Jack M Qian1,2, Allison M Martin1, Kate Martin1, Lubna Hammoudeh1, Paul J Catalano3,4, F Stephen Hodi5, Daniel N Cagney1, Daphne A Haas-Kogan1, Jonathan D Schoenfeld1, Ayal A Aizer1. 1. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts. 2. Harvard Radiation Oncology Program, Massachusetts General Hospital/Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts. 3. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts. 5. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear. METHODS: A total of 199 patients with melanoma and non-small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per-metastasis basis, using a sandwich estimator to account for intrapatient correlation. RESULTS: The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P < .001), with correspondingly lower rates of progressive disease (5% vs 26%; P < .001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18-2.63 [P = .006]) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23-0.78 [P = .006]). This effect appeared to be greater for melanoma than for non-small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression. CONCLUSIONS: Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted.
BACKGROUND: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear. METHODS: A total of 199 patients with melanoma and non-small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per-metastasis basis, using a sandwich estimator to account for intrapatient correlation. RESULTS: The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P < .001), with correspondingly lower rates of progressive disease (5% vs 26%; P < .001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18-2.63 [P = .006]) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23-0.78 [P = .006]). This effect appeared to be greater for melanoma than for non-small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression. CONCLUSIONS: Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted.
Authors: Ayal A Aizer; Nayan Lamba; Manmeet S Ahluwalia; Kenneth Aldape; Adrienne Boire; Priscilla K Brastianos; Paul D Brown; D Ross Camidge; Veronica L Chiang; Michael A Davies; Leland S Hu; Raymond Y Huang; Timothy Kaufmann; Priya Kumthekar; Keng Lam; Eudocia Q Lee; Nancy U Lin; Minesh Mehta; Michael Parsons; David A Reardon; Jason Sheehan; Riccardo Soffietti; Hussein Tawbi; Michael Weller; Patrick Y Wen Journal: Neuro Oncol Date: 2022-10-03 Impact factor: 13.029
Authors: Zhengfei Zhu; Jianjiao Ni; Xuwei Cai; Shengfa Su; Hongqing Zhuang; Zhenzhou Yang; Ming Chen; Shenglin Ma; Conghua Xie; Yaping Xu; Jiancheng Li; Hong Ge; Anwen Liu; Lujun Zhao; Chuangzhou Rao; Congying Xie; Nan Bi; Zhouguang Hui; Guangying Zhu; Zhiyong Yuan; Jun Wang; Lina Zhao; Wei Zhou; Chai Hong Rim; Arturo Navarro-Martin; Ben G L Vanneste; Dirk De Ruysscher; J Isabelle Choi; Jacek Jassem; Joe Y Chang; Lucyna Kepka; Lukas Käsmann; Michael T Milano; Paul Van Houtte; Rafal Suwinski; Alberto Traverso; Hiroshi Doi; Yang-Gun Suh; Georges Noël; Natsuo Tomita; Roman O Kowalchuk; Terence T Sio; Baosheng Li; Bing Lu; Xiaolong Fu Journal: Transl Lung Cancer Res Date: 2022-09