Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial

IF 4.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Gynecologic oncology Pub Date : 2024-10-15 DOI:10.1016/j.ygyno.2024.09.023
Aiko Ogasawara , Hirokazu Matsushita , Tuan Zea Tan , Daisuke Shintani , Jieru Ye , Shoji Nagao , Ayako Demachi-Okamura , Daisuke Muraoka , Yukari Kobayashi , Kazuhiro Kakimi , Rui Yamaguchi , Keitaro Matsuo , Kouji Yamamoto , Keiichi Fujiwara , Ruby Yun-Ju Huang , David Shao Peng Tan , Kosei Hasegawa
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Abstract

Background

The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy.

Methods

This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; n = 59), (IV; n = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment.

Results

Patients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into “immune Hot” and “immune Cold” groups based on hierarchical clustering analysis using four parameters representing “Innate immunity,” “T cells,” “IFNG response” and “Inhibitory molecules,” IP therapy significantly improved prognosis in the “immune Hot” group, but not in the “immune Cold” group compared to that of IV therapy.

Conclusions

IP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment.
(Japan Registry of Clinical Trials number, jRCTs031180141.)
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腹腔化疗和静脉化疗对卵巢癌免疫学的影响:iPocc 3 期试验的转化分析
背景iPocc试验是一项随机、全球性的三期研究,比较了上皮性卵巢癌(EOC)患者腹腔注射(IP)和静脉注射(IV)卡铂与剂量密集型紫杉醇化疗,结果显示接受IP化疗的患者无进展生存期有所改善。本研究旨在探讨肿瘤免疫在接受 IP 化疗患者临床预后中的作用。方法本研究分析了 iPocc 试验中的患者数据,选择性地分析了那些在初次手术时保留了肿瘤标本的患者。共对 116 个病例((IP;n = 59),(IV;n = 57))进行了芯片分析。结果IP组肿瘤浸润T细胞、自然杀伤(NK)细胞和细胞毒性淋巴细胞增多的患者的总生存期(OS)长于IV组,但浸润较少的患者的总生存期不长。IP疗法改善了CD8A和FOXP3等免疫相关基因高表达患者的OS。根据代表 "先天免疫"、"T 细胞"、"IFNG 反应 "和 "抑制分子 "的四个参数进行分层聚类分析,将患者细分为 "免疫热 "组和 "免疫冷 "组,与静脉注射疗法相比,IP 疗法显著改善了 "免疫热 "组的预后,而 "免疫冷 "组的预后则没有改善。结论IP化疗可提高治疗前肿瘤微环境中存在免疫热表型的EOC患者的生存率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Gynecologic oncology
Gynecologic oncology 医学-妇产科学
CiteScore
8.60
自引率
6.40%
发文量
1062
审稿时长
37 days
期刊介绍: Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy
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