Histologic-and genomic-directed adjuvant therapy for ampullary adenocarcinoma: A hidden genome–derived analysis Journal Article
| Authors: | Ecker, B. L.; Seier, K.; Choubey, A.; Eckhoff, A. M.; Tortorello, G. N.; Balachandran, V. P.; Blackburn, N.; D’Angelica, M. I.; DeMatteo, R. P.; Blazer, D. G. 3rd; Drebin, J. A.; Fisher, W. E.; Gill, A. J.; Gingras, M. C.; Kingham, T. P.; Lee, M. K. 4th; Lidsky, M. E.; Nussbaum, D. P.; Overman, M. J.; Samra, J. S.; Shen, R.; Sigel, C. S.; Vollmer, C. M. Jr; Wei, A. C.; Zani, S.; Australian Pancreatic Genome Initiative; Roses, R. E.; Gonen, M.; Jarnagin, W. R. |
| Article Title: | Histologic-and genomic-directed adjuvant therapy for ampullary adenocarcinoma: A hidden genome–derived analysis |
| Abstract: | Background: The benefit of adjuvant chemotherapy (AC) for ampullary adenocarcinoma is unclear. The Hidden Genome model classifies prognostic subtypes with greater accuracy than standard histologic classification (intestinal [INT] vs pancreatobiliary [PB]), but its predictive capacity to guide the use of AC remains unstudied. Methods: We applied the Hidden Genome model to an international cohort of 183 patients with resected ampullary adenocarcinoma who underwent genomic sequencing. The model quantified the predicted cell of origin (colorectal vs pancreas/distal bile duct) in all specimens. Overall survival (OS) was compared using Kaplan-Meier estimates, stratified by AC use versus surgery alone (SA). Results: Most patients (n5128; 69.9%) received AC, which was not associated with a significant improvement in OS (median, 50.9 months [95% CI, 36.5–76.9] vs 53.8 months [95% CI, 32.4–119.0]; P 5.816). Histologic subtype was neither associated with prognosis (P 5.241) nor predictive of chemotherapy efficacy for INT-subtype (P 5.379) or PB-subtype (P 5.544) tumors. When stratified by genomic subtype, the colorectal group had a favorable prognosis regardless of AC use (median OS, 74.4 months [95% CI, 33.8–97.8] for AC vs 98.7 months [95% CI, 32.4–140.9] for SA; P 5.889). Among patients with pancreas/distal bile duct tumors, those who received AC had longer survival compared with those who underwent SA (78.2 months [9.8–not reached] vs 22.7 months [2.3–not reached], respectively; hazard ratio, 0.17 [95% CI, 0.04–0.80]; P 5.024). Conclusions: AC regimens were not associated with improved survival in histologically defined INT- or PB-subtype ampullary adenocarcinoma. However, genomic classification better stratified risk groups and identified patients more likely to benefit from AC. © JNCCN—Journal of the National Comprehensive Cancer Network. |
| Journal Title: | Journal of the National Comprehensive Cancer Network |
| Volume: | 23 |
| Issue: | 6 |
| ISSN: | 1540-1405 |
| Publisher: | Harborside Press |
| Date Published: | 2025-06-01 |
| Start Page: | 234 |
| End Page: | 240 |
| Language: | English |
| DOI: | 10.6004/jnccn.2025.7008 |
| PROVIDER: | scopus |
| PUBMED: | 40499590 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: William R. Jarnagin -- Source: Scopus |
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