Contemporary Approach to Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.

Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a significantly elevated estimated lifetime frequency of 8%-13%. In the setting of NF1, MPNSTs arise from malignant transformation of benign plexiform neurofibroma and borderline atypical neurofibromas. Composed of neoplastic cells from the Schwannian lineage, these cancers recur in approximately 50% of individuals, and most patients die within five years of diagnosis, despite surgical resection, radiation, and chemotherapy.

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.

Racial and ethnic variation in presentation and outcomes of high-grade soft tissue sarcoma at a Southeastern United States comprehensive cancer center.

Background: High-grade soft tissue sarcoma is rare and associated with poor prognosis. This study examines racial and ethnic variation in presentation and outcomes at a Southeastern US cancer center.

Methods: Among an institutional cohort of patients seen between January 2016-December 2021, racial and ethnic differences were evaluated using chi-squared tests, Kaplan Meier curves, and Cox proportional hazards models.

Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA.

Unlabelled: Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA).

Immune checkpoint inhibitor resistance in soft tissue sarcoma.

The emergence of immunotherapy as a cancer therapy has dramatically changed the treatment paradigm of systemic cancer therapy. There have been several trials evaluating immune checkpoint blockade (ICI) in soft tissue sarcoma. While there is generally a limited response in sarcoma, a subset of patients has durable responses to immunotherapy.

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.

A phase II study of pazopanib as front-line therapy in patients with non-resectable or metastatic soft-tissue sarcomas who are not candidates for chemotherapy.

Background: Cytotoxic chemotherapy remains the standard of care first-line treatment for advanced and metastatic soft-tissue sarcomas (STSs). Certain patients may not be chemotherapy candidates based upon age or co-morbidities, leaving limited treatment options. Pazopanib is a multi-targeted tyrosine kinase inhibitor that is FDA-approved for metastatic STS after the first line.

Secondary Sarcomas: Biology, Presentation, and Clinical Care.

Secondary sarcomas are a subset of sarcomas that occur in patients with prior cancer diagnoses and are associated with environmental or genetic factors. Although secondary sarcomas are rare in general, there are predisposing factors that can substantially increase this risk in certain populations. Herein, we review the environmental factors with the strongest association of sarcoma risk, including chemical exposure, certain viruses, cytotoxic and immunosuppressive agents, chronic edema, and radiation exposure.