Monitoring Response Using Circulating Tumor DNA in Undifferentiated Pleomorphic Sarcoma: A Case Report.

Circulating tumor DNA (ctDNA) can be used to assess treatment response in patients with undifferentiated pleomorphic sarcoma (UPS). The importance of this is explored in our case of a 75-year-old man who was diagnosed with UPS of the right kidney. After a right nephrectomy and tumor resection, the patient was recovering well with initially undetectable, and then slightly elevated, circulating tumor DNA.

Histologic and immunologic factors associated with response to immune checkpoint inhibitors in advanced sarcoma.

Purpose: To characterize factors associated with response to immune checkpoint inhibitors (ICIs) in advanced sarcoma.

Experimental Design: This is a retrospective study with a cohort of 216 patients with advanced sarcoma treated with ICIs between 2016-2023 at Stanford Health Care. Overall survival (OS), progression free survival (PFS), objective response rates per RECIST criteria (ORR), and reason for ICI discontinuation were analyzed across histologic subtypes, ICI regimens, tumor mutational burden (TMB), and PD-L1 expression.

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.

Brain Metastases in Sarcomas: A Multicenter Retrospective Cohort Study.

Purpose: Brain metastases (BM) in sarcomas occur rarely and are associated with poor prognosis. This study is a large retrospective cohort describing the demographic and clinical characteristics of these patients, treatment strategies, and survival outcomes.

Methods: In total, 81 patients with BM from sarcomas were identified across five sarcoma centers.

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).

Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors.

Purpose: Desmoid tumors are bland fibroblastic tumors that do not metastasize but have a high rate of local recurrence. Previously published studies proposed two different transcriptomic signatures to predict relapse. Molecular heterogeneity has been well established in high-grade sarcomas, but little is known about molecular variability within locally aggressive tumors such as desmoids.

Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial.

Background: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma.

Methods: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe.

A Single-Arm Phase 2 Trial of Trametinib in Patients with Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.

Purpose: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 (calmodulinbinding transcription activator 1) operating as an oncogenic driver through activation of the MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE.

Molecular Imaging in Soft-tissue Sarcoma: Evolving Role of FDG PET.

Soft tissue sarcomas are a rare and heterogenous group of tumors that account for 2% of all cancer-related deaths. Molecular imaging with FDG PET can offer valuable metabolic information to help inform clinical management of soft tissue sarcomas that is unique and complementary to conventional diagnostic imaging techniques. FDG PET imaging often correlates with tumor grade, can help guide biopsy, and frequently detects additional sites of disease compared to conventional imaging in patients being considered for definitive or salvage therapy.

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.

Phase II Trial of Sirolimus in Patients With Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT): Long-Term Efficacy and Safety Update.

JCO -Sirolimus is approved in the United States for the treatment of metastatic or locally advanced malignant perivascular epithelioid cell tumor (PEComa) on the basis of the primary analysis results of the phase II Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT) trial (ClinicalTrials.gov identifier: NCT02494570). Results from the primary analysis were previously published; however, the median duration of response (mDOR) had not been reached at that time.

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.

A rare non-gadolinium enhancing sarcoma brain metastasis with microenvironment dominated by tumor-associated macrophages.

Brain metastases occur in 1% of sarcoma cases and are associated with a median overall survival of 6 months. We report a rare case of a brain metastasis with unique radiologic and histopathologic features in a patient with low grade fibromyxoid sarcoma (LGFMS) previously treated with immune checkpoint inhibitor (ICI) therapy. The lone metastasis progressed in the midbrain tegmentum over 15 months as a non-enhancing, T2-hyperintense lesion with peripheral diffusion restriction, mimicking a demyelinating lesion.

Surgery and stereotactic radiosurgery for spinal leiomyosarcoma: a single-institution retrospective series and systematic review.

Objective: Leiomyosarcoma (LMS) is a rare, aggressive soft-tissue sarcoma that seldom spreads to the bone. The spine can be either the site of LMS osseous metastases or the primary tumor site. The optimal treatment option for spinal LMS is still unclear.

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.

MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients.

Objective: To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids.

Methods: A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment.

Management Strategies and Outcomes in Primary Liver Angiosarcoma.

Objectives: Primary hepatic angiosarcoma is a rare tumor of the liver that originates from endothelial and fibroblastic tissue, with poor prognosis and lack of standardized treatment. We retrospectively analyzed the clinical characteristics and treatment outcomes of 23 patients with primary liver angiosarcoma treated at an academic sarcoma center.

Methods: We screened all patients with primary liver angiosarcoma treated at Stanford between 2000 and 2022.

Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis.

Unlabelled: Perivascular epithelioid cell tumors (PEComa) are a large family of mesenchymal neoplasms, with variable clinical course. Evidence regarding treatment of advanced PEComas is scarce, with only one FDA-approved treatment available. The goals of this study were to provide data regarding systemic treatments for advanced PEComas and to identify biomarkers of prognostic relevance.

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.

A Retrospective Multi-Institutional Cohort Analysis of Clinical Characteristics and Outcomes in Dedifferentiated Chondrosarcoma.

Background: Dedifferentiated chondrosarcoma (DDCS) is a rare subset of chondrosarcoma. It is an aggressive neoplasm characterized by a high rate of recurrent and metastatic disease with overall poor outcomes. Systemic therapy is often used to treat DDCS; however, the optimal regimen and timing are not well defined, with current guidelines recommending following osteosarcoma protocols.

Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis.

Purpose: Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STS), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STS.

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.

Long-term Outcomes of Diffuse or Recurrent Tenosynovial Giant Cell Tumor Treated with Postoperative External Beam Radiation Therapy.

Purpose: Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis. Primary treatment involves surgical resection; however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence.

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.