Intensity modulated proton therapy (IMPT) - The future of IMRT for head and neck cancer.

Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as "pencil beam proton therapy," is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care.

Rapidly progressive neurologic decline and morbilliform rash presenting in a patient with lymphoma.

A 67-year-old male with past medical history of mantle cell lymphoma and atrial fibrillation presented with a truncal rash, bilateral lower extremity weakness, and confusion. Within three days of presentation, his condition rapidly deteriorated with the onset of diffuse flaccid paralysis, aphasia, and severe alteration in mental status. Initial results from serum studies, lumbar puncture, magnetic resonance imaging, and electroencephalogram were not diagnostic.

Precocious subcutaneous abdominal stem cell development to adipocytes in normal-weight women with polycystic ovary syndrome.

Objective: To examine whether abnormal subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes in polycystic ovary syndrome (PCOS) correlates with hyperandrogenism.

Design: Prospective cohort study.

Setting: Academic medical center.

Dosimetric advantages of stereotactic radiosurgery as a boost to adjuvant conventional radiotherapy in the setting of adenoid cystic carcinoma of the parotid with skull base invasion.

This study highlights gamma knife stereotactic radiosurgery (GK-SRS) as boost therapy in a patient with adenoid cystic carcinoma of the parotid involving the skull base and invasion of the facial nerve. Using GK-SRS, dose to the brainstem and temporal lobe were reduced when compared to less conformal radiotherapy techniques.

Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial.

Background: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab-an antibody against the epidermal growth factor receptor-can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity.

Prognostic factors and survival in adenoid cystic carcinoma of the sinonasal cavity.

Background: Optimal treatment and prognostic factors affecting long-term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined.

Methods: We conducted a retrospective review of patients treated with curative intent from 1980-2015 at MD Anderson Cancer Center.

Results: One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone.

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.

Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction.

The Phosphate Binder Ferric Citrate Alters the Gut Microbiome in Rats with Chronic Kidney Disease.

In chronic kidney disease (CKD), the gut microbiome is altered and bacterial-derived uremic toxins promote systemic inflammation and cardiovascular disease. Ferric citrate complex is a dietary phosphate binder prescribed for patients with end-stage kidney disease to treat hyperphosphatemia and secondary hyperparathyroidism. Iron is an essential nutrient in both microbes and mammals.

Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy.

Through traditional medicine, there were diseases and disorders that previously remained untreated or were simply thought to be incurable. Since the discovery of mesenchymal stem cells (MSCs), there has been a flurry of research to develop MSC-based therapy for diseases and disorders. It is now well-known that MSCs do not typically engraft after transplantation and exhibit their therapeutic effect via a paracrine mechanism.

Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS.

Proteins in the RAS family are important regulators of cellular signaling and, when mutated, can drive cancer pathogenesis. Despite considerable effort over the last 30 years, RAS proteins have proven to be recalcitrant therapeutic targets. One approach for modulating RAS signaling is to target proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1).

Getting Our Fingers on the Pulse of Slow-Growing Bacteria in Hard-To-Reach Places.

Chronic infections with slow-growing pathogens have plagued humans throughout history. However, assessing the identities and growth rates of bacteria in an infection has remained an elusive goal. Neubauer et al.

Predicting treatment Response based on Dual assessment of magnetic resonance Imaging kinetics and Circulating Tumor cells in patients with Head and Neck cancer (PREDICT-HN): matching 'liquid biopsy' and quantitative tumor modeling.

Background: Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity.

A prospective in silico analysis of interdisciplinary and interobserver spatial variability in post-operative target delineation of high-risk oral cavity cancers: Does physician specialty matter?

Background: The aim of this study was to determine the interdisciplinary agreement in identifying the post-operative tumor bed.

Methods: Three radiation oncologists (ROs), four surgeons, and three radiologists segmented post-operative tumor and nodal beds for three patients with oral cavity cancer. Specialty cohort composite contours were created by STAPLE algorithm implementation results for interspecialty comparison.

Prospective study of the feasibility and dosimetric advantages of MRI-guided dose adaptation for human papillomavirus positive oropharyngeal cancer patients compared with standard IMRT.

Purpose: We aim to determine the feasibility and dosimetric benefits of a novel MRI-guided IMRT dose-adaption strategy for human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC).

