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Genomic-guided precision therapy for soft tissue sarcoma.

ABSTRACT: Soft tissue sarcoma (STS), although heterogeneous in histopathology presentation, has mostly been treated with chemotherapy agents as one entity. Our understanding of crucial genomic alterations in different STS histologies and the advent of molecular-targeted agents have reshaped the treatment paradigm for advanced STS. Small-molecule inhibitors of c-KIT, plate-derived growth factor receptor alpha, c-MET, BRAF, anaplastic lymphoma kinase, ROS1 and colony-stimulating factor-1 receptor have been successfully validated in clinical studies to yield practice-changing results. Inhibitors of other novel genomic targets including mouse double minute 2 homolog, cyclin-dependent kinase 4/6, mitogen-activated protein kinase and epigenetic regulators are expected to be developed in the near future. Furthermore, with the advancement and accessibility of molecular diagnosis and next-generation sequencing, a genomic-based therapeutic approach should be widely applicable to advanced STS patients. This review will focus on the progress of genomic-guided therapy tailored to each molecular alteration of different STS histologies.

SUBMITTER: Chen HW

PROVIDER: S-EPMC7059546 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Genomic-guided precision therapy for soft tissue sarcoma.

Chen Hsing-Wu HW Chen Tom Wei-Wu TW

ESMO open 20200301 2

Soft tissue sarcoma (STS), although heterogeneous in histopathology presentation, has mostly been treated with chemotherapy agents as one entity. Our understanding of crucial genomic alterations in different STS histologies and the advent of molecular-targeted agents have reshaped the treatment paradigm for advanced STS. Small-molecule inhibitors of c-KIT, plate-derived growth factor receptor alpha, c-MET, BRAF, anaplastic lymphoma kinase, ROS1 and colony-stimulating factor-1 receptor have been ...[more]

PMID: 32132106

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Project description:Soft-tissue sarcoma (STS) represent a rare tumor entity, accounting for less than 1% of adult malignancies. The cornerstone of curative intent treatment is surgery with free margins, although the extent of the surgical approach has been subject to change in the last decades. Multimodal approaches usually including radiation therapy have replaced extensive surgical procedures in order to preserve functionality while maintaining adequate local control. However, the possibility to apply adequate radiation doses by external beam radiation therapy (EBRT) can be limited in some situation especially in case of directly adjacent organs at risk with low radiation tolerance. Application of at least a part of the total dose via intraoperative radiation therapy (IORT) with a single fraction during the surgical procedure may overcome those limitations, because radiosensitive structures can be moved out of the radiation field resulting in reduced toxicity while the enhanced biological effectivity of the high single dose improves local control. The current review summarizes rationale, techniques, oncological and functional outcomes including possible pitfalls and associated toxicities based on the published literature for IORT focusing on extremity and retroperitoneal STS. In extremity STS, combination of limb-sparing surgery, IORT and pre- or postoperative EBRT with moderate doses consistently achieved excellent local control rates at least comparable to approaches using EBRT alone but usually including patient cohorts with higher proportions of unfavourable prognostic factors. Further on, IORT containing approaches resulted in very high limb preservation rates and good functional outcome, probably related to the smaller high dose volume. In retroperitoneal STS, the combination of preoperative EBRT, surgery and IORT consistently achieved high local control rates which seem superior to surgery alone or surgery with EBRT at least with regard to local control and in some reports even to overall survival. Further on, preoperative EBRT in combination with IORT seems to be superior to the opposite combination with regard to local control and toxicity. No major differences in wound healing disturbances or postoperative complication rates can be observed with IORT compared to non-IORT containing approaches. Neuropathy of major nerves remains a dose limiting toxicity requiring dose restrictions or exclusion from target volume. Gastrointestinal structures and ureters should be excluded from the IORT area whenever possible and the IORT volume should be restricted to the available minimum. Nevertheless, IORT represents an ideal boosting method if combined with EBRT and properly executed by experiences users which should be further evaluated preferably in prospective randomized trials.

Dataset Information

Genomic-guided precision therapy for soft tissue sarcoma.

Publications

Genomic-guided precision therapy for soft tissue sarcoma.

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