TY - JOUR
T1 - Multi-institutional Analysis of Prognostic Factors and Outcomes after Hypofractionated Stereotactic Radiotherapy to the Resection Cavity in Patients with Brain Metastases
AU - Eitz, Kerstin A.
AU - Lo, Simon S.
AU - Soliman, Hany
AU - Sahgal, Arjun
AU - Theriault, Aimee
AU - Pinkham, Mark B.
AU - Foote, Matthew C.
AU - Song, Andrew J.
AU - Shi, Wenyin
AU - Redmond, Kristin J.
AU - Gui, Chenchen
AU - Kumar, Aryavarta M.S.
AU - MacHtay, Mitchell
AU - Meyer, Bernhard
AU - Combs, Stephanie E.
N1 - Funding Information:
reported receiving nonfinancial support from Elekta outside the submitted work. Dr Soliman reported receiving grants from Elekta outside the submitted work. Dr Pinkham reported receiving personal fees from Astra Zeneca, Merck, Sharpe & Dohme, Roche, and Bristol-Myers Squibb outside the submitted work. Dr Foote reported receiving grants from Elekta and personal fees from Elekta AB and Varian outside the submitted work. Dr Shi reported receiving grants and personal fees from Brainlab, Varian, and Novocure and grants from Regeneron outside the submitted work. Dr Redmond reported receiving grants and travel expenses from Elekta, is a member of the data safety monitoring board for BioMimetix, and reported receiving grants, personal fees, and travel expenses from Accuray and nonfinancial support from Brainlab outside the submitted work. Dr Machtay reported receiving grants and travel support from Elekta Inc outside the submitted work. Dr Meyer reported receiving personal fees from Medtronic and Depuy, grants and personal fees from Brainlab, Ulrich Medical, and Icotec, personal fees and nonfinancial support from Spineart and Medacta, and grants from Bundesministerium für Bildung und Forschung outside the submitted work. Dr Combs reported receiving personal fees from Roche, Bristol-Myers Squibb, Brainlab, Daiichi Sankyo, ICOTEC, AstraZeneca, Dr. Sennewald, Elekta, Varian, and Accuray during the conduct of the study and outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Importance: For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking. Objective: To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases. Design, Setting, and Participants: An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment. Exposures: A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied. Main Outcomes and Measures: The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity. Results: A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P <.001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P =.02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P =.007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P =.03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P =.02) were significant in the multivariate analysis. Conclusions and Relevance: To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.
AB - Importance: For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking. Objective: To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases. Design, Setting, and Participants: An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment. Exposures: A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied. Main Outcomes and Measures: The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity. Results: A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P <.001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P =.02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P =.007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P =.03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P =.02) were significant in the multivariate analysis. Conclusions and Relevance: To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.
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U2 - 10.1001/jamaoncol.2020.4630
DO - 10.1001/jamaoncol.2020.4630
M3 - Article
C2 - 33057566
AN - SCOPUS:85093935807
SN - 2374-2437
VL - 6
SP - 1901
EP - 1909
JO - JAMA Oncology
JF - JAMA Oncology
IS - 12
ER -