Diagnostic performance of ARFI ultrasound elastography in spleen stiffness measurement to predict esophageal varices

Background: Presence esophageal varices are an independent predictor of mortality in patients with cirrhosis. Non-invasive assessment of cirrhotic patients to predict esophageal varices have been increasingly used instead of endoscopy. The aim of this study is to assess the diagnostic performance of ARFI elastography in measuring spleen stiffness to predict esophageal varices with endoscopy as the gold standard and compare these results with platelet count and spleen size. Methods: The patients included in the study underwent ARFI elastography and underwent endoscopy to determine esophageal varices stage, platelet count and spleen size values were calculated. The diagnostic performance of spleen stiffness by ARFI elastography, platelet count and spleen size was evaluated using receiver operating characteristic (ROC) curve analysis. Correlations of ARFI Elastography, platelet count and spleen size with endoscopy findings (as the reference standard) were determined using Spearman’s correlation coefficient. Results: Study included 102 patients of the 58 (56.86%) were grade 0 with mean ARFI elastography value of 20.80±0.92 kPa, 25(26.32%) were grade1 with mean ARFI elastography value of 24.89±2.02kPa, 12(11.76%) were grade 2 with mean ARFI elastography value of 33.50±1.36 kPa, and 07(6.86%) were grade 3 with mean ARFI elastography value of36.37±0.75 kPa. There was significant positive correlation between different stages of esophageal varices by endoscopy and spleen stiffness detected by ARFI elastography (r = 0.995, p < 0.001).ARFI elastography spleen stiffness exhibited higher diagnostic accuracy than the platelet and spleen size for the diagnosis of those without varices AUC 0.991 (0.949 to 1.000), 0.973(0.920 to 0.995), 0.968(0.913 to 0.993) and those with high grade varices AUC 1.000(0.964 to 1.000), 0.995(0.955 to 1.000), 0.901(0.826 to 0.952) respectively. Conclusions: ARFI elastography spleen stiffness measurement is a novel non-invasive method to use in the clinical practice, for the screening esophageal varices in cirrhotic patients, and thus reducing the number of endoscopic examinations burden with high diagnostic performance

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. Overall survival (OS), time to next treatment, time to distant metastasis, and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: At start of first-line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first-line therapy for SS was 24.7 months (95% CI, 20.9-29.4) and 7.5 months, respectively (95% CI, 6.4-8.4). Median OS and median PFS from start of first-line therapy for MRCL was 29.9 months (95% CI, 27-44.6) and 8.9 months (95% CI 4.5-12.0). CONCLUSIONS: To the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real-world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature

Multi-modal efficacy of a chimeric vesiculovirus expressing the Morreton glycoprotein in sarcoma

Vesiculoviruses are attractive oncolytic virus platforms due to their rapid replication, appreciable transgene capacity, broad tropism, limited preexisting immunity, and tumor selectivity through type I interferon response defects in malignant cells. We developed a synthetic chimeric virus (VMG) expressing the glycoprotein (G) from Morreton virus (MorV) and utilizing the remaining structural genes from vesicular stomatitis virus (VSV). VMG exhibited in vitro efficacy by inducing oncolysis in a broad range of sarcoma subtypes across multiple species. Notably, all cell lines tested showed the ability of VMG to yield productive infection with rapid replication kinetics and induction of apoptosis. Furthermore, pilot safety evaluations of VMG in immunocompetent, non-tumor-bearing mice showed an absence of toxicity with intranasal doses as high as 1e10 50% tissue culture infectious dose (TCID50)/kg. Locoregional administration of VMG in vivo resulted in tumor reduction in an immunodeficient Ewing sarcoma xenograft at doses as low as 2e5 TCID50. In a murine syngeneic fibrosarcoma model, while no tumor inhibition was achieved with VMG, there was a robust induction of CD8+ T cells within the tumor. The studies described herein establish the promising potential for VMG to be used as a novel oncolytic virotherapy platform with anticancer effects in sarcoma

A Retrospective Analysis of the Efficacy of Immunotherapy in Metastatic Soft-Tissue Sarcomas

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled. Logistic and Cox regression models were applied to determine the effect of patient characteristics, prior treatment, and baseline factors on achieving the best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by the treating physician. Eighty-eight patients with two median prior therapies received checkpoint inhibitors. Treatments included pembrolizumab in 47, nivolumab in 6, ipilimumab in 1, combination ipilimumab/nivolumab in 27, and other combination immunotherapies in 7 patients. Immunotherapy was discontinued in 54 patients&mdash;72.2% for progression, 16.7% for toxicity, and 11.1% for other reasons. Median progression-free survival (PFS) was 4.1 months and median overall survival was 19.1 months. One patient with undifferentiated pleomorphic sarcoma (UPS) achieved a CR, while 20 patients had a PR, including 7 UPS, 9 leiomyosarcoma (LMS), and 1 each with alveolar soft part sarcoma, fibroblastic sarcoma, sclerosing epithelioid fibrosarcoma, and myxofibrosarcoma. Forty-five percent (9 of 20) of LMS patients achieved a PR. Twenty-eight patients had SD. Our results confirm the activity and safety of anti-PD-1 therapy in metastatic STS. A notable response rate was observed in UPS and LMS subtypes. This study expands the knowledge base beyond what is currently available from clinical trials involving checkpoint inhibitors in metastatic STS

The Midwest Sarcoma Trials Partnership: Bridging Academic and Community Networks in a Collaborative Approach to Sarcoma

The treatment of sarcoma necessitates a collaborative approach, given its rarity and complex management. At a single institution, multidisciplinary teams of specialists determine and execute treatment plans involving surgical, radiation, and medical management. Treatment guidelines for systemic therapies in advanced or nonresectable soft tissue sarcoma have advanced in recent years as new immunotherapies and targeted therapies become available. Collaboration between institutions is necessary to facilitate accrual to clinical trials. Here, we describe the success of the Midwest Sarcoma Trials Partnership (MWSTP) in creating a network encompassing large academic centers and local community sites. We propose a new model utilizing online platforms to expand the reach of clinical expertise for the treatment of advanced soft tissue sarcoma