TY - JOUR
T1 - Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases
T2 - The FIRE-SCLC Cohort Study
AU - Rusthoven, Chad G.
AU - Yamamoto, Masaaki
AU - Bernhardt, Denise
AU - Smith, Derek E.
AU - Gao, Dexiang
AU - Serizawa, Toru
AU - Yomo, Shoji
AU - Aiyama, Hitoshi
AU - Higuchi, Yoshinori
AU - Shuto, Takashi
AU - Akabane, Atsuya
AU - Sato, Yasunori
AU - Niranjan, Ajay
AU - Faramand, Andrew M.
AU - Lunsford, L. Dade
AU - McInerney, James
AU - Tuanquin, Leonard C.
AU - Zacharia, Brad E.
AU - Chiang, Veronica
AU - Singh, Charu
AU - Yu, James B.
AU - Braunstein, Steve
AU - Mathieu, David
AU - Touchette, Charles J.
AU - Lee, Cheng Chia
AU - Yang, Huai Che
AU - Aizer, Ayal A.
AU - Cagney, Daniel N.
AU - Chan, Michael D.
AU - Kondziolka, Douglas
AU - Bernstein, Kenneth
AU - Silverman, Joshua S.
AU - Grills, Inga S.
AU - Siddiqui, Zaid A.
AU - Yuan, Justin C.
AU - Sheehan, Jason P.
AU - Cordeiro, Diogo
AU - Nosaki, Kename
AU - Seto, Takahashi
AU - Deibert, Christopher P.
AU - Verma, Vivek
AU - Day, Samuel
AU - Halasz, Lia M.
AU - Warnick, Ronald E.
AU - Trifiletti, Daniel M.
AU - Palmer, Joshua D.
AU - Attia, Albert
AU - Li, Benjamin
AU - Cifarelli, Christopher P.
AU - Brown, Paul D.
AU - Vargo, John A.
AU - Combs, Stephanie E.
AU - Kessel, Kerstin A.
AU - Rieken, Stefan
AU - Patel, Samir
AU - Guckenberger, Matthias
AU - Andratschke, Nicolaus
AU - Kavanagh, Brian D.
AU - Robin, Tyler P.
N1 - Funding Information:
reported receiving research funding from Takeda outside the submitted work as well as honoraria for educational talks from Genentech and AstraZeneca outside the submitted work. Dr Bernhardt reported receiving grants from Heidelberg University during the conduct of the study. Dr Lunsford reported receiving other from AB Elekta and Insightec during the conduct of the study. Dr McInerney reported receiving grants from Elekta outside the submitted work. Dr Zacharia reported receiving personal fees from NICO Corp and Medtronic outside the submitted work. Dr Yu reported receiving personal fees from Boston Scientific and Galera Pharmaceuticals outside the submitted work. Dr Aizer reported receiving grants from Varian Medical Systems outside the submitted work. Dr Chan reported receiving other from Monteris and Elekta outside the submitted work. Dr Kondziolka reported receiving grants from Brainlab outside the
Funding Information:
submitted work. Dr Seto reported receiving grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Merck Sharp & Dohme, Nippon Boehringer Ingelheim, Novartis Pharma, Pfizer Japan, and Takeda Pharmaceutical; personal fees from Astellas Pharma, Bristol-Myers Squibb, Kyowa Hakko Kirin, Ono Pharmaceutical, Taiho Pharmaceutical, Thermo Fisher Scientific, and Precision Medicine Asia Co Ltd outside the submitted work; and grants from AbbVie, Bayer Yakuhin, Kissei Pharmaceutical, Loxo Oncology Inc, and Merck Serono. Dr Trifiletti reported receiving other from Novocure and Springer outside the submitted work. Dr Palmer reported receiving grants from Varian Medical Systems as well as personal fees from Depuy Synthes, Huron Consulting Group, and MORE Health Inc outside the submitted work. Dr Attia reported receiving personal fees from Novocure and AstraZeneca outside the submitted work. Dr Brown reported receiving personal fees from UpToDate outside the submitted work. Dr Vargo reported receiving other from Elsevier outside the submitted work. Dr Combs reported receiving personal fees and nonfinancial support from Roche, AstraZeneca, Medac, Dr Sennewald Medizintechnik, Elekta, Accuray, Bristol-Myers Squibb, Brainlab, Daiichi Sankyo, and Icotec outside the submitted work. Dr Rieken reported receiving grants and personal fees from AstraZeneca, Merck, Novocure, Pfizer, and Novartis outside the submitted work. No other disclosures were reported.
Funding Information:
Funding/Support: This study was funded by grant P30CA046934 from the University of Colorado Cancer Center (Mr Smith and Dr Gao were partially supported by this grant).
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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..
AB - 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..
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U2 - 10.1001/jamaoncol.2020.1271
DO - 10.1001/jamaoncol.2020.1271
M3 - Article
C2 - 32496550
AN - SCOPUS:85086222246
VL - 6
SP - 1028
EP - 1037
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 7
ER -