Mutational Features and Tumor Microenvironment Alterations in High-Grade Appendiceal Cancers Treated With Iterative Hyperthermic Intraperitoneal Chemotherapy

High-grade appendiceal adenocarcinomas (HGAA) with peritoneal metastases (PMs) are associated with poor survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a novel treatment approach for unresectable HGAA-PM. However, its influence on immunogenomic profiles has not yet been fully explored...

Full description

Saved in:
Bibliographic Details
Published inJCO precision oncology Vol. 8; p. e2400149
Main Authors Su, David G, Dhiman, Ankit, Bansal, Varun V, Zha, Yuanyuan, Shergill, Ardaman, Polite, Blasé, Alpert, Lindsay, Turaga, Kiran K, Eng, Oliver S
Format Journal Article
LanguageEnglish
Published United States 01.09.2024
Subjects
Online AccessGet more information

Cover

Loading…
More Information
Summary:High-grade appendiceal adenocarcinomas (HGAA) with peritoneal metastases (PMs) are associated with poor survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a novel treatment approach for unresectable HGAA-PM. However, its influence on immunogenomic profiles has not yet been fully explored. We obtained 79 samples of metastatic peritoneal tumor deposits from patients diagnosed with HGAA and performed whole-exome sequencing, RNA sequencing, and immunoprofiling before and after HIPEC. Tumor biopsies were subjected to immunogenomic profiling to detect mutational signatures and immune populations associated with oncologic outcomes. Fifteen patients with HGAA-PMs were included in the study. The median progression-free survival (PFS) was 6.7 months (2.7-25.3) and the median overall survival was 11.4 months (4.7-42). Mucin-associated genes ( , , and ) and titin ( ) had the highest mutation frequencies. Mutational signatures such as single-base substitution 29 and doublet-base substitution 11 were present in >50% of single-base and double-base mutations. Higher PD-L1 coexpression on CD8 T cells demonstrated a higher PFS both intratumorally ( = .019) and at the margin ( = .025). HIPEC-associated mutational signatures were identified in HGAA-PMs. Elevated PD-L1+ cytotoxic T-cell populations after HIPEC had better PFS, offering valuable insights for prognostication in the context of HIPEC treatment.
ISSN:2473-4284
DOI:10.1200/PO.24.00149