BackgroundAt diagnosis, 10%-15% NSCLC patients have brain metastases. BM-NSCLC suffer worse prognosis. For BM-NSCLC, local therapies, e.g., surgery and radiation therapy, are the mainstream of treatment. Immunotherapy combined with or without chemotherapy is first-line standard of care for NSCLC. Immunotherapy showed trends for benefit in BM-NSCLC and a synergistic effect with radiation therapy. However, there is a lack of high-quality evidence on additional immunotherapy on chemotherapy for BM-NSCLC. The present phase III trial aims to confirm camrelizumab, an anti-programmed cell death protein-1 antibody, plus chemotherapy with or without stereotactic or whole brain RT as first-line treatment for BM-NSCLC without driver gene mutation.Trial DesignTreatment-naïve, EGFR/ALK-negative NSCLC aged 18-75 years, with ≥ three brain metastatic lesions or one to two unresectable brain metastatic lesions are eligible. Approximately 200 patients will be randomized (1:1) to receive camrelizumab (200 mg, D1) or placebo plus chemotherapy (D1) for a 21-day cycle. Stereotactic or whole brain RT will be performed at the discretion of investigator, which will be completed within 42 days after first dose of study drugs. Stratification factors include histological type (non-squamous, squamous NSCLC), number of brain metastatic lesions (one to five, ≥ six), and planned radiation therapy (yes, no). The chemotherapy regimens are pemetrexed (500 mg/m2) for non-squamous NSCLC or paclitaxel (175 mg/m2)/albumin-bound paclitaxel (260 mg/m2) for squamous NSCLC plus carboplatin (area under the curve 5)/cisplatin (75 mg/m2). After four to six cycles, camrelizumab or placebo plus pemetrexed, and single-agent camrelizumab or placebo will be administrated as maintenance treatment for non-squamous and squamous NSCLC, respectively. The primary endpoint is intracranial PFS. The secondary endpoints include intracranial ORR, ORR, PFS, OS, duration of response, quality of life, cognitive functioning, and safety. Recruitment began in Apr 2021.Clinical trial identificationNCT04768075.Editorial acknowledgementWe thank the medical writing support from Jiangsu Hengrui Pharmaceuticals Co., Ltd.Legal entity responsible for the studyGuangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences.FundingChinese Thoracic Oncology Group (CTONG).DisclosureAll authors have declared no conflicts of interest. BackgroundAt diagnosis, 10%-15% NSCLC patients have brain metastases. BM-NSCLC suffer worse prognosis. For BM-NSCLC, local therapies, e.g., surgery and radiation therapy, are the mainstream of treatment. Immunotherapy combined with or without chemotherapy is first-line standard of care for NSCLC. Immunotherapy showed trends for benefit in BM-NSCLC and a synergistic effect with radiation therapy. However, there is a lack of high-quality evidence on additional immunotherapy on chemotherapy for BM-NSCLC. The present phase III trial aims to confirm camrelizumab, an anti-programmed cell death protein-1 antibody, plus chemotherapy with or without stereotactic or whole brain RT as first-line treatment for BM-NSCLC without driver gene mutation. At diagnosis, 10%-15% NSCLC patients have brain metastases. BM-NSCLC suffer worse prognosis. For BM-NSCLC, local therapies, e.g., surgery and radiation therapy, are the mainstream of treatment. Immunotherapy combined with or without chemotherapy is first-line standard of care for NSCLC. Immunotherapy showed trends for benefit in BM-NSCLC and a synergistic effect with radiation therapy. However, there is a lack of high-quality evidence on additional immunotherapy on chemotherapy for BM-NSCLC. The present phase III trial aims to confirm camrelizumab, an anti-programmed cell death protein-1 antibody, plus chemotherapy with or without stereotactic or whole brain RT as first-line treatment for BM-NSCLC without driver gene mutation. Trial DesignTreatment-naïve, EGFR/ALK-negative NSCLC aged 18-75 years, with ≥ three brain metastatic lesions or one to two unresectable brain metastatic lesions are eligible. Approximately 200 patients will be randomized (1:1) to receive camrelizumab (200 mg, D1) or placebo plus chemotherapy (D1) for a 21-day cycle. Stereotactic or whole brain RT will be performed at the discretion of investigator, which will be completed within 42 days after first dose of study