PSM
non-CME
Ahmed B. Hamed, MD
Post-doctoral associate
University of Pittsburgh
Allison Park, Pennsylvania, United States
Disclosure(s): No financial relationships to disclose
Ahmed B. Hamed, MD
Post-doctoral associate
University of Pittsburgh
Allison Park, Pennsylvania, United States
Disclosure(s): No financial relationships to disclose
Yongli Shuai, PhD
Biostatistician
University of Pittsburgh Medical Center Hillman Biostatistics Facility, United States
Disclosure information not submitted.
Joshua Derby, BA
Data Coordinator and Analyst
University of Pittsburgh Medical Center, United States
Disclosure information not submitted.
Matthew Holtzman, MD
Assistant Professor of Surgery
University of Pittsburgh Medical Center, United States
Disclosure information not submitted.
Melanie Ongchin, MD
Assistant Professor of Surgery
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Disclosure information not submitted.
.jpg "David L. Bartlett, MD photo")
David L. Bartlett, MD
System Chair
Allegheny Health Network Cancer Institute
Pittsburgh, Pennsylvania, United States
Disclosure information not submitted.
James F. Pingpank, Jr., MD
Associate Professor
University of Pittsburgh
Pittsburgh, PA, United States
Disclosure information not submitted.
Reetesh Pai, MD
Professor of Pathology
University of Pittsburgh Medical Center, United States
Disclosure information not submitted.
Aatur Singhi, MD, PhD
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Disclosure information not submitted.
Mohammad Haroon A. Choudry, MD
Associate Professor of Surgery
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States
Disclosure information not submitted.
This retrospective cohort study included CRS-HIPEC cases for CRPM at a high-volume center from 2001-2020. Next-generation sequencing and microsatellite testing defined the RAS, BRAF, and MMR/MSI genotypes. Adjusted effects of tumor sidedness and genomics on overall survival (OS) were evaluated using a multivariable Cox proportional hazards model. We analyzed these variables’ effects on progression-free survival (PFS) and the effects of immune checkpoint-inhibitors.
Results: 250 patients underwent CRS-HIPEC (median age 56.3 yrs, 48% female) with testing for RAS, BRAF, and MMR/MSI. Of these, 50.8% of patients were RAS-mutated, 12.4% were BRAF-mutated, and 6.8% were deficient-MMR/MSI-high (dMMR/MSI-H). Genomic alterations predominated in right-sided cancers. After adjustment for comorbidities, oncological, and perioperative factors, rectal origin (hazard ratio/HR 1.9, p=0.01), RAS mutation (HR 1.6, p=0.01), and BRAF mutation (HR 1.7, p=0.05) were associated with worse OS. RAS mutation was also associated with worse PFS (HR 1.6, p=0.01 at 6 months post-operatively). dMMR/MSI-H status was associated with superior OS (HR 0.3, p=0.01 at 2 years). The model discriminated OS well (Harrell’s concordance index 0.72). dMMR/MSI-H patients receiving immune checkpoint-inhibitors trended toward superior OS.
Conclusions: Rectal origin, RAS mutations, BRAF mutations are each associated with poorer OS after CRS-HIPEC for CRPM. dMMR/MSI-H CRPM patients have superior OS. Further research should evaluate immune checkpoint-inhibitors in this subgroup. Our data provide molecular and oncologic information for patient selection and prognostication.