Materials/methods: Patients with locally advanced HPV+ OPC underwent pre-treatment and in-treatment MRIs every two weeks using RT immobilization setup. For each patient, two IMRT plans were created (i.

Effect of the Synthetic Bile Salt Analog CamSA on the Hamster Model of Clostridium difficile Infection.

infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and the high incidence of recurrence. We previously reported protection of mice from CDI using the antigerminant bile salt analog CamSA. Here we describe the effects of CamSA in the hamster model of CDI.

Significance of Negative Posttreatment 18-FDG PET/CT Imaging in Patients With p16/HPV-Positive Oropharyngeal Cancer.

Purpose: Patients with p16/human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma have a favorable outcome after treatment. In this group of patients who could have a long life expectancy, the optimal surveillance strategy and modality is not well established. We aim to determine the ability of a negative postradiation positron emission tomography (PET)/computed tomography scan to predict the risk of subsequent relapse in these patients.

Inadequate Hepatocellular Carcinoma Screening in Patients With Nonalcoholic Steatohepatitis Cirrhosis.

Background: Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease which can progress to cirrhosis and hepatocellular carcinoma (HCC). American Association for the Study of Liver Diseases (AASLD) guidelines recommend abdominal ultrasound, with or without serum alpha-fetoprotein, every 6 months for HCC surveillance in cirrhotic patients.

Goals: Describe HCC surveillance rates in NASH cirrhosis compared with hepatitis C (HCV) cirrhosis and the impact of surveillance on tumor size, treatment, and mortality.

Hyperlipidemia and Nonalcoholic Steatohepatitis Predispose to Hepatocellular Carcinoma Development Without Cirrhosis.

Background: Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease.

Discovery of Potent 2-Aryl-6,7-dihydro-5 H-pyrrolo[1,2- a]imidazoles as WDR5-WIN-Site Inhibitors Using Fragment-Based Methods and Structure-Based Design.

WDR5 is a chromatin-regulatory scaffold protein overexpressed in various cancers and a potential epigenetic drug target for the treatment of mixed-lineage leukemia. Here, we describe the discovery of potent and selective WDR5-WIN-site inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified several chemically distinct hit series that bind to the WIN site within WDR5.

Managing Incidental Pancreatic Cysts.

Purpose Of Review: The goal of this review is to critically analyze the current literature regarding the management of incidental pancreatic cysts. Given their increased rates of detection due to the frequent use of cross-sectional imaging, correctly identifying the subset of high risk lesions that are appropriate for surgical resection is critical. However, the existing consensus and societal guidelines discussed in this review lack high quality data to create evidence-based recommendations, making achieving this important aim challenging.

Nasopharyngeal carcinoma outcome with induction chemotherapy followed by concurrent chemoradiotherapy.

Treatment of Nasopharyngeal Carcinoma (NPC) has been based on the Intergroup 0999 trial with chemoradiation (CRT) and consolidation chemotherapy (CT). While effective, toxicities are significant. As a result, many oncologists use induction chemotherapy (IC) followed by CRT, citing better tolerance with anecdotally no worse outcome.

Barriers to Follow-up Colonoscopies for Patients With Positive Results From Fecal Immunochemical Tests During Colorectal Cancer Screening.

Background & Aims: Colorectal cancer is common yet largely preventable. The fecal immunochemical test (FIT) is a highly recommended screening method, but patients with positive results must receive a follow-up colonoscopy to determine if they have precancerous or cancerous lesions. We characterized colonoscopic follow-up evaluations and reasons for lack of follow-up in a Veterans Affairs (VA) cohort.

Biopharmaceutical Characterization and Oral Efficacy of a New Rapid Acting Antidepressant Ro 25-6981.

Ro 25-6981 is a highly potent and selective blocker of N-methyl-d-aspartate receptors that has been shown to possess both rapid and sustained antidepressant activity. In the present study, we report the biopharmaceutical characterization of Ro 25-6981 by evaluating gastrointestinal stability, transepithelial permeability, stability in human liver microsomes, and in silico metabolic prediction. Moreover, in vivo efficacy of Ro 25-6981 after oral administration was evaluated in animal models of depression.