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Case Report: Neoadjuvant PD-1 Blockade Plus Concurrent Chemoradiotherapy in Unresectable Locally Advanced Gastric Cancer Patients.

ABSTRACT: Programmed death 1(PD-1) blockade has shown promising efficacy in advanced gastric cancer. Here, we performed a retrospective analysis of three patients with locally advanced gastric cancer who received adjuvant PD-1 plus chemoradiotherapy as neoadjuvant treatment. Neoadjuvant sintilimab plus concurrent chemoradiotherapy had an acceptable side-effect profile. All three patients underwent surgical gastrectomy after a median of 3.9 months. A major pathological response occurred in two resected tumors and a pathologic complete response was observed in one patient. Our results suggest that PD-1 blockade combined with chemoradiotherapy is a promising strategy as a neoadjuvant therapy in patients with unresectable locally advanced gastric cancer.

SUBMITTER: Wei J

PROVIDER: S-EPMC7901487 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Case Report: Neoadjuvant PD-1 Blockade Plus Concurrent Chemoradiotherapy in Unresectable Locally Advanced Gastric Cancer Patients.

Wei Jia J Lu Xiaofeng X Liu Qin Q Li Lin L Liu Song S Liu Fangcen F Fu Yao Y Fan Xiangshan X Yang Yang Y Qi Chuang C Yu Yangyang Y Guan Wenxian W Liu Baorui B

Frontiers in oncology 20210205

Programmed death 1(PD-1) blockade has shown promising efficacy in advanced gastric cancer. Here, we performed a retrospective analysis of three patients with locally advanced gastric cancer who received adjuvant PD-1 plus chemoradiotherapy as neoadjuvant treatment. Neoadjuvant sintilimab plus concurrent chemoradiotherapy had an acceptable side-effect profile. All three patients underwent surgical gastrectomy after a median of 3.9 months. A major pathological response occurred in two resected tum ...[more]

PMID: 33634011

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Project description:PurposeInduction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma.MethodsWe thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1.ResultsSeven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively).ConclusionsInduction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Dataset Information

Case Report: Neoadjuvant PD-1 Blockade Plus Concurrent Chemoradiotherapy in Unresectable Locally Advanced Gastric Cancer Patients.

Publications

Case Report: Neoadjuvant PD-1 Blockade Plus Concurrent Chemoradiotherapy in Unresectable Locally Advanced Gastric Cancer Patients.

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