To Quiesce or Senesce, That Is the Question for Dedifferentiated Liposarcoma.

Dedifferentiated liposarcoma (DDLPS) has an appealing therapeutic target due to its CDK4 amplification on chromosome 12q. The understanding of geroconversion from quiescent cells to senescent cells defines a patient's response to CDK4 inhibitors. This new observation will inform not only the ongoing phase III clinical trial of abemaciclib, but all future clinical trials in DDLPS. See related article by Gleason et al., p. 703.

COL1A1::PDGFB fusion-associated uterine sarcoma and response to Imatinib: A case report.

Uterine sarcomas are rare neoplasms of the uterus, some of which are associated with distinctive gene fusions. COL1A1::PDGFB fusion uterine sarcoma is a recently described entity that shares the same genetic alteration as dermatofibrosarcoma protuberans. These uterine sarcomas have a nonspecific spindle cell sarcoma appearance and are CD34 positive by immunohistochemistry. Accurate diagnosis relies on identification of the characteristic fusion by molecular genetic methods. The importance of diagnosing this entity lies in its potential response to targeted therapy with imatinib, a tyrosine kinase inhibitor successfully used in dermatofibrosarcoma protuberans, but only one prior case of COL1A1::PDGFB fusion uterine sarcoma treated with imatinib has been reported. Here, we describe a case of COL1A1::PDGFB fusion uterine sarcoma with response to imatinib after recurrence, with a brief review of this rare tumor.

The Midwest Sarcoma Trials Partnership: Bridging Academic and Community Networks in a Collaborative Approach to Sarcoma.

The treatment of sarcoma necessitates a collaborative approach, given its rarity and complex management. At a single institution, multidisciplinary teams of specialists determine and execute treatment plans involving surgical, radiation, and medical management. Treatment guidelines for systemic therapies in advanced or nonresectable soft tissue sarcoma have advanced in recent years as new immunotherapies and targeted therapies become available. Collaboration between institutions is necessary to facilitate accrual to clinical trials. Here, we describe the success of the Midwest Sarcoma Trials Partnership (MWSTP) in creating a network encompassing large academic centers and local community sites. We propose a new model utilizing online platforms to expand the reach of clinical expertise for the treatment of advanced soft tissue sarcoma.

Relapsed Synovial Sarcoma: Treatment Options.

OPINION STATEMENT: Synovial sarcoma (SS) is a fusion-driven subtype of sarcoma that is a more chemo-sensitive subtype of soft tissue sarcoma. While chemotherapy options are currently standard of care, our fundamental understanding of the biology of SS is driving new therapies. We will review the current standard of care, as well as the current therapies showing promise in a clinical trial. It is our hope that by encouraging participation in clinical trials, the fundamental therapies available for SS will change the current treatment paradigm.

Systemic Treatment of Soft Tissue Sarcomas in the Geriatric Population.

OPINION STATEMENT: As the population ages, there will be an increase in the incidence and prevalence of soft tissue sarcoma (STS) within the geriatric population. As this disease disproportionately affects older adults, the percentage of adults >65 years old is expected to increase in the coming years. Geriatric patients are often more vulnerable to disease-related symptoms and have more difficulty tolerating treatment-related side effects. While there are no formal existing guidelines to direct the care of this geriatric patient population, it is of utmost importance to consider each patients' fitness and co-morbidities when selecting treatment plans. This review focuses on the current state of research of older adults with advanced or metastatic soft tissue sarcoma, highlighting the lack of representation of this patient population in clinical trials. Given that chronological age does not necessarily equate to physiologic age, integration of comprehensive geriatric and quality of life assessments is needed in the care of geriatric patients to help guide therapeutic decisions.

The clinical utility of next-generation sequencing for bone and soft tissue sarcoma.

Background: Sarcomas are a rare and heterogeneous tumor group composed of a variety of histologic subtypes. Targeted next-generation sequencing (NGS) of bone and soft tissue sarcomas is a nascent field with limited evidence for its use within clinical practice. Therefore, further research is needed to validate NGS in sarcoma and assess the clinical utility of these techniques with the hope of improving treatment options.Methods: Comprehensive molecular profiling with NGS was performed on 136 tumors (116 soft tissue, 20 bone) using two commercial vendors. Patient records were retrospectively reviewed, and the clinical impact of NGS-related findings were qualitatively analyzed to determine actionable mutations and number of changes in treatment.Results: The median age was 55.0 years (IQR 42-67 years), and most patients were non-metastatic at presentation (80.9%, n = 110). Prior to performing NGS, 72.1% (n = 98) were treated with a mean 1.1 ± 1.2 lines of systemic chemotherapy. NGS identified 341 putative alterations with at least one mutation present in 89.7% (n = 122) of samples. In a subset of 111 patients with available TMB data, 78.7% (n = 107) had a low (<6 m/Mb) mutational burden. Among all 136 cases, 47.1% (n = 64) contained clinically actionable alterations, and 12 patients had a change in medical treatment based on NGS. Those who underwent a treatment change all had metastatic or recurrent disease; three of these patients experienced a clinical benefit.Conclusion: Most bone and soft tissue sarcomas harbor at least one genetic alteration, and it appears a sizeable number of tumors contain mutations that are clinically actionable. While a change in treatment based off NGS-related findings occurred in 12 cases, three patients experienced a clinical benefit. Our data provide further proof-of-concept for NGS in sarcoma and suggest a clinical benefit may be observed in select patients.

Truly Man's Best Friend: Canine Cancers Drive Drug Repurposing in Osteosarcoma.

While metastatic osteosarcoma is rare in humans, it is the most common bone tumor found in any breed of dog. Given the genetic similarities between canine and human osteosarcomas, canine clinical trials allow for rapid testing and drug repurposing at a speed that cannot be achieved using patients with osteosarcoma. See related article by Regan et al., p. 662.

Phase II study of dacarbazine given with modern prophylactic anti-emetics and growth factor support to patients with metastatic, resistant soft tissue, and bone sarcoma.

Historically, administration of dacarbazine to sarcoma patients was limited by frequent treat-ment-related nausea/vomiting and neutropenia. These toxicities are now largely preventable with contemporary antiemetics and growth factor support. In this single-arm, phase II study, dacarbazine 850 mg/m2 was given on day 1 of each 3-week cycle until disease progression or intolerance with prophylactic serotonin-3 receptor, neurokinin-1 antagonists, corticosteroids, and pegfilgrastim. Coprimary endpoints included clinical benefit rate (CBR), and any grade of nausea/vomiting and/or grade 3-4 neutropenia. With a sample size of 80 patients, >24 patients with clinical benefit would indicate that the CBR exceeds the historical (<20%) [Power 0.80; alpha 0.05]. In addition, we hypothesized that the rates of nausea/vomiting would be 27% and grade 3-4 neutropenia would be 1% (historical: 90% and 36%, respectively) [power 0.95; alpha 0.05]. The CBR was 30% (24 patients: PR-2 and stable-22). The rate of nausea/vomiting was 37.5% (31 patients) and grades 3-4 neutropenia was 10% (8 patients). Median time-to-progression was 8.1 weeks (95% CI 8-9.7) and median overall survival was 35.8 weeks (95% CI 26.2-55.4). PET scans demonstrated no association with response. Modern prophylactic anti-emetics and pegfilgrastim given with dacarbazine reduced the rates of treatment related nausea/vomiting and serious neutropenia.