Bader Justin M, Ospina Ava, Liu Sean, Reddy Biren, Gupta Princy, Tomlin Ricarda, Cecchini Michael, Sundar Raghav, Turaga Kiran
Yale New Haven Hospital, New Haven, CT, USA.
T32 Fellow National Cancer Institute of the National Institutes of Health, New Haven, CT, USA.
Ann Surg Oncol. 2025 May 30. doi: 10.1245/s10434-025-17517-0.
Current treatment of metastatic peritoneal surface malignancies (PSM) arising from colorectal cancer (CRC) and appendiceal cancer involves cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) [Elias (J Clin Oncol 28:63-68, 2010), McMullen (Oncotarget 8: 43481-43490, 2017), Lemoine (Int J Hyperthermia 33:582-592, 2017)]. There have been several intraperitoneal (IP) trials of appendix and colon cancer with conflicting results and insufficient evidence regarding both HIPEC efficacy and optimal HIPEC regimens [Quenet (Lancet Oncology 22:256-266, 2021), Arjona-Sánchez (JAMA Surgery 158:683, 2023), Verwaal (Ann Surg Oncol 12:65-71, 2004), Benzaquen (Can J Surg 64: E111-E118, 2021), Turaga (Ann Surg Oncol 21: 1501-1505, 2014), Nash (J Clin Oncol 41: 160, 2023)]. Given the heterogeneity of prior data and the variability in patient responses to different HIPEC regimens, further research is needed to optimize and personalize treatment.
This is a single-center, phase II, open-label clinical trial evaluating the feasibility of performing mass-based response testing to identify and deliver personalized intraperitoneal chemotherapy regimens to patients with unresectable high-grade appendiceal or colorectal peritoneal metastases undergoing HIPEC. Per SOC, there are currently multiple chemotherapy combinations used for HIPEC [Lemoine (Int J Hyperthermia 33:582-592, 2017), Dubé (Curr Oncol 22:100-112, 2015), Valle (Indian J Surg Oncol 7:152-159, 2016)]. MRT analysis will identify which SOC regimen to use for HIPEC based on the patient's tumor susceptibility.
Mass-based response testing (MRT) is a novel screening tool that enables rapid and reliable assessment of tumor susceptibility to various HIPEC drugs. MRT generates a report of patient-specific intraperitoneal chemotherapy sensitivities by analyzing a portion of biopsy tissue collected from the patient's standard of care (SOC) diagnostic laparoscopy [Kimmerling (J Clin Oncol 41: 3132, 2024)]. With multiple HIPEC regimens currently used as the SOC for PSM from appendiceal and colorectal cancer, MRT facilitates the selection of personalized SOC regimens tailored to each patient.Results of this study will inform future clinical trials evaluating the efficacy of MRT-selected HIPEC regimens for patients with PM from appendiceal cancer and CRC.
目前，结直肠癌（CRC）和阑尾癌引起的转移性腹膜表面恶性肿瘤（PSM）的治疗方法包括细胞减灭术（CRS）联合腹腔内热灌注化疗（HIPEC）[伊莱亚斯（《临床肿瘤学杂志》28:63 - 68, 2010年）、麦克马伦（《肿瘤靶向》8: 43481 - 43490, 2017年）、勒莫因（《国际热疗杂志》33:582 - 592, 2017年）]。已有多项关于阑尾癌和结肠癌的腹腔内（IP）试验，结果相互矛盾，且关于HIPEC疗效和最佳HIPEC方案的证据不足[凯内（《柳叶刀肿瘤学》22:256 - 266, 2021年）、阿尔霍纳 - 桑切斯（《美国医学会外科杂志》158:683, 2023年）、韦尔瓦尔（《外科肿瘤学年鉴》12:65 - 71, 2004年）、本扎昆（《加拿大外科杂志》64: E111 - E118, 2021年）、图拉加（《外科肿瘤学年鉴》21: 1501 - 1505, 2014年）、纳什（《临床肿瘤学杂志》41: 160, 2023年）]。鉴于先前数据的异质性以及患者对不同HIPEC方案反应的可变性，需要进一步研究以优化和个性化治疗。
这是一项单中心、II期、开放标签的临床试验，旨在评估对接受HIPEC的不可切除的高级别阑尾或结直肠腹膜转移患者进行基于肿块的反应测试，以确定并提供个性化腹腔内化疗方案的可行性。按照标准治疗（SOC），目前有多种化疗组合用于HIPEC[勒莫因（《国际热疗杂志》33:582 - 592, 2017年）、杜贝（《当代肿瘤学》22:100 - 112, 2015年）、瓦莱（《印度外科肿瘤学杂志》7:152 - 159, 2016年）]。MRT分析将根据患者的肿瘤易感性确定用于HIPEC的SOC方案。
基于肿块的反应测试（MRT）是一种新型筛查工具，能够快速、可靠地评估肿瘤对各种HIPEC药物的易感性。MRT通过分析从患者标准治疗（SOC）诊断性腹腔镜检查中采集的一部分活检组织，生成患者特异性腹腔内化疗敏感性报告[金默林（《临床肿瘤学杂志》41: 3132, 2024年）]。由于目前多种HIPEC方案被用作阑尾癌和结直肠癌PSM的SOC，MRT有助于为每位患者选择个性化的SOC方案。本研究结果将为未来评估MRT选择的HIPEC方案对阑尾癌和CRC腹膜转移患者疗效的临床试验提供参考。
