Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1–WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1–WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials

Sarcoma European & Latin American Network (SELNET) recommendations on prioritization in sarcoma care during covid‐19 pandemic

Background COVID‐19 outbreak has resulted in collision between SARS‐CoV‐2‐infected patients and cancer patients on different fronts. Serious SARS‐CoV‐2 cases overwhelmed hospital capacity, especially in intensive care units, causing a domino effect, displacing areas from their primary use. Cancer patient has been impacted by deferral, modification or even cessation of therapy. Adaptive measures to minimize hospital exposure, following the precautionary principle have been proposed for cancer care during COVID‐19 era. We present here a consensus on prioritizing recommendations across the continuum of sarcoma patient care. Material and methods A total of 125 recommendations were proposed in soft‐tissue, bone and visceral sarcoma care. Recommendations were assigned as higher‐ or lower‐priority if they cannot or can be postponed at least 2‐3 months, respectively. The consensus level for each recommendation was classified as “strongly recommended” (SR) if more than 90% of experts agreed, “recommended” (R) if 75‐90% of experts agreed and “no consensus” (NC) if fewer than 75% agreed. Sarcoma experts from 11 countries within the SELNET consortium participated, including countries in the Americas and Europe. The ESMO‐Magnitude of clinical benefit scale was applied to systemic‐treatment recommendations to support prioritization. Results There were 80 SR, 35 R and 10 NC among the 125 recommendations issued and completed by 31 multidisciplinary sarcoma experts. The consensus was higher among the 75 higher‐priority recommendations (85%, 12% and 3% for SR, R and NC, respectively) than in the 50 lower‐priority recommendations (32%, 52% and 16% for SR, R and NC, respectively). Conclusion The consensus on 115 of 125 recommendations indicates a high‐level of convergence among experts. The SELNET consensus provides a tool for sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak. The details of different recommendations and the distinction between two priority levels enables a practical approach for both Latin‐American and other health‐care providers, and sarcoma expert centres. Implications for Practice SELNET consensus on sarcoma prioritization care during the COVID‐19 era, issued 125 pragmatical recommendations distributed as higher or lower priority, to protect critical decisions on sarcoma care during COVID‐19 pandemic. A multidisciplinary team from 11 countries, including countries in the Americas and Europe, reached consensus on 115 recommendations. The consensus was lower among lower‐priority recommendations, which shows reticence to postpone actions even in indolent tumors. The ESMO‐magnitude of clinical benefit scale was applied as support for prioritizing systemic treatment. Consensus on 115 of 125 recommendations indicates a high‐level of convergence among experts. The SELNET consensus provides a practice tool for the guidance in the decisions of sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak.Peer reviewe