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Abstract：
BACKGROUND: While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors.
METHODS: Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study\'s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples.
CONCLUSIONS: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials.
BACKGROUND: Clinicaltrials.gov identifier: NCT03511391 . Registered 17 April 2018.
METHODS: Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study\'s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples.
CONCLUSIONS: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials.
BACKGROUND: Clinicaltrials.gov identifier: NCT03511391 . Registered 17 April 2018.
摘要：
背景：虽然引入检查点抑制剂（CPIs）作为各种肿瘤类型的护理治疗标准已导致临床结果的显着改善，大多数患者仍然没有反应。临床前数据表明，立体定向放射治疗（SBRT）可以通过作为原位癌疫苗与CPIs协同作用，从而有可能提高应答率和延长疾病控制。尽管SBRT与CPIs同时施用已被证明是安全的，大型随机试验仍缺乏其疗效的证据.这项多中心随机II期试验的目的是评估与CPIs同时给药的SBRT是否可以延长晚期实体瘤患者的无进展生存期。
方法：98例局部晚期或转移性疾病患者将以1：1的方式随机接受CPI治疗联合SBRT（A组）或CPI单一疗法（B组）。随机化将根据肿瘤组织学分层(黑色素瘤，肾,尿路上皮,头颈部鳞状细胞或非小细胞肺癌）和疾病负担（≤或>3个癌症病变）。推荐的SBRT剂量为3分24Gy，将对最多3个病变进行给药，并在第二个或第三个CPI周期之前完成（取决于CPI治疗时间表）。该研究的主要终点是根据iRECIST的无进展生存期。次要终点包括总生存期，客观反应,本地控制,生活质量和毒性。将使用血液进行转化分析，粪便和组织样本。
结论：CHEERS试验将进一步了解SBRT与CPIs联合治疗晚期实体瘤患者的临床和免疫学影响。此外，研究结果将为未来的免疫放射治疗试验的设计提供信息。
背景：Clinicaltrials.gov标识符：NCT03511391。2018年4月17日注册
方法：98例局部晚期或转移性疾病患者将以1：1的方式随机接受CPI治疗联合SBRT（A组）或CPI单一疗法（B组）。随机化将根据肿瘤组织学分层(黑色素瘤，肾,尿路上皮,头颈部鳞状细胞或非小细胞肺癌）和疾病负担（≤或>3个癌症病变）。推荐的SBRT剂量为3分24Gy，将对最多3个病变进行给药，并在第二个或第三个CPI周期之前完成（取决于CPI治疗时间表）。该研究的主要终点是根据iRECIST的无进展生存期。次要终点包括总生存期，客观反应,本地控制,生活质量和毒性。将使用血液进行转化分析，粪便和组织样本。
结论：CHEERS试验将进一步了解SBRT与CPIs联合治疗晚期实体瘤患者的临床和免疫学影响。此外，研究结果将为未来的免疫放射治疗试验的设计提供信息。
背景：Clinicaltrials.gov标识符：NCT03511391。2018年4月17日注册
