRO, EFOMP and National Societies, with expertise covering all subfields of RT physics, have revised the CC for recent advances in RT. The ESTRO and EFOMP Education Councils, all European National Societies and international stakeholders have been involved in the revision process. Results: A 4-year training period has been proposed, with a total of 240 ECTS (European Credit Transfer and Accumulation System). Training entrance levels have been defined ensuring the necessary physics and mathematics background. The concept of competency-based education has been reinforced by introducing the CanMEDS role framework. The updated CC includes (ablative) stereotactic-, MR-guided- and adaptive RT, particle therapy, advanced automation, complex quantitative data analysis (big data/artificial intelligence), use of biological images, and personalized treatments. Due to the continuously increasing RT complexity, more emphasis has been given to quality management. Clear requirements for a research project ensure a proper preparation of MPE residents for their central role in science and innovation in RT. Conclusion: This updated, 3rd edition of the CC provides an MPE training framework for safe and effective practice of modern RT, while acknowledging the significant efforts needed in some countries to reach this level. The CC can contribute to further harmonization of MPE training in Europe.
CRIS-Team Scopus Importer:2022-05-13
Keywords: Core curriculum (CC); Education and training; ESTRO-EFOMP; Medical Physics Expert (MPE); Radiotherapy physics

The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells - Groetsch, Bettina; Brachs, Sebastian; Lang, Christiane; Luther, Julia; Derer, Anja; Schlötzer-Schrehardt, Ursula; Bozec, Aline; Fillatreau, Simon; Berberich, Ingolf; Hobeika, Elias; Reth, Michael; Wagner, Erwin F.; et al. (Journal of Experimental Medicine, 2014)
The cornerstone of humoral immunity is the differentiation of B cells into antibody-secreting plasma cells. This process is tightly controlled by a regulatory gene network centered on the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp1). Proliferation of activated B cells is required to foster Blimp1 expression but needs to be terminated to avoid overshooting immune reactions. Activator protein 1 (AP-1) transcription factors become quickly up-regulated upon B cell activation. We demonstrate that Fra1, a Fos member of AP-1, enhances activation-induced cell death upon induction in activated B cells. Moreover, mice with B cell-specific deletion of Fra1 show enhanced plasma cell differentiation and exacerbated antibody responses. In contrast, transgenic overexpression of Fra1 blocks plasma cell differentiation and immunoglobulin production, which cannot be rescued by Bcl2. On the molecular level, Fra1 represses Blimp1 expression and interferes with binding of the activating AP-1 member c-Fos to the Blimp1 promoter. Conversely, overexpression of c-Fos in Fra1 transgenic B cells releases Blimp1 repression. As Fra1 lacks transcriptional transactivation domains, we propose that Fra1 inhibits Blimp1 expression and negatively controls plasma cell differentiation through binding to the Blimp1 promoter. In summary, we demonstrate that Fra1 negatively controls plasma cell differentiation by repressing Blimp1 expression.
EVALuna2:13013

The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts - Friščić, Jasna; Böttcher, Martin; Reinwald, Christiane; Bruns, Heiko; Wirth, Benjamin; Popp, Sebastian; Walker, Kellie Irene; Ackermann, Jochen A.; Chen, Xi; Turner, Jason; Zhu, Honglin; Seyler, Lisa; et al. (Immunity, 2021)
Arthritis typically involves recurrence and progressive worsening at specific predilection sites, but the checkpoints between remission and persistence remain unknown. Here, we defined the molecular and cellular mechanisms of this inflammation-mediated tissue priming. Re-exposure to inflammatory stimuli caused aggravated arthritis in rodent models. Tissue priming developed locally and independently of adaptive immunity. Repeatedly stimulated primed synovial fibroblasts (SFs) exhibited enhanced metabolic activity inducing functional changes with intensified migration, invasiveness and osteoclastogenesis. Meanwhile, human SF from patients with established arthritis displayed a similar primed phenotype. Transcriptomic and epigenomic analyses as well as genetic and pharmacological targeting demonstrated that inflammatory tissue priming relies on intracellular complement C3- and C3a receptor-activation and downstream mammalian target of rapamycin- and hypoxia-inducible factor 1α-mediated metabolic SF invigoration that prevents activation-induced senescence, enhances NLRP3 inflammasome activity, and in consequence sensitizes tissue for inflammation. Our study suggests possibilities for therapeutic intervention abrogating tissue priming without immunosuppression.
CRIS-Team Scopus Importer:2021-04-19
Keywords: arthritis; cell metabolism; cellular senescence; complement system; inflammasome; inflammation; mechanistic target of rapamycin; synovial fibroblasts; tissue priming; trained immunity

The COVID-19 pandemic and its consequences for the diagnosis and therapy of head and neck malignancies - Rupp, Robin; de Vasconcelos Craveiro, Antonio; Allner, Moritz; Grundtner, P.; Eckstein, Markus; Hecht, Markus; Iro, Heinrich; Gostian, Antoniu-Oreste; Balk, Matthias (European Review for Medical and Pharmacological Sciences, 2022)
OBJECTIVE: The COVID-19 pandemic and the measures accompanying it have been accused of having a negative influence on the frequency and methods of treatment of various diseases including head and neck cancer (HNSCC). To go further into this assumption, the diagnoses made, and treatments performed at one of Germany's largest head and neck cancer centres were evaluated.
CRIS-Team WoS Importer:2022-02-04

The Differential Diagnosis and Inter - disciplinary Treatment of Anal Carcinoma - Raptis, Dimitrios; Schneider, Ignaz Hans Friedrich; Matzel, Klaus E.; Ott, Oliver; Fietkau, Rainer; Hohenberger, Werner (Deutsches Ärzteblatt international, 2015)
Anal carcinoma accounts for 2-4% of all cases of colorectal and anorectal carcinoma. Its peak incidence is from age 58 to age 64; women are affected somewhat more commonly than men. Its incidence has risen markedly in the past three decades.This article is based on a selective review of the literature, including the guidelines of the National Comprehensive Cancer Network and the European Society of Medical Oncology.Anal carcinoma is often an incidental finding. About 85% of newly diagnosed cases are associated with an HPV infection with strain 16, 18, or 33. Radiochemotherapy with 5-fluorouracil and mitomycin C is the treatment of choice. The 5-year survival rate is 80-90%. Primary surgery with curative intent is indicated only for well-differentiated carcinoma of the anal margin (T1, N0). 10-30% of patients now undergo radical resection. The utility of endosonography and positron emission tomography for staging is debated and needs further study.The treatment of patients with anal carcinoma requires a specialized multidisciplinary approach in accordance with the current evidence-based guidelines. The potential role of prophylactic vaccination against oncogenic types of HPV in the prevention of anal carcinoma merits further investigation.
EVALuna2:15196

The Distribution of Pelvic Nodal Metastases in Prostate Cancer Reveals Potential to Advance and Personalize Pelvic Radiotherapy - Filimonova, Irina; Schmidt, Daniela; Mansoorian, Sina; Weissmann, Thomas; Siavooshhaghighi, Hadi; Kuwert, Torsten; Bert, Christoph; Frey, Benjamin; Distel, Luitpold; Lettmaier, Sebastian; Fietkau, Rainer; Putz, Florian; et al. (Frontiers in Oncology, 2021)
Background: Traditional clinical target volume (CTV) definition for pelvic radiotherapy in prostate cancer consists of large volumes being treated with homogeneous doses without fully utilizing information on the probability of microscopic involvement to guide target volume design and prescription dose distribution. Methods: We analyzed patterns of nodal involvement in 75 patients that received RT for pelvic and paraaortic lymph node metastases (LNs) from prostate cancer in regard to the new NRG-CTV recommendation. Non-rigid registration-based LN mapping and weighted three-dimensional kernel density estimation were used to visualize the average probability distribution for nodal metastases. As independent approach, the mean relative proportion of LNs observed for each level was determined manually and NRG and non-NRG levels were evaluated for frequency of involvement. Computer-automated distance measurements were used to compare LN distances in individual patients to the spatial proximity of nodal metastases at a cohort level. Results: 34.7% of patients had pelvic LNs outside NRG-consensus, of which perirectal was most common (25.3% of all patients) followed by left common iliac nodes near the left psoas major (6.7%). A substantial portion of patients (13.3%) had nodes at the posterior edge of the NRG obturator level. Observer-independent mapping consistently visualized high-probability hotspots outside NRG-consensus in the perirectal and left common iliac regions. Affected nodes in individual patients occurred in highly significantly closer proximity than at cohort-level (mean distance, 6.6 cm vs. 8.7 cm, p < 0.001). Conclusions: Based on this analysis, the common iliac level should extend to the left psoas major and obturator levels should extend posteriorly 5 mm beyond the obturator internus. Incomplete coverage by the NRG-consensus was mostly because of perirectal involvement. We introduce three-dimensional kernel density estimation after non-rigid registration-based mapping for the analysis of recurrence data in radiotherapy. This technique provides an estimate of the underlying probability distribution of nodal involvement and may help in addressing institution- or subgroup-specific differences. Nodal metastases in individual patients occurred in highly significantly closer proximity than at a cohort-level, which supports that personalized target volumes could be reduced in size compared to a “one-size-fits-all” approach and is an important basis for further investigation into individualized field designs.
CRIS-Team Scopus Importer:2021-02-05
Keywords: lymph node metastases; mapping; patterns of recurrence; pelvic radiotherapy; prostate cancer

The dual role of NK cells in antitumor reactions triggered by ionizing radiation in combination with hyperthermia - Finkel, Patrick; Frey, Benjamin; Mayer, Friederike; Bösl, Karina; Werthmöller, Nina; Mackensen, Andreas; Gaipl, Udo; Ullrich, Evelyn (OncoImmunology, 2016)
Classical tumor therapy consists of surgery, radio(RT)- and/or chemotherapy. Additive immunotherapy has gained in impact and antitumor in situ immunization strategies are promising to strengthen innate and adaptive immune responses. Immunological effects of RT and especially in combination with immune stimulation are mostly described for melanoma. Since hyperthermia (HT) in multimodal settings is capable of rendering tumor cells immunogenic, we analyzed the in vivo immunogenic potential of RT plus HT-treated B16 melanoma cells with an immunization and therapeutic assay. We focused on the role of natural killer (NK) cells in the triggered antitumor reactions. In vitro experiments showed that RT plus HT-treated B16 melanoma cells died via apoptosis and necrosis and released especially the danger signal HMGB1. The in vivo analyses revealed that melanoma cells are rendered immunogenic by RT plus HT. Especially, the repetitive immunization with treated melanoma cells led to an increase in NK cell number in draining lymph nodes, particularly of the immune regulatory CD27(+)CD11b(-) NK cell subpopulation. While permanent NK cell depletion after immunization led to a significant acceleration of tumor outgrowth, a single NK cell depletion two days before immunization resulted in significant tumor growth retardation. The therapeutic model, a local in situ immunization closely resembling the clinical situation when solid tumors are exposed locally to RT plus HT, confirmed these effects. We conclude that a dual and time-dependent impact of NK cells on the efficacy of antitumor immune reactions induced by immunogenic tumor cells generated with RT plus HT exists.
EVALuna2:18356

The Early Landscape of Immune Cell Subsets in Metastatic NSCLC Patients Treated with Immune Checkpoint Inhibitors - Zhou, Jianguo; Donaubauer, Anna-Jasmina; Frey, Benjamin; Becker, Ina; Rutzner, Sandra; Sun, R.; Ma, H.; Fietkau, Rainer; Deutsch, E.; Gaipl, Udo; Hecht, Markus (JOURNAL OF THORACIC ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-05-07

The effect of calyculin A on the dephosphorylation of the histone γ-H2AX after formation of X-ray-induced DNA double-strand breaks in human blood lymphocytes - Kuefner, Michael A.; Brand, Michael; Engert, Christina; Kappey, Hanna; Uder, Michael; Distel, Luitpold (International Journal of Radiation Biology, 2013)
Purpose: The purpose of this study was to investigate the effect of calyculin A on the number of γ-H2AX foci (phosphorylated histone variant 2AX) in lymphocytes after in vitro and in vivo irradiation with rather low doses as they are used in diagnostic and interventional radiology. Materials and methods: For in vitro experiments blood samples of 14 healthy volunteers were irradiated with different doses (10, 50, 100 mGy) and incubated with (0.01, 0.1, 1, 10 nM) or without calyculin A for up to 2 hours. Non-irradiated samples with and without calyculin A served as controls. For in vivo evaluation blood samples were collected from seven patients undergoing computed tomography (CT) both with 1 nM calyculin A containing vials and vials without calyculin A. Foci were quantified in isolated lymphocytes using γ-H2AX immunofluorescence microscopy. Results: 1 nM calyculin A led to a complete inhibition of γ-H2AX foci loss in irradiated samples whereas no inhibition of p53 binding protein 1 (53 BP1) foci was found. Lower concentrations of the phosphatase inhibitor did not have a sufficient effect on foci decrease. Calyculin A did not affect foci levels in non-irradiated samples. If no calyculin A was added into the vial before the blood draws detectable CT-induced foci levels were lower in all patients with a reduction of the medians of 35%. Conclusions: Using γ-H2AX immunofluorescence microscopy calyculin A can be a useful tool to mark the induced γ-H2AX foci after low dose irradiation and to avoid an underestimation of the real deoxyribonucleic acid (DNA) damage in in vitro and in vivo experiments. © 2013 Informa UK, Ltd.
CRIS-Team Scopus Importer:2023-03-08
Keywords: γ-H2AX; Calyculin A; DNA double-strand break repair

The Effect of Hyperthermia and Radiotherapy Sequence on Cancer Cell Death and the Immune Phenotype of Breast Cancer Cells - Sengedorj, Azzaya; Hader, Michael; Heger, Lukas; Frey, Benjamin; Dudziak, Diana; Fietkau, Rainer; Ott, Oliver; Scheidegger, Stephan; Barba, Sergio Mingo; Gaipl, Udo; Rückert, Michael (Cancers, 2022)
Hyperthermia (HT) is an accepted treatment for recurrent breast cancer which locally heats the tumor to 39–44◦C, and it is a very potent sensitizer for radiotherapy (RT) and chemotherapy. However, currently little is known about how HT with a distinct temperature, and particularly, how the sequence of HT and RT changes the immune phenotype of breast cancer cells. Therefore, human MDA-MB-231 and MCF-7 breast cancer cells were treated with HT of different temperatures (39, 41 and 44◦C), alone and in combination with RT (2 × 5 Gy) in different sequences, with either RT or HT first, followed by the other. Tumor cell death forms and the expression of immune checkpoint molecules (ICMs) were analyzed by multicolor flow cytometry. Human monocyte-derived dendritic cells (moDCs) were differentiated and co-cultured with the treated cancer cells. In both cell lines, RT was the main stressor for cell death induction, with apoptosis being the prominent cell death form in MCF-7 cells and both apoptosis and necrosis in MDA-MB-231 cells. Here, the sequence of the combined treatments, either RT or HT, did not have a significant impact on the final outcome. The expression of all of the three examined immune suppressive ICMs, namely PD-L1, PD-L2 and HVEM, was significantly increased on MCF-7 cells 120 h after the treatment of RT with HT of any temperature. Of special interest for MDA-MB-231 cells is that only combinations of RT with HT of both 41 and 44◦C induced a significantly increased expression of PD-L2 at all examined time points (24, 48, 72, and 120 h). Generally, high dynamics of ICM expression can be observed after combined RT and HT treatments. There was no significant difference between the different sequences of treatments (either HT + RT or RT + HT) in case of the upregulation of ICMs. Furthermore, the co-culture of moDCs with tumor cells of any treatment had no impact on the expression of activation markers. We conclude that the sequence of HT and RT does not strongly affect the immune phenotype of breast cancer cells. However, when HT is combined with RT, it results in an increased expression of distinct immune suppressive ICMs that should be considered by including immune checkpoint inhibitors in multimodal tumor treatments with RT and HT. Further, combined RT and HT affects the immune system in the effector phase rather than in the priming phase.
CRIS-Team Scopus Importer:2022-04-29
Keywords: breast cancer; dendritic cell activation; hyperthermia; hyperthermia treatment sequence; immune checkpoint molecules; immune phenotype; radiotherapy

The Emerging Evidence Supporting Integration of Deep Regional Hyperthermia With Chemoradiation in Bladder Cancer - Ott, Oliver; Gaipl, Udo; Lamrani, Allison; Fietkau, Rainer (Seminars in Radiation Oncology, 2023)
For decades, the antineoplastic potential of hyperthermia alone or in combination with radiotherapy and/or chemotherapy has been subject of intensive preclinical and clinical research in various tumor entities. The clinical evidence on the beneficial effects of additional hyperthermia in combination with intravesical Mitomycin C for superficial non-muscle-invasive bladder cancer as well as for deep regional microwave hyperthermia techniques applied during an external beam radiotherapy or chemoradiation treatment for more advanced tumors are summarized. In some series, deep regional hyperthermia in combination with an initial transurethral resection and Cisplatin-based chemoradiation increased the 5-year overall survival rates up to 20%. The presented data justifies a fresh irrespective chance for mild regional hyperthermia in the context of new progressive prospective trials on multimodality treatment for bladder preservation.
CRIS-Team Scopus Importer:2022-12-23

The Erlangen Dose Optimization trial for low-dose radiotherapy of benign painful elbow syndrome. Long-term results - Ott, O. J.; Hertel, Sascha; Gaipl, Udo; Frey, Benjamin; Schmidt, M.; Fietkau, Rainer (Strahlentherapie und Onkologie, 2014)
To evaluate the long-term efficacy of pain reduction by two dose fractionation schedules used for low-dose radiotherapy of painful elbow syndrome.Between February 2006 and February 2010, 199 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS).Median follow-up was 35 months (range 9-57 months). The overall early, delayed and long-term response rates for all patients were 80, 90 and 94 %, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 59.6 ± 20.2 and 55.7 ± 18.0 (p = 0.46); 32.1 ± 24.5 and 34.4 ± 22.5 (p = 0.26); 27.0 ± 27.7 and 23.5 ± 21.6 (p = 0.82) and 10.7 ± 15.0 and 21.5 ± 26.9 (p = 0.12), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 8.7 ± 2.9 and 8.1 ± 3.1 (p = 0.21); 4.5 ± 3.2 and 5.0 ± 3.4 (p = 0.51); 3.9 ± 3.6 and 2.8 ± 2.8 (p = 0.19) and 1.5 ± 2.3 and 2.4 ± 3.5 (p = 0.27), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p = 0.28).Low-dose radiotherapy is an effective treatment for the management of benign painful elbow syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy.
EVALuna2:18200

