Evaluation of Overall Survival Rate of Patients with Metastatic Colorectal Cancer Depending on Choice of Treatment, Location of Primary Focus and RAS Genes Mutation Status

Abstract

INTRODUCTION: Morbidity with colorectal cancer (CRC) in the Yaroslavl region (YR) accounts for 13.4% of all cases identified in 2021, and ranks third after skin cancer and lung cancer. In the mortality structure, CRC makes 14.2% and is the second leading cause of death. Locally advanced and metastatic forms of the tumor process are identified in more than half the patients.

AIM: To evaluate the overall survival rate of patients with metastatic CRC (mCRC) in the territory of the YR depending on the volume of surgical treatment, chemo- and targeted treatment regimens and the presence of RAS genes mutations.

MATERIALS AND METHODS: On the base of the Yaroslavl Regional Clinical Oncology Hospital, the data of 291 patients with mCRC who underwent treatment in the period from 2015 to 2022, were analyzed. The mean age of patients was 63.0 ± 8.6 years. There were 52% of men (n = 151), and 48% of women (n = 140). The patients were divided to two groups depending on the status of RAS genes mutations: group I (n = 145) — patients with the identified mutation; group II (n = 146) — patients with ‘wild-type’ mutation. The patients were additionally divided to three subgroups depending on the type of treatment: subgroup A (58.1%; n = 169) — removal of the primary focus (PF) in combination with antitumor chemotherapy (CT); subgroup B (31.6%; n = 92) — CT without surgical treatment; subgroup C (10.3%; n = 30) — removal of the PF and resection of liver metastases in combination with CT.

RESULTS: The overall survival rate (OSR) depending on the type of treatment was in subgroup A — 21.0 (95% confidence interval (CI) 18.6-23.3) months; in subgroup B — 11.2 (95% CI 9.9–12.5) months; in subgroup C — 21.0 (95% confidence interval (CI) 18.6–23.3) months. OSR with RAS mutation: in subgroup 1A — 17.7 (95% CI 13.8–21.7) months; in subgroup IB — 11.1 (95% CI 8.3–13.2) months; in subgroup IC — 13.2 (95% CI 4.07–22.7) months. OSR with ‘wild-type’ mutation: subgroup IIA: Cetuximab — 33.6 (95% CI 26.7–40.4) months, Panitumumab — 23.8 (95% CI 19.7–27.9) months (p = 0.01); subgroup IIB: Cetuximab — 22.3 (95% CI 17.0–27.5) months, Panitumumab — 15.2 (95% CI 10.7–19.6) months (p = 0.012); subgroup IIC: Cetuximab — 27.5 (95% CI 17.8–37.1) months, Panitumumab — 38.8 (95% CI 13.9–63.6) months (p = 0.013).

CONCLUSIONS: In patients with mutation in RAS genes, the best OSR values were noted in case of surgical removal of the PF in combination with palliative drug therapy. In patients with ‘wild-type’ mutation of RAS genes the best OSR parameters were recorded in surgical removal of the PF and of metastases in the liver in combination with palliative polyCT and Panitumumab. The lowest OSR was found in the subgroup of patients with use of CT without surgical treatment in the presence of RAS mutation. High OSR parameters were found with mutation in G13codon, and with use of surgical treatment with mutation in A146 codon.

Keywords

colorectal cancer / RAS mutations / metastases in liver / Cetuximab / Panitumumab

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