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Objectives: Longitudinal assessment of the role of specific proteins on radiotherapy caries (RC) onset in head and neck cancer patients(HNC) up to one-year post-IMRT using a 5000ppm fluoride paste daily., Materials and Methods: Dental status/salivary protein data were obtained from 40 HNC patients pre-IMRT, six months (T1) and 12 months (T2) post-IMRT (ethical approval/consent). DMFT/salivary parameters were quantified, including flow rate, mucin 5B/7, Immunoglobulin A (IgA), cystatin S and α-amylase., Results: 45% patients had at least one carious lesion at T2, a significant reduction in the number of remaining teeth (65% <21), salivary flow rate (< 50%) and, protein secretion (< 0.05) post-IMRT. T1 IgA concentration/secretion rate was associated with RC (p < 0.05). Finally, IgA and total protein concentration obtained at T1 could provide a predictive pattern (AUC 82.3%) for the patients more predisposed to developing RC at T2., Conclusions: This study demonstrated the significant association of RC with salivary proteins in HNC patients treated with IMRT, revealing the potential role of salivary proteins in the early diagnosis of RC., Clinical Relevance: This research contributes to revealing salivary proteins association with RC, and its role in early diagnosis. Therefore, this could be the first step towards personalized medicine approaches to improve this group quality-of-life., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT)., Methods: Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified., Results: 95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT., Conclusion: This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results., Clinical Significance: The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL)., Research Question: What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients?, Aim: To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy., Null Hypothesis: There is no association between salivary proteins and onset/severity of OM in HNC patients., (© 2024. The Author(s).)

Salivary gland atrophy is a frequent consequence of head and neck cancer irradiation therapy but can potentially be regulated through the mammalian target of rapamycin (mTOR). Excretory duct ligation of the mouse submandibular gland provokes severe glandular atrophy causing activation of mTOR. This study aims to discover the effects of blocking mTOR signaling in ligation-induced atrophic salivary glands. Following 1 week of unilateral submandibular excretory duct ligation: gland weights were significantly reduced, 4E-BP1 and S6rp were activated, and tissue morphology revealed typical signs of atrophy. However, 3 days following ligation with rapamycin treatment, a selective mTOR inhibitor, gland weights were maintained, 4E-BP1 and S6rp phosphorylation was inhibited, and there were morphological signs of recovery from atrophy. However, following 5 and 7 days of ligation and rapamycin treatment, glands expressed active mTOR and showed signs of considerable atrophy. This evidence suggests that inhibition of mTOR by rapamycin delays ligation-induced atrophy of salivary glands.