The Erlangen Dose Optimization Trial for radiotherapy of benign painful shoulder syndrome. Long-term results - Ott, O. J.; Hertel, Sascha; Gaipl, Udo; Frey, Benjamin; Schmidt, M.; Fietkau, Rainer (Strahlentherapie und Onkologie, 2014)
To evaluate the long-term efficacy of pain reduction by two dose-fractionation schedules for radiotherapy of painful shoulder syndrome.Between February 2006 and February 2010, 312 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS).Median follow-up was 35 months (range 11-57). The overall early, delayed and long-term response rates for all patients were 83, 85 and 82 %, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.16); 38.2 ± 36.1 and 34.0 ± 24.5 (p = 0.19); 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.04) and 27.9 ± 25.8 and 32.1 ± 26.9 (p = 0.25), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.31); 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.10); 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.05) and 4.0 ± 3.9 and 5.3 ± 4.4 (p = 0.05), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p = 0.28).Radiotherapy is an effective treatment for the management of benign painful shoulder syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy.
EVALuna2:18186

The Growth of primary and abscopal Tumors as well as their immunological Microenvironment are differently influenced by different Combinations of Radiation and Immunotherapies - Rückert, Michael; Deloch, Lisa; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

The health-related quality of life of sarcoma patients treated with neoadjuvant versus adjuvant radiotherapy – Results of a multi-center observational study - Singer, Susanne; Semrau, Sabine; Golcher, Henriette; Fechner, Katja; Kallies, Annett; Zapata Bonilla, Sergio; Grützmann, Robert; Fietkau, Rainer; Kluba, Torsten; Jentsch, Christina; Andreou, Dimosthenis; Bornhäuser, Martin; et al. (Radiotherapy and Oncology, 2023)
Aim: The sequence of radiotherapy and resection in patients with soft tissue sarcomas is usually discussed on an individual basis. Better understanding of potential differences of health-related quality of life (QoL) between patients undergoing adjuvant (ART) versus neoadjuvant radiotherapy (NART) is therefore helpful for clinical decision making. Methods: Adult sarcoma patients from 39 hospitals completed the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30). Differences in global QoL, physical functioning, role functioning, fatigue, pain, and insomnia between ART versus NART were investigated with multivariate regression, adjusting for age, gender, chemotherapy, grading, stage, tumor location, recurrence/distant metastasis, sarcoma type, time since last treatment, and treatment status using validated thresholds. Results: A total of 1110 patients participated. Of them, 340 had received radiotherapy (NART: n = 95, 28%; ART: n = 245, 72%). Global QoL was 59.3 on average after NART and 60.5 after ART (Badj = 1.0, p = 0.74). Physical functioning was 65.9 compared to 70.5 (Badj = 4.2; p = 0.16), role function 48.8 vs. 56.7 (Badj = 7.0, p = 0.08), fatigue 47.5 vs. 45.4 (Badj = -1.2; p = 0.71), pain 40.2 vs. 34.1 (Badj = -6.8; p = 0.08), and insomnia 33.7 vs. 41.6 (Badj = 5.5, p = 0.16). Among patients with NART, clinically relevant QoL impairments were less frequent 2 years after treatment compared to < 2 years thereafter (n = 6 vs. n = 4 on average). Conclusion: There is little evidence for QoL differences in most domains and overall QoL between the two irradiation groups. However, patients after NART might experience worse role functioning and pain but fewer problems with insomnia compared to patients after ART.
CRIS-Team Scopus Importer:2023-10-20
Keywords: Leiomyosarcoma; Liposarcoma; Neoadjuvant Therapy; Neoplasms; Connective and Soft Tissue; Patient Reported Outcome Measures; Radiotherapy; Adjuvant

The IMMO-LDRT01 Study - Analgesic and immunomodulatory Effects of LDRT in Patients with chronic degenerative and inflammatory Diseases - Donaubauer, Anna-Jasmina; Fröhlich, Birgitta; Becker, Ina; Weissmann, Thomas; Fietkau, Rainer; Ott, Oliver; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

The IMMO-LDRT01 Study: Immunomodulatory Effects of X-ray Irradiation in chronic degenerative and inflammatory Diseases - Donaubauer, Anna-Jasmina; Gryc, Thomas; Froehlich, B.; Becker, I.; Ott, O. J.; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2019)
CRIS-Team WoS Importer:2019-06-07

The immune reaction against allogeneic necrotic cells is reduced in Annexin A5 knock out mice whose macrophages display an anti-inflammatory phenotype - Frey, Benjamin; Munoz, Luis Enrique; Pausch, Friederike; Sieber, Renate; Franz, Sandra; Brachvogel, Bent; Poschl, Ernst; Schneider, Holm; Roedel, Franz; Sauer, Rolf; Fietkau, Rainer; Herrmann, Martin; et al. (Journal of Cellular and Molecular Medicine, 2009)
Proteins of the annexin family bind to phospholipids in a Ca2+ dependent manner. The exposure of phosphatidylserine (PS) by apoptotic as well as necrotic cells is one major eat-me-signal for macrophages. Annexin A5 (Anx A5) preferentially binds to PS. The availability of Anx A5 knock out (KO) mice allowed us to investigate for the first time if endogenous Anx A5 modulates the immune response towards allogeneic cells. Furthermore, the effect of Anx A5 gene deletion on the phagocytic process as well as on the inflammatory reaction of macrophages was explored. We found that Anx A5 KO mice have a strongly reduced allogeneic cellular immune reaction against primary as well as secondary necrotic cells. In vivo phagocytosis experiments revealed that macrophages of Anx A5 KO mice displayed an increased uptake of necrotic cells. Additionally, an increased secretion of the anti-inflammatory cytokine IL-10 of isolated macrophages of Anx A5 KO mice after contact with necrotic cells was observed. Furthermore, the promoter activity of the Anx A5 gene was enhanced after stimulation of macrophages. The tumour size of an allogeneic tumour regressed faster when endogenous Anx A5 was present. These data demonstrate that endogenous Anx A5 influences the phagocytosis of necrotic cells, modulates the immune response towards allogeneic cells and acts as an inflammatory protein. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
CRIS-Team Scopus Importer:2020-07-01
Keywords: Allogeneic cells; Annexin A5; Immune modulation; Inflammation; Macrophages; Phagocytosis; Primary necrosis; Secondary necrosis

The Immune System in Cancer Prevention, Development and Therapy - Candeias, Serge M.; Gaipl, Udo (Anti-Cancer Agents in Medicinal Chemistry, 2015)
The immune system plays a pivotal role in the maintenance of the integrity of an organism. Besides the protection against pathogens, it is strongly involved in cancer prevention, development and defense. This review focuses on how the immune system protects against infections and trauma and on its role in cancer development and disease. Focus is set on the interactions of the innate and adaptive immune system and tumors. The role of IFN-? as a pleiotropic cytokine that plays a very important role at the interface of innate and adaptive immune systems in tumor development and induction of anti-tumor immune responses is outlined. Further, immune cells as prognostic and predictive markers of cancer will be discussed. Data are provided that even the brain as immune privileged organ is subjected to immune surveillance and consequently also brain tumors. Immune therapeutic approaches for glioblastoma multiforme, the most frequent and malignant brain tumor, based on vaccination with dendritic cells are outlined and application of hyperthermia in form of magnetic nanoparticles is discussed. We conclude that the immune system and developing tumors are intimately intertwined. Anti-tumor immune responses can be prominently boosted by multimodal therapies aiming on the one hand to induce immunogenic tumor cell death forms and on the other hand to actively counteract the immune suppressive microenvironment based on the tumor itself.
EVALuna2:18300

The Impact of Irradiation and Lipotransfer on Healthy Mammary Cells after Breast-Conserving Surgery - Kutz, Chiara-Sophia; Jost, Tina; Distel, Luitpold; Kengelbach-Weigand, Annika; Hauck, Theresa; Horch, Raymund E. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-12-16

THE IMPACT OF LOW-DOSE RADIATION ON INFLAMMATORY DISEASES - Deloch, Lisa; Derer, Anja; Hueber, Axel; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo (2016)
EVALuna2:32924

The impact of surgical quality on prognosis in patients undergoing rectal carcinoma surgery after preoperative chemoradiation - Kiehlmann, Marcus; Weber, Klaus; Göhl, Jonas; Fietkau, Rainer; Agaimy, Abbas; Hohenberger, Werner; Merkel, Susanne (International Journal of Colorectal Disease, 2016)
The aim of the study was to analyse the impact of surgical quality on the prognosis of rectal carcinoma patients who underwent preoperative long-term chemoradiation and TME surgery.In a total of 314 patients, four quality indicators, including plane of surgery, pathological circumferential resection margin (pCRM), intraoperative local tumour cell dissemination and anastomotic leakage, were analysed with respect to locoregional recurrence, distant metastasis and overall survival.In 260 (82.8 %) of the patients, all four quality indicators were fulfilled. In 30 (9.6 %) of the patients, at least one quality indicator was not fulfilled; in 24 (7.6 %) of the patients, the data were not complete. Locoregional recurrence was significantly increased in patients who underwent surgery in the muscularis propria plane, who had a pCRM <= 1 mm or who experienced local tumour cell dissemination. In patients who had at least one quality indicator that was not fulfilled (suboptimal surgical quality), the 5-year rate of locoregional recurrence in those patients was 23.1 % compared to 4.8 % in patients who underwent optimal surgery (P = 0.001). In multivariate analysis, suboptimal surgery (hazard ratio (HR) 3.9; P = 0.020), abdominoperineal excision (HR 4.7; P = 0.003) and poor regression of primary tumours (HR 8.5; P < 0.001) were identified as independent prognostic factors for locoregional recurrence. In contrast to type of surgical treatment, ypT, ypN and regression grade, the quality of surgery did not significantly influence distant metastasis or overall survival.Even after preoperative chemoradiation, the surgical quality still has a strong impact on local control in patients with rectal carcinoma.
EVALuna2:6711

The impact of the coronavirus disease (COVID-19) pandemic on outpatient epilepsy care: An analysis of physician practices in Germany - Müller, Tamara; Kostev, Karel; Gollwitzer, Stephanie; Lang, Johannes; Stritzelberger, Jenny; Westermayer, Vivien; Reindl, Caroline; Hamer, Hajo (Epilepsy & Behavior, 2021)
Objective: To gain insight into epilepsy care during coronavirus disease (COVID-19) pandemic, we analyzed prescription data of a large cohort of persons with epilepsy (PWE) during lockdown in Germany. Methods: Information was obtained from the Disease Analyzer database, which collects anonymous demographic and medical data from practice computer systems of general practitioners (GP) and neurologists (NL) throughout Germany. We retrospectively compared prescription data for anti-seizure medication (ASM) and physicians’ notes of “known” and “new” PWE from January 2020 until May 2020 with the corresponding months in the three preceding years 2017–2019. Adherence was estimated by calculating the proportion of patients with follow-up prescriptions within 90 days after initial prescriptions in January or February. We additionally analyzed hospital referrals of PWE. The significance level was set to 0.01 to adjust for multiple comparisons. Results: A total of 52,844 PWE were included. Anti-seizure medication prescriptions for known PWE increased in March 2020 (GP + 36%, NL + 29%; P < 0.01). By contrast, a decrease in prescriptions to known and new PWE was observed in April and significantly in May 2020 ranging from −16% to −29% (P < 0.01). The proportion of PWE receiving follow-up prescriptions was slightly higher in 2020 (73.5%) than in 2017–2019 (70.7%, P = 0.001). General practitioners and NL referred fewer PWE to hospitals in March 2020 (GP: −30%, P < 0.01; NL: −12%), April 2020 (GP: −29%, P < 0.01; NL: −37%), and May 2020 (GP: −24%, P < 0.01; NL: −16%). Conclusion: Adherence of known PWE to ASM treatment appeared to remain stable during lockdown in Germany. However, this study revealed findings which point to reduced care for newly diagnosed PWE as well as fewer hospital admissions. These elements may warrant consideration during future lockdown situations.
CRIS-Team Scopus Importer:2021-03-05
Keywords: Anti-seizure drugs; COVID-19; Epilepsy care

The Influence of Different Irradiation Regimens on Inflammation and Vascularization in a Random-Pattern Flap Model - Müller-Seubert, Wibke; Ostermaier, Patrick; Horch, Raymund E.; Distel, Luitpold; Frey, Benjamin; Erber, Ramona; Arkudas, Andreas (Journal of Personalized Medicine, 2023)
Background: Irradiation plays an important role in the oncological treatment of various tumor entities. The aim of the study was to investigate the influence of different irradiation regimens on random-pattern flaps at the molecular and histopathological levels. Methods: Twenty-five rats underwent harvesting of bilateral random-pattern fasciocutaneous flaps. The right flaps received irradiation, while the left flaps served as non-irradiated intraindividual controls. Five rats served as a non-irradiated control group. Four different irradiation regimens with give rats each were tested: 20 Gy postoperatively, 3 × 12 Gy postoperatively, 20 Gy preoperatively, and 3 × 12 Gy preoperatively. Two weeks after surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis to detect Interleukin 6, HIF-1α, and VEGF, were performed. Results: A postoperative cumulative higher dose of irradiation appeared to result in an increase in necrosis, especially in the superficial layers of the flap compared to preoperative or single-stage irradiation. In addition, we observed increased expression of VEGF and HIF-1α in all irradiation groups. Conclusion: Even though no statistically significant differences were found between the different groups, there was a tendency for fractional postoperative irradiation with a higher total dose to have a more harmful effect compared to preoperative or single-dose irradiation.
CRIS-Team Scopus Importer:2023-11-10
Keywords: irradiation; random-pattern flaps; vascularization

The Influence of Iron(II) Clathrochelates and Irradiation on Cell Death, reactive Oxygen Radicals, and Danger Signals in the human SK-MES1 Lung Cancer Cell Line - Roessel, T.; Becker, I.; Alomo, Jannik; Denzler, M.; Heim, L.; Klemt, Insa; Voloshin, Y.; Selin, R.; Mokhir, Andriy; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

The influence of radiation on bone and bone cells—differential effects on osteoclasts and osteoblasts - Donaubauer, Anna-Jasmina; Becker, Ina; Fietkau, Rainer; Frey, Benjamin; Gaipl, Udo; Deloch, Lisa (International Journal of Molecular Sciences, 2020)
The bone is a complex organ that is dependent on a tight regulation between bone formation by osteoblasts (OBs) and bone resorption by osteoclasts (OCs). These processes can be influenced by environmental factors such as ionizing radiation (IR). In cancer therapy, IR is applied in high doses, leading to detrimental effects on bone, whereas radiation therapy with low doses of IR is applied for chronic degenerative and inflammatory diseases, with a positive impact especially on bone homeostasis. Moreover, the effects of IR are of particular interest in space travel, as astronauts suffer from bone loss due to space radiation and microgravity. This review summarizes the current state of knowledge on the effects of IR on bone with a special focus on the influence on OCs and OBs, as these cells are essential in bone remodeling. In addition, the influence of IR on the bone microenvironment is discussed. In summary, the effects of IR on bone and bone remodeling cells strongly depend on the applied radiation dose, as differential results are provided from in vivo as well as in vitro studies with varying doses of IR. Furthermore, the isolated effects of IR on a single cell type are difficult to determine, as the bone cells and bone microenvironment are building a tightly regulated network, influencing on one another. Therefore, future research is necessary in order to elucidate the influence of different bone cells on the overall radiation-induced effects on bone.
CRIS-Team Scopus Importer:2020-09-18
Keywords: Bone; Bone microenvironment; Ionizing radiation; Osteoblast; Osteoclast; Osteocyte; Radiation therapy

The influence of tumour site on prognosis in metastatic colorectal carcinomas with primary tumour resection - Merkel, Susanne; Schellerer, Vera; Wein, Axel; Semrau, Sabine; Geppert, Carol-Immanuel; Göhl, Jonas; Hohenberger, Werner; Weber, Klaus; Grützmann, Robert (International Journal of Colorectal Disease, 2018)
PURPOSE: The aim of our study was to compare the characteristics and prognosis between right- and left-sided metastatic colorectal carcinomas. METHODS: Data from 937 patients with stage IV colorectal carcinomas (synchronous distant metastasis) who had a resection of the primary tumour between 1985 and 2014 were analysed. Carcinomas in the caecum to transverse colon were defined as right-sided (n = 250; 26.7%). They were compared to tumours located from the splenic flexure to the rectum categorised as left-sided (n = 687; 73.3%). RESULTS: In right-sided carcinomas, we observed significantly more female patients (50.8 vs 36.2%; p < 0.001), more unfavourable histological types (24.0 vs 8.6%; p < 0.001), more M1c carcinomas (metastases to the peritoneum ± others; 32.0 vs 14.4%; p < 0.001) and more emergencies (11.6 vs 7.1%; p = 0.029), while multimodal treatment was utilised in fewer patients (51.6 vs 63.8%; p = 0.001) and curative resections were less frequently (24.1 vs 35.4%; p = 0.002). Prognosis was significantly worse in patients with right-sided carcinomas (2-year-survival 27.2 vs 44.6%, p < 0.01). This difference was more pronounced after R2 resection (15.3 vs 29.7%; p < 0.001), than after macroscopic curative resection (2-year-survival 63.9 vs 71.9%; p = 0.106). In multivariate Cox regression analysis, tumour site was found to be an independent prognostic factor for overall survival (HR 1.2; 95% CI 1.0-1.5; p = 0.012). During the three 10-year periods, the prognosis improved equally in patients with right- and left-sided carcinomas, while the differences in survival remained identical. CONCLUSIONS: In a surgical patient cohort undergoing primary tumour resection, significant differences in prognosis were observed between patients with metastatic right- and left-sided colorectal carcinomas.
EVALuna2:35146

The in vitro immunogenic potential of caspase-3 proficient breast cancer cells with basal low immunogenicity is increased by hypofractionated irradiation - Kötter, Bernhard; Frey, Benjamin; Winderl, Markus; Rubner, Yvonne; Scheithauer, Heike; Sieber, Renate; Fietkau, Rainer; Gaipl, Udo (Radiation Oncology, 2015)
Radiotherapy is an integral part of breast cancer treatment. Immune activating properties of especially hypofractionated irradiation are in the spotlight of clinicians, besides the well-known effects of radiotherapy on cell cycle and the reduction of the clonogenic potential of tumor cells. Especially combination of radiotherapy with further immune stimulation induces immune-mediated anti-tumor responses. We therefore examined whether hypofractionated irradiation alone or in combination with hyperthermia as immune stimulants is capable of inducing breast cancer cells with immunogenic potential.Clonogenic assay, AnnexinA5-FITC/Propidium iodide assay and ELISA analyses of heat shock protein 70 and high mobility group box 1 protein were applied to characterize colony forming capability, cell death induction, cell death forms and release of danger signals by breast cancer cells in response to hypofractionated radiation (4x4Gy, 6x3Gy) alone and in combination with hyperthermia (41.5 °C for 1 h). Caspase-3 deficient, hormone receptor positive, p53 wild type MCF-7 and caspase-3 intact, hormone receptor negative, p53 mutated MDA-MB231 breast cancer cells, the latter in absence or presence of the pan-caspase inhibitor zVAD-fmk, were used. Supernatants of the treated tumor cells were analyzed for their potential to alter the surface expression of activation markers on human-monocyte-derived dendritic cells.Irradiation reduced the clonogenicity of caspase deficient MCF-7 cells more than of MDA-B231 cells. In contrast, higher amounts of apoptotic and necrotic cells were induced in MDA-B231 cells after single irradiation with 4Gy, 10Gy, or 20Gy or after hypofractionated irradiation with 4x4Gy or 6x3Gy. MDA-B231 cells consecutively released higher amounts of Hsp70 and HMGB1 after hypofractionated irradiation. However, only the release of Hsp70 was further increased by hyperthermia. Both, apoptosis induction and release of the danger signals, was dependent on caspase-3. Only supernatants of MDA-B231 cells after hypofractionated irradiation resulted in slight changes of activation markers on dendritic cells; especially that of CD86 was upregulated and HT did not further impact on it.Hypofractionated irradiation is the main stimulus for cell death induction and consecutive dendritic cell activation in caspase proficient breast cancer cells. For the assessment of radiosensitivity and immunological effects of radio- and immunotherapies the readout system is crucial.
EVALuna2:18306

