Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study

Rusthoven CG, Yamamoto M, Bernhardt D, Smith DE, Gao D, Serizawa T, Yomo S, Aiyama H, Higuchi Y, Shuto T, Akabane A, Sato Y, Niranjan A, Faramand AM, Lunsford LD, Mcinerney J, Tuanquin LC, Zacharia BE, Chiang V, Singh C, Yu JB, Braunstein S, Mathieu D, Touchette CJ, Lee CC, Yang HC, Aizer AA, Cagney DN, Chan MD, Kondziolka D, Bernstein K, Silverman JS, Grills IS, Siddiqui ZA, Yuan JC, Sheehan JP, Cordeiro D, Nosaki K, Seto T, Deibert CP, Verma V, Day S, Halasz LM, Warnick RE, Trifiletti DM, Palmer JD, Attia A, Li B, Cifarelli CP, Brown PD, Vargo JA, Combs SE, Kessel KA, Rieken S, Patel S, Guckenberger M, Andratschke N, Kavanagh BD, Robin TP (2020)

Publication Type: Journal article

Publication year: 2020


Book Volume: 6

Pages Range: 1028-1037

Journal Issue: 7

DOI: 10.1001/jamaoncol.2020.1271


Importance: Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited. Objective: To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT. Design, Setting, and Participants: FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019. Interventions: SRS and WBRT for small cell lung cancer brain metastases. Main Outcomes and Measures: Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses. Results: In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P <.001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P =.003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P =.79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results. Conclusions and Relevance: Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established..

Involved external institutions

University of Colorado System US United States (USA) (US) Universitätsklinikum Heidelberg DE Germany (DE) Tsukiji Neurological Clinic JP Japan (JP) Aizawa Hospital / 相澤病院 JP Japan (JP) Chiba University / 千葉大学 JP Japan (JP) Yokohama Rosai Hospital JP Japan (JP) Nippon Telegraph and Telephone (NTT) / 日本電信電話株式会社 JP Japan (JP) Keio University / 慶應義塾大学 JP Japan (JP) University of Pittsburgh US United States (USA) (US) Penn State Milton S. Hershey Medical Center US United States (USA) (US) Yale University US United States (USA) (US) University of California San Francisco (UCSF) US United States (USA) (US) Université de Sherbrooke CA Canada (CA) Taipei Veterans General Hospital / 台北榮民總醫院 TW Taiwan (TW) Harvard University US United States (USA) (US) Wake Forest University US United States (USA) (US) New York University (NYU) US United States (USA) (US) Beaumont Health System US United States (USA) (US) University of Virginia (UVA) US United States (USA) (US) National Hospital Organization Kyushu Medical Center JP Japan (JP) Emory University US United States (USA) (US) Allegheny Health Network US United States (USA) (US) University of Washington US United States (USA) (US) Mercy Health US United States (USA) (US) Mayo Clinic US United States (USA) (US) Ohio State University US United States (USA) (US) Vanderbilt University US United States (USA) (US) West Virginia University (WVU) US United States (USA) (US) Technische Universität München (TUM) DE Germany (DE) University of Alberta CA Canada (CA) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH)

How to cite


Rusthoven, C.G., Yamamoto, M., Bernhardt, D., Smith, D.E., Gao, D., Serizawa, T.,... Robin, T.P. (2020). Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study. JAMA Oncology, 6(7), 1028-1037. https://doi.org/10.1001/jamaoncol.2020.1271


Rusthoven, Chad G., et al. "Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study." JAMA Oncology 6.7 (2020): 1028-1037.

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