Genetic and epigenetic characterization of sarcoma stem cells across subtypes identifies EZH2 as a therapeutic target.

High-grade soft tissue sarcomas (STS) are a heterogeneous and aggressive set of cancers. Failure to respond anthracycline chemotherapy, standard first-line treatment, is associated with poor outcomes. We investigated the contribution of STS cancer stem cells (STS-CSCs) to doxorubicin resistance.

Genetic Screen in a Preclinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities.

Purpose: High-grade complex karyotype sarcomas are a heterogeneous group of tumors with a uniformly poor prognosis. Within complex karyotype sarcomas, there are innumerable genetic changes but identifying those that are clinically relevant has been challenging.

Experimental Design: To address this, we utilized a pooled genetic screening approach, informed by The Cancer Genome Atlas (TCGA) data, to identify key drivers and modifiers of sarcoma development that were validated in vivo.

Genetic and Epigenetic Characterization of Sarcoma Stem Cells Across Subtypes Identifies EZH2 as a Therapeutic Target.

High-grade complex karyotype soft tissue sarcomas (STS) are a heterogeneous and aggressive set of cancers that share a common treatment strategy. Disease progression and failure to respond to anthracycline based chemotherapy, standard first-line treatment, is associated with poor patient outcomes. To address this, we investigated the contribution of STS cancer stem cells (STS-CSCs) to doxorubicin resistance.

Wild-type C-Raf gene dosage and dimerization drive prostate cancer metastasis.

Mutated Ras and Raf kinases are well-known to promote cancer metastasis via flux through the Ras/Raf/MEK/ERK (mitogen-activated protein kinase [MAPK]) pathway. A role for non-mutated Raf in metastasis is also emerging, but the key mechanisms remain unclear. Elevated expression of any of the three wild-type Raf family members (C, A, or B) can drive metastasis.

Emerging innovations and advancements in the treatment of extremity and truncal soft tissue sarcomas.

In this special edition update on soft tissue sarcomas (STS), we cover classifications, emerging technologies, prognostic tools, radiation schemas, and treatment disparities in extremity and truncal STS. We discuss the importance of enhancing local control and reducing complications, including the role of innovative imaging, surgical guidance, and hypofractionated radiation. We review advancements in systemic and immunotherapeutic treatments and introduce disparities seen in this vulnerable population that must be considered to improve overall patient care.

Scrutinizing the use of contrasted chest CTs in extremity sarcoma staging and surveillance.

Background: Since 2015, the American College of Radiology (ACR) has recommended staging for lung metastasis via chest computed tomography (CT) without contrast for extremity sarcoma staging and surveillance. The purpose of this study was to determine our institutional compliance with this recommendation.

Methods: This was a retrospective chart review of patients diagnosed with sarcoma in the extremities who received CT imaging of the chest for pulmonary staging and surveillance at our institution from 2005 to 2023.

Human soft tissue sarcomas harbor an intratumoral viral microbiome which is linked with natural killer cell infiltrate and prognosis.

Background: Groundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures.

Case report: Treatment of metastatic dedifferentiated chondrosarcoma with pembrolizumab yields sustained complete response.

Dedifferentiated chondrosarcomas (DDCS) are aggressive tumors with poor outcomes. Treatment of localized DDCS is primarily surgical, though most patients present with unresectable or metastatic disease. Systemic treatment options for advanced DDCS are limited, and the benefits of chemotherapy in this patient population remain controversial.

NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors.

Head and Neck Cutaneous Soft-Tissue Sarcoma Demonstrate Sex and Racial/Ethnic Disparities in Incidence and Socioeconomic Disparities in Survival.

Background: Cutaneous soft-tissue sarcoma (CSTS) of the head and neck are rare and are known to have aggressive clinical course. The current study utilizes a population-based registry in the U.S.

Socioeconomic and insurance-related disparities in disease-specific survival among patients with metastatic bone disease.

Background: Approximately 5% of cancer patients in the United States presented with metastatic bone disease (MBD) at diagnosis. Current study explores the disparities in survival for patients with MBD.

Methods: Patients with the diagnosis of MBD at presentation for the five most common primary anatomical sites were extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset (2010-2016).

Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors.

Impact of local treatment modality on overall- and disease-specific survival for nonmetastatic pelvic and sacral Ewing sarcoma.

Purpose: The ideal local treatment modality for pelvic and sacral Ewing sarcoma (EWS) is controversial.

Methods: We present the data from the American College of Surgeon's National Cancer Database (NCDB) and the National Cancer Institute's Surveillance, Epidemiology and End Result (SEER) database to investigate the impact of local treatment modalities on survival for nonmetastatic pelvic and sacral Ewing sarcoma. Local treatment includes "surgery," "radiation," and a combination of "surgery and radiation.

Non-Private Health Insurance Predicts Advanced Stage at Presentation and Amputation in Lower Extremity High Grade Bone Sarcoma: A National Cancer Database Study : Amputation Predicts Survival: An Effect Most Pronounced in Pediatric and AYA Age Group.

Introduction: Advances in diagnostic and treatment modalities for high grade bone sarcomas (HGBS) of lower extremity (LE) have enabled limb salvage resections as a feasible first-line surgical option. However, amputations are still performed. Impact of amputation on survival and predictive factors for amputation and the stage at presentation for HGBS of LE remain unknown.

Sex, racial/ethnic and socioeconomic disparities in patients with metastatic bone disease.

Background: We have analyzed sex, race/ethnicity or socioeconomic disparities in the incidence of metastatic bone disease (MBD).

Methods: Patients with the diagnosis of MBD at presentation for five most common primary anatomical sites was extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset. Mean incidence of MBD for different sex, racial/ethnic and socioeconomic groups were compared.

Prognostic factors, disparity, and equity variables impacting prognosis in bone sarcomas of the hand: SEER database review.

Background: Primary sarcomas originating from the bones of hand and wrist are rare but carry a significant burden of morbidity.

Methods: National Cancer Institute's Surveillance, Epidemiology and End Result database from 1975 to 2017 was queried to report incidence and survival data in 237 patients in the United States. Kaplan-Meier and Cox regression were used to determine the prognostic factors affecting survival.