Sarcomas are rare malignant mesenchymal neoplasms, and the knowledge of tumor biology and genomics is scarce. Chemotherapy is the standard of care in advanced disease, with poor outcomes. Identifying actionable genomic alterations may offer effective salvage therapeutic options when previous lines have failed. Here, we report a retrospective cohort study of sarcoma patients followed at our center and submitted to comprehensive genomic profiling between January 2020 and June 2021. Thirty patients were included, most (96.7%) with reportable genomic alterations. The most common alterations were linked to cell cycle regulation (TP53, CDKN2A/B, and RB1 deletions and CDK4, MDM2, and MYC amplifications). Most patients (96.7%) had microsatellite stability and low tumor mutational burden (≤10 muts/megabase (Mb); median 2 Muts/Mb). Two-thirds of patients had actionable mutations for targeted treatments, including five cases with alterations amenable to targeted therapies with clinical benefit within the patient’s tumor type, ten cases with targetable alterations with clinical benefit in other tumor types, and five cases with alterations amenable to targeting with drugs under investigation in a clinical trial setting. A significant proportion of cases in this study had actionable genomic alterations with available targeted drugs. Next-generation sequencing is a feasible option for identifying molecular drivers that can provide therapeutic options for individual patients. Molecular Tumor Boards should be implemented in the clinical practice to discuss genomic findings and inform clinically relevant targeted therapies.

Bone sarcomas (BS) are rare mesenchymal tumors usually located in the extremities and pelvis. While surgical resection is the cornerstone of curative treatment, some locally advanced tumors are deemed unresectable and hence not suitable for curative intent. This is often true for pelvic sarcoma due to anatomic complexity and proximity to vital structures, making treatment options for these tumors generally limited and not unanimous, with decisions being made on an individual basis after multidisciplinary discussion. Several studies have been published in recent years focusing on innovative treatment options for patients with locally advanced sarcoma not amenable to local surgery. The present article reviews the evidence regarding the treatment of patients with locally advanced and unresectable pelvic BS, with the goal of providing an overview of treatment options for the main BS histologic subtypes involving this anatomic area and exploring future therapeutic perspectives. The management of unresectable localized pelvic BS represents a major challenge and is hampered by the lack of comprehensive and standardized guidelines. As such, the optimal treatment needs to be individually tailored, weighing a panoply of patient- and tumor-related factors. Despite the bright prospects raised by novel therapeutic approaches, the role of each treatment option in the therapeutic armamentarium of these patients requires solid clinical evidence before becoming fully established.

Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a “fit for all” principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors.

Appendicular soft tissue sarcoma (aSTS) is a group of highly heterogeneous tumors of mesenchymal origin for which standard care usually includes surgical resection with or without radiation therapy. The main goal of surgical treatment in aSTS is to achieve wide tumor resection with negative margins while promoting the best function possible for the affected limb. Orthoplastic surgery represents the concept of a multidisciplinary approach comprising a synergistic collaboration between orthopedic and plastic surgeons. The development of this philosophy allows us to push forward the concept of limb salvage surgery for sarcomas, even when dealing with extremely complex cases. Reconstruction techniques integrated with orthoplastic principles range from simple to highly complex surgeries. Vascularized auto- or allo-graft tissue transfers illustrate how far reconstruction options can go, allowing for repair of large soft tissue defects or even restoration of muscle function in key anatomic segments after oncological resection. The reported experience with orthoplastic philosophy in aSTS suggests that it is a feasible and reproducible strategy that can achieve limb salvage rates above 90%, optimal oncologic local control characterized by more than 95% of wide margin resection, and improved functional and esthetic results. Most patients with aSTS treated under orthoplastic principles present good-to-excellent postoperative Musculoskeletal Oncology Society (MSTS) scores, confirming the advantages of this comprehensive approach. While there is significant experience with the orthoplastic approach for trauma cases, the road still needs to be paved for musculoskeletal oncologic reconstruction. Nonetheless, the results are promising and could inspire a wider adoption of structured orthoplastic protocols for sarcoma patient care. Herein, the authors explore the current practice regarding the application of collaborative orthoplastic approaches for the management of appendicular soft tissue sarcomas, reporting on outcomes and elaborating on future trends.