E342: Clinical implications of tumor mutational burden in patients with colorectal peritoneal metastasis

Molecular profiling of gastrointestinal tumors is becoming the standard practice but the clinical implications of tumor mutational burden (TMB) status haven’t been studied yet in patients with colorectal peritoneal metastasis (CRPM). We aimed to investigate whether TMB correlates with surgical characteristics among CRPM patients undergoing curative or palliative surgery.

Methods:

We reviewed our prospectively collected database to identify pathology-proven CRPM patients for whom the primary tumor or metastases were analyzed using our institutional next-generation sequencing 100-gene assay. Patients were divided into low (TMB-L) vs. high (TMB-H) TMB, using the median TMB as a cutoff. The two groups were compared in terms of demographics, perioperative parameters and long-term outcomes.

Results:

Out of 339 CRPM patients screened, our study included 73 patients with available TMB data who underwent surgery between 5/2016-6/2023. Sixty patients (82.2%) underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. The median TMB was 5.7 mutations/megabase (range 0-14). Demographics and baseline tumor characteristics were similar in the TMB-L and TMB-H groups. TMB-L patients were more likely to present with synchronous CRPM (median time from diagnosis to CRPM: 3.8 (0-149) vs. 19.7 (0-121) months, p=0.008). Intraoperatively, TMB-L patients had a significantly higher peritoneal cancer index (PCI) score (Figure 1, 11.5 (2-35) vs. 6 (0-23), p= 0.003) and were less likely to undergo complete cytoreduction (CC, 54.3% vs. 84.2%, p=0.005). Among patients who underwent complete cytoreduction, the rate of surgical complications and length of hospitalization did not differ significantly between the TMB-L and TMB-H groups.

For a subgroup of patients with TMB≤3 mutations/megabase, median overall survival measured from disease diagnosis, appearance of CRPM or surgical intervention was worse compared with those who had higher TMB (all p≤0.006). On multivariate analysis incorporating the PCI, CC status, TMB and tumor grade, TMB≤3 correlated independently with overall survival from disease diagnosis (HR 0.26, 95%CI 0.11-0.60, p=0.002).

Conclusions:

Among CRPM patients undergoing surgery, lower TMB may be correlated with higher rates of synchronous CRPM, higher tumor burden, lower rates of complete cytoreduction and worse survival outcomes. These findings may bear clinical implications for patient selection, perioperative management and prognosis.