The long-term influence of hospital and surgeon volume on local control and survival in the randomized German Rectal Cancer Trial CAO/ARO/AIO-94 - Sprenger, Thilo; Beissbarth, Tim; Sauer, Rolf; Tschmelitsch, Joerg; Fietkau, Rainer; Hohenberger, Werner; Staib, Ludger; Raab, Hans-Rudolf; Roedel, Claus; Ghadimi, Michael (Surgical Oncology-Oxford, 2020)
Background: The association of treatment volume and oncological outcome of rectal cancer patients undergoing multidisciplinary treatment is subject of an ongoing debate. Prospective data on long-term local control and overall survival (OS) are not available so far. This study investigated the long-term influence of hospital and surgeon volume on local recurrence (LR) and OS in patients with locally advanced rectal cancers.
CRIS-Team WoS Importer:2021-01-08

The OAR Turing-Test Study: A blinded Comparison of expert-Based Organ at Risk Creation and three commercial Auto-Segmentation Solutions - Putz, Florian; Lamrani, Allison; Weissmann, Thomas; Mansoorian, Sina; Frey, Benjamin; Bert, Christoph; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Theoretical evaluation of the impact of hyperthermia in combination with radiation therapy in an artificial immune—tumor-ecosystem - Scheidegger, Stephan; Barba, Sergio Mingo; Gaipl, Udo (Cancers, 2021)
There is some evidence that radiotherapy (RT) can trigger anti-tumor immune responses. In addition, hyperthermia (HT) is known to be a tumor cell radio-sensitizer. How HT could enhance the anti-tumor immune response produced by RT is still an open question. The aim of this study is the evaluation of potential dynamic effects regarding the adaptive immune response induced by different combinations of RT fractions with HT. The adaptive immune system is considered as a trainable unit (perceptron) which compares danger signals released by necrotic or apoptotic cell death with the presence of tumor-and host tissue cell population-specific molecular patterns (antigens). To mimic the changes produced by HT such as cell radio-sensitization or increase of the blood perfusion after hyperthermia, simplistic biophysical models were included. To study the effectiveness of the different RT+HT treatments, the Tumor Control Probability (TCP) was calculated. In the considered scenarios, the major effect of HT is related to the enhancement of the cell radio-sensitivity while perfusion or heat-based effects on the immune system seem to contribute less. Moreover, no tumor vaccination effect has been observed. In the presented scenarios, HT boosts the RT cell killing but it does not fundamentally change the anti-tumor immune response.
CRIS-Team Scopus Importer:2021-11-26
Keywords: Antigen pattern; Danger signal; Fractionation; Immune response; Immune system in silico; Perceptron; Systems medicine

The potential of predictive and prognostic breast MRI (P2-bMRI) - Dietzel, Matthias; Trimboli, Rubina Manuela; Zanardo, Moreno; Schultz-Wendtland, Rudiger; Uder, Michael; Clauser, Paola; Sardanelli, Francesco; Baltzer, Pascal A. T. (European Radiology Experimental, 2022)
Magnetic resonance imaging (MRI) is an important part of breast cancer diagnosis and multimodal workup. It provides unsurpassed soft tissue contrast to analyse the underlying pathophysiology, and it is adopted for a variety of clinical indications. Predictive and prognostic breast MRI (P2-bMRI) is an emerging application next to these indications. The general objective of P2-bMRI is to provide predictive and/or prognostic biomarkers in order to support personalisation of breast cancer treatment. We believe P2-bMRI has a great clinical potential, thanks to the in vivo examination of the whole tumour and of the surrounding tissue, establishing a link between pathophysiology and response to therapy (prediction) as well as patient outcome (prognostication). The tools used for P2-bMRI cover a wide spectrum: standard and advanced multiparametric pulse sequences; structured reporting criteria (for instance BI-RADS descriptors); artificial intelligence methods, including machine learning (with emphasis on radiomics data analysis); and deep learning that have shown compelling potential for this purpose. P2-bMRI reuses the imaging data of examinations performed in the current practice. Accordingly, P2-bMRI could optimise clinical workflow, enabling cost savings and ultimately improving personalisation of treatment. This review introduces the concept of P2-bMRI, focusing on the clinical application of P2-bMRI by using semantic criteria.
CRIS-Team WoS Importer:2022-09-02

The Prognostic and Predictive Significance of Tumor-Infiltrating Memory T Cells Is Reversed in High-Risk HNSCC - Hartan, Rebekka; Schnellhardt, Sören; Büttner-Herold, Maike; Daniel, Christoph; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (Cells, 2022)
Tumor-infiltrating CD45RO+ memory T cells have unanimously been described as a positive prognostic factor in head and neck squamous cell carcinomas (HNSCCs). Here, we investigated the long-term prognostic relevance of CD45RO+ memory T cells in HNSCC with special regard to the influence of clinical characteristics. Pre-treatment biopsy samples from 306 patients with predominantly advanced HNSCC were analyzed. Immunohistochemistry was used to stain tissue microarrays for CD45RO+ memory T cells. CD45RO cell densities were semi-automatically registered and used for survival analysis. High CD45RO+ cell densities were clearly associated with prolonged overall survival (OS) and recurrence-free survival as well as no evidence of disease status after 10 years (p < 0.05). In contrast, the prognostic significance of tumor-infiltrating memory T cells was completely reversed in high-risk groups: in poorly differentiated tumors (G3, G4) and in cases with lymph node involvement (N+), high memory T cell densities correlated with reduced 10-year OS (p < 0.05). In conclusion, an increased density of tumor-infiltrating CD45RO+ cells in HNSCC can be a positive as well as a negative prognostic factor, depending on disease stage and histological grade. Therefore, if CD45RO+ cell density is to be used as a prognostic biomarker, further clinical characteristics must be considered.
CRIS-Team WoS Importer:2022-07-08
Keywords: CD45RO; head and neck cancer; memory T cells; prognostic value; reversal of prognostic value

The prognostic Relevance of tumor infiltrating Inflammatory Cells in early Breast Cancer - Schnellhardt, Sören (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

The prognostic Significance of Tumor-associated Macrophages (TAM) and of Tumor-infiltrating Lymphocytes (TIL) in radiolabelled Patients with an Adenocarcinoma of the Pancreas - Zoske, Hanno; Distel, Luitpold; Fietkau, Rainer; Hecht, Markus (2017)
EVALuna2:32899

The Prognostic Value of FoxP3+Tumour-Infiltrating Lymphocytes in Rectal Cancer Depends on Immune Phenotypes Defined by CD8+Cytotoxic T Cell Density - Schnellhardt, Sören; Hirneth, Johannes; Büttner-Herold, Maike; Daniel, Christoph; Haderlein, Marlen; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (Frontiers in Immunology, 2022)
Tumour-infiltrating FoxP3+ regulatory T cells have been identified as both positive and negative prognostic factors in colorectal cancer (CRC) and rectal cancer (RC). In this study we investigated whether immune phenotypes, defined by CD8+ cytotoxic T cell density, may influence the prognostic association of FoxP3+ T cell densities in RC. Tissue microarrays from 154 rectal cancer resections were immunohistochemically double stained for CD8 and FoxP3. CD8+ and FoxP3+ cell densities were measured in the stromal and intraepithelial compartment. Stromal FoxP3+ cell densities were not associated with 10-year overall survival (OS). In the "immune-desert" phenotype, defined by very low stromal CD8+ cell density, a high density of stromal FoxP3+ T cells displayed a tendency towards an association with decreased 10-year OS (p = 0.179). In "inflamed" tumours, defined by high intraepithelial CD8+ T cell infiltration, the opposite was the case and high stromal FoxP3+ T cell densities were a positive prognostic factor (p = 0.048). Additionally, patients with an increased FoxP3/CD8 cell density ratio demonstrated a strong trend towards decreased 10-year OS (p = 0.066). These contrasting findings suggest functional heterogeneity within the group of FoxP3+ T cells. They are consistent with experimental studies which reported suppressive and non-suppressive populations of FoxP3+ T cells in CRC. Furthermore, our study demonstrates that CD8 immunohistochemistry may act as an instrument to identify tumours infiltrated by possibly functionally differing FoxP3+ T cell subtypes.
CRIS-Team WoS Importer:2022-02-18

The radiation-induced Activation of Anti-tumor Immune Mechanisms is enhanced by Inhibtion of the Heat Shock Protein 90 - Ernst, A.; Hennel, R.; Krombach, J.; Kapfhammer, H.; Brix, N.; Zuchtriegel, G.; Uhl, B.; Reichel, C.; Frey, Benjamin; Gaipl, Udo; Winssinger, N.; Shirasawa, S.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents - Dürr, Pauline; Schlichtig, Katja; Kelz, Carolin; Deutsch, Birgit; Maas, Renke; Eckart, Michael J.; Wilke, Jochen; Wagner, Harald; Wolff, Kerstin; Preuß, Caroline; Brückl, Valeska; Meidenbauer, Norbert; et al. (Journal of Clinical Oncology, 2021)
PURPOSE: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS: Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug-related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS: Two hundred two patients were included. Antitumor drug-related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION: Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.
CRIS-Team Scopus Importer:2021-07-02

Therapies for synchronous malignomas - the importance of interdisciplinary oncology - Mueller, Sarina K.; Haderlein, Marlen; Traxdorf, Maximilian; Semrau, Sabine; Agaimy, Abbas; Lettmaier, Sebastian; Gostian, Antoniu-Oreste; Schubart, Christoph; Mantsopoulos, Konstantinos; Schmidt, Daniela; Wiesmüller, Marco; Sievert, Matti; et al. (Laryngo-Rhino-Otologie, 2021)
CRIS-Team WoS Importer:2021-08-06

Thermal dosimetry for bladder hyperthermia treatment. An overview - Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D.; Hartmann, Josefin; Hulshof, Maarten C. C. M.; Kok, H. Petra; Paulides, Margarethus M.; Sousa-Escandon, Alejandro; Stauffer, Paul R.; et al. (International Journal of Hyperthermia, 2016)
The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.
EVALuna2:18341

The Role of local radical Therapy Approach in the metastatic Stage of Small Cell Lung Cancer (SCLC) - Zoske, Hanno; Lettmaier, S.; Fietkau, Rainer; Putz, Florian (2018)
EVALuna2:36511

The Role of ncRNAs in Solid Tumors Prognosis: From Laboratory to Clinical Utility - Zhou, Jianguo; Huang, Zhaohui; Slaby, Ondrej; Navarro, Alfons (Frontiers in Oncology, 2021)
CRIS-Team Scopus Importer:2021-03-05
Keywords: circular RNA; gene expression omnibus (GEO); long non-coding RNA; microRNA; the cancer genome atlas (TCGA)

The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducing resolution of inflammation in arthritis - Royzman, Dmytro; Andreev, Darja; Stich, Lena; Peckert, Katrin; Wild, Andreas; Zinser, Elisabeth; Mühl-Zürbes, Petra; Jones, Evan; Adam, Susanne; Frey, Silke; Fuchs, Maximilian; Kunz, Meik; et al. (Frontiers in Immunology, 2022)
Here we show that soluble CD83 induces the resolution of inflammation in an antigen-induced arthritis (AIA) model. Joint swelling and the arthritis-related expression levels of IL-1 beta, IL-6, RANKL, MMP9, and OC-Stamp were strongly reduced, while Foxp3 was induced. In addition, we observed a significant inhibition of TRAP(+) osteoclast formation, correlating with the reduced arthritic disease score. In contrast, cell-specific deletion of CD83 in human and murine precursor cells resulted in an enhanced formation of mature osteoclasts. RNA sequencing analyses, comparing sCD83- with mock treated cells, revealed a strong downregulation of osteoclastogenic factors, such as Oc-Stamp, Mmp9 and Nfatc1, Ctsk, and Trap. Concomitantly, transcripts typical for pro-resolving macrophages, e.g., Mrc1/2, Marco, Klf4, and Mertk, were upregulated. Interestingly, members of the metallothionein (MT) family, which have been associated with a reduced arthritic disease severity, were also highly induced by sCD83 in samples derived from RA patients. Finally, we elucidated the sCD83-induced signaling cascade downstream to its binding to the Toll-like receptor 4/(TLR4/MD2) receptor complex using CRISPR/Cas9-induced knockdowns of TLR4/MyD88/TRIF and MTs, revealing that sCD83 acts via the TRIF-signaling cascade. In conclusion, sCD83 represents a promising therapeutic approach to induce the resolution of inflammation and to prevent bone erosion in autoimmune arthritis.
CRIS-Team WoS Importer:2022-09-09

The Treatment Reality of Octogenarians with Bladder Cancer in a Maximum Care Hospital - Sikic, D.; Wach, S.; Taubert, Helge; Richterstetter, M.; Kunath, F.; Lieb, V.; Krause, S.; Merten, Ricarda; Ott, O.; Fietkau, Rainer; Wullich, Bernd; Keck, Bastian (2016)
EVALuna2:18333

THE USE OF BOLUS IN POSTMASTECTOMY RADIATION THERAPY FOR BREAST CANCER: A SYSTEMATIC REVIEW - Dahn, Hannah; Boersma, Liesbeth; De Ruysscher, Dirk; Meattini, Icro; Offersen, Birgitte; Pignol, Jean-Philippe; Belkacemi, Yazid; Benjamin, Dori; Bese, Nuran; Coles, Charlotte; Franco, Pierfrancesco; Ho, Alice; et al. (Radiotherapy and Oncology, 2021)
Purpose Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT. Results 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus. Conclusions Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT.
CRIS-Team WoS Importer:2021-12-10
Keywords: breast cancer; mastectomy; radiation therapy; post-mastectomy; PMRT; bolus; tissue compensator

The use of bolus in postmastectomy radiation therapy for breast cancer: A systematic review - Dahn, Hannah M.; Boersma, Liesbeth J.; de Ruysscher, Dirk; Meattini, Icro; Offersen, Birgitte V.; Pignol, Jean Philippe; Aristei, Cynthia; Belkacemi, Yazid; Benjamin, Dori; Bese, Nuran; Coles, Charlotte E.; Franco, Pierfrancesco; et al. (Critical Reviews in Oncology Hematology, 2021)
Purpose: Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT. Results: 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus. Conclusions: Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT.
CRIS-Team Scopus Importer:2021-06-25
Keywords: bolus; breast cancer; mastectomy; PMRT; post-mastectomy; radiation therapy; tissue compensator

THE USE OF TTFIELDS FOR NEWLY DIAGNOSED GBM PATIENTS IN GERMANY IN ROUTINE CLINICAL CARE (TIGER: TTFIELDS IN GERMANY IN ROUTINE CLINICAL CARE) - Baehr, O.; Tabatabai, G.; Fietkau, Rainer; Goldbrunner, R.; Glas, M. (NEURO-ONCOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-20

The use of TTFields for newly diagnosed GBM patients in Germany in routine clinical care (TIGER: TTFields in Germany in routine clinical care) - Baehr, O.; Tabatabai, G.; Fietkau, Rainer; Goldbrunner, R.; Glas, M. (2019)
EVALuna2:213635

The various functions and phenotypes of macrophages are also reflected in their responses to irradiation: A current overview - Deloch, Lisa; Rückert, Michael; Weissmann, Thomas; Lettmaier, Sebastian; Titova, Eva; Wolff, Teresa; Weinrich, Felix; Fietkau, Rainer; Gaipl, Udo (International Review of Cell and Molecular Biology, 2023)
Macrophages are a vital part of the innate immune system that are involved in healthy biological processes but also in disease modulation and response to therapy. Ionizing radiation is commonly used in the treatment of cancer and, in a lower dose range, as additive therapy for inflammatory diseases. In general, lower doses of ionizing radiation are known to induce rather anti-inflammatory responses, while higher doses are utilized in cancer treatment where they result, next to tumor control, in rather inflammatory responses. Most experiments that have been carried out in ex vivo on macrophages find this to be true, however in vivo, tumor-associated macrophages, for example, show a contradictory response to the respective dose-range. While some knowledge in radiation-induced modulations of macrophages has been collected, many of the underlying mechanisms remain unclear. Due to their pivotal role in the human body, however, they are a great target in therapy and could potentially aid in better treatment outcome. We therefore summarized the current knowledge of macrophage mediated radiation responses.
CRIS-Team Scopus Importer:2023-04-07
Keywords: Immune cells; Immunology; Low-dose radiotherapy; Macrophage polarization; Macrophages; Radiotherapy; Rheumatoid arthritis; Tumor associated macrophages

Third-generation dual-source 70-kVp chest CT angiography with advanced iterative reconstruction in young children: image quality and radiation dose reduction - Rompel, Oliver; Glöckler, Martin; Janka, Rolf Matthias; Dittrich, Sven; Cesnjevar, Robert; Lell, Michael; Uder, Michael; Hammon, Matthias (Pediatric Radiology, 2016)
Many technical updates have been made in multi-detector CT.To evaluate image quality and radiation dose of high-pitch second- and third-generation dual-source chest CT angiography and to assess the effects of different levels of advanced modeled iterative reconstruction (ADMIRE) in newborns and children.Chest CT angiography (70 kVp) was performed in 42 children (age 158 ± 267 days, range 1-1,194 days). We evaluated subjective and objective image quality, and radiation dose with filtered back projection (FBP) and different strength levels of ADMIRE. For comparison were 42 matched controls examined with a second-generation 128-slice dual-source CT-scanner (80 kVp).ADMIRE demonstrated improved objective and subjective image quality (P < .01). Mean signal/noise, contrast/noise and subjective image quality were 11.9, 10.0 and 1.9, respectively, for the 80 kVp mode and 11.2, 10.0 and 1.9 for the 70 kVp mode. With ADMIRE, the corresponding values for the 70 kVp mode were 13.7, 12.1 and 1.4 at strength level 2 and 17.6, 15.6 and 1.2 at strength level 4. Mean CTDIvol, DLP and effective dose were significantly lower with the 70-kVp mode (0.31 mGy, 5.33 mGy*cm, 0.36 mSv) compared to the 80-kVp mode (0.46 mGy, 9.17 mGy*cm, 0.62 mSv; P < .01).The third-generation dual-source CT at 70 kVp provided good objective and subjective image quality at lower radiation exposure. ADMIRE improved objective and subjective image quality.
EVALuna2:14476

