Tumor growth rate as a validated early radiological biomarker able to reflect treatment-induced changes in neuroendocrine tumors: The GREPONET-2 study

Lamarca A, Ronot M, Moalla S, Crona J, Opalinska M, Lopez CL, Pezzutti D, Najran P, Carvhalo L, Bezerra ROF, Borg P, Violi NV, Trueba HV, de Mestier L, Scaefer N, Baudin E, Sundin A, Costa F, Pavel ME, Dromain C (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Clinical Cancer Research American Association for Cancer Research

Book Volume: 25

Pages Range: 6692-6699

Journal Issue: 22

DOI: 10.1158/1078-0432.CCR-19-0963

Abstract

Purpose: Tumor growth rate (TGR) represents the percentage change in tumor volume per month (%/m). Previous results from the GREPONET study showed that TGR measured after 3 months (TGR3m) of starting systemic treatment (ST) or watch and wait (WW) was an early biomarker predicting progression-free survival (PFS) in neuroendocrine tumors (NET). Experimental Design: Patients from 7 centers with advanced grade (G) 1/2 NETs from the pancreas (P)/small bowel (SB) initiating ST/WW were eligible. Computed tomography (CT)/MRI performed at prebaseline, baseline, and 3 (±1) months of study entry were retrospectively reviewed. Aim-1: explore treatment-induced changes in TGR (DTGR3mBL; paired T test), and Aim-2: validate TGR3m (<0.8%/m vs. ≥0.8%/m) as an early biomarker in an independent cohort (Kaplan–Meier/Cox regression). Results: Of 785 patients screened, 127 were eligible. Mean (SD) TGR0 and TGR3m were 5.4%/m (14.9) and -1.4%/m (11.8), respectively. Mean (SD) DTGR3m-BL paired-difference was -6.8%/m (19.3; P < 0.001). Most marked DTGR3m-BL [mean (SD)] were identified with targeted therapies [-11.3%/m (4.7); P ¼ 0.0237] and chemotherapy [-7.9%/m (3.4); P ¼ 0.0261]. Multivariable analysis confirmed the absence of previous treatment (OR ¼ 4.65; 95% CI, 1.31–16.52; P ¼ 0.018) and low TGR3m (continuous variable; OR 1.09; 95% CI, 1.01–1.19; P ¼ 0.042) to be independent predictors of radiologic objective response. When the multivariable survival analysis for PFS (Cox regression) was adjusted to grade (P ¼ 0.004) and stage (P ¼ 0.017), TGR3m ≥ 0.8 (vs. <0.8) maintained its significance as a prognostic factor (P < 0.001), whereas TGR0 and DTGR3m-BL did not. TGR3m ≥ 0.8%/m was confirmed as an independent prognostic factor for PFS [external validation; Aim-2; multivariable HR 2.21 (95% CI, 1.21–3.70; P ¼ 0.003)]. Conclusions: TGR has a role as a biomarker for monitoring response to therapy for early identification of treatment-induced changes and for early prediction of PFS and radiologic objective response.

Authors with CRIS profile

Marianne Ellen Pavel Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

Christie NHS Foundation Trust GB United Kingdom (GB) Beaujon Hospital / Hôpital Beaujon FR France (FR) Uppsala University Hospital / Akademiska sjukhuset SE Sweden (SE) Szpital Uniwersytecki w Krakowie PL Poland (PL) Marqués de Valdecilla University Hospital / Hospital Universitario de Marqués de Valdecilla (HUMV) ES Spain (ES) Hospital Israelita Albert Einstein BR Brazil (BR) Hospital Sírio-Libanês BR Brazil (BR) Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV) CH Switzerland (CH) Institut Gustave-Roussy FR France (FR)

How to cite

APA:

Lamarca, A., Ronot, M., Moalla, S., Crona, J., Opalinska, M., Lopez, C.L.,... Dromain, C. (2019). Tumor growth rate as a validated early radiological biomarker able to reflect treatment-induced changes in neuroendocrine tumors: The GREPONET-2 study. Clinical Cancer Research, 25(22), 6692-6699. https://doi.org/10.1158/1078-0432.CCR-19-0963

MLA:

Lamarca, Angela, et al. "Tumor growth rate as a validated early radiological biomarker able to reflect treatment-induced changes in neuroendocrine tumors: The GREPONET-2 study." Clinical Cancer Research 25.22 (2019): 6692-6699.

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