Proton therapy re-irradiation outcomes and genomic landscape of patients with recurrent head and neck cancer.

INTRODUCTION: Re-irradiation (re-RT) for recurrent head and neck cancer (rHNC) is challenging. We describe clinical outcomes and toxicity of proton therapy (PT) for recurrent HNC, and report genomic alterations associated with patterns of failure. MATERIALS & METHODS: We performed a retrospective analysis of rHNC patients treated with PT. Outcomes were estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analyses (MVA) were performed to assess multiple patient factors. Next-generation sequencing and genomic analyses were performed on available samples. RESULTS: Eighty-nine patients treated with PBS-PT for rHNC with a median follow-up of 12 mo (0-71 mo) were included. The 1- and 2-y local control (LC) rates were 80.8 % (95 % CI: 70.8-90.8) and 66.2 % (95 % CI: 50.7-81.7), and 1- and 2-y distant metastasis-free survival (DMFS) were 41.0 % (95 % CI: 30.0-52.0) and 26.3 % (95 % CI: 15.7-36.9). The median overall survival (OS) was 13 mo (95 % CI: 9.3-16.7). On UVA and MVA, smaller gross tumor volume (GTV) was associated with improved OS (HR 1.002, P = 0.004), DMFS (HR 1.002, P = 0.004), and PFS (HR 1.002, P = 0.014). There were 35 late Gr3 + toxicity events (30.3 %). Patients with higher candidate gene-specific mutation burden (genes with [OR] > 2, P < 0.05) had inferior PFS. TP53, NOTCH4, and ARID1B mutations were associated with inferior DMFS (OR > 2, P < 0.05). CONCLUSIONS: PBS-PT is effective at achieving LC for rHNC with favorable toxicity. Distant metastases are common, and associated with TP53, NOTCH4, and ARID1B mutations. Inclusion of genomic alterations in the clinical decision process may be warranted.

A Longitudinal Metagenomic Comparative Analysis of Oral Microbiome Shifts in Patients Receiving Proton Radiation versus Photon Radiation for Head and Neck Cancer.

Introduction: Due to the radiation-sparing effects on salivary gland acini, changes in the composition of the oral microbiome may be a driver for improved outcomes in patients receiving proton radiation, with potentially worse outcomes in patients exposed to photon radiation therapy. To date, a head-to-head comparison of oral microbiome changes at a metagenomic level with longitudinal sampling has yet to be performed in these patient cohorts. Methods and Materials: To comparatively analyze oral microbiome shifts during head and neck radiation therapy, a prospective pilot cohort study was performed at the Maryland Proton Treatment Center and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. A longitudinal metagenomic comparative analysis of oral microbiome shifts was performed at three time points (pre-radiation, during radiation, and immediately post-radiation). Head and neck cancer patients receiving proton radiation (n = 4) were compared to photon radiation (n = 4). Additional control groups included healthy age- and sex-matched controls (n = 5), head and neck cancer patients who never received radiation therapy (n = 8), and patients with oral inflammatory disease (n = 3). Results: Photon therapy patients presented with lower microbial alpha diversity at all timepoints, and there was a trend towards reduced species richness as compared with proton therapy. Healthy controls and proton patients exhibited overall higher and similar diversity. A more dysbiotic state was observed in patients receiving photon therapy as compared to proton therapy, in which oral microbial homeostasis was maintained. Mucositis was observed in 3/4 photon patients and was not observed in any proton patients during radiation therapy. The bacterial de novo pyrimidine biosynthesis pathway and the nitrate reduction V pathway were comparatively higher following photon exposure. These functional changes in bacterial metabolism may suggest that photon exposure produces a more permissive environment for the proliferation of pathogenic bacteria. Conclusion: Oral microbiome dysbiosis in patients receiving photon radiation may be associated with increased mucositis occurrence. Proton radiation therapy for head and neck cancer demonstrates a safer side effect profile in terms of oral complications, oral microbiome dysbiosis, and functional metabolic status.

Physical activity in the prevention of benign paroxysmal positional vertigo: probable association.

Introduction Physical inactivity is an important risk factor for many age-related diseases and symptoms such as dizziness and vertigo. Objective The aim of the study was to investigate the possible association between benign paroxysmal positional vertigo (BPPV) and regular physical activity in elderly subjects. Methods This cross-sectional study included 491 elderly individuals who lived independently. Physical exercise was assessed through a questionnaire and BPPV by history and the Dix-Hallpike maneuver. Results The present study indicates no significant association between BPPV with lack of physical activity in men and in the total population. We have confirmed associations between BPPV with lack of physical activity in women (p = 0.01). Women with a sedentary lifestyle who do not practice physical activity are 2.62 more likely to have BPPV than those with regular physical activity. Conclusion These results highlight the importance of identifying risk factors for BPPV that can be modified through specific interventions. Regular physical activity is a lifestyle with potential to decrease the risk of vertigo in women.

Physical Activity in the Prevention of Benign Paroxysmal Positional Vertigo: Probable Association

Introduction Physical inactivity is an important risk factor for many age-related diseases and symptoms such as dizziness and vertigo. Objective The aim of the study was to investigate the possible association between benign paroxysmal positional vertigo (BPPV) and regular physical activity in elderly subjects. Methods This cross-sectional study included 491 elderly individuals who lived independently. Physical exercise was assessed through a questionnaire and BPPV by history and the Dix-Hallpike maneuver. Results The present study indicates no significant association between BPPV with lack of physical activity in men and in the total population. We have confirmed associations between BPPV with lack of physical activity in women (p = 0.01). Women with a sedentary lifestyle who do not practice physical activity are 2.62 more likely to have BPPV than those with regular physical activity. Conclusion These results highlight the importance of identifying risk factors for BPPV that can be modified through specific interventions. Regular physical activity is a lifestyle with potential to decrease the risk of vertigo in women...