Thrombose genähter vs. gekoppelter Anastomosen bei mikrovaskulären Kopf- und Halsrekonstruktionen - Sievert, Matti; Koch, Michael; Goncalves, Miguel; Richter, Daniel; Tamse, Rosalie; Mueller, Sarina K.; Gostian, Antoniu-Oreste; Traxdorf, Maximilian; Harreus, Uli; Iro, Heinrich (Laryngo-Rhino-Otologie, 2020)
Objective The Anastomotic Coupling Device for microvascular anastomoses has become widely used in free tissue transplantation. This study compares the thrombosis rate and flap failure as a function of the anastomosis technique at a large head and neck cancer center. Material and Methods Retrospective analysis of all patients receiving free flap reconstructions in the period 2001-2019. Reconstruction type, recipient vessels, number of venous anastomoses, coupler size, and operation time were investigated. We compared the rates of venous thrombosis between hand sewn and coupled anastomoses, as well as the rate of flap failure. Results A total of 403 free flap reconstructions were performed for over 17 years. The venous anastomosis was sewn in 113 flaps in single suture technique, and in 290 cases, coupler device was used. The rate of venous thrombosis requiring immediate surgical revision was 6.2 % (7/113) in the sewn group compared to 7.6 % in the coupled group (22/290; p = 0.627). With an overall success rate of 95.0 % (383/403), the rate of flap failure was 3.6 % (4/113) and 5.5 % (16/290; p = 0.421), respectively. Surgical time is comparable with 680 ± 144 minutes in the hand-sewn group and 688 ± 167 minutes in the coupled group (p = 0.678). Conclusions With similar success rates, the coupler device is an effective alternative to venous anastomosis in single suture technique. Due to the generally low rate of pedicle thrombosis in both groups, we cannot separate the influence of the anastomosis technique from possible interfering variables.
CRIS-Team Scopus Importer:2020-10-02
Keywords: anastomotic coupling device; flap failure; free flap reconstruction; pedicle thrombosis; venous anastomosis

Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia—a prospective observational study - Koca, Selim; Distel, Luitpold; Lubgan, Dorota; Weissmann, Thomas; Lambrecht, Ulrike; Lang-Welzenbach, Marga; Eyüpoglu, Ilker Yasin; Bischoff, Barbara; Buchfelder, Michael; Semrau, Sabine; Fietkau, Rainer; Lettmaier, Sebastian; et al. (Strahlentherapie und Onkologie, 2019)
Purpose: To prospectively evaluate the time course of pain response and toxicity after linear accelerator-based whole-nerve-encompassing radiosurgery (LINAC-SRS) using a uniform treatment schedule for dosing and target volume definition in patients with refractory trigeminal neuralgia. Methods: From December 2012 to December 2016, 21 patients were treated using a standardized protocol. Patients received LINAC-SRS with 70 Gy to the cisternal portion while aiming for the 90% isodose to fully envelope the nerve in one cross-sectional plane. Data on pain, analgesics, and toxicity were gathered prospectively. Four time intervals (1–6, 6–12, 12–18, and 18–24 months) were defined and compared to baseline and each other. Results: The median follow-up from radiotherapy was 16 months. Freedom from pain was achieved at least once in 90.5, 81.0, and 85.7% of patients for everyday pain, rest pain, and pain peaks, respectively. At 1–6 months, pain was significantly reduced in everyday routine (mean VAS, 2.0/10 vs. 5.8/10; P = 0.004), at rest (1.5/10 vs. 4.0/10; P = 0.002), and for pain peaks (2.9/10 vs. 10/10; P < 0.001), as was the number of analgesics (mean 1.5 vs. 2.9; P < 0.001). No significant increase in pain or analgesics was observed for subsequent time intervals. At last follow-up, reduction in pain compared to baseline for everyday routine (2.1/10 vs. 5.8/10; P = 0.010) and for pain peaks (3.3/10 vs. 10/10; P < 0.001) was significant, whereas it was not for rest pain (1.8/10 vs. 3.9/10; P = 0.073). Most toxicities were related to trigeminal nerve impairment, with 42.9% reporting new-onset hypoesthesia at last follow-up. Conclusion: This study provides prospective data after whole nerve encompassing LINAC-SRS for trigeminal neuralgia. No significant pain relapse was observed.
CRIS-Team Scopus Importer:2019-08-02
Keywords: Facial pain; Radiosurgery; SRS; Toxicity; Trigeminal neuralgia

Time dependency of adjuvant therapy in advanced head-and-necksquamous-cell-carcinoma of unknown primary (CUP)-patients - Balk, Matthias; Rupp, Robin; Grundtner, Philipp; Mueller, Sarina K.; Allner, Moritz; Traxdorf, Maximilian; Eckstein, Markus; Hecht, Markus; Iro, Heinrich; Gostian, Antoniu-Oreste (ORAL ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-07-16

Time-dependent risk factors for epileptic seizures in glioblastoma patients: A retrospective analysis of 520 cases - Stritzelberger, Jenny; Gesmann, Anna; Fuhrmann, Imke; Brandner, Sebastian; Welte, Tamara; Balk, Stefanie; Eisenhut, Felix; Dörfler, Arnd; Coras, Roland; Adler, Werner; Schwab, Stefan; Putz, Florian; et al. (Epilepsia, 2023)
Objective: Epilepsy is a common comorbidity of glioblastoma. Seizures may occur in various phases of the disease. We aimed to assess potential risk factors for seizures in accordance with the point in time at which they occurred. Methods: We retrospectively analyzed medical files of adult patients with de novo glioblastoma treated at our institution between January 2006 and January 2020. We categorized seizures as preoperative seizures (POS), early postoperative seizures (EPS; before initiation of radio[chemo]therapy [RCT]), seizures during radiotherapy (SDR; during or <30 days after RCT), and posttherapeutic seizures (PTS; ≥30 days after completion of RCT). We addressed associations between patients' characteristics and their seizures. Results: In the final cohort (N = 520), 292 patients experienced seizures. POS, EPS, SDR, and/or PTS occurred in 29.6% (154/520), 6.0% (31/520), 13.8% (70/509), and 36.1% (152/421) of patients, respectively. POS occurred more frequently in patients with higher Karnofsky Performance Scale scores (odds ratio [OR] = 3.27, p =.001) and tumor location in the temporal lobe (OR = 1.51, p =.034). None of the parameters we analyzed was related to the occurrence of EPS. SDR were independently associated with tumor location (parietal lobe, OR = 1.86, p =.027) and POS, but not EPS, and were independent of RCT. PTS were independently associated with tumor progression (OR = 2.32, p <.001) and with occurrence of SDR (OR = 3.36, p <.001), and negatively correlated with temporal lobe location (OR =.58, p <.014). In patients with tumors exclusively located in the temporal lobe, complete tumor resection was associated with a decreased risk of postoperative seizures. Significance: Seizures in glioblastoma patients have various, time-dependent risk factors. Temporal lobe localization was a risk factor for preoperative seizures; surgery may have had a protective effect in these patients. RCT did not have dose-dependent pro- or anticonvulsive effects. PTS were associated with tumor progression.
CRIS-Team Scopus Importer:2023-07-07
Keywords: glioblastoma; radiochemotherapy; seizures; surgery

TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination - Bohnert, Simone; Seiffert, Anja; Trella, Stefanie; Bohnert, Michael; Distel, Luitpold; Ondruschka, Benjamin; Monoranu, Camelia Maria (International Journal of Legal Medicine, 2020)
The aim of the present study was a refined analysis of neuroinflammation including TMEM119 as a useful microglia-specific marker in forensic assessments of traumatic causes of death, e.g., traumatic brain injury (TBI). Human brain tissue samples were obtained from autopsies and divided into cases with lethal TBI (n = 25) and subdivided into three groups according to their trauma survival time and compared with an age-, gender-, and postmortem interval-matched cohort of sudden cardiovascular fatalities as controls (n = 23). Brain tissue samples next to cortex contusions and surrounding white matter as well as samples of the ipsilateral uninjured brain stem and cerebellum were collected and stained immunohistochemically with antibodies against TMEM119, CD206, and CCR2. We could document the highest number of TMEM119-positive cells in acute TBI death with highly significant differences to the control numbers. CCR2-positive monocytes showed a significantly higher cell count in the cortex samples of TBI cases than in the controls with an increasing number of immunopositive cells over time. The number of CD206-positive M2 microglial cells increased survival time-dependent. After 3 days of survival, the cell number increased significantly in all four regions investigated compared with controls. In sum, we validate a specific and robustly expressed as well as fast reacting microglia marker, TMEM119, which distinguishes microglia from resident and infiltrating macrophages and thus offers a great potential for the estimation of the minimum survival time after TBI.
CRIS-Team Scopus Importer:2020-08-07
Keywords: Biomarker; Cerebrospinal fluid; Forensic neuropathology; Forensic neurotraumatology; Immunocytochemistry; Immunohistochemistry

TNT in rectal cancer: Final results of the CAO/ARO/AIO-12 randomized phase 2 trial - Fokas, E.; Schlenska-Lange, A.; Polat, B.; Klautke, G.; Fietkau, Rainer; Kuhnt, T.; Brunner, T.; Grosu, A.; Kirste, S.; Flentje, M.; Germer, C.; Bechstein, W.; et al. (RADIOTHERAPY AND ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-11-26

Total Neoadjuvant Therapy as Organ Preserving Therapy for Rectal Cancer: The CAO/ARO/AIO-16 Phase II Study - Gani, C.; Polat, B.; Ott, Oliver; Germer, E.; Koenigsrainer, A.; Kirschniak, A.; Clasen, S.; Grosse, U.; Diefenhardt, M.; Reibetanz, J.; Bitzer, M.; Martus, P.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)
CRIS-Team WoS Importer:2022-06-03

Toward a deep learning-based magnetic resonance imaging only workflow for postimplant dosimetry in I-125 seed brachytherapy for prostate cancer - Grigo, Johanna; Karius, Andre; Hanspach, Jannis; Mücke, Lion; Laun, Frederik B.; Huang, Yixing; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph; Putz, Florian (Brachytherapy, 2024)
Background and purpose: The current standard imaging-technique for creating postplans in seed prostate brachytherapy is computed tomography (CT), that is associated with additional radiation exposure and poor soft tissue contrast. To establish a magnetic resonance imaging (MRI) only workflow combining improved tissue contrast and high seed detectability, a deep learning-approach for automatic seed segmentation on MRI-scans was developed. Material and methods: Patients treated with I-125 seed brachytherapy received a postplan-CT and a 1.5 T MRI-scan on nominal day 30 after implantation. For MRI-based seed visualization, DIXON-sequences were acquired and deep learning-based quantitative susceptibility maps (QSM) were generated from 3D-gradient-echo-sequences from 20 patients. Seed segmentations created on CT served as ground truth. For automatic seed segmentation on MRI, a 3D nnU-net model was trained using QSM and DIXON, both solely and combined. Results: Of the implanted seeds 94.8 ± 2.4% were detected with deep learning automatic segmentation entrained on both QSM and DIXON data. Models trained on the individual sequence data-sets performed worse with detection rates of 87.5 ± 2.6% or 88.6 ± 7.5% for QSM and DIXON respectively. The seed centers identified on CT versus QSM and DIXON were on average 1.8 ± 1.3 mm apart. Postimplant dosimetry for evaluation of positioning inaccuracies revealed only small variations of up to 0.4 ± 4.26 Gy in D90 (dose 90% of the prostate receives) between the standard CT-approach and our MRI-only workflow. Conclusion: The proposed deep learning-based MRI-only workflow provided a promisingly accurate and robust seed localization and thus has the potential to compete with current state-of-the-art CT-based postimplant dosimetry in the future.
CRIS-Team Scopus Importer:2024-02-02
Keywords: Magnetic resonance imaging; Magnetic resonance only workflow; Permanent brachytherapy; Postimplant dosimetry; Radiotherapy; Seed brachytherapy

Towards a Computable Data Corpus of Temporal Correlations between Drug Administration and Lab Value Changes - Newe, Axel; Wimmer, Stefan; Neubert, Antje; Becker, Linda; Prokosch, Hans-Ulrich; Beckmann, Matthias; Fietkau, Rainer; Forster, Christian; Neurath, Markus; Schett, Georg; Ganslandt, Thomas (PLoS ONE, 2015)
Background The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though. Methods In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration. Result The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations. Discussion The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in retrospective data. With this lab value curve data as a basis, algorithms for detecting temporal relationships can be developed, and with the classification made by human experts, these algorithms can immediately be validated. Due to the normalization of the lab value data, it allows for a generic approach rather than for specific or solitary drug/lab value combination

Trainable joint bilateral filters for enhanced prediction stability in low-dose CT - Wagner, Fabian; Thies, Mareike; Denzinger, Felix; Gu, Mingxuan; Patwari, Mayank; Ploner, Stefan; Maul, Noah; Pfaff, Laura; Huang, Yixing; Maier, Andreas (Scientific Reports, 2022)
Low-dose computed tomography (CT) denoising algorithms aim to enable reduced patient dose in routine CT acquisitions while maintaining high image quality. Recently, deep learning (DL)-based methods were introduced, outperforming conventional denoising algorithms on this task due to their high model capacity. However, for the transition of DL-based denoising to clinical practice, these data-driven approaches must generalize robustly beyond the seen training data. We, therefore, propose a hybrid denoising approach consisting of a set of trainable joint bilateral filters (JBFs) combined with a convolutional DL-based denoising network to predict the guidance image. Our proposed denoising pipeline combines the high model capacity enabled by DL-based feature extraction with the reliability of the conventional JBF. The pipeline’s ability to generalize is demonstrated by training on abdomen CT scans without metal implants and testing on abdomen scans with metal implants as well as on head CT data. When embedding RED-CNN/QAE, two well-established DL-based denoisers in our pipeline, the denoising performance is improved by 10%/82% (RMSE) and 3%/81% (PSNR) in regions containing metal and by 6%/78% (RMSE) and 2%/4% (PSNR) on head CT data, compared to the respective vanilla model. Concluding, the proposed trainable JBFs limit the error bound of deep neural networks to facilitate the applicability of DL-based denoisers in low-dose CT pipelines.<br

Transcriptomes of MPO-deficient patients with generalized pustular psoriasis reveals expansion of CD4+cytotoxic T cells and an involvement of complement system and interferon pathways - Hüffmeier, Ulrike; Frey, Benjamin; Becker, Ina; Atreya, Imke; Berking, Carola; Moessner, R.; Wilsmann-Theis, D.; Uebe, Steffen; Kirchner, P.; Haskamp, Stefan (JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2021)
CRIS-Team WoS Importer:2021-11-05

Transcriptomes of MPO-Deficient Patients with Generalized Pustular Psoriasis Reveals Expansion of CD4+ Cytotoxic T Cells and an Involvement of the Complement System - Haskamp, Stefan; Frey, Benjamin; Becker, Ina; Schulz-Kuhnt, Anja; Atreya, Imke; Berking, Carola; Pauli, David; Ekici, Arif Bülent; Berges, Johannes; Mößner, Rotraut; Wilsmann-Theis, Dagmar; Sticherling, Michael; et al. (Journal of Investigative Dermatology, 2022)
Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state. Cell-type annotation by multimodal reference mapping of single-cell RNA-sequencing data was verified by flow cytometry of surface and intracellular markers; the proportions of CD4+ cytotoxic T lymphocytes and other CD4+ effector cells were increased in generalized pustular psoriasis, whereas the frequencies of naïve CD4+ T cells were significantly lower. The expression of FGFBP2 marking CD4+ cytotoxic T lymphocytes and CD8+ effector memory T cells was elevated in patients with generalized pustular psoriasis with disease-contributing variants compared with that in noncarriers (P = 0.0015). In neutrophils, differentially expressed genes were significantly enriched in genes of the classical complement activation pathway. Future studies assessing affected cell types and pathways will show their contribution to generalized pustular psoriasis's pathogenesis and indicate whether findings can be transferred to the acute epidermal situation and whether depletion or inactivation of CD4+ cytotoxic T lymphocytes may be a reasonable therapeutic approach.
CRIS-Team Scopus Importer:2022-07-08

Transient Enlargement in Meningiomas Treated with Stereotactic Radiotherapy - Maksoud, Ziad; Schmidt, Manuel; Huang, Yixing; Rutzner, Sandra; Mansoorian, Sina; Weissmann, Thomas; Bert, Christoph; Distel, Luitpold; Semrau, Sabine; Lettmaier, Sebastian; Eyüpoglu, Ilker Yasin; Fietkau, Rainer; et al. (Cancers, 2022)
To investigate the occurrence of pseudoprogression/transient enlargement in meningiomas after stereotactic radiotherapy (RT) and to evaluate recently proposed volumetric RANO meningioma criteria for response assessment in the context of RT. Sixty-nine meningiomas (benign: 90%, atypical: 10%) received stereotactic RT from January 2005–May 2018. A total of 468 MRI studies were segmented longitudinally during a median follow-up of 42.3 months. Best response and local control were evaluated according to recently proposed volumetric RANO criteria. Transient enlargement was defined as volumetric increase ≥20% followed by a subsequent regression ≥20%. The mean best volumetric response was −23% change from baseline (range, −86% to +19%). According to RANO, the best volumetric response was SD in 81% (56/69), MR in 13% (9/69) and PR in 6% (4/69). Transient enlargement occurred in only 6% (4/69) post RT but would have represented 60% (3/5) of cases with progressive disease if not accounted for. Transient enlargement was characterized by a mean maximum volumetric increase of +181% (range, +24% to +389 %) with all cases occurring in the first year post-RT (range, 4.1–10.3 months). Transient enlargement was significantly more frequent with SRS or hypofractionation than with conventional fractionation (25% vs. 2%, p = 0.015). Five-year volumetric control was 97.8% if transient enlargement was recognized but 92.9% if not accounted for. Transient enlargement/pseudoprogression in the first year following SRS and hypofractionated RT represents an important differential diagnosis, especially because of the high volumetric control achieved with stereotactic RT. Meningioma enlargement during subsequent post-RT follow-up and after conventional fractionation should raise suspicion for tumor progression. <
Keywords: meningioma; volumetric analysis; segmentation; transient enlargement; pseudoprogression; stereotactic radiotherapy; radiosurgery; response assessment

