Recent advances in sarcoma therapy: new agents, strategies and predictive biomarkers.

Soft tissue and bone sarcomas are a heterogenous group of uncommon mesenchymal tumors with high unmet needs for novel therapeutic and diagnostic strategies. Despite many challenges that persist, innovative therapeutics are emerging. Here we provide a review of the studies presented at the 2024 American Society of Clinical Oncology annual meeting that were focused on sarcoma.

PTEN pathogenic variants are associated with poor prognosis in patients with advanced soft tissue sarcoma.

Background: We aimed to examine whether PTEN pathogenic variants (mutPTEN) were associated with overall survival (OS) in patients with advanced soft tissue sarcoma (STS) with the presence of one or more of the most common genomic alterations including p53, CDKN2A, RB1, and ATRX pathogenic variants.

Methods: This study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 or higher locally advanced and metastatic STS.

Results: A total of 174 patients had leiomyosarcoma (LMS), 136 had undifferentiated pleomorphic sarcoma (UPS), 78 had Liposarcoma (LPS), and 214 had other histology subtypes (Others).

The ATP-exporting channel Pannexin 1 promotes CD8 T cell effector and memory responses.

Sensing of extracellular ATP (eATP) controls CD8 T cell function. Their accumulation can occur through export by specialized molecules, such as the release channel Pannexin 1 (Panx1). Whether Panx1 controls CD8 T cell immune responses , however, has not been previously addressed.

Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy.

Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets.

Response to Immunotherapy in Sclerosing Epithelioid Fibrosarcoma: Case Report and Literature Review.

Sclerosing epithelioid fibrosarcoma (SEF) is an extremely rare subtype of sarcoma that appears histologically low-grade yet usually has a clinically aggressive course with a high rate of local recurrence and distant metastasis. However, these recurrences and metastases often occur years after initial treatment. Metastases can be to the lung as well as extra-pulmonary sites.

Epstein Barr Virus-Positive Lymphoproliferative Disorder Following Lymphodepletion for MAGE A4 Adoptive Cellular Therapy in a Patient with Synovial Sarcoma: A Case Report.

Lymphoproliferative disorder (LPD) associated with viral reactivation is a known risk of immunocompromised patients. With development of novel cellular therapies utilizing lymphodepletion regimens in advanced cancer, the risk of LPDs should be a consideration. Here, we report a case of a 61-year-old treated male with history of metastatic synovial sarcoma and multiple treatment lines treated with cell therapy (lymphodepleting chemotherapy and afami-cel, formerly ADP-A2M4, T-cell treatment) on clinical study that developed Epstein Barr virus-positive LPD.

Sex-dependent Prognosis of Patients with Advanced Soft Tissue Sarcoma.

Purpose: To examine whether overall survival (OS) differs for male and female patients with advanced soft-tissue sarcoma (STS).

Experimental Design: The study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 and 3 locally advanced or metastatic STS whose tumor underwent next-generation sequencing. We used Cox regression modeling to examine association of sex and OS adjusting for other important factors.

Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy.

Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of chromosome region 12q13-15, which contains the genes and . DDLPS exhibits higher amplification ratios of these two and carries additional genomic lesions, including the amplification of chromosome region 1p32 and chromosome region 6q23, which may explain the more aggressive biology of DDLPS.

The ATP-exporting channel Pannexin-1 promotes CD8 T cell effector and memory responses.

Sensing of extracellular ATP (eATP) controls CD8 T cell function. Their accumulation can occur through export by specialized molecules, such as the release channel Pannexin-1 (Panx1). Whether Panx1 controls CD8 T cell immune responses , however, has not been previously addressed.

Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma.

: Leiomyosarcomas (LMS) are aggressive malignancies with a propensity for early relapse. Current surveillance modalities include physical exam and imaging; however, radiological response to therapy may only manifest after 4-6 cycles of treatment. Herein, we evaluated the feasibility of longitudinal circulating tumor DNA (ctDNA) assessment in LMS patients to identify disease progression.

P2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy.

Expression of the purinergic receptor P2RX7 by CD8+ T cells promotes the generation of memory populations following acute infections. However, data suggest that P2RX7 may limit the efficacy of antitumor responses. Herein, we show that P2RX7 is beneficial for optimal melanoma control in a mouse CD8+ T-cell adoptive transfer model.

Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review.

Objectives: We review our institution's experience in treating leiomyosarcomas involving the inferior vena cava, and we offer guidance on the management.

