Pelvic irradiation induces behavioural and neuronal damage through gut dysbiosis in a rat model.

Radiation exposure can cause gut dysbiosis and there is a positive correlation between gut microbial imbalance and radiation-induced side effects in cancer patients. However, the influence of radiation on the gut-brain axis (GBA) and its neurological consequences are not well understood. Therefore, this study aimed to investigate the impact of pelvic irradiation on gut microbiota and the brain. Sprague Dawley rats were irradiated with a single dose of 6 Gy, and faecal samples were collected at different time points (7 and 12-days post-irradiation) for microbial analysis. Behavioural, histological, and gene expression analysis were performed to assess the effect of microbial dysbiosis on the brain. The findings indicated alterations in microbial diversity, disrupted intestinal morphology and integrity, neuronal death-related brain changes, neuroinflammation and reduced locomotor activity. Hippocampal gene expression analysis also showed a reduced expression of neural plasticity-related genes. Overall, this study demonstrated that pelvic irradiation affects gut microbiota, intestinal morphology, integrity, brain neuronal maturation, neural plasticity gene expression, and behaviour.

Dosimetric analysis and clinical outcomes of brachial plexus as an organ-at-risk in head-and-neck cancer patients treated with intensity-modulated radiotherapy.

OBJECTIVES: To document the dose received by brachial plexus (BP) in patients treated with intensity-modulated radiotherapy (IMRT) for head-and-neck squamous cell carcinoma (HNSCC) and report the incidence of brachial plexopathy. METHODS: Newly diagnosed patients of HNSCC treated with radical or adjuvant IMRT were included in this retrospective study. No dosimetric constraints were applied for BP maximum dose equivalent dose (EQD2 α/ß = 3). Patients with minimum 6-month follow-up were included and patients with suspicion of plexopathy were evaluated further. RESULTS: Sixty-seven patients were eligible and 127 BP were analyzed. The mean BP maximum dose (BPmax) was 62.4 Gy (+6.9), while mean BP volume was 28.1 cc (+4.1). Proportion of patients receiving BPmax >66 and >70 Gy were 34.7% and 14.2%. The mean BPmax for T4 tumors was significantly higher than T1 tumors (65 vs. 57.5 Gy, P = 0.005) but when adjusted for N-category, T-category was not independently significant in accounting for BPmax >66 or >70 Gy. Mean BPmax for N0 versus N2+ was 59.8 versus 65.6 Gy (P = 0.0001) and N1 versus N2+ was 61.6 versus 65.6 Gy (P = 0.018). After adjusting for T-category, patients with N2+ had a mean 4.2 Gy higher BPmax than N0-N1 (P = 0.0001). Stage III-IV patients had a mean six Gy higher BPmax doses than Stage I-II disease (P = 0.0001). With a median follow-up of 28 months (interquartile range 16-42), no patient had brachial plexopathy. CONCLUSION: Clinically significant plexopathy was not seen in spite of majority having over 2-years follow-up and a third of patients having dose above the recommended tolerance. Only nodal category independently influenced dose to the brachial plexii.