Transvenous renal transplant biopsy via a transfemoral approach - Schmid, Axel; Jacobi, Johannes; Kuefner, M. A.; Lell, Michael; Wüst, Wolfgang; Mayer-Kadner, I.; Benz, Kerstin; Schmid, Matthias; Amann, Kerstin Ute; Uder, Michael (American Journal of Transplantation, 2013)
Percutaneous renal biopsy (PRB) of kidney transplants might be prevented by an elevated risk of bleeding or limited access to the allograft. In the following, we describe our initial experience with 71 transvenous renal transplant biopsies in 53 consecutive patients with unexplained reduced graft function who were considered unsuitable candidates for PRB (4.2% of all renal transplant biopsies at our institution). Biopsies were performed via the ipsilateral femoral vein with a renal biopsy set designed for transjugular renal biopsy (TJRB) of native kidneys. Positioning of the biopsy system within the transplant vein was achievable in 58 of 71 (81.7%) procedures. The specimen contained a median of 10 glomeruli (range 0-38). Tissue was considered as adequate for diagnosis in 56 of 57 (98.2%) biopsies. With respect to BANFF 50.9% of the specimen were adequate (>10 glomeruli), 47.4% marginally adequate (1-9 glomeruli) and 1.8% inadequate (no glomeruli). After implementation of real-time assessment all specimen contained glomeruli. One of the fifty-eight (1.8%) procedure-related major complications occurred (hydronephrosis requiring nephrostomy due to gross hematuria). Transfemoral renal transplant biopsy (TFRTB) is feasible and appears to be safe compared to PRB. It offers a useful new alternative for histological evaluation of graft dysfunction in selected patients with contraindications to PRB. The authors report on an experience using transvenous renal transplant biopsy to enable histological evaluation in patients unsuitable for percutaneous transplant biopsy. © 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
CRIS-Team Scopus Importer:2023-03-08
Keywords: Kidney transplant; percutaneous renal transplant biopsy; renal allograft; renal transplant biopsy; transjugular renal biopsy; transvenous biopsy

Treatment Characteristics and Real-World Progression-Free Survival in Patients With Unresectable Stage III NSCLC Who Received Durvalumab After Chemoradiotherapy: Findings From the PACIFIC-R Study - Girard, Nicolas; Bar, Jair; Garrido, Pilar; Garassino, Marina C.; McDonald, Fiona; Mornex, Françoise; Filippi, Andrea R.; Smit, Hans J.M.; Peters, Solange; Field, John K.; Christoph, Daniel C.; Sibille, Anne; et al. (Journal of Thoracic Oncology, 2022)
Introduction: The phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III NSCLC and no disease progression after definitive chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program. Here, we report treatment characteristics and a preplanned analysis of real-world progression-free survival (rwPFS). Methods: PACIFIC-R (NCT03798535) is an ongoing, international, retrospective study of patients who started durvalumab (intravenously; 10 mg/kg every 2 wk) within an early access program between September 2017 and December 2018. The primary end points are investigator-assessed rwPFS and overall survival (analyzed by Kaplan–Meier method). Results: As of November 30, 2020, the full analysis set comprised 1399 patients from 11 countries (median follow-up duration, 23.5 mo). Patients received durvalumab for a median of 11.0 months. Median rwPFS was 21.7 months (95% confidence interval: 19.1–24.5). RwPFS was numerically longer among patients who received concurrent versus sequential CRT (median, 23.7 versus 19.3 mo) and among patients with programmed cell death-ligand 1 expression greater than or equal to 1% versus less than 1% (22.4 versus 15.6 mo). Overall, 16.5% of the patients had adverse events leading to treatment discontinuation; 9.5% of all patients discontinued because of pneumonitis or interstitial lung disease. Conclusions: Consolidation durvalumab after definitive CRT was well tolerated and effective in this large, real-world cohort study of patients with unresectable, stage III NSCLC. As expected, rwPFS was longer among patients who received concurrent versus sequential CRT and patients with higher programmed cell death-ligand 1 expression. Nevertheless, favorable rwPFS outcomes were observed regardless of these factors.
CRIS-Team Scopus Importer:2022-12-02
Keywords: Consolidation therapy; Immunotherapy; Locally advanced NSCLC; PD-L1 inhibition; Real-world data

Treatment of arrhythmias by external charged particle beams: a Langendorff feasibility study - Prall, Matthias; Lehmann, H. Immo; Prokesch, Hannah; Richter, Daniel; Graeff, Christian; Kaderka, Robert; Sonnenberg, Karin; Hauswald, Henrik; Weymann, Alexander; Bauer, Julia; Constantinescu, Anna; Haberer, Thomas; et al. (Biomedizinische Technik, 2015)
Hadron therapy has already proven to be successful in cancer therapy, and might be a noninvasive alternative for the ablation of cardiac arrhythmias in humans. We present a pilot experiment investigating acute effects of a 12C irradiation on the AV nodes of porcine hearts in a Langendorff setup. This setup was adapted to the requirements of charged particle therapy. Treatment plans were computed on calibrated CTs of the hearts. Irradiation was applied in units of 5 and 10 Gy over a period of about 3 h until a total dose of up to 160 Gy was reached. Repeated application of the same irradiation field helped to mitigate motion artifacts in the resulting dose distribution. After irradiation, PET scans were performed to verify accurate dose application. Acute AV blocks were identified. No other acute effects were observed. Hearts were kept in sinus rhythm for up to 6 h in the Langendorff setup. We demonstrated that 12C ions can be used to select a small target in the heart and, thereby, influence the electrical conduction system. Second, our pilot study seems to suggest that no adverse effects have to be expected immediately during heavy ion irradiation in performing subsequent experiments with doses of 30-60 Gy and intact pigs.
EVALuna2:18316

Treatment of cervical paragangliomas: is surgery the only way? - Künzel, Julian; Koch, Michael; Brase, Christoph; Fietkau, Rainer; Iro, Heinrich; Zenk, Johannes (American Journal of Otolaryngology, 2014)
To analyze the results after surgery or stereotactic radiotherapy (SRT) in the treatment of cervical paragangliomas. Against this background, the decision-making algorithm used in the treatment of carotid body tumors (CBTs) and vagal paragangliomas (VPs) was reevaluated relative to the existing literature on the topic.Retrospective study between 2000 and 2012. A total of 27 CBTs and nine VPs in 32 patients were treated. Shamblin class I: 59.3% (n=16); class II: 29.6% (n=8); class III: 11.1% (n=3). Treatment modalities were surgery, radiotherapy, or observation. The end points for analysis were long-term tumor control and integrity of the cranial nerves.21 CBTs and seven VPs underwent surgery; SRT was performed in three CBTs and two VPs. Three CBTs were clinically observed. Permanent nerve paresis followed after surgery for CBTs in five patients (20%) and in all patients with VPs. No impaired cranial nerve function resulted after SRT. The median follow-up period was 4.7 years. The tumor control rate after therapy for CBTs and VPs was 100%. One CBT that received clinical observation showed slow tumor progression.A surgical procedure should be regarded as the treatment of choice in patients with small CBTs. In larger CBTs, particularly in elderly patients with unimpaired cranial nerves, radical surgery should be regarded critically. As surgery for VPs caused regularly impairment of cranial nerves with functional disturbances of various degrees a comprehensive consultation with the patient is mandatory and nonsurgical strategies should be discussed.
EVALuna2:18181

Treatment Parameters Optimization to Compensate for Interfractional Anatomy Variability and Intrafractional Tumor Motion - Brevet, Romain; Richter, Daniel; Graeff, Christian; Durante, Marco; Bert, Christoph (Frontiers in Oncology, 2015)
Scanned ion beam therapy of lung tumors is severely limited in its clinical applicability by intrafractional organ motion, interference effects between beam and tumor motion (interplay), as well as interfractional anatomic changes. To compensate for dose deterioration caused by intrafractional motion, motion mitigation techniques, such as gating, have been developed. However, optimization of the treatment parameters is needed to further improve target dose coverage and normal tissue sparing. The aim of this study was to determine treatment-planning parameters that permit to recover good target coverage for each fraction of lung tumor treatments. For 9 lung tumor patients from MD Anderson Cancer Center (Houston, Texas), a total of 70 weekly time-resolved computed tomography (4DCT) datasets, which depict the evolution of the patient anatomy over the several fractions of the treatment, were available. Using the GSI in-house treatment planning system TRiP4D, 4D simulations were performed on each weekly 4DCT for each patient using gating and optimization of a single treatment plan based on a planning CT acquired prior to treatment. The impact on target dose coverage (V 95%,CTV) of variations in focus size and length of the gating window, as well as different additional margins and the number of fields was analyzed. It appeared that interfractional variability could potentially have a larger impact on V 95%,CTV than intrafractional motion. However, among the investigated parameters, the use of a large beam spot size, a short gating window, additional margins, and multiple fields permitted to obtain an average V 95%,CTV of 96.5%. In the presented study, it was shown that optimized treatment parameters have an important impact on target dose coverage in the treatment of moving tumors. Indeed, intrafractional motion occurring during the treatment of lung tumors and interfractional variability were best mitigated using a large focus, a short gating window, additional margins, and three fields.
EVALuna2:18368

Treatment planning facilitates clinical decision making for hyperthermia treatments - Kok, H. P.; van der Zee, J.; Guirado, F. Navarro; Bakker, A.; Datta, N. R.; Abdel-Rahman, S.; Schmidt, Manfred; Wust, P.; Crezee, J. (International Journal of Hyperthermia, 2021)
Background: Treatment quality is important in clinical hyperthermia. Guideline-based treatment protocols are used to determine system settings and treatment strategies to ensure effective tumor heating and prevent unwanted treatment-limiting normal tissue hot spots. Realizing both these goals can prove challenging using generic guideline-based and operator-dependent treatment strategies. Hyperthermia treatment planning (HTP) can be very useful to support treatment strategies. Although HTP is increasingly integrated into the standard clinical workflow, active clinical application is still limited to a small number of hyperthermia centers and should be further stimulated. Purpose: This paper aims to serve as a practical guide, demonstrating how HTP can be applied in clinical decision making for both superficial and locoregional hyperthermia treatments. HTP in clinical decision making: Seven problems that occur in daily clinical practice are described and we show how HTP can enhance insight to formulate an adequate treatment strategy. Examples use representative commercially available hyperthermia devices and cover all stages during the clinical workflow. Problems include selecting adequate phase settings, heating ability analysis, hot spot suppression, applicator selection, evaluation of target coverage and heating depth, and predicting possible thermal toxicity in case of an implant. Since we aim to promote a general use of HTP in daily practice, basic simulation strategies are used in these problems, avoiding a need for the application of dedicated advanced optimization routines that are not generally available. Conclusion: Even fairly basic HTP can facilitate clinical decision making, providing a meaningful and clinically relevant contribution to maintaining and improving treatment quality.
CRIS-Team Scopus Importer:2021-04-16
Keywords: clinical decision making; Hyperthermia; optimization; treatment planning; treatment quality; treatment strategy

Treatment planning for spinal radiosurgery - Moustakis, Christos; Chan, Mark K. H.; Kim, Jinkoo; Nilsson, Joakim; Bergman, Alanah; Bichay, Tewfik J.; Palazon Cano, Isabel; Cilla, Savino; Deodato, Francesco; Doro, Raffaela; Dunst, Juergen; Eich, Hans Theodor; et al. (Strahlentherapie und Onkologie, 2018)
To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. All 12 centers could reach equality (n= 4) or outperform (n= 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p= 0.002). High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.
EVALuna2:213677

Treatment Planning Studies in Patient Data With Scanned Carbon Ion Beams for Catheter-Free Ablation of Atrial Fibrillation - Constantinescu, Anna; Lehmann, H. Immo; Packer, Douglas L.; Bert, Christoph; Durante, Marco; Graeff, Christian (Journal of Cardiovascular Electrophysiology, 2016)
Catheter ablation with isolation of the pulmonary veins is a common treatment option for atrial fibrillation but still has insufficient success rates and carries several interventional risks. These treatment planning studies assessed if high-dose single fraction treatment with scanned carbon ions (12C) can be reliably delivered for AF ablation, while sparing risk structures and considering respiratory and contractile target motion.Time resolved CT scans of complete respiratory and cardiac cycles of 9 and 5 patients, respectively, were obtained. Ablation lesions and organs at risk for beam delivery were contoured. Single fraction intensity-modulated particle therapy with target doses of 25 and 40 Gy were studied and motion influences on these deliveries mitigated. Respiration had a large influence on lesion displacement (<= 2 cm). End expiration could be exploited as a stable gating window. Smaller, but less predictable, heartbeat displacements (< 6 mm) remained to be mitigated because cardiac contraction resulted in insufficient dose coverage (V95 < 90%) if uncompensated. Repeated irradiation (12C beam rescanning) during breath hold was used to accommodate contractile motion, resulting in good dose coverage. Dose depositions to all organs at risk were carefully examined and did not exceed values for X-ray cancer treatment.Treatment planning of 12C with delivery of physical ionizing radiation doses that have been described to induce complete block is feasible for AF ablation, considering human anatomy, dose constraints, and encasing underlying motion patterns from respiration and cardiac contraction at the LA-PV junction into treatment planning.
EVALuna2:18342

Treatment Response and Prophylactic Cranial Irradiation Are Important Prognostic Factors in LD SCLC Patients Staged with cMRI - Eze, Chukwuka; Roengvoraphoj, Olarn; Niyazi, Maximilian; Hildebrandt, Guido; Fietkau, Rainer; Belka, Claus; Manapov, Farkhad (2017)
EVALuna2:32914

Treatment Response and Prophylactic Cranial Irradiation Are Prognostic Factors in a Real-life Limited-disease Small-cell Lung Cancer Patient Cohort Comprehensively Staged With Cranial Magnetic Resonance Imaging - Eze, Chukwuka; Roengvoraphoj, Olarn; Niyazi, Maximilian; Hildebrandt, Guido; Fietkau, Rainer; Belka, Claus; Manapov, Farkhad (Clinical Lung Cancer, 2017)
INTRODUCTION: Prophylactic cranial irradiation (PCI) has proven to decrease the incidence of brain metastases (BMs), with a modest improvement in survival. PATIENTS AND METHODS: The impact of PCI was evaluated in 184 patients treated with chemoradiotherapy. PCI was applied to patients with disease with partial and complete response only when cranial magnetic resonance imaging before and after primary treatment revealed no BMs. Correlation between PCI and overall survival (OS), BM-free survival (BMFS), and time to progression (TTP) was analyzed to describe survival within subgroups. RESULTS: Concurrent and sequential chemoradiotherapy was applied in 71 patients (39%) and 113 patients (61%), respectively. Seventy-one patients (39%) with partial and complete response were treated with PCI. Metachronous BMs were detected in 16 (23%) of 71 patients in the PCI group compared to 42 (37%) of 113 patients in the non-PCI group. Median BMFS in the PCI group was not reached; it was 23.6 months in the non-PCI group. Median OS and TTP were 26 months (range, 19.4-32.6 months) in the PCI group versus 14 months (range, 11.4-16.6 months) in patients without PCI whose disease responded to therapy versus 9 months in patients with disease that did not respond to therapy (P < .0001), and 27 versus 14.5 months (range, 9.0-19.9 months) versus 8.8 months (range, 7.7-9.9 months) (P < .0001) in the PCI group versus those with response without PCI versus those with nonresponse. The effect of PCI was independent of gender. On multivariate analysis, PCI was a variable correlating with OS (hazard ratio = 1.899; 95% confidence interval, 1.370-2.632; P < .0001) and TTP (hazard ratio = 2.164; 95% confidence interval, 1.371-3.415; P = .001) after adjustment for other prognostic factors. CONCLUSION: In real-life patients comprehensively staged with cranial magnetic resonance imaging, treatment response and PCI strongly correlated with prolonged OS, TTP, and BMFS.
EVALuna2:36447

Treatment response lowers tumor symptom burden in recurrent and/or metastatic head and neck cancer - Hecht, Markus; Hahn, Dennis; Wolber, Philipp; Hautmann, Matthias G.; Reichert, Dietmar; Weniger, Steffi; Belka, Claus; Bergmann, Tobias; Göhler, Thomas; Welslau, Manfred; Große-Thie, Christina; Guntinas-Lichius, Orlando; et al. (BMC Cancer, 2020)
Background: Head and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC. Methods: In this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0-100), which were summarized to the overall VAS score. Results: Fourhundred seventy patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (-2.13 vs. non-responders + 1.15, p = 0.048), and even more for the best post-baseline assessment (-7.82 vs. non-responders-1.97, p = 0.0005). The VAS for pain (-16.37 vs. non-responders-8.89, p = 0.001) and swallowing of solid food (-16.67 vs. non-responders-5.06, p = 0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05-1.20, p = 0.0009). Conclusion: In unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC.
CRIS-Team Scopus Importer:2020-10-23
Keywords: Cetuximab; Chemotherapy; HNSCC; Response; Symptom

Treatment strategy by radioiodine refractory differentiated thyroid cancer - Mantsopoulos, Konstantinos; Mueller, Sarina K.; Pavel, Marianne Ellen; Kuwert, Torsten; Meidenbauer, Norbert; Fietkau, Rainer; Sievert, Matti; Iro, Heinrich (Laryngo-Rhino-Otologie, 2021)
Zusammenfassung Traditionell besteht das multimodale Therapiekonzept bei den differenzierten Schilddrusenkarzinomen in der Thyreoidektomie mit Neck-Dissection (bei cN+-Halsstatus) und adjuvanten Radiojodablation mit abschlie ss ender risikoadaptierter TSH-Suppression. Das Ausma ss der Radiojodaufnahme beim metastasierten Schilddrusenkarzinom spielt eine signifikante Rolle bei der Einschatzung der Prognose. Das fehlende Jodspeicherungsvermogen einer Lasion in Zusammenschau mit dem fehlenden Abfall des Tumormarkers Thyreoglobulin sowie radiologische Zeichen einer Tumorprogression charakterisieren den Radiojod-refraktaren Patienten. Aufgrund des meistens uber einen langen Zeitraum indolenten Verlaufs erscheint in den meisten Fallen ein abwartendes Verhalten in Kombination mit lokaler Metastasenbehandlung sowie Symptomlinderung primar sinnvoll zu sein. Der Nachweis einer Veranderung der Tumordynamik ist der Zeitpunkt, um eine Systemtherapie zu evaluieren. Diese beruht auf Multi-Tyrosinkinase-Inhibitoren (Sorafenib, Lenvatinib). Diese Substanzen sind gro ss tenteils mit einem ungunstigen Nebenwirkungsprofil assoziiert (Diarrho, Hautauschlage, arterielle Hypertonie mit hypertensiver Entgleisung, lokale Wundheilungsstorungen), welches zu einer nicht vernachlassigbaren Rate einer therapieassoziierten Morbiditat sowie einer hohen Anzahl an Therapieunterbrechungen fuhrt. Daher sind im Jahr 2020 2 selektive RET-Inhibitoren (Selpercatinib, Pralsetinib) fur die differenzierten Schilddrusenkarzinome von der FDA zugelassen worden. Eine neue Perspektive fur die Zukunft waren die unterschiedlichen Redifferenzierungsstrategien, welche auf die Steigerung der Sensitivitat der Tumorzellen auf Radiojod abzielen.
CRIS-Team WoS Importer:2021-10-08

