Mutational profiles and prognostic impact in colorectal and high‐grade appendiceal adenocarcinoma with peritoneal metastases

• Published in: Journal of surgical oncology Vol. 127; no. 5; pp. 831 - 840
• Main Authors: Morgan, Ryan B., Dhiman, Ankit, Sood, Divya, Ong, Cecilia T., Wu, Xiaoyang, Shergill, Ardaman, Polite, Blase, Turaga, Kiran K., Eng, Oliver S.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-04-2023
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - therapy; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; appendiceal cancer; Appendiceal Neoplasms - genetics; Appendiceal Neoplasms - therapy; Appendix; Cancer; Chemotherapy, Cancer, Regional Perfusion; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - therapy; Cytoreduction Surgical Procedures; cytoreductive surgery and hyperthermic intraperitoneal chemotherapy; Gastric cancer; Gastrointestinal cancer; genomics; Humans; Hyperthermia, Induced; Metastasis; Mutation; peritoneal carcinomatosis; Peritoneal Neoplasms - genetics; Peritoneal Neoplasms - pathology; Peritoneal Neoplasms - therapy; Prognosis; Survival Rate; genomics; colorectal cancer; cytoreductive surgery and hyperthermic intraperitoneal chemotherapy; peritoneal carcinomatosis; appendiceal cancer
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.27203

Background
Next‐generation sequencing (NGS) personalizes cancer treatments. In this study, we analyze outcomes based on NGS testing for colorectal cancer (CRC) and high‐grade appendiceal adenocarcinoma (HGA) with peritoneal metastases.
Methods
Retrospective review of genomic analyses and outcomes in patients with CRC or HGA with peritoneal metastases at a high‐volume center from 2012 to 2019.
Results
Ninety‐two patients (57 CRC, 35 HGA) were identified. Overall survival was longer for CRC (52.8 vs. 30.5 months, p = 0.03), though rates of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were similar. Multiple genes were more frequently mutated in CRC, including KRAS (51% vs. 29%, p = 0.04), TP53 (47% vs. 20%, p < 0.01), and APC (46% vs. 6%, p < 0.01). For CRC, multivariate regression showed an increased hazard ratio (HR) with increasing peritoneal cancer index (1.06 [1.01–1.11], p = 0.02) and a decreased HR following CRS/HIPEC (0.30 [0.11–0.80], p = 0.02). PIK3CA mutation associated with significantly increased HR (3.62 [1.06–12.41], p = 0.04), though only in non‐CRS/HIPEC patients. Multivariate analysis in the HGA group showed a benefit following CRS/HIPEC (0.18 [0.06–0.61], p = 0.01) and for mucinous disease (0.38 [0.15–0.96], p = 0.04), while there was an increased HR with TP53 mutation (6.89 [2.12–22.44], p < 0.01).
Conclusion
CRC and HGA with peritoneal spread have distinct mutational profiles. PIK3CA and TP53 mutations are associated with survival for CRC or HGA with peritoneal metastases, respectively.