Chad G Rusthoven1, Masaaki Yamamoto2, Denise Bernhardt3, Derek E Smith4, Dexiang Gao4, Toru Serizawa5, Shoji Yomo6, Hitoshi Aiyama2, Yoshinori Higuchi7, Takashi Shuto8, Atsuya Akabane9, Yasunori Sato10, Ajay Niranjan11, Andrew M Faramand11, L Dade Lunsford11, James McInerney12, Leonard C Tuanquin12, Brad E Zacharia12, Veronica Chiang13, Charu Singh13, James B Yu13, Steve Braunstein14, David Mathieu15, Charles J Touchette15, Cheng-Chia Lee16, Huai-Che Yang16, Ayal A Aizer17, Daniel N Cagney17, Michael D Chan18, Douglas Kondziolka19, Kenneth Bernstein19, Joshua S Silverman19, Inga S Grills20, Zaid A Siddiqui20, Justin C Yuan20, Jason P Sheehan21, Diogo Cordeiro21, Kename Nosaki22, Takahashi Seto22, Christopher P Deibert23, Vivek Verma24, Samuel Day25, Lia M Halasz25, Ronald E Warnick26, Daniel M Trifiletti27, Joshua D Palmer28, Albert Attia29, Benjamin Li29, Christopher P Cifarelli30, Paul D Brown31, John A Vargo11,30, Stephanie E Combs32, Kerstin A Kessel32, Stefan Rieken3, Samir Patel33, Matthias Guckenberger34, Nicolaus Andratschke34, Brian D Kavanagh1, Tyler P Robin1. 1. University of Colorado School of Medicine, Department of Radiation Oncology, Aurora. 2. Katsuta Hospital Mito Gamma House, Hitachi-naka, Japan. 3. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. 4. University of Colorado Cancer Center, Biostatistics Core, Aurora. 5. Tokyo Gamma Unit Center, Tsukiji Neurological Clinic, Tokyo, Japan. 6. Aizawa Comprehensive Cancer Center, Division of Radiation Oncology, Aizawa Hospital, Matsumoto, Japan. 7. Chiba University Graduate School of Medicine, Department of Neurological Surgery, Chiba, Japan. 8. Yokohama Rosai Hospital, Department of Neurosurgery, Yokohama, Japan. 9. Gamma Knife Center, NTT Medical Center Tokyo, Tokyo, Japan. 10. Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan. 11. Department of Neurological Surgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 12. Department of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania. 13. Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut. 14. Department of Radiation Oncology, University of California, San Francisco, San Francisco. 15. Division of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, Quebec, Canada. 16. Taipei Veterans General Hospital, Department of Neurosurgery, Neurological Institute, Taipei, Taiwan. 17. Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 18. Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina. 19. Department of Neurosurgery, New York University Langone Medical Center, New York. 20. Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan. 21. Department of Neurological Surgery, University of Virginia, Charlottesville. 22. National Hospital Organization Kyushu Cancer Center, Department of Thoracic Oncology, Fukuoka, Japan. 23. Department of Radiation Oncology, Emory University, Atlanta, Georgia. 24. Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania. 25. Department of Radiation Oncology, University of Washington School of Medicine, Seattle. 26. Department of Neurosurgery, Jewish Hospital-Mercy Health, Cincinnati, Ohio. 27. Department of Radiation Oncology, Mayo Clinic Jacksonville, Jacksonville, Florida. 28. Department of Radiation Oncology, Ohio State University, Columbus. 29. Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee. 30. Department of Neurosurgery, West Virginia University, Morgantown. 31. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. 32. Department of Radiation Oncology, Technical University of Munich, Munich, Germany. 33. Department of Radiation Oncology, University of Alberta, Edmonton, Alberta, Canada. 34. Department of Radiation Oncology, University Hospital Zurich, The University of Zurich, Zurich, Switzerland.
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.
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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