Trends in radiotherapy inpatient admissions in Germany: a population-based study over a 10-year period - Medenwald, Daniel; Fietkau, Rainer; Klautke, Gunther; Langer, Susan; Wuerschmidt, Florian; Vordermark, Dirk (Strahlentherapie und Onkologie, 2021)
Objective With the increasing complexity of oncological therapy, the number of inpatient admissions to radiotherapy and non-radiotherapy departments might have changed. In this study, we aim to quantify the number of inpatient cases and the number of radiotherapy fractions delivered under inpatient conditions in radiotherapy and non-radiotherapy departments. Methods The analysis is founded on data of all hospitalized cases in Germany based on Diagnosis-Related Group Statistics (G-DRG Statistics, delivered by the Research Data Centers of the Federal Statistical Office). The dataset includes information on the main diagnosis of cases (rather than patients) and the performed procedures during hospitalization based on claims of reimbursement. We used linear regression models to analyze temporal trends. The considered data encompass the period from 2008 to 2017. Results Overall, the number of patients treated with radiotherapy as inpatients remained constant between 2008 (N = 90,952) and 2017 (N = 88,998). Starting in January 2008, 48.9% of 4000 monthly cases received their treatment solely in a radiation oncology department. This figure decreased to 43.7% of 2971 monthly cases in October 2017. We found a stepwise decrease between December 2011 and January 2012 amounting to 4.3%. Fractions received in radiotherapy departments decreased slightly by 29.3 (95% CI: 14.0–44.5) fractions per month. The number of days hospitalized in radiotherapy departments decreased by 83.4 (95% CI: 59.7, 107.0) days per month, starting from a total of 64,842 days in January 2008 to 41,254 days in 2017. Days per case decreased from 16.2 in January 2008 to 13.9 days in October 2017. Conclusion Our data give evidence to the notion that radiotherapy remains a discipline with an important inpatient component. Respecting reimbursement measures and despite older patients with more comorbidities, radiotherapy institutions could sustain a constant number of cases with limited temporal shifts.
CRIS-Team WoS Importer:2021-09-10
Keywords: Inpatient cases; Radiotherapy departments; DRG data; Germany; Non-radiotherapy departments

Tricks and tips for target volume definition and delineation in breast cancer: Lessons learned from ESTRO breast courses - Kaidar-Person, Orit; Offersen, Birgitte V.; Boersma, Liesbeth; Meattini, Icro; Dodwell, David; Wyld, Lynda; Aznar, Marianne; Major, Tibor; Kuehn, Thorsten; Strnad, Vratislav; Palmu, Miika; Hol, Sandra; et al. (Radiotherapy and Oncology, 2021)
Delineation of target and ‘organ at risk’ volumes is a critical part of modern radiation therapy planning, the next essential step after deciding the indication, patient discussion and image acquisition. Adoption of volume-based treatment planning for non-metastatic breast cancer has increased greatly along with the use of improved planning techniques, essential for modern therapy. However, identifying the volumes on a planning CT is no easy task. The current paper is written by ESTRO's breast course faculty, providing tricks and tips for target volume definition and delineation for optimal postoperative breast cancer irradiation.
CRIS-Team Scopus Importer:2021-08-13
Keywords: Breast cancer; Delineation; ESTRO; Lymph nodes; Radiation therapy

TTFIELDS IN ROUTINE CLINICAL CARE OF NEWLY DIAGNOSED GBM PATIENTS IN GERMANY - FIRST REPORT ON THE FULLY ENROLLED TIGER STUDY POPULATION - Baehr, Oliver; Tabatabai, Ghazaleh; Fietkau, Rainer; Goldbrunner, Roland; Glas, Martin (NEURO-ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-12-04

Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment - Seitz, Christoph; Ruckert, Michael; Weiss, Eva-Maria; Utz, Sebastian; Izydor, Marika; Ebel, Nina; Schlücker, Eberhard; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin; Deloch, Lisa (Frontiers in Oncology, 2019)
Dendritic cell (DC)-based vaccines pulsed with high hydrostatic pressure (HHP)-inactivated tumor cells have been demonstrated to be a promising immunotherapy for solid tumors. We focused on sole injection of tumor cells that were inactivated by HHP and their combination with local radiotherapy (RTx) for in vivo induction of anti-tumor immune responses. HHP-treatment of tumor cells resulted in pre-dominantly necrotic cells with degraded DNA. We confirmed that treatments at 200 MPa or higher completely inhibited the formation of tumor cell colonies in vitro. No tumor growth was seen in vivo after injection of HHP-treated tumor cells. Single vaccination with HHP-killed tumor cells combined with local RTx significantly retarded tumor growth and improved the survival as shown in B16-F10 and CT26 tumor models. In B16-F10 tumors that were irradiated with 2 x 5Gy and vaccinated once with HHP-killed tumor cells, the amount of natural killer (NK) cells, monocytes/macrophages, CD4+ T cells and NKT cells was significantly increased, while the amount of B cells was significantly decreased. In both models, a trend of increased CD8+ T cell infiltration was observed. Generally, in irradiated tumors high amounts of CD4+ and CD8+ T cells expressing PD-1 were found. We conclude that HHP generates inactivated tumor cells that can be used as a tumor vaccine. Moreover, we show for the first time that tumor cell-based vaccine acts synergistically with RTx to significantly retard tumor growth by generating a favorable anti-tumor immune microenvironment.
CRIS-Team WoS Importer:2019-09-10

Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer - Ruiz-Fernández de Córdoba, Borja; Moreno, Haritz; Valencia, Karmele; Perurena, Naiara; Ruedas, Pablo; Walle, Thomas; Pezonaga-Torres, Alberto; Hinojosa, Juan; Guruceaga, Elisabet; Pineda-Lucena, Antonio; Abengózar-Muela, Marta; Cochonneau, Denis; et al. (Cancer Discovery, 2022)
ABSTRACT: Locoregional failure (LRF) in patients with breast cancer post-surgery and post-irradiation is linked to a dismal prognosis. In a refined new model, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1/CD203a (ENPP1) to be closely associated with LRF. ENPP1hi circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of polymorphonuclear myeloid-derived suppressor cells and neutrophil extracellular trap (NET) formation. Genetic and pharmacologic ENPP1 inhibition or NET blockade extends relapse-free survival. Furthermore, in combination with fractionated irradiation, ENPP1 abrogation obliterates LRF. Mechanistically, ENPP1-generated adenosinergic metabolites enhance haptoglobin (HP) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse. SIGNIFICANCE: CTC exploit the ENPP1/HP axis to promote local recurrence post-surgery and post-irradiation by subduing myeloid suppressor cells in breast tumors. Blocking this axis impairs tumor engraftment, impedes immunosuppression, and obliterates NET formation, unveiling new opportunities for therapeutic intervention to eradicate local relapse and ameliorate patient survival. This article is highlighted in the In This Issue feature, p. 1171.
CRIS-Team Scopus Importer:2022-05-20

Tumor Immunology The new fourth Pillar of Tumor Treatment - Kasper, Stefan; Rammensee, Hans-Georg; Gaipl, Udo; Hoeffken, Klaus (Onkologe, 2021)
CRIS-Team WoS Importer:2021-11-05

Tumor infiltrating cells - cell-to-cell distances enable differentiation between functionally active and suppressed inflammatory cells - Distel, Luitpold; Nagl, Sandra; Fietkau, Rainer; Haas, M. (2016)
EVALuna2:18330

Tumor Infiltrating Inflammatory Cells as a prognostic Factor in Glioblastoma - Schnellhardt, Sören; Zorob, Alexander; Polat, B.; Lisowski, D.; Daniel, Christoph; Monoranu, C-M; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Tumor-infiltrating Memory T Cells in Head and Neck Tumors: An ambivalent prognostic Factor - Hartan, R.; Schnellhardt, Sören; Büttner-Herold, Maike; Daniel, Christoph; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer - Fokas, Emmanouil; Stroebel, Philipp; Fietkau, Rainer; Ghadimi, Michael; Liersch, Torsten; Grabenbauer, Gerhard G.; Hartmann, Arndt; Kaufmann, Marco; Sauer, Rolf; Graeven, Ullrich; Hoffmanns, Hans; Raab, Hans-Rudolf; et al. (Journal of the National Cancer Institute, 2017)
Background: We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial. Methods: TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided. Results: With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4. Conclusions: Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.
EVALuna2:32865

Tumor regression grading after preoperative chemoradiotherapy as prognostic factor and individual-level surrogate for disease-free survival in rectal cancer: Results of the CAO/ARO/AIO-04 multicentre, open-label, randomised, phase 3 trial - Fokas, E.; Stroebel, P.; Fietkau, Rainer; Ghadimi, M.; Liersch, T.; Grabenbauer, G.; Hartmann, Arndt; Kaufmann, M.; Sauer, Rolf; Graeven, U.; Hoffmanns, H.; Raab, H-R; et al. (2017)
EVALuna2:32881

Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial - Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Beissbarth, Tim; Hess, Clemens; Becker, Heinz; Ghadimi, Michael; Mrak, Karl; Merkel, Susanne; Raab, Hans-Rudolf; Sauer, Rolf; et al. (Journal of Clinical Oncology, 2014)
We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months.TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS).Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026).Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.
EVALuna2:15168

Tumor-specific radiosensitizing effect of the ATM inhibitor AZD0156 in melanoma cells with low toxicity to healthy fibroblasts - Scheper, Julian; Hildebrand, Laura; Faulhaber, Eva-Maria; Deloch, Lisa; Gaipl, Udo; Symank, Julia-Alice; Fietkau, Rainer; Distel, Luitpold; Hecht, Markus; Jost, Tina (Strahlentherapie und Onkologie, 2022)
Purpose Despite new treatment options, melanoma continues to have an unfavorable prognosis. DNA damage response (DDR) inhibitors are a promising drug class, especially in combination with chemotherapy (CT) or radiotherapy (RT). Manipulating DNA damage repair during RT is an opportunity to exploit the genomic instability of cancer cells and may lead to radiosensitizing effects in tumors that could improve cancer therapy. Methods A panel of melanoma-derived cell lines of different origin were used to investigate toxicity-related clonogenic survival, cell death, and cell cycle distribution after treatment with a kinase inhibitor (KI) against ATM (AZD0156) or ATR (VE-822, berzosertib), irradiation with 2 Gy, or a combination of KI plus ionizing radiation (IR). Two fibroblast cell lines generated from healthy skin tissue were used as controls. Results Clonogenic survival indicated a clear radiosensitizing effect of the ATM inhibitor (ATMi) AZD0156 in all melanoma cells in a synergistic manner, but not in healthy tissue fibroblasts. In contrast, the ATR inhibitor (ATRi) VE-822 led to additive enhancement of IR-related toxicity in most of the melanoma cells. Both inhibitors mainly increased cell death induction in combination with IR. In healthy fibroblasts, VE-822 plus IR led to higher cell death rates compared to AZD0156. A significant G2/M block was particularly induced in cancer cells when combining AZD0156 with IR. Conclusion ATMi, in contrast to ATRi, resulted in synergistic radiosensitization regarding colony formation in melanoma cancer cells, while healthy tissue fibroblasts were merely affected with respect to cell death induction. In connection with an increased number of melanoma cells in the G2/M phase after ATMi plus IR treatment, ATMi seems to be superior to ATRi in melanoma cancer cell treatments when combined with RT.
CRIS-Team WoS Importer:2022-10-28

Tumor-specific Toxicity to malignant Melanoma Cells by the dual DNA-PK and mTOR Inhibitor CC115 in Combination with ionizing Radiation - Burkel, F.; Jost, Tina; Proebstle, Stephanie; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold (2018)
EVALuna2:36482

Tumour-infiltrating inflammatory cells in early breast cancer: An underrated prognostic and predictive factor? - Schnellhardt, Sören; Erber, Ramona; Büttner-Herold, Maike; Rosahl, Marie Charlotte; Ott, Oliver; Strnad, Vratislav; Beckmann, Matthias; King, Lillian; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (International Journal of Molecular Sciences, 2020)
The role of tumour-infiltrating inflammatory cells (TIICs) in the disease progression of hormone-receptor-positive breast cancer (HR+ BC) is largely unclear since it is generally regarded as the least immunogenic BC subtype. This study investigated the prognostic significance of CD1a+ dendritic cells, CD20+ B cells, CD45RO+ memory T cells and CD4+ T-helper cells in HR+ BC. One hundred and forty-six patients were treated for early stage, distant-metastases-free HR+ BC in an accelerated partial breast irradiation (APBI) phase II trial. Immunohistochemistry was used to double-stain two adjoining sets of tissue microarrays from pre-RT (radiotherapy) tumour resection samples for CD1a/CD20 and CD45RO/CD4. Cell densities of CD1a+, CD20+, CD45RO+ and CD4+ TIICs in the stromal and intraepithelial compartment were registered semiautomatically. High densities of CD20+ and CD4+ TIICs were strongly associated with reduced disease-free survival (DFS), while high stromal CD45RO+ TIIC densities were indicators of subsequent successful treatment. An immunoscore based on CD20+ and CD45RO+ TIIC densities identified three different risk groups (p < 0.001). Thus, contrary to current assumptions, intratumoural immune cell composition might be an important prognostic indicator and a possible contributing factor in the outcome of HR+ BC and should be the subject of further research. Specifically, B-cell infiltration entailed an increased relapse rate and could play an important role in disease progression.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Accelerated partial breast irradiation; Breast cancer; CD1a; CD20; CD4; CD45RO; Hormone receptor positive; Immunoscore; Prognosis; TIL

Two-ways validation of the feasibility of AI-based synthetic CT for MR-only brain radiotherapy - Masitho, Siti; Szkitsak, Juliane; Grigo, Johanna; Putz, Florian; Fietkau, Rainer; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-07-22

Understanding the Role of Surface Charge in Cellular Uptake and X‑ray-Induced ROS Enhancing of Au−Fe3O4 Nanoheterodimers - Klein, Stefanie; Stiegler, Lisa; Harreiß, Christina; Distel, Luitpold; Neuhuber, Winfried; Spiecker, Erdmann; Hirsch, Andreas; Kryschi, Carola (ACS Applied Bio Materials, 2018)
Au−Fe3O4 nanoheterodimers were obtained by thermally decomposing iron oleate on presynthesized gold nanoparticles. Water solubility as well as surface charges were achieved by encapsulating the initially hydrophobic Au−Fe3O4 nanoheterodimers in a self-assembled bilayer shell formed either by 1-octadecylpyridinium, providing positive surface charges, or by 4-dodecylbenzenesulfonate, yielding a negatively charged surface. The surface charge and surface architecture were shown to control both the cellular entry and the intracellular trafficking of the Au−Fe3O4 nanoheterodimers. The positively charged (1-octylpyridinium-terminated) Au−Fe3O4 nanoheterodimers were internalized by both breast cancer cells (MCF-7) and epithelial cells (MCF-10 A), wherein they were electrostatically bound at the negatively charged membranes of the cell organelles and, in particular, adsorbed onto the mitochondrial membrane. The treatment of MCF-7 and MCF-10 cells with a fractional X-radiation dose of 1 Gy resulted into a large increase of superoxide production, which arose from the Au−Fe3O4 nanoheterodimer-induced mitochondrial depolarization. In contrast, the negatively charged (4-dodecylbenzenesulfonateterminated) Au−Fe3O4 nanoheterodimers preferentially invaded the cancerous MCF-7 cells by direct permeation. X-ray treatment of MCF-7 cells, loaded with anionic Au−Fe3O4 nanoheterodimers, yielded the increase of both hydroxyl radical and cytoplasmic superoxide formation. The X-radiation-induced activation of the Fe3O4 surfaces, consisting of Fe2+ and Fe3+ cations, triggered the catalysis of the hydroxyl radical production, whereas superoxide formation presumably occurred through X-rayinduced photoelectron emission near the Au surface. Since hydroxyl radicals are highly cytotoxic and the negatively charged Au−Fe3O4 NHDs spare the healthy MCF-10A cells, these Au−Fe3O4 nanoheterodimers exhibit a higher potential for radiation therapy than the positively charged Au−Fe3O4 nanoheterodimers. Encouraging results from the clonogenic cell survival assay and DMF calculations corroborate the excellent performance of the anionic Au−Fe3O4 nanoheterodimers as an X-ray dosage enhance
Keywords: Au−Fe3O4 nanoheterodimers; self-assembled bilayer; surface charge; reactive oxygen species; radiation therapy

Unified risk analysis in radiation therapy - Lohmann, Daniel; Shariff, Maya; Schubert, Philipp; Sauer, Tim-Oliver; Fietkau, Rainer; Bert, Christoph (Zeitschrift für Medizinische Physik, 2022)
Purpose: The increasing complexity of new treatment methods as well as the Information Technology (IT) infrastructure within radiotherapy require new methods for risk analysis. This work presents a methodology on how to model the treatment process of radiotherapy in different levels. This subdivision makes it possible to perform workflow-specific risk analysis and to assess the impact of IT risks on the overall treatment workflow. Methods: A Unified Modeling Language (UML) activity diagram is used to model the workflows. The subdivision of the workflows into different levels is done with the help of swim lanes. The model created in this way is exported in an xml-compatible format and stored in a database with the help of a Python program. Results: Based on an existing risk analysis, the workflows CT Appointment, Glioblastoma Multiforme, and Deep Inspiration Breath Hold (DIBH) were modeled in detail. Part of the analysis are automatically generated workflow-specific risk matrices including risks of medical devices incorporated into a specific workflow. In addition, SQL queries allow to quickly retrieve e.g., the details of the medical device network installed in a department. Conclusion: Activity diagrams of UML can be used to model workflows in radiotherapy. Through this, a connection between the different levels of the entire workflow can be established and workflow-specific risk analysis is possible.
CRIS-Team Scopus Importer:2022-10-21
Keywords: Activity diagram; IEC 80001-1; Risk analysis; UML

Union of light ion therapy centers in Europe (ULICE EC FP7) - Objectives and achievements of joint research activities - Poetter, Richard; Balosso, Jaques; Baumann, Michael; Bert, Christoph; Davies, Jim; Enghardt, Wolfgang; Fossati, Piero; Harris, Steve; Jones, Bleddyn; Kraemer, Michael; Mayer, Ramona; Mock, Ulrike; et al. (Radiotherapy and Oncology, 2018)
Under the umbrella of the European Network for Light Ion Therapy (ENLIGHT), the project on Union of Light Ion Centers in Europe (ULICE), which was funded by the European Commission (EC/FP7), was carried out from 2009 to 2014. Besides the two pillars on Transnational Access (TNA) and Networking Activities (NA), six work packages formed the pillar on Joint Research Activities (JRA). The current manuscript focuses on the objectives and results achieved within these research work packages: "Clinical Research Infrastructure", "Biologically Based Expert System for Individualized Patient Allocation", "Ion Therapy for Intra-Fractional Moving Targets", "Adaptive Treatment Planning for Ion Radiotherapy", "Carbon Ion Gantry", "Common Database and Grid Infrastructures for Improving Access to Research Infrastructures". The objectives and main achievements are summarized. References to either publications or open access deliverables from the five year project work are given. Overall, carbon ion radiotherapy is still not as mature as photon or proton radiotherapy. Achieved results and open questions are reflected and discussed in the context of the current status of carbon ion therapy and particle and photon beam therapy. Most research topics covered in the ULICE JRA pillar are topical. Future research activities can build upon these ULICE results. Together with the continuous increase in the number of particle therapy centers in the last years ULICE results and proposals may contribute to the further growth of the overall particle therapy field as foreseen with ENLIGHT and new joint initiatives such as the European Particle Therapy Network (EPTN) within the overall radiotherapy community.
EVALuna2:36474

