Genomic Profiling and Clinical Outcomes of Targeted Therapies in Adult Patients with Soft Tissue Sarcomas

Abstract

Genomic profiling has improved our understanding of the pathogenesis of different cancers and led to the development of several targeted therapies, especially in epithelial tumors. In this review, we focus on the clinical utility of next-generation sequencing (NGS) to inform therapeutics in soft tissue sarcoma (STS). The role of NGS is still controversial in patients with sarcoma, given the low mutational burden and the lack of recurrent targetable alterations in most of the sarcoma histotypes. The clinical impact of genomic profiling in STS has not been investigated prospectively. A limited number of retrospective, mainly single-institution, studies have addressed this issue using various NGS technologies and platforms and a variety of criteria to define a genomic alteration as actionable. Despite the detailed reports on the different gene mutations, fusions, or amplifications that were detected, data on the use and efficacy of targeted treatment are very scarce at present. With the exception of gastrointestinal stromal tumors (GISTs), these targeted therapies are administered either through off-label prescription of an approved drug or enrollment in a matched clinical trial. Based mainly on anecdotal reports, the outcome of targeted therapies in the different STS histotypes is discussed. Prospective studies are warranted to assess whether genomic profiling improves the management of STS patients.

Inflammatory Biomarker Correlations and Prognosis in High-risk Gastrointestinal Stromal Tumor Patients: A Multicenter Retrospective Analysis

“…The increasing incidence of GISTs, a form of soft tissue sarcoma, is becoming a signi cant concern in the medical eld, likely due to enhanced health awareness and advancements in diagnostic methods 21 . The evolution of therapeutic strategies for GISTs, transitioning from conventional surgical resection to a combination of surgery and targeted therapies such as imatinib, represents a signi cant advancement in this domain 22,23,24 .…”