Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions.

Abstract

Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.

• Authors: Rita T Lawlor, Paola Mattiolo, Andrea Mafficini, Seung-Mo Hong, Maria L Piredda, Sergio V Taormina, Giuseppe Malleo, Giovanni Marchegiani, Antonio Pea, Roberto Salvia, Valentyna Kryklyva, Jae Il Shin, Lodewijk A Brosens, Michele Milella, Aldo Scarpa, Claudio Luchini
• Journal: Cancers (Cancers (Basel)) Vol. 13 Issue 13 (Jun 22 2021) ISSN: 2072-6694 [Print] Switzerland
• PMID: 34206554 (Publication Type: Journal Article, Review)