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联合免疫治疗和放化疗对局部晚期不可切除食管鳞癌患者生存获益的影响:基于 SEER 数据库的分析。

Survival benefit of combined immunotherapy and chemoradiotherapy in locally advanced unresectable esophageal cancer: an analysis based on the SEER database.

机构信息

Hebei Medical University, Shijiazhuang, China.

Department of Radiation Oncology, Affiliated Tangshan Worker's Hospital, Hebei Medical University, Tangshan, China.

出版信息

Front Immunol. 2024 Jan 16;15:1334992. doi: 10.3389/fimmu.2024.1334992. eCollection 2024.

Abstract

BACKGROUND

While simultaneous chemoradiotherapy remains the established therapeutic modality for patients afflicted with locally advanced esophageal cancer, the effectiveness of this radical approach falls short of the desired outcome. Numerous investigations have illuminated the prospect of enhancing therapeutic efficacy through the amalgamation of chemoradiotherapy and immunotherapeutic interventions. Consequently, we embarked on an examination to scrutinize the potential survival advantages conferred by the confluence of chemoradiotherapy and immunotherapy in relation to locally advanced unresectable esophageal carcinoma, drawing upon the extensive SEER database for our analysis.

METHODS

We extracted clinicopathological attributes and survival statistics of patients afflicted with locally advanced unresectable esophageal carcinoma, diagnosed within the temporal span encompassing the years 2004-2014 and 2019-2020, from the extensive SEER database. To discern disparities in both overall survival (OS) and cancer-specific survival (CSS) between the cohorts subjected to chemoradiotherapy combined with immunotherapy and chemoradiotherapy alone, we employed analytical tools such as Kaplan-Meier analysis, the Log-rank test, the Cox regression proportional risk model, and propensity-matched score (PSM) methodology.

RESULTS

A total of 7,758 eligible patients were encompassed in this research, with 6,395 individuals having undergone chemoradiotherapy alone, while 1,363 patients received the combined treatment of chemoradiotherapy and immunotherapy. After 1:4 propensity score matching, 6,447 patients were successfully harmonized, yielding a well-balanced cohort. The Kaplan-Meier curves demonstrated a substantial enhancement in OS (P = 0.0091) and CSS (P < 0.001) for the group subjected to chemoradiotherapy combined with immunotherapy as compared to chemoradiotherapy alone. Further multivariable analysis with PSM confirmed that chemoradiotherapy combined with immunotherapy benefits OS(HR=0.89, 95% CI 0.81-0.98) and CSS (HR=0.68, 95% CI 0.61-0.76). In addition, Univariable and multivariable Cox regression analyses of the matched patient groups unveiled several independent prognostic factors for OS and CSS, including sex, age, marital status, tumor location, tumor size, pathologic grade, SEER historic staging, and treatment modality. Among these factors, being female, married, and receiving chemoradiotherapy combined with immunotherapy emerged as independent protective factors, while age exceeding 75 years, non-superior segment tumor location, tumor size greater than 6 cm, Grade 3-4 pathology, and regional SEER historic staging were all found to be independent risk factors. The survival advantage of the chemoradiotherapy combined with the immunotherapy group over the chemoradiotherapy alone group was substantial.

CONCLUSIONS

This investigation furnishes compelling evidence that the integration of immunotherapy with chemoradiotherapy confers a noteworthy survival advantage when contrasted with conventional chemoradiotherapy for individuals grappling with locally advanced unresectable esophageal carcinoma.

摘要

背景

虽然同步放化疗仍然是局部晚期食管癌患者的既定治疗模式,但这种激进方法的效果仍未达到预期的结果。许多研究表明,通过将放化疗与免疫治疗干预相结合,可以提高治疗效果。因此,我们利用广泛的 SEER 数据库进行了一项研究,旨在探讨局部晚期不可切除食管癌患者接受放化疗和免疫治疗联合治疗的潜在生存优势。

方法

我们从广泛的 SEER 数据库中提取了局部晚期不可切除食管癌患者的临床病理特征和生存统计数据,这些患者的诊断时间涵盖了 2004-2014 年和 2019-2020 年。为了比较接受放化疗联合免疫治疗和单纯放化疗的两组患者的总生存率(OS)和癌症特异性生存率(CSS)差异,我们使用了 Kaplan-Meier 分析、对数秩检验、Cox 回归比例风险模型和倾向评分匹配(PSM)方法。

结果

本研究共纳入了 7758 名符合条件的患者,其中 6395 名患者接受了单纯放化疗,1363 名患者接受了放化疗联合免疫治疗。经过 1:4 的倾向评分匹配后,成功匹配了 6447 名患者,得到了一个均衡的队列。Kaplan-Meier 曲线显示,与单纯放化疗相比,接受放化疗联合免疫治疗的患者 OS(P = 0.0091)和 CSS(P < 0.001)有显著提高。进一步的 PSM 多变量分析证实,放化疗联合免疫治疗可改善 OS(HR=0.89,95%CI 0.81-0.98)和 CSS(HR=0.68,95%CI 0.61-0.76)。此外,对匹配患者组的单变量和多变量 Cox 回归分析揭示了 OS 和 CSS 的几个独立预后因素,包括性别、年龄、婚姻状况、肿瘤位置、肿瘤大小、病理分级、SEER 历史分期和治疗方式。在这些因素中,女性、已婚和接受放化疗联合免疫治疗是独立的保护因素,而年龄超过 75 岁、非上段肿瘤位置、肿瘤大小大于 6cm、病理分级 3-4 级和区域 SEER 历史分期是独立的危险因素。与单纯放化疗相比,接受放化疗联合免疫治疗的患者生存优势显著。

结论

本研究提供了有力的证据,表明对于局部晚期不可切除食管癌患者,免疫治疗联合放化疗与单纯放化疗相比,具有显著的生存优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f774/10825045/7370837e0426/fimmu-15-1334992-g001.jpg

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