Kerstin A Eitz1,2, Simon S Lo3, Hany Soliman4, Arjun Sahgal4, Aimee Theriault4, Mark B Pinkham5,6, Matthew C Foote5,6, Andrew J Song7, Wenyin Shi7, Kristin J Redmond8, Chenchen Gui8, Aryavarta M S Kumar9, Mitchell Machtay10, Bernhard Meyer11, Stephanie E Combs1,2. 1. Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany. 2. Institute for Radiation Medicine (IRM), Helmholtz Zentrum München, Neuherberg, Germany. 3. Department of Radiation Oncology, University of Washington, Seattle. 4. Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada. 5. Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 6. Department of Radiation Oncology, University of Queensland, Brisbane, Queensland, Australia. 7. Department of Radiation Oncology, Sidney Kimmel Medical College & Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania. 8. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. 9. Radiation Oncology Service, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio. 10. Department of Radiation Oncology, University Hospital Cleveland Medical Center, Cleveland, Ohio. 11. Department of Neurosurgery, Technical University of Munich (TUM), Munich, Germany.
Abstract
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.
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.
Authors: S Rogers; A Stauffer; N Lomax; S Alonso; B Eberle; S Gomez Ordoñez; T Lazeroms; E Kessler; M Brendel; L Schwyzer; O Riesterer Journal: J Neurooncol Date: 2021-09-21 Impact factor: 4.130
Authors: Brett H Diamond; Vikram Jairam; Shaharyar Zuberi; Jessie Y Li; Timothy J Marquis; Charles E Rutter; Henry S Park Journal: J Radiosurg SBRT Date: 2021
Authors: Giuseppe Minniti; Maximilian Niyazi; Nicolaus Andratschke; Matthias Guckenberger; Joshua D Palmer; Helen A Shih; Simon S Lo; Scott Soltys; Ivana Russo; Paul D Brown; Claus Belka Journal: Radiat Oncol Date: 2021-04-15 Impact factor: 3.481