Recurrence Patterns of Resected Ampullary Adenocarcinoma and Implications for Multimodal Therapy: A Hidden Genome-Derived Analysis from the Ampullary Cancer Collaborative.

BACKGROUND

Ampullary adenocarcinoma is characterized by significant clinical heterogeneity that may preclude rational application of adjuvant therapies. The Hidden Genome Classifier defines distinct prognostic subtypes of ampullary adenocarcinoma. The impact of genomic subtype on recurrence patterns is unknown and may provide novel biomarkers to optimize treatment selection.

METHODS

The previously validated Hidden Genome Classifier was applied to an international, six-institution cohort of 218 patients with resected ampullary adenocarcinoma. Genomic classification was correlated with pattern of disease recurrence (local vs distant) and with recurrence-free survival (RFS) and overall survival (OS) using the log-rank test and Cox proportional hazard models.

RESULTS

Genomic subtype, but not immunohistologic subtype, was associated with RFS (colorectal [55.5 months] vs pancreas/distal bile duct [18.3 months]; p = 0.022). Isolated local recurrence was infrequent (22.4%) and did not vary across genomic subtypes (p = 0.933), traditional immunohistologic subtypes (p = 0.505), or margin status (p = 0.557). The pancreas/distal bile duct genomic subtype was associated with a greater rate of distant recurrence (44.0% vs 21.0%; p = 0.005). In a multivariable model accounting for American Joint Committee on Cancer (AJCC) stage, the use of radiation was not associated with RFS (ref: surgery alone; radiation: hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.49-1.39). Adjuvant chemotherapy was associated with improved OS (ref: surgery alone; HR, 0.52; 95% CI, 0.32-0.84; p = 0.008).

CONCLUSIONS

Genomic and clinical biomarkers failed to identify patients at increased risk for local recurrence for whom radiation may be best applied. Distant recurrence was common, and adjuvant chemotherapy was associated with improved survival.