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Genomic Profiling and Clinical Outcomes of Targeted Therapies in Adult Patients with Soft Tissue Sarcomas
Stefania Kokkali1,2, Eleni Georgaki2, Georgios Mandrakis1
1First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece.
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.
Insights
Next-generation sequencing (NGS) for soft tissue sarcoma (STS) shows limited clinical utility due to few targetable alterations. More prospective studies are needed to determine if genomic profiling improves STS patient management.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Genomic profiling advances cancer pathogenesis understanding and targeted therapies, particularly in epithelial tumors.
- Next-generation sequencing (NGS) is increasingly used, but its role in soft tissue sarcoma (STS) remains debated.
- Sarcomas often exhibit low mutational burden and lack recurrent targetable alterations, complicating therapeutic strategies.
Purpose of the Study:
- To review the clinical utility of NGS for guiding therapeutics in soft tissue sarcoma (STS).
- To evaluate the current evidence and identify gaps in prospective research regarding genomic profiling in STS.
Main Methods:
- Review of retrospective studies and anecdotal reports on NGS in STS.
- Analysis of data on gene mutations, fusions, and amplifications detected by various NGS platforms.
- Assessment of the use and efficacy of targeted treatments in different STS histotypes.
Main Results:
- The clinical impact of genomic profiling in STS has not been prospectively investigated.
- Data on the use and efficacy of targeted treatments in STS are scarce, with limited actionable alterations identified.
- Targeted therapies, except for gastrointestinal stromal tumors (GISTs), are often administered off-label or via clinical trials.
Conclusions:
- The clinical utility of NGS in STS is controversial due to low actionable alteration rates.
- Current evidence relies heavily on retrospective data and anecdotal reports, necessitating caution in interpreting treatment outcomes.
- Prospective studies are essential to establish whether genomic profiling truly improves the management and outcomes for STS patients.
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