Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul;30(7):4459-4470.
doi: 10.1245/s10434-023-13463-x. Epub 2023 Apr 21.

Impact of Primary Tumor Location and Genomic Alterations on Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Colorectal Peritoneal Metastases

Ahmed B Hamed  1   2 , Yongli Shuai  3 , Joshua Derby  1 , Matthew P Holtzman  1 , Melanie Ongchin  1 , David L Bartlett  4 , James F Pingpank  1 , Reetesh Pai  5 , Aatur Singhi  5 , Haroon A Choudry  6
Affiliations

Impact of Primary Tumor Location and Genomic Alterations on Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Colorectal Peritoneal Metastases

Ahmed B Hamed et al. Ann Surg Oncol. 2023 Jul.

Abstract

Background: Colorectal cancer leads to peritoneal metastases (CRPM) in 10% of cases. Cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) improves survival. Primary tumor location and abnormalities in RAS, BRAF, and mismatch repair/microsatellite stability (MMR/MSI) may affect post-CRS-HIPEC survival, but studies have not been consistent. We estimated the effects of primary tumor site and genomic alterations on post-CRS-HIPEC survival.

Methods: This retrospective cohort study included CRS-HIPEC cases for CRPM at a high-volume center from 2001 to 2020. Next-generation sequencing and microsatellite testing defined the RAS, BRAF, and MMR/MSI genotypes. Adjusted effects of tumor sidedness and genomics on survival were evaluated using a multivariable Cox proportional hazards model. We analyzed these variables' effects on progression-free survival and the effects of immune checkpoint-inhibitors.

Results: A total of 250 patients underwent CRS-HIPEC with testing for RAS, BRAF, and MMR/MSI; 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 and oncological and perioperative variables, 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 survival. RAS mutation was also associated with shorter progression-free survival (HR 1.6, p = 0.01 at 6 months post-operatively), and dMMR/MSI-H status was associated with superior survival (HR 0.3, p = 0.01 at 2 years). dMMR/MSI-H patients receiving immune checkpoint-inhibitors trended toward superior survival.

Conclusions: Rectal origin, RAS mutations, and BRAF mutations are each associated with poorer survival after CRS-HIPEC for CRPM. Patients with CRPM and dMMR/MSI-H status have superior survival. Further research should evaluate benefits of immune checkpoint-inhibitors in this subgroup.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
Study enrollment flowchart
FIG. 2
FIG. 2
Distribution of key pathologic variables and genomic alterations in patients with CRPM who underwent CRS-HIPEC; (WHO grade: pathologic grade, CC-score: cytoreduction completeness score)
FIG. 3
FIG. 3
Exploratory associations of primary tumor site, RAS mutation, BRAF mutation, MMR/MSI status, and PIK3CA mutation with survival after CRS-HIPEC; associations of primary tumor site, RAS mutation, and BRAF mutation with survival (a, b). Association of BRAF mutation and MMR/MSI status with survival (c); association of BRAF and PIK3CA mutations with survival (d); p-Value: logrank test p-value; OS overall survival, WT wildtype, M/mut mutated; the mutant category in a, b includes cases with either RAS mutation or BRAF mutation and the wildtype category includes cases that were wildtype for both genes
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

References

    1. Franko J, Shi Q, Meyers JP, Maughan TS, Adams RA, Seymour MT, Saltz L, Punt CJA, Koopman M, Tournigand C, Tebbutt NC, Diaz-Rubio E, Souglakos J, et al. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the analysis and research in cancers of the digestive system (ARCAD) database. Lancet Oncol. 2016;17(12):1709–19. - PubMed
    1. Quenet F, Elias D, Roca L, Goere D, Ghouti L, Pocard M, Facy O, Arvieux C, Lorimier G, Pezet D, Marchal F, Loi V, Meeus P, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):256–66. - PubMed
    1. Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tin-teren H, Boot H, Zoetmulder FA. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21(20):3737–43. - PubMed
    1. Goodman MD, McPartland S, Detelich D, Saif MW. Chemo-therapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy. J Gastrointest Oncol. 2016;7(1):45–57. - PMC - PubMed
    1. Mistry P, Mohamed F, Dayal S, Cecil TD, Moran BJ. Cytoreductive surgery with intraperitoneal chemotherapy in the management of peritoneal surface malignancy: a pharmacist’s perspective. Eur J Hosp Pharm. 2016;23(4):233–8. - PMC - PubMed

Substances