DOI: 10.1200/po-25-01168 ISSN: 2473-4284

Performance and Clinical Benefit of Comprehensive Genomic Profiling of GI Tumors in a Comprehensive Cancer Center

Giulia Maddalena, Valentina Angerilli, Federico Nichetti, Gianmarco Ricagno, Jessica Gasparello, Elena Mattiuzzo, Maria Caterina De Grandis, Elena Carcea, Carlotta Ceccon, Anna Roma, Eleonora Perissinotto, Sara Sperotto, Giacomo Di Paolo, Marta Sbaraglia, Marco Maruzzo, Francesca Bergamo, Angelo Paolo Dei Tos, Matteo Fassan, Sara Lonardi
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PURPOSE

Comprehensive genomic profiling (CGP) is increasingly adopted in the management of patients affected by GI cancers. However, the applicability, performance, and clinical utility of CGP in the real-world setting are still undefined.

METHODS

We retrospectively evaluated CGP performance and clinical benefit in consecutive patients with GI tumor at the Veneto Institute of Oncology-IRCCS, Padua. We assessed CGP success and its advantage over routine diagnostics in detecting actionable molecular targets. A custom list of gain alterations was defined, including targets not classified as ESMO Scale for Clinical Actionability of molecular Targets tier IA at the time of analysis.

RESULTS

Of the 1,450 samples, 140 (9.7%) were inadequate for CGP. Failure was mainly due to low quantity of extracted tumor DNA ( P = .002). Of the 1,265 metastatic patients, GAs were detected in 355 (28.1%) cases, of whom 55 (15.5%) were treated with targeted therapy. Survival did not differ between patients with no GAs and those with GAs who were not treated accordingly (median overall survival 12.0 v 10.9 months), whereas it was significantly longer for those receiving treatment for actionable GAs (26.4 months). This advantage was confirmed in an exploratory, inverse probability of treatment-weighted analysis (adjusted hazard ratio, 0.72 [95% CI, 0.58 to 0.89]; P = .002). Among 283 (83.7%) untreated patients with complete follow-up, 41.6% did not receive targeted therapy due to lack of clinical trial or failure to meet inclusion criteria.

CONCLUSION

Appropriate specimen selection and early molecular assessment at the time of advanced disease diagnosis are essential to detect clinically actionable molecular alterations and therapeutic opportunities in patients with GI cancers. Our results support CGP in comprehensive cancer centers.

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