Case Report Traumatic Page Kidney Induced Hypertension in Critical Care: Immediately Resolved or Long-Term Resistant Problem

Page kidney is a well-known phenomenon causing hypertension, due to compression of renal parenchyma by a subcapsular hematoma, of either traumatic or non-traumatic origin. The main therapeutic approach is based on surgical approach (nephrectomy or hematoma evacuation) and antihypertensive treatment. In this paper we present a post-traumatic case of Page Kidney in a Critical Care unit. We discuss different therapeutical opportunities to extremely elevated systemic blood pressure resistant to traditional drug therapy

655MO Quality of life in patients with p16+ oropharyngeal cancer receiving accelerated radiotherapy (RT) with either cisplatin or cetuximab in NRG/RTOG 1016

Background: This phase 3 randomized non-inferiority de-escalation trial compared cetuximab (cetux) vs cisplatin (cis), concurrent with accelerated RT 70 Gy/6 weeks, in p16+ oropharyngeal cancer (OPC). Quality of life (QOL) was an important secondary endpoint. Methods: EORTC QLQ-C30/HN35 was completed at baseline, end of treatment, 3, 6, and 12 months post. The substudy aimed for 400 eligible patients. We report completion rates and compare by arm for change from baseline in each domain (0.05 two-sided alpha and MID of 10 points) using linear mixed models. Results: Consent was 91% (381/419 offered substudy); 6 protocol deviations excluded (n=375). No significant differences in patient/tumor characteristics were found by participation status. Completion rates (%) at the 5 times did not differ by arm (cis/cetux): 92/94, 74/77, 76/81, 76/81, and 73/74. The swallowing domain of HN35 (previously reported) did not differ significantly by arm. No significant difference was seen by arm for the 6-mo change from baseline on any domain. At end of RT (only), dry mouth was significantly worse for RT+cetux. At end of treatment, all domains showed statistically and clinically significant mean worsening across both arms except Emotional Functioning, Dyspnea, Diarrhea, and Teeth. Most domains returned within 10 points of baseline by 6 mo, with the following maintaining significant impairment: Senses (taste/smell), Social Eating, Opening Mouth, Dry Mouth, Sticky Saliva. At 12 mo post-treatment, worsening from baseline persisted for Senses, Dry Mouth, Sticky Saliva, and Weight Gain. Pain Killer use improved significantly from baseline to 3, 6, and 12 mo. Conclusions: Although replacing RT+cis with RT+cetux did not benefit QOL, this study has confirmed the responsiveness of EORTC QLQ-C30/HN35 to the effects of concurrent systemic/RT for OPC. Dry Mouth, Sticky Saliva, and Senses showed large, significant, and persistent impairments, and remain worthwhile targets for future de-escalation efforts. Domains related to eating (Swallowing, Appetite, Nutritional Supplements, Social Eating, Weight Loss) did not show sustained significant impairment on this instrument in this study. Clinical trial identification: NCT01302834

Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test

Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan–Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for Class 1 and ≥50% for Class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies

Dose Escalation Methods in Phase I Cancer Clinical Trials

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

The diagnosis of and emergent care for the patient with subarachnoid haemorrhage in resource-limited settings

Non-traumatic subarachnoid haemorrhage (SAH) is a neurosurgical emergency that may present similarly to a benign headache, yet poses high morbidity and mortality in what often times are young and otherwise healthy patients. While the diagnosis may be made via several different modalities, not all of these are available to every emergency physician. A high suspicion for SAH along with a good history and physical examination may best serve patients in these resource-limited settings. Adequate resuscitative and supportive care, combined with prompt transfer to a facility with neurosurgical capabilities is integral to optimizing patient outcomes