Updated analysis of the phase II CheckRad-CD8 trial: First-line treatment of locally advanced head and neck squamous cell carcinoma with induction chemoimmunotherapy followed by radioimmunotherapy - Hecht, Markus; Eckstein, Markus; Kallies, Annett; Von Der Grun, Jens; Illmer, Thomas; Klautke, Gunther; Laban, Simon; Hautmann, Matthias; Brunner, Thomas; Tamaskovics, Balint; Hinke, Axel; Zhou, Jianguo; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-12-16

Update of the ESTRO-EFOMP core curriculum for medical physics experts in radiotherapy - Garibaldi, C.; Essers, M.; Heijmen, B.; Bertholet, J.; Koutsouveli, E.; Schwarz, M.; Bert, Christoph; Jornet, N.; Clark, C. H. (RADIOTHERAPY AND ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-11-26

Upregulation of CCR4 in activated CD8(+) T cells indicates enhanced lung homing in patients with severe acute SARS-CoV-2 infection - Spoerl, Silvia; Kremer, Anita; Aigner, Michael; Eisenhauer, Nina; Koch, Pauline; Meretuk, Lina; Loeffler, Patrick; Tenbusch, Matthias; Maier, Clara; Überla, Klaus; Heinzerling, Lucie; Frey, Benjamin; et al. (European Journal of Immunology, 2021)
COVID-19 is a life-threatening disease leading to bilateral pneumonia and respiratory failure. The underlying reasons why a smaller percentage of patients present with severe pulmonary symptoms whereas the majority is only mildly affected are to date not well understood.
CRIS-Team WoS Importer:2021-05-07

Usability of magnetic resonance images acquired at a novel low-field 0.55 T scanner for brain radiotherapy treatment planning - Grigo, Johanna; Masitho, Siti; Fautz, Hans Peter; Voigt, Raphaela; Schonath, Miriam; Oleszczuk, Annika; Uder, Michael; Heiß, Rafael; Fietkau, Rainer; Putz, Florian; Bert, Christoph (Physics and Imaging in Radiation Oncology, 2023)
Background and Purpose: Low-field magnetic resonance imaging (MRI) may offer specific advantages over high-field MRI, e.g. lower susceptibility-dependent distortions and simpler installation. The study aim was to evaluate if a novel 0.55 T MRI scanner provides sufficient image accuracy and quality for radiotherapy (RT) treatment planning. Material and methods: The geometric accuracy of images acquired at a low-field MRI scanner was evaluated in phantom measurements regarding gradient non-linearity-related distortions. Patient-induced B0-susceptibility changes were investigated via B0-field-mapping in ten volunteers. Patients were positioned in RT-setup using a 3D-printed insert for the head/neck-coil that was tested for sufficient signal-to-noise-ratio (SNR). The suitability of the MRI-system for detection of metastases was evaluated in eleven patients. In comparison to diagnostic images, acquired at ≥1.5 T, three physicians evaluated the detectability of metastases by counting them in low- and high-field-images, respectively. Results: The phantom measurements showed a high imaging fidelity after 3D-distortion-correction with (1.2 ± 0.9) mm geometric distortion in 10 cm radius from isocentre. At the edges remaining distortions were greater than at 1.5 T. The mean susceptibility-induced distortions in the head were (0.05 ± 0.05) mm and maximum 0.69 mm. SNR analysis showed that optimised positioning of RT-patients without signal loss in the head/neck-coil was possible with the RT-insert. No significant differences (p = 0.48) in detectability of metastases were found. Conclusion: The 0.55 T MRI system provided sufficiently geometrically accurate and high-resolution images that can be used for RT-planning for brain metastases. Hence, modern low-field MRI may contribute to simply access MRI for RT-planning after further investigations.
CRIS-Team Scopus Importer:2023-02-17
Keywords: Low-Field-MRI; MRI; Radiotherapy

Use of NGS Gene Panel Analyzes for molecularly targeted System Therapy - Roesch, Johannes; Haller, Florian; Lettmaier, Sebastian; Haderlein, Marlen; Hartmann, Arndt; Moskalev, Evgeny; Tögel, Lars; Putz, Florian; Weissmann, T.; Schubert, P.; Höfler, Daniel; Fietkau, Rainer; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Variability in catheter reconstruction for multi-catheter interstitial brachytherapy - Kallis, Karoline; Kaltsas, Theodoros; Kreppner, Stephan; Lotter, M.; Strnad, Vratislav; Fietkau, Rainer; Bert, Christoph (RADIOTHERAPY AND ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-06-18

Verbesserung der Deep Learning basierten Autodetektion von Hirnmetastasen durch Integration von MRT-Voraufnahmen - Huang, Yixing; Bert, Christoph; Sommer, Philipp; Frey, Benjamin; Gaipl, Udo; Distel, Luitpold; Weissmann, Thomas; Uder, Michael; Schmidt, Manuel; Dörfler, Arnd; Maier, Andreas; Fietkau, Rainer; et al. (Strahlentherapie und Onkologie, 2022)
Keywords: Deep learning; brain metastasis

Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort - Hannoun-Levi, Jean Michel; Gimeno Morales, Marta; Gal, Jocelyn; Anchuelo, Javier; Guinot, Jose Luis; Gastanaga, Miren; Meszaros, Norbert; Polgar, Csaba; Strnad, Vratislav; Schiappa, Renaud; Gutierrez, Cristina (Radiotherapy and Oncology, 2024)
Purpose: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. Materials: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. Results: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39–46]. Median age was 71 years [40–100]. Median tumor size was 12 mm [1–35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0–3] and 1 % [95 %CI 0–2] respectively. Conclusions: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.
CRIS-Team Scopus Importer:2024-03-22
Keywords: APBI; Brachytherapy; Breast cancer; De-escalation; Fractionation; Toxicity

Volume Course of Acoustic Neuromas after stereotactic Radiotherapy - Putz, Florian; Lettmaier, S.; Knippen, S.; Gryc, Thomas; Fietkau, Rainer (2017)
EVALuna2:32889

Volumetric assessment of paragangliomas of the head and neck following stereotactic radiotherapy - Putz, Florian; Weissmann, T.; Lettmaier, S.; Semrau, S.; Fietkau, Rainer (2018)
EVALuna2:36506

Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance - Oft, Dominik; Schmidt, Manuel; Weissmann, Thomas; Roesch, Johannes; Mengling, Veit; Masitho, Siti; Bert, Christoph; Lettmaier, Sebastian; Frey, Benjamin; Distel, Luitpold; Fietkau, Rainer; Putz, Florian (Frontiers in Oncology, 2021)
Background: There is insufficient understanding of the natural course of volumetric regression in brain metastases after stereotactic radiotherapy (SRT) and optimal volumetric criteria for the assessment of response and progression in radiotherapy clinical trials for brain metastases are currently unknown. Methods: Volumetric analysis via whole-tumor segmentation in contrast-enhanced 1 mm³-isotropic T1-Mprage sequences before SRT and during follow-up. A total of 3,145 MRI studies of 419 brain metastases from 189 patients were segmented. Progression was defined using a volumetric extension of the RANO-BM criteria. A subset of 205 metastases without progression/radionecrosis during their entire follow-up of at least 3 months was used to study the natural course of volumetric regression after SRT. Predictors for volumetric regression were investigated. A second subset of 179 metastases was used to investigate the prognostic significance of volumetric response at 3 months (defined as ≥20% and ≥65% volume reduction, respectively) for subsequent local control. Results: Median relative metastasis volume post-SRT was 66.9% at 6 weeks, 38.6% at 3 months, 17.7% at 6 months, 2.7% at 12 months and 0.0% at 24 months. Radioresistant histology and FSRT vs. SRS were associated with reduced tumor regression for all time points. In multivariate linear regression, radiosensitive histology (p=0.006) was the only significant predictor for metastasis regression at 3 months. Volumetric regression ≥20% at 3 months post-SRT was the only significant prognostic factor for subsequent control in multivariate analysis (HR 0.63, p=0.023), whereas regression ≥65% was no significant predictor. Conclusions: Volumetric regression post-SRT does not occur at a constant rate but is most pronounced in the first 6 weeks to 3 months. Despite decreasing over time, volumetric regression continues beyond 6 months post-radiotherapy and may lead to complete resolution of controlled lesions by 24 months. Radioresistant histology is associated with slower regression. We found that a cutoff of ≥20% regression for the volumetric definition of response at 3 months post-SRT was predictive for subsequent control whereas the currently proposed definition of ≥65% was not. These results have implications for standardized volumetric criteria in future radiotherapy trials for brain metastases.
CRIS-Team Scopus Importer:2021-02-05
Keywords: brain metastases; longitudinal analysis; MRI; stereotactic radiosurgery; stereotactic radiotherapy; volumetric analysis; volumetric regression

Volumetric regression in brain metastases after stereotactic RT: Time course and significance - Putz, Florian; Oft, Dominik; Perrin, R.; Mengling, Veit; Weissmann, Thomas; Roesch, Johannes; Mansoorian, Sina; Distel, Luitpold; Bert, Christoph; Fietkau, Rainer (RADIOTHERAPY AND ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-06-18

Vulnerabilitäten bei Radiomics: Warum die populärste Radiomics-Signatur unbemerkt das Tumorvolumen gemessen hat - Putz, Florian; Fietkau, Rainer (Strahlentherapie und Onkologie, 2021)
CRIS-Team WoS Importer:2021-02-26

„Watchful Waiting“ als Alternative zur Rektumexstirpation nach kompletter Tumorremission infolge neoadjuvant intendierter Radiochemotherapie? - Hohenberger, Werner; Sauer, Rolf (Strahlentherapie und Onkologie, 2016)
EVALuna2:15230

Website on the individual Radiation Sensitivity of Tumor Patients - Rzepka, Dinah; Fietkau, Rainer; Distel, Luitpold (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Weighted Filtered Back-Projection for Source Translation Computed Tomography Reconstruction - Chen, Jie; Yu, Haijun; Ni, Song; Liu, Chuanjiang; Ge, Wenjie; Huang, Yixing; Liu, Fenglin (IEEE Transactions on Instrumentation and Measurement, 2023)
Micro-computed tomography (micro-CT) is an indispensable tool to provide attenuation-based, high-resolution 3-D images in scientific research. However, its current available configuration limits the size of objects that can be imaged. Previously, we have proposed a multiple source translation computed tomography (mSTCT) imaging geometry to extend the field-of-view (FOV) of micro-CT, and developed a corresponding reconstruction algorithm called virtual projection-based filtered back-projection (V-FBP). V-FBP achieves high-resolution reconstructions when the source is densely sampled but fails if the source is coarsely sampled. In this article, to achieve high-resolution reconstruction at a low source sampling rate, we propose a full-scan multiple-STCT (F-mSTCT) scanning configuration, which allows for a simple and effective weighting function to deal with data redundancy and truncation simultaneously. Based on this concept, we develop a weighted FBP (W-FBP) algorithm. The numerical and physical experiments demonstrate that W-FBP is able to reconstruct high-resolution images at a low source sampling rate, and can reduce 1/2-3/4 projections compared with V-FBP at the same resolution.
CRIS-Team Scopus Importer:2023-10-06
Keywords: Filtered back-projection (FBP); high-resolution; multiple source translation computed tomography (mSTCT); truncation; weighting function

When is a nonsurgical approach possible for metastatic primary tumors and lymph node metastases of the urinary bladder and prostate? - Fietkau, Rainer (Urologe, 2017)
For metastatic carcinomas of the urinary bladder and prostate, systemic therapy is of primary importance. Due to technological advances in radiation oncology such as stereotactic radiotherapy, intensity-modulated radiotherapy, interstitial radiotherapy, and the combination of radiotherapy and chemotherapy, pelvic irradiation can nowadays be carried out effectively and without the risk of major side effects. New data from other tumor entities and retrospective analyses suggest that the use of these technologies can lead to a clinical benefit in terms of improvement in quality of life, local control, and overall survival. For the time being, the decision to administer radiotherapy to the pelvic region should be made on an individual basis. Retrospective analyses of data from prostate carcinomas in particular are currently being planned. This review article introduces potential indications which are supported with real patient examples and discusses future developments giving an overview of the literature and referring to data from prospective randomized trials.
EVALuna2:32905

Which fractionation of radiotherapy is best for limited-stage small-cell lung cancer? - Fietkau, Rainer (Lancet Oncology, 2017)
EVALuna2:32872

Whole-Body Electromyostimulation combined with personalized Nutritional Support improves the Body Composition of Patients with advanced Cancer - Schink, Kristin; Herrmann, Hans Joachim; Schwappacher, Raphaela; Orlemann, Till; Meyer, Julia; Waldmann, Elisabeth; Wullich, Bernd; Kahlmeyer, Andreas; Fietkau, Rainer; Lubgan, Dorota; Beckmann, Matthias; Hack, Carolin; et al. (2018)
EVALuna2:35187

Wirkung von Flap Endonuclease 1 Inhibitor FEN1-IN-4 in Kombination mit ionisierender Strahlung auf Mammakarzinomzellen - Berfelde, Johanna; Hildebrand, Laura; Jost, Tina; Distel, Luitpold; Fietkau, Rainer (STRAHLENTHERAPIE UND ONKOLOGIE, 2022)

Work-related bladder cancer -The BK 1301 matrix as an algorithm and decision aid in the context of an assessment of an occupational disease Das beruflich bedingte Harnblasenkarzinom-Die BK 1301-Matrix als Algorithmus und Entscheidungshilfe fur eine Zusammenhangsbegutachtung - Weistenhöfer, Wobbeke; Golka, K.; Bolm-Audorff, U.; Bolt, H. M.; Bruning, T.; Hallier, E.; Pallapies, D.; Prager, H. M.; Schilling, Teresa; Schmitz-Spanke, Simone; Uter, Wolfgang; Weis, T.; et al. (Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 2022)
The risk of developing bladder cancer can be influenced by various occupational and non-occupational risk factors. These need to be evaluated in the context of an assessment of an occupational disease according to no. 1301 (BK 1301: Mucosal changes, cancer and other neoplasms of the urinary tract (hereinafter referred to as "bladder cancer") caused by aromatic amines) of the Annex to the Ordinance on Occupational Diseases. The BK 1301 matrix presented here for the assessment of the causal relationship in urinary bladder cancers after proven and relevant occupational exposure to carcinogenic aromatic amines was derived as a convention by a working group, based on the results of a workshop with more than 230 participants. It can be applied even in the absence of an individual cumulative exposure dose. The decision matrix is intended to support experts experienced in occupational medicine in the field of BK 1301 in the assessment procedure. It also provides an overview of relevant aspects of work-related bladder cancer for the purposes of accident insurance institutions and courts. The BK 1301 matrix includes occupational indicators such as exposure duration, exposure frequency and exposure intensity, as well as the age of onset, the latency period and competing non-occupational risk factors such as smoking behaviour. Based on the BK 1301 matrix, the relevant arguments favouring or refuting a causal occupational relationship in the individual case can be evaluated in detail by the occupational physician, resulting in a recommendation for or against recognition of the bladder cancer as an occupational disease. This notwithstanding, the decision as to whether an occupational disease is indeed present is ultimately an administrative act of the responsible accident insurance institution, which may be subject to review by the social courts.
CRIS-Team Scopus Importer:2022-05-06
Keywords: aromatic amines; bladder cancer; convention; expert opinion; matrix; occupational disease 1301

X-ray dose-enhancing impact of functionalized Au-Fe3O4nanoheterodimers on MCF-7 and A549 multicellular tumor spheroids - Klein, Stefanie; Distel, Luitpold; Neuhuber, Winfried (ACS Applied Bio Materials, 2021)
The efficiency of nanoparticle-enhanced radiotherapy was studied by loading MCF-7 and A549 multicellular tumor spheroids (MCTSs) with caffeic acid- and nitrosoniumfunctionalized Au-Fe3O4 nanoheterodimers (Au-Fe3O4 NHDs). Transmission electron microscope images of MCTS crosssectional sections visualized the invasion and distribution of the nitrosonium- and caffeic acid-functionalized Au-Fe3O4 NHDs (NO- and CA-NHDs) in the A549 and MCF-7 MCTSs, whereas the iron content of the MCTSs were quantified using the ferrozine assay. The synergistic impact of intracellular NO- and CA-NHDs and X-ray irradiation on the growth dynamics of the A549 and MCF-7 MCTSs was surveyed by monitoring their temporal evolution under a light microscope over a period of 14 days. The emergence of hypoxia during the spheroid growth was followed by detecting the lactate efflux of MCTSs without and with NO- and CA-NHDs. The performance of the NO- and CA-NHDs as X-ray dose-enhancing agents in the A549 and MCF-7 MCTSs was clarified by performing clonogenic cell survival assays and determining the respective dose-modifying factors for X-ray doses of 0, 2, 4, and 6 Gy. The NO- and CA-NHDs were shown to perform as potent X-ray dose-enhancing agents in A549 and MCF-7 MCTSs. Moreover, the CA-NHDs boosted their radio-sensitizing efficacy by inhibiting the lactate efflux as impairing metabolic reprogramming. A synergistic effect on the MCTS destruction was observed for the combination of both NHDs since the surfactants differ in their antitumor effect.
CRIS-Team Scopus Importer:2021-04-16
Keywords: A549 cells; Au-Fe; MCF-7 cells; Multicellular tumor spheroids; X-ray dose enhancement

