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Multicenter Study
. 2020 Jul 1;6(7):1028-1037.
doi: 10.1001/jamaoncol.2020.1271.

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

Chad G Rusthoven  1 , Masaaki Yamamoto  2 , Denise Bernhardt  3 , Derek E Smith  4 , Dexiang Gao  4 , Toru Serizawa  5 , Shoji Yomo  6 , Hitoshi Aiyama  2 , Yoshinori Higuchi  7 , Takashi Shuto  8 , Atsuya Akabane  9 , Yasunori Sato  10 , Ajay Niranjan  11 , Andrew M Faramand  11 , L Dade Lunsford  11 , James McInerney  12 , Leonard C Tuanquin  12 , Brad E Zacharia  12 , Veronica Chiang  13 , Charu Singh  13 , James B Yu  13 , Steve Braunstein  14 , David Mathieu  15 , Charles J Touchette  15 , Cheng-Chia Lee  16 , Huai-Che Yang  16 , Ayal A Aizer  17 , Daniel N Cagney  17 , Michael D Chan  18 , Douglas Kondziolka  19 , Kenneth Bernstein  19 , Joshua S Silverman  19 , Inga S Grills  20 , Zaid A Siddiqui  20 , Justin C Yuan  20 , Jason P Sheehan  21 , Diogo Cordeiro  21 , Kename Nosaki  22 , Takahashi Seto  22 , Christopher P Deibert  23 , Vivek Verma  24 , Samuel Day  25 , Lia M Halasz  25 , Ronald E Warnick  26 , Daniel M Trifiletti  27 , Joshua D Palmer  28 , Albert Attia  29 , Benjamin Li  29 , Christopher P Cifarelli  30 , Paul D Brown  31 , John A Vargo  11   30 , Stephanie E Combs  32 , Kerstin A Kessel  32 , Stefan Rieken  3 , Samir Patel  33 , Matthias Guckenberger  34 , Nicolaus Andratschke  34 , Brian D Kavanagh  1 , Tyler P Robin  1
Affiliations
Multicenter Study

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

Chad G Rusthoven et al. JAMA Oncol. .

Erratum in

  • Middle Initial Omitted From Author Name.
    [No authors listed] [No authors listed] JAMA Oncol. 2020 Sep 1;6(9):1473. doi: 10.1001/jamaoncol.2020.3404. JAMA Oncol. 2020. PMID: 32701125 Free PMC article. No abstract available.

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rusthoven 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 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.

Figures

Figure 1.
Figure 1.. Overall Survival (OS) and Time to Central Nervous System Progression (TTCP) After First-line Stereotactic Radiosurgery
CNS indicates central nervous system. The dashed lines indicate the median values.
Figure 2.
Figure 2.. Overall Survival (OS) and Time to Central Nervous System Progression (TTCP) After First-line Stereotactic Radiosurgery (SRS) vs Whole-Brain Radiotherapy (WBRT)
CNS indicates central nervous system. The dashed lines indicate the median values.
See this image and copyright information in PMC

Comment in

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