Methods: A text-based search was performed to identify all patients who underwent surgical resection between January 2002 and October 2020. Clinicopathologic data, intraoperative variables, and outcomes were extracted from chart review.

Safety and Feasibility of Cryoablation during Immunotherapy in Patients with Metastatic Soft Tissue Sarcoma.

Purpose: Patients with metastatic soft tissue sarcoma (STS) undergo a wide array of treatments, including surgery, radiation, chemotherapy, immunotherapy, and ablative therapies, to control their disease. The combination of cryoablation and immunotherapy may lead to an enhanced antitumor immune response via the abscopal effect. It is hypothesized that the combination of cryoablation and immunotherapy in patients with metastatic STS is safe and feasible.

Management Strategies for Patients With Epithelioid Hemangioendothelioma: Charting an Indolent Disease Course.

Background: Epithelioid hemangioendothelioma (EHE) is a malignant vascular neoplasm representing ∼1% of sarcomas. Due to its rarity, its clinical course is not well characterized and optimal treatment remains unknown.

Materials And Methods: This was a retrospective review of patients with EHE treated at Stanford University between 1998 and 2020.

Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression.

Checkpoint inhibitor therapy has been shown to improve outcomes in multiple solid malignancies; however, data are limited in soft tissue sarcoma. We present two cases of patients with advanced soft tissue sarcoma of different subtypes (dedifferentiated liposarcoma and myxofibrosarcoma) with zero percent PD-L1 expression by immunohistochemistry who were treated with ipilimumab and nivolumab followed by maintenance nivolumab. Both patients had failed multiple lines of systemic treatment and experienced long-term remission after starting ipilimumab and nivolumab.

Sinonasal FUS-ERG-Rearranged Ewing's Sarcoma Mimicking Glomangiopericytoma.

Ewing's sarcoma is a rare and aggressive tumor that typically arises in the long bones of the extremities. It belongs in the family of small round blue cell tumors and is characterized immunohistochemically by diffuse CD99 expression and molecularly by one of several oncogenic translocations, most commonly t(11;22)(q24;q12) between the gene and the gene. Here we present a rare case of Ewing's sarcoma in the sinonasal tract with gene arrangement that was regarded for almost a decade as a sinonasal-type hemangiopericytoma (glomangiopericytoma).

Systemic Corticosteroid Use after Central Serous Chorioretinopathy Diagnosis.

Purpose: To analyze the frequency of systemic corticosteroid prescriptions before and after central serous chorioretinopathy (CSC) diagnosis.

Design: Retrospective claims-based analysis.

Participants: A nationally representative sample of commercial insurance beneficiaries who received care between 2007 and 2015.

Comparative Study of Four Endodontic File Systems to Assess Changes in Working Length during Root Canal Instrumentation and the Effect of Canal Curvature on Working Length Change.

Introduction: The aim of this study was to compare a reduction in working length and area of canal enlargement resulting from instrumentation with Hedström (Kerr Dental, Orange, CA), K (Kerr Dental), ProTaper Next (Dentsply Sirona, York, PA), and TF Adaptive (Kerr Dental) files. The effect of the canal curvature on the working length and area of canal enlargement was also assessed.

Methods: A total of 80 plastic canal models were used, 40 with a canal curvature of 10° and another 40 with a canal curvature of 30°.

Risk factors for incident central serous retinopathy: case-control analysis of a US national managed care population.

Aim: To evaluate clinical comorbidities and steroid use as risk factors for central serous retinopathy (CSR).

Methods: Using national insurance databases, we conducted a case-control study of beneficiaries with an incident diagnosis of CSR between 2007 and 2015 (n=35 492) and randomly selected controls matched on age-based and sex-based propensity scores (n=1 77 460).

Results: The mean age (SD) of cases was 49.

Different Raf protein kinases mediate different signaling pathways to stimulate E3 ligase RFFL gene expression in cell migration regulation.

We previously characterized a Gα12-specific signaling pathway that stimulates the transcription of the E3 ligase RFFL via the protein kinase ARAF and ERK. This pathway leads to persistent PKC activation and is important for sustaining fibroblast migration. However, questions remain regarding how Gα12 specifically activates ARAF, which transcription factor is involved in Gα12-mediated RFFL expression, and whether RFFL is important for cell migration stimulated by other signaling mechanisms that can activate ERK.