Hypofractionated accelerated radiation dose-painting (HARD) improves outcomes in unresected soft-tissue sarcoma.

Soft tissue sarcomas (STS) are radioresistant with a low α/β, which may have a biologic benefit with hypofractionation. For unresectable STS, the dose escalation required to achieve durable control is often limited by long-term toxicity risk. We sought to compare an isotoxic approach utilizing hypofractionated accelerated radiation dose-painting (HARD) versus standard fractionated radiation therapy (SFT) in patients with unresected STS.

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.

Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial.

INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KIT mutations.

Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study.

Purpose: In the INTRIGUE trial, ripretinib showed no significant difference versus sunitinib in progression-free survival for patients with advanced gastrointestinal stromal tumour (GIST) previously treated with imatinib. We compared the impact of these treatments on health-related quality of life (HRQoL).

Patients And Methods: Patients were randomised 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off).

Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype?

Background: Immune checkpoint inhibitors (ICIs) have shown modest antitumor activity in unselected advanced sarcomas. Histology driven approach to patient selection is the current standard for off-label anti-programmed cell death 1 (PD1) immunotherapy use.

Methods: We retrospectively reviewed the clinical characteristics and outcomes of patients with advanced sarcoma who were treated with off label anti-PD1 immunotherapy at our center.

A Case of Hepatic Malignant Solitary Fibrous Tumor: A Case Report and Review of the Literature.

A 73-year-old man with a history of atrial myxoma and basal cell carcinoma presented with unexplained fever. Contrast-enhanced CT abdomen showed a large left hepatic lobe mass with early enhancement and delayed venous washout, concerning for hepatocellular carcinoma. Fine needle aspiration showed numerous spindle cells with malignant nuclear features, suggestive of malignant spindle cell neoplasm.

Autologous T cell therapy for MAGE-A4 solid cancers in HLA-A*02 patients: a phase 1 trial.

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ).

Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma.

Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343043) has been previously reported, however, biomarkers predictive of response and resistance remain to be better defined. This post-hoc analysis identifies associations of response to lete-cel with lymphodepleting chemotherapy regimen (LDR), product attributes, cell expansion, cytokines, and tumor gene expression.

A Phase 1b Study Evaluating the Safety, Tolerability, and Immunogenicity of CMB305, a Lentiviral-Based Prime-Boost Vaccine Regimen, in Patients with Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1.

Preclinical data suggest that a "prime-boost" vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broad anti-NY-ESO-1 immune response. It is composed of LV305, which is an NY-ESO-1 expressing lentiviral vector, and G305, a recombinant adjuvanted NY-ESO-1 protein.

Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors.

Background: Pexidartinib is approved in the U.S. for tenosynovial giant cell tumors (TGCTs).

Results of treating primary pulmonary sarcomas and pulmonary carcinosarcomas.

Objective: Primary pulmonary sarcomas (PPS) and pulmonary carcinosarcomas (PCS) are rare aggressive lung malignancies. We reviewed our 21-year experience with the surgical and nonsurgical treatment of both tumors, comparing their clinical, histopathologic, and treatment results.

Methods: All patients with PPS or PCS who underwent surgical and nonsurgical treatment between 1998 and 2019 at our cancer center were retrospectively reviewed.

Adrenal crisis and death following transarterial chemoembolization of sarcoma liver metastases.

Adrenal crisis is a life-threatening complication of adrenal insufficiency which is triggered by physiological stressors such as injury, infection or a surgical procedure when the plasma concentration of adrenal corticosteroids is insufficient for physiological requirements. It is associated with a high mortality rate unless early diagnosis and treatment is initiated. We report a case of a patient with metastatic sarcoma and adrenal insufficiency who underwent right hepatic artery chemoembolization to control his intrahepatic metastases.

Liver-directed treatments of liver-dominant metastatic leiomyosarcoma.

Purpose: The purpose of this study was to determine the safety and efficacy of liver-directed therapies in patients with unresectable metastatic leiomyosarcoma to the liver. Liver-directed therapies included in this study were transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE), yttrium-90 (Y90) radioembolization, and percutaneous microwave ablation.

Methods: This is a single institution retrospective study of unresectable metastatic leiomyosarcoma to the liver treated with DEB-TACE, radioembolization, or microwave ablation.

Chemotherapy improves distant control in localized high-grade soft tissue sarcoma of the extremity/trunk.

