Zucchini Valentina, D'Acapito Fabrizio, Rapposelli Ilario Giovanni, Framarini Massimo, Di Pietrantonio Daniela, Turrini Riccardo, Pozzi Eleonora, Ercolani Giorgio
Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
General and Oncologic Department of Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy.
Int J Hyperthermia. 2025 Dec;42(1):2479527. doi: 10.1080/02656736.2025.2479527. Epub 2025 Mar 18.
Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefits in select patients with peritoneal metastases (PM) from colorectal cancer (CRC). Molecular alterations, particularly RAS/BRAF mutations and Microsatellite Instability (MSI), play crucial roles in prognostic stratification and treatment planning, influencing both disease-free survival (DFS) and overall survival (OS). This scoping review evaluates the prognostic role of MSI and RAS/BRAF mutations in patients with PM-CRC treated with CRS-HIPEC.
A literature search was conducted across several databases to identify papers published between 2000 and September 2024. We selected 18 publications that considered DFS and OS as primary or secondary outcomes in patients with RAS/BRAF mutations and MSI following CRS-HIPEC treatment. Studies involving appendiceal cancer, peritoneal disease from non-CRC, pediatric patients, or subjects not treated with CRS-HIPEC were excluded.
Most studies suggest that RAS and BRAF mutations have a negative influence on survival outcomes. While inconsistencies exist, RAS mutations are generally associated with worse DFS. Specific KRAS subtypes such as KRASMUT2 or KRAS G12V and the BRAF V600 variant correlate with poorer prognosis. MSI status appears to attenuate the adverse effects of RAS/BRAF mutations on survival, although conflicting data persist.
RAS and BRAF mutations correlate with poorer outcomes in PM-CRC, underscoring the need for mutation-informed strategies to refine HIPEC and systemic therapies. Recognizing subtypes may improve patient selection for CRS-HIPEC, optimizing both local disease control and long-term survival. Future research should incorporate these molecular profiles to enhance therapeutic decision-making and better address this challenging condition.
减瘤手术（CRS）联合腹腔热灌注化疗（HIPEC）已在部分结直肠癌（CRC）腹膜转移（PM）患者中显示出生存获益。分子改变，特别是RAS/BRAF突变和微卫星不稳定性（MSI），在预后分层和治疗规划中起着关键作用，影响无病生存期（DFS）和总生存期（OS）。本综述评估了MSI和RAS/BRAF突变在接受CRS-HIPEC治疗的PM-CRC患者中的预后作用。
在多个数据库中进行文献检索，以识别2000年至2024年9月期间发表的论文。我们选择了18篇将DFS和OS作为CRS-HIPEC治疗后RAS/BRAF突变和MSI患者的主要或次要结局的出版物。排除涉及阑尾癌、非CRC引起的腹膜疾病、儿科患者或未接受CRS-HIPEC治疗的受试者的研究。
大多数研究表明，RAS和BRAF突变对生存结局有负面影响。虽然存在不一致之处，但RAS突变通常与较差的DFS相关。特定的KRAS亚型，如KRASMUT2或KRAS G12V以及BRAF V600变体与较差的预后相关。MSI状态似乎减弱了RAS/BRAF突变对生存的不利影响，尽管存在相互矛盾的数据。
RAS和BRAF突变与PM-CRC的较差结局相关，强调需要基于突变的策略来优化HIPEC和全身治疗。识别亚型可能改善CRS-HIPEC的患者选择，优化局部疾病控制和长期生存。未来的研究应纳入这些分子特征，以加强治疗决策并更好地应对这一具有挑战性的疾病。
