Complete Response of a Colonic High-Grade Neuroendocrine Carcinoma to Platinum-Based Therapy: Insights from Comprehensive Genomic Profiling
Abstract Background Comprehensive genomic profiling (CGP) is an essential tool in precision medicine, providing diagnostic, prognostic, and predictive (therapeutic) information that enables personalized optimal care for cancer patients. We present the case of a 54-year-old woman with stage IV large-cell neuroendocrine carcinoma (LCNEC) of the colon with liver and nodal metastases with complete response to therapy and demonstrate the value of CGP in identifying potential targets for treatment in these tumors. Results CGP performed on the tumor showed pathogenic mutations in multiple oncogenes and tumor suppressor genes including BRCA1, BAP1, and BRAF, high tumor mutation burden (TMB), and high microsatellite instability (MSI-H). Treatment with platinum-based therapy resulted in a complete radiographic response of the metastases, with no evidence of recurrence after 6.5 years. Assessment by Medical Genetics did not identify any evidence of hereditary cancer syndrome. The dramatic response to therapy is likely due to loss of BRCA1 and/or BAP1 function, as deleterious mutations in both genes predict response to platinum-based therapy through exploitation of deficient homologous recombination repair (HRR). The information provided by CGP also suggested potential tumor sensitivity to poly(ADP-Ribose) polymerase inhibitors (PARPi), immunotherapy (IT) and BRAF/MEK inhibitor therapy, should the tumor recur. Conclusion This case highlights the value of CGP in guiding diagnosis and management of rare and aggressive tumors.