Background: Soft tissue sarcomas (STS) are rare and heterogeneous tumors making chemotherapy use controversial. Our goal was to identify a subset of patients with primary STS that benefit with the addition of chemotherapy.

Methods: A retrospective chart review included intermediate to high-grade localized primary STS of the extremity/trunk, and tumor size > 5 cm.

Clinical outcomes of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma treated at major cancer centers in the United States.

Background: Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials.

Methods: In this multi-center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first-line systemic anticancer therapy and had records of tumor imaging were included.

Case of pembrolizumab-induced myocarditis presenting as torsades de pointes with safe re-challenge.

Introduction: Pembrolizumab is an immune checkpoint inhibitor targeting the programmed death receptor with clinical effect on multiple malignancies including sarcoma. Associated cardio-toxicities include myocarditis, cardiomyopathy, heart failure, and arrhythmias. Although in most cases of immune checkpoint inhibitor cardiotoxicity the offending agent is discontinued, we report a case of successful and safe re-challenge with a checkpoint inhibitor in a patient with mild myocarditis.

Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma.

Background: Gene-modified autologous T cells expressing NY-ESO-1, an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1-specific HLA-A*02-restricted peptide SLLMWITQC (NY-ESO-1 SPEAR T-cells; GSK 794), have demonstrated clinical activity in patients with advanced synovial sarcoma (SS). The factors contributing to gene-modified T-cell expansion and the changes within the tumor microenvironment (TME) following T-cell infusion remain unclear. These studies address the immunological mechanisms of response and resistance in patients with SS treated with NY-ESO-1 SPEAR T-cells.

Clinical, pathological, and genomic features of EWSR1-PATZ1 fusion sarcoma.

Molecular diagnostics of sarcoma subtypes commonly involve the identification of characteristic oncogenic fusions. EWSR1-PATZ1 is a rare fusion partnering in sarcoma, with few cases reported in the literature. In the current study, a series of 11 cases of EWSR1-PATZ1 fusion positive malignancies are described.

Clinical Utility of Genomic Profiling in the Treatment of Advanced Sarcomas: A Single-Center Experience.

Purpose: Sarcomas are a diverse group of malignant tumors that arise from soft tissues or bone. For most advanced cases, there is a substantial need for improved therapeutic options and, therefore, a desire to more precisely tailor therapy in individual cases. In this study, we review our institutional experience with next-generation sequencing (NGS)-based molecular profiling for non-GI stromal tumors sarcomas, with a focus on the clinical utility of the results.

Practical Issues for Retroperitoneal Sarcoma.

Background: Retroperitoneal sarcoma is rare. Using initial specimens on biopsy, a definitive diagnosis of histological subtypes is ideal but not always achievable.

Methods: A retrospective institutional review was performed for all cases of adult retroperitoneal sarcoma from 1996 to 2015.

Outcomes and clinical predictors of improved survival in a patients undergoing pulmonary metastasectomy for sarcoma.

Background: Pulmonary metastasectomy (PM) for metastatic sarcoma can result in long-term survival. The purpose of this study was to describe factors associated with survival in a series of patients undergoing PM for metastatic sarcoma.

Methods: We reviewed all patients undergoing PM for metastatic sarcoma over a 12-year period (2000-2012).

Metabolic syndrome and colorectal cancer: is hyperinsulinemia/insulin receptor-mediated angiogenesis a critical process?

Objective: Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking.

Materials And Methods: Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE).

Outcomes following resection of pancreatic adenocarcinoma: 20-year experience at a single institution.

Background: Pancreatectomy for ductal adenocarcinoma has been performed with increasing frequency since the late 1980s as postoperative mortality decreased and long-term survival became more common. However, the belief persists among some clinicians that pancreatectomy offers little survival benefit. This report reviews our institutional experience with pancreatectomy for pancreatic adenocarcinoma and provides a critical overview of the controversies regarding the benefits of surgical intervention for patients who are candidates for curative resection.

Measuring quality of care in the treatment of colorectal cancer: the moffitt quality practice initiative.

Purpose: The Moffitt Quality Practice Initiative (MQPI) is a practice-based system of quality self-assessment, the ultimate goal of which is to improve the quality of cancer care at a statewide level. The initial phase of this project focused on developing procedures, determining feasibility, and evaluating utility for assessing quality of care for colorectal cancer within an existing affiliate network.

Patients And Methods: Representatives from four oncology groups selected quality measures consistent with evidence-, consensus-, and safety-based guidelines that could be abstracted from medical records.