X-Ray Induced Formation of γ-H2AX Foci after Full-Field Digital Mammography and Digital Breast-Tomosynthesis - Schwab, Siegfried; Brand, Michael; Schlude, Ina-Kristin; Wüst, Wolfgang; Meier-Meitinger, Martina; Distel, Luitpold; Schulz-Wendtland, Rüdiger; Uder, Michael; Uder, Michael; Kuefner, Michael A. (PLoS ONE, 2013)
Purpose:To determine in-vivo formation of x-ray induced γ-H2AX foci in systemic blood lymphocytes of patients undergoing full-field digital mammography (FFDM) and to estimate foci after FFDM and digital breast-tomosynthesis (DBT) using a biological phantom model.Materials and Methods:The study complies with the Declaration of Helsinki and was performed following approval by the ethic committee of the University of Erlangen-Nuremberg. Written informed consent was obtained from every patient. For in-vivo tests, systemic blood lymphocytes were obtained from 20 patients before and after FFDM. In order to compare in-vivo post-exposure with pre-exposure foci levels, the Wilcoxon matched pairs test was used. For in-vitro experiments, isolated blood lymphocytes from healthy volunteers were irradiated at skin and glandular level of a porcine breast using FFDM and DBT. Cells were stained against the phosphorylated histone variant γ-H2AX, and foci representing distinct DNA damages were quantified.Results:Median in-vivo foci level/cell was 0.086 (range 0.067-0.116) before and 0.094 (0.076-0.126) after FFDM (p = 0.0004). In the in-vitro model, the median x-ray induced foci level/cell after FFDM was 0.120 (range 0.086-0.140) at skin level and 0.035 (range 0.030-0.050) at glandular level. After DBT, the median x-ray induced foci level/cell was 0.061 (range 0.040-0.081) at skin level and 0.015 (range 0.006-0.020) at glandular level.Conclusion:In patients, mammography induces a slight but significant increase of γ-H2AX foci in systemic blood lymphocytes. The introduced biological phantom model is suitable for the estimation of x-ray induced DNA damages in breast tissue in different breast imaging techniques. © 2013 Schwab et al.
CRIS-Team Scopus Importer:2023-03-08

ypN0 nodal status after neoadjuvant chemoradiotherapy for rectal carcinoma is not associated with adverse prognosis as compared with pN0 after primary surgery - Erlenbach-Wuensch, Katharina; Semrau, Sabine; Fietkau, Rainer; Weber, Klaus; Hohenberger, Werner; Rau, Tilman; Hartmann, Arndt; Merkel, Susanne; Agaimy, Abbas (International Journal of Colorectal Disease, 2014)
Neoadjuvant chemoradiotherapy (nCRT) has been established as standard treatment for locally advanced rectal cancer (cT3/4 or cN+ cM0, distance from circumferential resection margin <=1 mm) to enhance local disease control and minimize the rate of locoregional recurrence. As a consequence of downstaging, a significant proportion of patients show non-viable tumor deposits within regional lymph nodes that qualify as ypN0 according to the current TNM classification irrespective of the actual pre-treatment status. Accordingly, the prognostic relevance of ypN0 status as compared with true pN0 without preceding nCRT is not known.We retrospectively analyzed 132 patients who underwent standard total mesorectal excision (TME) surgery after nCRT for rectal carcinoma and were classified as ypN0, and compared their prognoses with those of 341 patients with pN0 without nCRT.Re-evaluation of regional lymph nodes after nCRT showed no evidence of previous metastasis in 91 cases (ypN0(-)), sure but non-viable metastasis in 14 patients (ypN0(+)), and unsure status in 27 patients (ypN0(X)). The local recurrence rate, distant metastases, and disease-free, observed, and cancer-related survival were similar in all subgroups (p = 0.447, 0.695, 0.759, 0.655, and 0.354, respectively).Our results showed a similar outcome in patients with ypN0 and in the control group with pN0 regarding local recurrence rate, distant metastases, and disease-free, observed, and cancer-related survival. Validation of these results is necessary to clarify the questions regarding postoperative adjuvant chemotherapy for patients with ypN0(+).
EVALuna2:6516

Correlating Dose Variables with Local Tumor Control in Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Modeling Study on 1500 Individual Treatments - Klement, Rainer J.; Sonke, Jan Jakob; Allgäuer, Michael; Andratschke, Nicolaus; Appold, Steffen; Belderbos, José; Belka, Claus; Blanck, Oliver; Dieckmann, Karin; Eich, Hans T.; Mantel, Frederick; Eble, Michael; et al. (International Journal of Radiation Oncology Biology Physics, 2020)
Background: Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription. Methods and Materials: We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BEDmin); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BEDmax); and (3) the average between near-minimum and near-maximum doses (yielding BEDave). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion. Results: There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BEDave was the best predictor of risk of local recurrence, and a model based on BEDmin had substantially less evidential support. In univariable logistic regression, the model based on BEDave also performed best. Multivariable classification using fast and frugal trees revealed BEDmax to be the most important predictor, followed by BEDave. Conclusions: BEDave was generally better correlated with tumor control probability than either BEDmax or BEDmin. Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation.
CRIS-Team Scopus Importer:2020-04-24

Dose Escalation and local Control after stereotactic Radiotherapy of adrenal Metastases of the Non-Small Cell Lung Carcinoma (NSCLC) - A multicenter Analysis - Buergy, D.; Wurschmidt, F.; Hoerner-Rieber, J.; Gkika, E.; Knippen, S.; Gerum, S.; Balermpas, P.; Henkenberens, C.; Voglhuber, T.; Kornhuber, C.; Barczyk, S.; Roeper, B.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

Dose–volume predictors of early esophageal toxicity in non-small cell lung cancer patients treated with accelerated-hyperfractionated radiotherapy - Bütof, Rebecca; Löck, Steffen; Soliman, Maher; Haase, Robert; Perrin, Rosalind; Richter, Christian; Appold, Steffen; Krause, Mechthild; Baumann, Michael (Radiotherapy and Oncology, 2020)
Background and purpose: Early radiation-induced esophageal toxicity (RIET) is one of the major side effects in patients with non-small cell lung cancer (NSCLC) and can be a reason for treatment interruptions. As the age of patients with NSCLC and corresponding comorbidities continue to increase, primary radiotherapy alone is a commonly used alternative treatment in these cases. The aim of the present study is to compare dosimetric and clinical parameters from the previously reported CHARTWEL trial for their ability to predict esophagitis and investigate potential differences in the accelerated and conventional fractionation arm. Material and methods: 146 patients of the Dresden cohort of the randomized phase III CHARTWEL trial were included in this post-hoc analysis. Side effects were prospectively scored weekly during the first 8 weeks from start of radiotherapy. To compare both treatment arms, recorded dose–volume parameters were adjusted for the different fractionation schedules. Logistic regression was performed to predict early RIET for the entire study group as well as for the individual treatment arms. Different dosimetric and clinical parameters were tested. Results: Patients receiving the accelerated CHARTWEL schedule experienced earlier and more severe esophagitis (e.g. 20.5% vs. 9.6% ≥grade 2 at week 3, respectively). In contrast, the median time period for recovery of grade 1 esophagitis was significantly longer for patients with conventional fractionation compared to the CHARTWEL group (median [range]: 21 [12–49] days vs. 15 [7–84] days, p = 0.028). In univariable logistic regression none of the dose–volume parameters showed a significant correlation with early RIET grade ≥ 2 in the conventional irradiation group. In contrast, for patients receiving CHARTWEL, the physical dose–volumes parameters V40 and V50; and re-scaled values VEQD2,50 and VEQD2,60 were significant predictors of early RIET grade ≥ 2. Dose–volume parameters remained different between CHARTWEL and conventional fractionation even after biological rescaling. Conclusion: Our results show a more dominant dose-volume effect in the CHARTWEL arm compared to conventional fractionation, especially for higher esophageal doses. These findings support the notion that dose–volume parameters for radiation esophagitis determined in a specific and time dependent setting of field arrangements can not be easily transferred to another setting. In clinical practice esophageal volumes receiving 40 Gy or more should be strictly limited in hyperfractionated-accelerated fraction schemes.
CRIS-Team Scopus Importer:2020-03-17
Keywords: Accelerated; Dose–volume parameters; Esophagitis; Non-small cell lung cancer; Prediction; Radiotherapy

GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell carcinomas: 1st update - Improvement by cross sectional imaging based treatment planning and stepping source technology - Kovacs, Gyorgy; Martinez-Monge, Rafael; Budrukkar, Ashwini; Luis Guinot, Jose; Johansson, Bengt; Strnad, Vratislav; Skowronek, Janusz; Rovirosa, Angeles; Siebert, Frank-Andre (Radiotherapy and Oncology, 2017)
The Head and Neck Working Group of the GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology) published in 2009 the consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy in head & neck cancers. The use of brachytherapy in combination with external beam radiotherapy and/or surgery was also covered as well as the use of brachytherapy in previously irradiated patients. Given the developments in the field, these recommendations needed to be updated to reflect up-to-date knowledge. The present update does not repeat basic knowledge which was published in the first recommendation but covers in a general part developments in (1) dose and fractionation, (2) aspects of treatment selection for brachytherapy alone versus combined BT+EBRT and (3) quality assurance issues. Detailed expert committee opinion intends to help the clinical practice in lip-, oral cavity-, oropharynx-, nasopharynx-, and superficial cancers. Different aspects of adjuvant treatment techniques and their results are discussed, as well the possibilities of salvage brachytherapy applications.
EVALuna2:33042

High Dose Rate Brachytherapy as Monotherapy for Localised Prostate Cancer: Review of the Current Status - Tselis, N.; Hoskin, P.; Baltas, D.; Strnad, Vratislav; Zamboglou, N.; Roedel, C.; Chatzikonstantinou, G. (Clinical Oncology, 2017)
The aim of this article is to review and present the published data on high dose rate (HDR) brachytherapy as monotherapy in the treatment of localised prostate cancer. A search and review of the literature was carried out on PubMed and MedLine using the medical subject headings 'high-dose-rate, brachytherapy, prostate cancer, monotherapy' as search terms. The search yielded more than 100 articles and abstracts published between 2000 and 2016. Only original clinical data on HDR monotherapy reporting oncological outcomes were included. When more than one series from the same institution were identified, the most recent one encompassing the largest patient number was considered for analysis. For citation crosscheck, the ISI web of science database was used employing the same search terms. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control and toxicity scores. Fifteen articles comprising 3546 patients reported clinical outcome and toxicity, with follow-up ranging from median 1.4 to 8.0 years. A variety of dose and fractionation schedules were described, including 19.0 Gy as a single fraction to 54.0 Gy in nine fractions. Biochemical control rates ranged from 66 to 100% in low-risk, 63 to 98% in intermediate-risk and 81-93% in high-risk patients. Late grade 3 genitourinary and gastrointestinal toxicity was 0-16% and 0-2%, respectively. The reported potency preservation rates ranged from 60 to 90%. In conclusion, high biochemical control and low complication rates are reported with HDR monotherapy. It is a safe and effective local treatment modality for organ-confined prostate cancer with reproducible high-quality dosimetry.
EVALuna2:33036

Perspective on Fibroblast Activation Protein-Specific PET/CT in Fibrotic Interstitial Lung Diseases: Imaging Fibrosis-A New Paradigm for Molecular Imaging? - Schmidkonz, Christian (Journal of Nuclear Medicine, 2022)
CRIS-Team WoS Importer:2022-01-21

Radiochemotherapy of bladder cancer. An alternative to radical cystectomy - Rodel, C.; Ott, O.; Weiss, C. (Onkologe, 2018)
Background. The standard treatment of muscle invasive carcinoma is cystectomy with pelvic lymphadenectomy. The primary organ-preserving, trimodal therapy is considered an alternative to radical surgery. Objective. The concept and results of trimodal therapy, consisting of initial transurethral resection of the bladder tumor (TUR-B) followed by simultaneous radiochemotherapy (RCT) are presented. Material and methods. Evaluation of retrospective cohorts and prospective therapy optimization studies on organ preservation regimens. Comparative meta-analyses comparing cystectomy with trimodal treatment are presented. Results. A complete TUR-B including bladder mapping and tumor ground biopsy should be carried out before RCT. Radio-sensitization should be cisplatin-based or with a combination of 5-fluorouracil and mitomycin C. Complete response rates after TUR-B plus RCT are achieved in 60-90% of patients as well as 5-year survival rates between 40% and 75% and with preservation of the bladder in approximately 80% of surviving patients. Conclusion. Trimodal therapy is a viable alternative to radical cystectomy with curative intention for patients with muscle invasive urinary bladder carcinoma. Patients with early stage tumors (cT2/3N0) are particularly suitable in whom the initial TUR-B leads to as complete a tumor resection as possible (R0).
EVALuna2:33027

Response to Escande et al.: Magnetic guided brachytherapy: Time for non-pelvic cancer? Example from tongue brachytherapy [1] - Kovács, György; Martinez-Monge, Rafael; Budrukkar, Ashwini; Guinot, Jose Luis; Johansson, Bengt; Strnad, Vratislav; Rovirosa, Angeles; Siebert, Frank André; Tagliaferri, Luca (Radiotherapy and Oncology, 2021)
CRIS-Team Scopus Importer:2021-03-19

S2k-Leitlinie Therapie pathologischer Narben (hypertrophe Narben und Keloide) –Update 2020 - Nast, Alexander; Gauglitz, Gerd; Lorenz, Kerstin; Metelmann, Hans Robert; Paasch, Uwe; Strnad, Vratislav; Weidmann, Michael; Werner, Ricardo Niklas; Bauerschmitz, Jürgen (Journal der Deutschen Dermatologischen Gesellschaft, 2021)
CRIS-Team Scopus Importer:2021-02-26

Salvage Mastectomy Versus Second Conservative Treatment for Second Ipsilateral Breast Tumor Event: A Propensity Score-Matched Cohort Analysis of the GEC-ESTRO Breast Cancer Working Group Database - Hannoun-Levi, Jean Michel; Gal, Jocelyn; Van Limbergen, Erik; Chand, Marie Eve; Schiappa, Renaud; Smanyko, Viktor; Kauer-Domer, Daniela; Pasquier, David; Lemanski, Claire; Racadot, Séverine; Houvenaeghel, Gilles; Guix, Benjamin; et al. (International Journal of Radiation Oncology Biology Physics, 2021)
Purpose: Second conservative treatment has emerged as an option for patients with a second ipsilateral breast tumor event after conserving surgery and breast irradiation. We aimed to address the lack of evidence regarding second breast event treatment by comparing oncologic outcomes after conservative treatment or mastectomy. Methods and Materials: Oncologic outcomes were analyzed using a propensity score-matched cohort analysis study on patients who received a diagnosis of a second breast event between January 1995 and June 2017. Patient data were collected from 15 hospitals/cancer centers in 7 European countries. Patients were offered mastectomy or lumpectomy plus brachytherapy. Propensity scores were calculated with logistic regression and multiple imputations. Matching (1:1) was achieved using the nearest neighbor method, including 10 clinical/pathologic data related to the second breast event. The primary endpoint was 5-year overall survival from the salvage surgery date. Secondary endpoints were 5-year cumulative incidence of third breast event, regional relapse and distant metastasis, and disease-free and specific survival. Complications and 5-year incidence of mastectomy were investigated in the conservative treatment cohort. Results: Among the 1327 analyzed patients (mastectomy, 945; conservative treatment, 382), 754 were matched by propensity score (mastectomy, 377; conservative treatment, 377). The median follow-up was 75.4 months (95% confidence interval [CI], 65.4-83.3) and 73.8 months (95% CI, 67.5-80.8) for mastectomy and conservative treatment, respectively (P = .9). In the matched analyses, no differences in 5-year overall survival and cumulative incidence of third breast event were noted between mastectomy and conservative treatment (88% [95% CI, 83.0-90.8] vs 87% [95% CI, 82.1-90.2], P = .6 and 2.3% [95% CI, 0.7-3.9] vs 2.8% [95% CI, 0.8-4.7], P = .4, respectively). Similarly, no differences were observed for all secondary endpoints. Five-year cumulative incidence of mastectomy was 3.1% (95% CI, 1.0-5.1). Conclusions: To our knowledge, this is the largest matched analysis of mastectomy and conservative treatment combining lumpectomy with brachytherapy for second breast events. Compared with mastectomy, conservative treatment does not appear to be associated with any differences in terms of oncologic outcome. Consequently, conservative treatment could be considered a viable option for salvage treatment.
CRIS-Team Scopus Importer:2021-01-29

Stereotactic or intensity modulated Radiotherapy of adrenal Metastases - Patient Characteristics and Therapy Results of a multicenter Analysis - Buergy, D.; Wuerschmidt, F.; Gkika, E.; Hoerner-Rieber, J.; Knippen, S.; Gerum, S.; Balermpas, P.; Henkenberens, C.; Voglhuber, T.; Kornhuber, C.; Barczyk, S.; Roeper, B.; et al. (STRAHLENTHERAPIE UND ONKOLOGIE, 2020)
CRIS-Team WoS Importer:2020-10-02

The influence of postoperative complications on long-term prognosis in patients with colorectal carcinoma - Beck, Clemens; Weber, Klaus; Brunner, Maximilian; Agaimy, Abbas; Semrau, Sabine; Grützmann, Robert; Schellerer, Vera; Merkel, Susanne (International Journal of Colorectal Disease, 2020)
Background: The impact of postoperative complications (POCs) on the long-term prognosis of patients with colorectal carcinoma was analysed with respect to their severity according to the Clavien-Dindo classification (CDC). Methods: The prospectively collected data of 2158 patients who underwent curative resection of a colorectal carcinoma (1168 rectal carcinomas, 990 colon carcinomas) without distant metastases from 1995 to 2014 were analysed. The POCs were documented in a standardized form and graded with the CDC. Patients who died postoperatively (CDC grade V, 1.7%) were excluded. Results: In total, 467 patients (21.6%) had POCs: CDC I, 141 (6.5%); CDC II, 162 (7.5%); CDC III, 112 (5.2%); and CDC IV, 52 (2.4%). More POCs and higher CDC grades were found in men, ASA III-IV patients, rectal carcinoma patients, and patients who underwent abdominoperineal excisions or multivisceral resections. The 5-year locoregional recurrence rate was 5.3% in patients without POCs and 6.6% in patients with POCs. It was highest in CDC III patients (12.9%), which was confirmed in multivariate analysis (HR 2.2; p = 0.005). The 5-year distant metastasis rate was 15.9% in CDC 0 patients and 19.5% in CDC I–IV patients. In multivariate analysis, distant metastasis was highest in CDC III patients (HR 1.7; p = 0.020). The 5-year overall survival rate was 83.5% in patients without POCs and 73.5% in patients with POCs. It was worst in CDC IV patients (63.1%), which was confirmed by multivariate analysis (HR 1.9; p = 0.001). Conclusion: Patients with POCs after colorectal surgery have a poor long-term prognosis. As the CDC grade increases, survival deteriorates.
CRIS-Team Scopus Importer:2020-04-14
Keywords: Clavien-Dindo classification; Colorectal carcinoma; Postoperative complications; Prognosis

The role of plastic reconstructive surgery in surgical therapy of soft tissue sarcomas - Götzl, Rebekka; Sterzinger, Sebastian; Arkudas, Andreas; Boos, Anja; Semrau, Sabine; Vassos, Nikolaos; Grützmann, Robert; Agaimy, Abbas; Hohenberger, Werner; Horch, Raymund E.; Beier, Justus (Cancers, 2020)
Background: Soft tissue sarcoma (STS) treatment is an interdisciplinary challenge. Along with radio(chemo)therapy, surgery plays the central role in STS treatment. Little is known about the impact of reconstructive surgery on STS, particularly whether reconstructive surgery enhances STS resection success with the usage of flaps. Here, we analyzed the 10-year experience at a university hospital’s Comprehensive Cancer Center, focusing on the role of reconstructive surgery. Methods: We performed a retrospective analysis of STS-patients over 10 years. We investigated patient demographics, diagnosis, surgical management, tissue/function reconstruction, complication rates, resection status, local recurrence and survival. Results: Analysis of 290 patients showed an association between clear surgical margin (R0) resections and higher-grade sarcoma in patients with free flaps. Major complications were lower with primary wound closure than with flaps. Comparison of reconstruction techniques showed no significant differences in complication rates. Wound healing was impaired in STS recurrence. The local recurrence risk was over two times higher with primary wound closure than with flaps. Conclusion: Defect reconstructions in STS are reliable and safe. Plastic surgeons should have a permanent place in interdisciplinary surgical STS treatment, with the full armamentarium of reconstruction methods.
CRIS-Team Scopus Importer:2020-12-04
Keywords: Plastic surgery; Reconstruction; Reconstructive surgery; Soft tissue sarcoma; STS