Early Stage Testicular Seminoma: A Multicenter Review of Treatment Outcomes and Patterns of Recurrence

Purpose/Objective(s): Although overall survival for early stage testicular seminoma is generally excellent, certain pathologic factors can increase recurrence risk for those undergoing observation, while radiation therapy (RT) can be associated with long-term morbidity. We sought to identify disease-related and treatment-related factors that influenced the outcomes, with particular emphasis on recurrence risk, patterns and timing of recurrence, as well as RT-induced malignancy. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

The GUCY2C Tumor Suppressor is the Nexus of a Paracrine Hormone Axis Preventing Radiotherapy-Induced Gastrointestinal (GI) Toxicity

Purpose/Objective: Radiation-induced GI toxicity is the primary dose limitation compromising therapy in cancer patients treated with radiation therapy. GUCY2C is the intestinal receptor for diarrheagenic bacterial enterotoxins and the endogenous paracrine hormones guanylin and uroguanylin. Following genomic insult, cyclic (c)GMP produced by ligand activation of GUCY2C enhances DNA damage sensing and repair in intestinal cells. Here, we show that the GUCY2C-cGMP axis mediates p53-dependent radioprotection of intestinal epithelial cells. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Chart Rounds in the Digital Age: A Survey of North American Institutions

Purpose/Objective(s): In light of public concerns regarding the quality of radiation treatment delivery, we surveyed the utilization of “chart rounds” or peer-review quality assurance meetings, within North American academic institutions. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Results of a Phase I Trial of Induction Cisplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib with Radiotherapy for Advanced Head and Neck Cancer

Background: A phase I trial of induction cisplatin, docetaxel, 5-FU and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced head and neck cancer (HNC) was conducted. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

GUCY2C Signaling Opposes the Acute Radiation-Induced GI Syndrome.

High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. Eliminating GUCY2C signaling exacerbated RIGS, amplifying radiation-induced mortality, weight loss, mucosal bleeding, debilitation, and intestinal dysfunction. Durable expression of GUCY2C, guanylin, and uroguanylin mRNA and protein by intestinal epithelial cells was preserved following lethal irradiation inducing RIGS. Oral delivery of the heat-stable enterotoxin (ST), an exogenous GUCY2C ligand, opposed RIGS, a process requiring p53 activation mediated by dissociation from MDM2. In turn, p53 activation prevented cell death by selectively limiting mitotic catastrophe, but not apoptosis. These studies reveal a role for the GUCY2C paracrine hormone axis as a novel compensatory mechanism opposing RIGS, and they highlight the potential of oral GUCY2C agonists (Linzess; Trulance) to prevent and treat RIGS in cancer therapy and nuclear disasters. Cancer Res; 77(18); 5095-106. ©2017 AACR