Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via ...mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy.
•Errors in manual radiotherapy treatment procedures and their evolution with time.•The use of more advanced radiotherapy equipment should improve safety and quality.•Long waiting period and ...incomplete setup instructions affect radiotherapy quality.•Learning from past errors should raise awareness in staff leading to safer treatments.
In Uganda, two-dimensional (2D) radiotherapy treatments have been in use since the establishment of radiotherapy in 1995. Preliminary investigations of treatment records in November 2019 showed evidence of gaps requiring urgent attention. The purpose of this study was to improve the safety of the treatments.
Records of 1164 patients treated in 1387 courses (1412 sites) on Cobalt-60 units were reviewed todetermine the frequency and dosimetric implications of events that occurred at different stepsof the radiotherapy process. The results were presented and discussed with the differentprofessionals for learning purposes.
Most common dosimetric eventswere omission of block tray, bolus and couch transmission factors in time calculations, incorrect field sizes and depths, wrong beam weighting, independent calculations and prescription doses contributing 28.6 %, 10.1 %, 6.0 %,11.9 %, 10.1 %, 5.4 %, 4.8 % and 8.9 % to the 168 observed errors. Comparison of the calculated treatment doses with the prescribed doses showed that 88 % of the 1412 sites were treated with radiation doses within an accuracy of ± 5 %. However, an analysis of the evolution along the years demonstrated an improvement from 82.8 % in 2018 to 86.1 % in 2019, and 93.2 % in 2020. Most common procedural events were incomplete setup instructions and missing patient data in the record and verify system of the Co-60 units for 57 % and 60.1 % of the 1164 patients.
Opportunities for improvement of safety in the delivery of radiotherapy treatments were identified. Learning from these past errors should raise awareness in the team leading to a safer treatments.
