Real-world impact of comprehensive genomic profiling in colon cancer: Evidence from community oncology centers in western India.

Abstract

e15587 Background: NGS-based mutation profiling is increasingly used to guide oncology treatment. This study compares comprehensive genomic profiling (CGP) with limited panels & evaluates its role in precision medicine in a developing-country setting. Methods: This retrospective study included consecutive colon cancer patients from community oncology centers in Western India diagnosed between March 2018 & May 2025. Clinical, molecular & survival data were extracted from EMR & analyzed using the Kaplan–Meier method. Results: A total of 1100 colon cancer patients were evaluated who underwent NGS testing (10.54%; 116/1100) & the mean age was 63 years (IQR 54.3-72.0); with M:F ratio 1.9:1 & stage distribution being 13.8%, 38.8%, & 47.4% for Stage I/II, III & IV respectively. CGP was performed in 87.9% (102/116) to evaluate SNVs, CNVs & indels spanning across over 15000 loci for 1080 tumor while short panel testing was done in 12.0% (14/116) to assess mutation detection rates for key genes (BRAF, ERBB2, KRAS, NRAS, PIK3CA, TP53, NTRK) wherein 79.4% were tissue-based & 20.7% were liquid biopsy-based. Majority (59.5%) of the patients tested were therapy naive while 40.5% were pre-treated. The most common subtype in the cohort was adenocarcinoma (96.6%); commonly involved primary sites were sigmoid colon (n = 46) & ascending colon (n = 41) with a predominance of left-sided over right-sided disease (56.0% vs 38.8%). The common mutations reported were: TP53 (n = 59), KRAS (n = 41), APC (n = 25), PIK3CA (n = 14), BRAF(n = 9), HER2 (n = 3) NRAS (n = 1); comutation commonly observed were KRAS + TP53 ( n = 18) & BRAF + TP53 ( n = 6). MSI high & TMB high ( > 10 muts) were reported in 11.3%(10/88) & 26.6% (4/15) respectively. PD-L1 testing was done in 53.4% (62/116) with positivity (CPC/TPS > 1) in 51.6% (32/62). First line therapy mainly constituted chemotherapy (n = 94) & surgery (n = 81); common chemotherapy regimens were FOLFOX (n = 43) & CAPOX (n = 31). Targeted therapy was administered in first line to 19.8% (n = 22/111) mostly: Bevacizumab (n = 18), Cetuximab (n = 5) & regorafenib (n = 2) with 77.3% ORR. Immunotherapy was administered to 6% (7/116) with distribution: Pembrolizumab (n = 3), Nivolumab(n = 2) Dostarlimab (n = 1), Atezolizumab (n = 1) & 50% CBR. Among first line recipients, best responses were complete response in 30.6%, partial response in 33.3% & stable disease in 3.6%. Median overall survival (mOS) was 21.4 mo in BRAF mutant cohort vs 49.5 mo in other mutations (p = 0.035). mOS for NRAS/KRAS mutant cohort was 28.8 mo vs not reached in others (p = 0.032). TP53 mutant cases had mOS of 28.8 mo vs 49.5 mo in non-mutants (p = 0.191). mOS was not reached in immunotherapy marker mutant patients vs 49.5 mo in non-mutants (p = 0.091). Conclusions: This study supports CGP as a clinically impactful tool in precision oncology emphasizing its importance & improving its integration and accessibility in resource-limited healthcare settings.