drugs. Stratification factors include histological type (non-squamous, squamous NSCLC), number of brain metastatic lesions (one to five, ≥ six), and planned radiation therapy (yes, no). The chemotherapy regimens are pemetrexed (500 mg/m2) for non-squamous NSCLC or paclitaxel (175 mg/m2)/albumin-bound paclitaxel (260 mg/m2) for squamous NSCLC plus carboplatin (area under the curve 5)/cisplatin (75 mg/m2). After four to six cycles, camrelizumab or placebo plus pemetrexed, and single-agent camrelizumab or placebo will be administrated as maintenance treatment for non-squamous and squamous NSCLC, respectively. The primary endpoint is intracranial PFS. The secondary endpoints include intracranial ORR, ORR, PFS, OS, duration of response, quality of life, cognitive functioning, and safety. Recruitment began in Apr 2021. Treatment-naïve, EGFR/ALK-negative NSCLC aged 18-75 years, with ≥ three brain metastatic lesions or one to two unresectable brain metastatic lesions are eligible. Approximately 200 patients will be randomized (1:1) to receive camrelizumab (200 mg, D1) or placebo plus chemotherapy (D1) for a 21-day cycle. Stereotactic or whole brain RT will be performed at the discretion of investigator, which will be completed within 42 days after first dose of study drugs. Stratification factors include histological type (non-squamous, squamous NSCLC), number of brain metastatic lesions (one to five, ≥ six), and planned radiation therapy (yes, no). The chemotherapy regimens are pemetrexed (500 mg/m2) for non-squamous NSCLC or paclitaxel (175 mg/m2)/albumin-bound paclitaxel (260 mg/m2) for squamous NSCLC plus carboplatin (area under the curve 5)/cisplatin (75 mg/m2). After four to six cycles, camrelizumab or placebo plus pemetrexed, and single-agent camrelizumab or placebo will be administrated as maintenance treatment for non-squamous and squamous NSCLC, respectively. The primary endpoint is intracranial PFS. The secondary endpoints include intracranial ORR, ORR, PFS, OS, duration of response, quality of life, cognitive functioning, and safety. Recruitment began in Apr 2021. Clinical trial identificationNCT04768075. NCT04768075. Editorial acknowledgementWe thank the medical writing support from Jiangsu Hengrui Pharmaceuticals Co., Ltd. We thank the medical writing support from Jiangsu Hengrui Pharmaceuticals Co., Ltd. Legal entity responsible for the studyGuangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences. Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences. FundingChinese Thoracic Oncology Group (CTONG). Chinese Thoracic Oncology Group (CTONG).

Purpose. - A meta-analysis aimed to systematically evaluate the safety and efficiency of I-125 irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT). Materials and methods. - The Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12 -month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software. Results. - Totally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I-125 irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I-125 irradiation stent improved the cumulative stent patency rates in 6 months [OR= 1.65, 95% CI (1.32-2.05), P<0.001] and 12 months [OR= 2.55, 95% CI (1.90-3.42), P< 0.001] and the survival rates in 6 months [OR= 1.77, 95% CI (1.41-2.22), P< 0.001], 12 months [OR= 3.14, 95% CI (2.24-4.40), P< 0.001] and 24 months [OR= 7.39, 95% CI (3.55-15.41), P< 0.001]. However, there was no difference in the objective response rate of PVTT [OR= 1.13, 95% CI (0.87-1.48), P = 0.365], main portal venous pressure and the occurrence adverse event [OR= 0.88, CI = 0.72-1.08, P= 0.212] between two groups. Conclusion. -I-125 irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCT5, are requisite to support the above promising results. (C) 2020 Published by Elsevier Masson SAS on behalf of Societe francaise de radiotherapie oncologique (SFRO).

Platinum-based chemotherapy is the standard first-line treatment for advanced or metastatic ESCC. Toripalimab, a humanized monoclonal antibody against PD-1, showed promising efficacy results as first-line treatment for ESCC in combination with paclitaxel plus cisplatin (TP) in a phase Ib trial. Here, we report the results of JUPITER-06 (NCT03829969), a randomized, double-blind phase III trial of toripalimab in combination with TP for advanced or metastatic ESCC.