Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV-related tumors remain associated with an improved prognosis among older patients. METHODS: In a retrospective study of OPSCCs diagnosed from 1995 to 2013 at 2 National Comprehensive Cancer Network-designated cancer centers, p16 immunohistochemistry and in situ hybridization (ISH) for HPV-16, high-risk DNA, and/or E6/E7 RNA were performed. The median age at diagnosis was compared by p16 and ISH tumor status. Trends in age were analyzed with nonparametric trends. Survival was analyzed with the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Among 239 patients, 144 (60%) were p16-positive. During 1998-2013, the median age increased among p16-positive patients (Ptrend = .01) but not among p16-negative patients (Ptrend = .71). The median age of p16-positive patients increased from 53 years (interquartile range [IQR] in 1995-2000, 45-65 years) to 58 years (IQR for 2001-2013, 53-64 years). Among patients ≥ 65 years old, the proportion of OPSCCs that were p16-positive increased from 41% during 1995-2000 to 75% during 2007-2013 (Ptrend = .04). Among all age groups, including older patients, a p16-positive tumor status conferred improved overall survival in comparison with a p16-negative status. CONCLUSIONS: The median age at diagnosis for HPV-related OPSCC is increasing as the proportion of OPSCCs caused by HPV rises among older adults. The favorable survival conferred by an HPV-positive tumor status persists in older adults. Cancer 2018;124:2993-9. © 2018 American Cancer Society.

The advantages and drawbacks of routine magnetic resonance imaging for long-term post-treatment locoregional surveillance of oral cavity squamous cell carcinoma.

PURPOSE: Assess the clinical utility and accuracy of routine surveillance head and neck magnetic resonance imaging (HN-MRI) for the detection of locoregional recurrence in patients with a history of oral cavity squamous cell carcinoma (OCSCC) without concurrent suspicious symptoms or signs 6 months or more after treatment. MATERIALS AND METHODS: For OCSCC patients who underwent routine (defined as: without concurrent suspicious symptoms or signs) surveillance HN-MRI at 6 months or more after treatment completion, we retrospectively determined the detection rate of locoregional disease and false positive rate. RESULTS: Out of an original cohort of 533 OCSCC patients, 46 patients, who were disease-free 6 months after treatment, had undergone 108 routine HN-MRIs from 6 to 48 months after surgery without the presence of concurrent suspicious symptoms or signs and had 6 months of subsequent follow up. 1 out of 46 (2.2%) had a true positive regional recurrence. 10 out of 46 (21.7%) patients experienced a false positive locoregional finding. CONCLUSIONS: Routine HN-MRI for locoregional surveillance of OCSCC, when used in patients without concurrent suspicious symptoms or exam findings over 6 months since treatment, may be unnecessary and costly given the very low rate of recurrence and high false positive rate. Our study supports the National Comprehensive Cancer Network guideline of limiting imaging after 6 months of primary treatment completion to patients with suspicious clinical findings. Nonetheless, managing physicians should continue to be empowered to use surveillance imaging based on risk profiles and unique circumstances for each patient.

Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1 inhibitors for the treatment of obesity and diabetes.

A novel series of DGAT-1 inhibitors was discovered from an oxadiazole amide high throughput screening (HTS) hit. Optimisation of potency and ligand lipophilicity efficiency (LLE) resulted in a carboxylic acid containing clinical candidate 53 (AZD3988), which demonstrated excellent DGAT-1 potency (0.6 nM), good pharmacokinetics and pre-clinical in vivo efficacy that could be rationalised through a PK/PD relationship.