Tumor Genomic Profiling Identifies High-Risk Gallbladder Cancer

Five-year survival is often below 10%, and only an estimated 10%–20% of patients are eligible for curative surgical resection at presentation. While stage and treatment remain key determinants of prognosis, clinicians are also seeking molecular factors that may help explain differences in outcomes. New findings show that specific tumor DNA alterations are associated with shorter survival in this disease.

Researchers at Boston University Chobanian & Avedisian School of Medicine evaluated whether actionable genomic alterations (AGAs) independently predict survival in gallbladder cancer. Using real-world medical records from the TriNetX international database, they compared outcomes in patients whose tumors had documented AGAs with those without such findings. AGAs are specific DNA changes in cancer cells.

The team identified more than 40,000 individuals with gallbladder cancer and stratified them into two cohorts based on the presence or absence of a documented AGA. They then applied statistical matching so that the groups were comparable by age, sex, race and ethnicity, disease spread, surgical management, and receipt of chemotherapy. After establishing these matched cohorts, overall survival was assessed between the two groups.

Survival analyses showed that tumors harboring AGAs—including KRAS, ERBB2/HER2, PIK3CA, IDH1, FGFR1, TP53, or ARID1A—were associated with lower survival than tumors without documented alterations. The investigators also noted disparities in who had genomic results recorded: in the group without a documented AGA, 51.0% of patients had race listed as unknown versus 3.7% among those with documented genomics. Among patients with known race, white patients represented 67.1% of the documented-genomics group compared with 32.6% of the comparison group. The analysis is published in Cancers. The researchers stated that these findings could help move gallbladder cancer care toward a more personalized approach, with decisions guided by both stage and tumor biology.

"Genetic changes inside the cancer cells may help explain why some gallbladder patients do worse than others, even when they receive similar treatment," said Eduardo Vega, MD, assistant professor of surgery at Boston University Chobanian & Avedisian School of Medicine and hepato-bilio-pancreatic surgeon at Boston Medical Center.

"Ultimately, we want genomic testing to help identify higher-risk patients earlier, expand access to targeted therapies and clinical trials, and improve outcomes for a disease that remains very difficult to treat," added Dr. Vega.

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Boston University Chobanian & Avedisian School of Medicine