PDF(Pubmed)
Abstract：
BACKGROUND: Selected patients with peritoneal metastases of colorectal cancer (PM-CRC) can benefit from potentially curative cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC), with a median overall survival (OS) of more than 40 months.
OBJECTIVE: The aims of this evidence-based consensus were to define the indications for HIPEC, to select the preferred HIPEC regimens, and to define research priorities regarding the use of HIPEC for PM-CRC.
METHODS: The consensus steering committee elaborated and formulated pertinent clinical questions according to the PICO (patient, intervention, comparator, outcome) method and assessed the evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Standardized evidence tables were presented to an international expert panel to reach a consensus (4-point, weak and strong positive/negative) on HIPEC regimens and research priorities through a two-round Delphi process. The consensus was defined as ≥ 50% agreement for the 4-point consensus grading or ≥ 70% for either of the two combinations.
RESULTS: Evidence was weak or very weak for 9/10 clinical questions. In total, 70/90 eligible panelists replied to both Delphi rounds (78%), with a consensus for 10/10 questions on HIPEC regimens. There was strong negative consensus concerning the short duration, high-dose oxaliplatin (OX) protocol (55.7%), and a weak positive vote (53.8-64.3%) in favor of mitomycin-C (MMC)-based HIPEC (preferred choice: Dutch protocol: 35 mg/m2, 90 min, three fractions), both for primary cytoreduction and recurrence. Determining the role of HIPEC after CRS was considered the most important research question, regarded as essential by 85.7% of the panelists. Furthermore, over 90% of experts suggest performing HIPEC after primary and secondary CRS for recurrence > 1 year after the index surgery.
CONCLUSIONS: Based on the available evidence, despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended to patients with PM-CRC after CRS. While more preclinical and clinical data are eagerly awaited to harmonize the procedure further, the MMC-based Dutch protocol remains the preferred regimen after primary and secondary CRS.
OBJECTIVE: The aims of this evidence-based consensus were to define the indications for HIPEC, to select the preferred HIPEC regimens, and to define research priorities regarding the use of HIPEC for PM-CRC.
METHODS: The consensus steering committee elaborated and formulated pertinent clinical questions according to the PICO (patient, intervention, comparator, outcome) method and assessed the evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Standardized evidence tables were presented to an international expert panel to reach a consensus (4-point, weak and strong positive/negative) on HIPEC regimens and research priorities through a two-round Delphi process. The consensus was defined as ≥ 50% agreement for the 4-point consensus grading or ≥ 70% for either of the two combinations.
RESULTS: Evidence was weak or very weak for 9/10 clinical questions. In total, 70/90 eligible panelists replied to both Delphi rounds (78%), with a consensus for 10/10 questions on HIPEC regimens. There was strong negative consensus concerning the short duration, high-dose oxaliplatin (OX) protocol (55.7%), and a weak positive vote (53.8-64.3%) in favor of mitomycin-C (MMC)-based HIPEC (preferred choice: Dutch protocol: 35 mg/m2, 90 min, three fractions), both for primary cytoreduction and recurrence. Determining the role of HIPEC after CRS was considered the most important research question, regarded as essential by 85.7% of the panelists. Furthermore, over 90% of experts suggest performing HIPEC after primary and secondary CRS for recurrence > 1 year after the index surgery.
CONCLUSIONS: Based on the available evidence, despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended to patients with PM-CRC after CRS. While more preclinical and clinical data are eagerly awaited to harmonize the procedure further, the MMC-based Dutch protocol remains the preferred regimen after primary and secondary CRS.
摘要：
背景：选定的结直肠癌腹膜转移（PM-CRC）患者可以从潜在治愈性细胞减灭术（CRS）±腹腔热化疗（HIPEC）中受益，中位总生存期（OS）超过40个月。
目的：这一循证共识的目的是确定HIPEC的适应症，为了选择首选的HIPEC方案，并确定将HIPEC用于PM-CRC的研究重点。
方法：共识指导委员会根据PICO（患者，干预，比较器,结果)方法，并根据建议分级评估证据，评估,发展,和评估（等级）框架。标准化的证据表提交给一个国际专家小组，以达成共识(4点，弱和强的积极/消极）通过两轮德尔菲过程对HIPEC方案和研究重点。共识定义为4点共识分级≥50％或两种组合中的任一种≥70％。
结果：9/10个临床问题的证据较弱或非常弱。总的来说,70/90合格的小组成员回答了德尔福两轮(78%)，就HIPEC方案的10/10问题达成共识。关于持续时间短，有强烈的负面共识，大剂量奥沙利铂（OX）方案（55.7％），和微弱的正面投票（53.8-64.3％）赞成基于丝裂霉素C（MMC）的HIPEC（首选：荷兰方案：35mg/m2，90分钟，三个分数)，原发性细胞减少和复发。确定CRS后HIPEC的作用被认为是最重要的研究问题，被85.7%的小组成员认为是必不可少的。此外，超过90%的专家建议在初次和继发性CRS复发后进行HIPEC,治疗初次手术后1年以上复发.
结论：根据现有证据，尽管PRODIGE7的结果为阴性,但HIPEC可以有条件地推荐给CRS后PM-CRC患者.虽然更多的临床前和临床数据急切地等待进一步协调的程序，基于MMC的荷兰方案仍然是主要和次要CRS后的首选方案.
目的：这一循证共识的目的是确定HIPEC的适应症，为了选择首选的HIPEC方案，并确定将HIPEC用于PM-CRC的研究重点。
方法：共识指导委员会根据PICO（患者，干预，比较器,结果)方法，并根据建议分级评估证据，评估,发展,和评估（等级）框架。标准化的证据表提交给一个国际专家小组，以达成共识(4点，弱和强的积极/消极）通过两轮德尔菲过程对HIPEC方案和研究重点。共识定义为4点共识分级≥50％或两种组合中的任一种≥70％。
结果：9/10个临床问题的证据较弱或非常弱。总的来说,70/90合格的小组成员回答了德尔福两轮(78%)，就HIPEC方案的10/10问题达成共识。关于持续时间短，有强烈的负面共识，大剂量奥沙利铂（OX）方案（55.7％），和微弱的正面投票（53.8-64.3％）赞成基于丝裂霉素C（MMC）的HIPEC（首选：荷兰方案：35mg/m2，90分钟，三个分数)，原发性细胞减少和复发。确定CRS后HIPEC的作用被认为是最重要的研究问题，被85.7%的小组成员认为是必不可少的。此外，超过90%的专家建议在初次和继发性CRS复发后进行HIPEC,治疗初次手术后1年以上复发.
结论：根据现有证据，尽管PRODIGE7的结果为阴性,但HIPEC可以有条件地推荐给CRS后PM-CRC患者.虽然更多的临床前和临床数据急切地等待进一步协调的程序，基于MMC的荷兰方案仍然是主要和次要CRS后的首选方案.
