Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer.

BACKGROUND: Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein. RESULTS: Treatment of SCC was associated with a reduction in overall bacterial richness and diversity. There were significant changes in the microbial community structure, including a decrease in the abundance of Porphyromonaceae and Prevotellaceae and an increase in Lactobacillaceae. There were also significant changes in the microbial community structure before and after treatment with chemoradiotherapy, but not with surgery alone. In patients treated with chemoradiotherapy alone, several bacterial populations were differentially abundant between responders and non-responders before and after therapy. Microbiome changes were associated with a change in the expression of DMBT1, an anti-microbial protein in human saliva. Additionally, we found that salivary DMBT1, which increases after treatment, could serve as a post-treatment salivary biomarker that links to microbial changes. Specifically, post-treatment increases in human salivary DMBT1 correlated with increased abundance of Gemella spp., Pasteurellaceae spp., Lactobacillus spp., and Oribacterium spp. This is the first longitudinal study to investigate treatment-associated changes (chemoradiotherapy and surgery) in the oral microbiome in patients with SCC along with changes in expression of an anti-microbial protein in saliva. CONCLUSIONS: The composition of the oral microbiota may predict treatment responses; salivary DMBT1 may have a role in modulating the oral microbiome in patients with SCC. After completion of treatment, 6 months after diagnosis, patients had a less diverse and less rich oral microbiome. Leptotrichia was a highly prevalent bacteria genus associated with disease. Expression of DMBT1 was higher after treatment and associated with microbiome changes, the most prominent genus being Gemella Video Abstract.

Cytokines in saliva increase in head and neck cancer patients after treatment.

OBJECTIVE: Approximately one-third of advanced head and neck squamous cell carcinomas (HNSCCs) recur within 2 years of treatment. Due to ease of collection, saliva is of interest to monitor changes that correlate with treatment. Previously this was a challenge due to xerostomia after conventional radiation. The emergence of gland-sparing radiation has made it possible to collect saliva post-treatment. This study investigated changes in cytokines in saliva pre- and post-treatment to provide foundational knowledge for future studies exploring the use of saliva to monitor treatment response. STUDY DESIGN: Pre- and post-treatment saliva was evaluated for 8 cytokines by multiplex assay and enzyme-linked immunosorbent assay. RESULTS: In oropharyngeal HNSCC, secretion of epidermal growth factor (EGF), GROα (Growth-regulated protein alpha), interleukin (IL)-1α, IL-ß, IL-6, IL-8, tumor necrosis factor-α, and vascular endothelial growth factor increased significantly post-treatment. In additional patients, significant increases of GR-α and IL-6 were validated, but EGF showed no change. CONCLUSIONS: The uniqueness of this study is its comparison of salivary cytokines from HNSCC patients pre- and post-treatment.

Symptom management during and after treatment with concurrent chemoradiotherapy for oropharyngeal cancer: A review of the literature and areas for future research.

Patients with locally advanced oropharyngeal cancer are at risk for poor outcomes due to the multi-modal nature of treatment and the potential for treatment-related toxicity. Although treatment with concurrent chemotherapy and radiotherapy has drastically reduced the need for a debilitating and disfiguring surgery, treatment related toxicities are often difficult to control. Acute toxicities include mucositis, skin desquamation, depression, cachexia, fatigue and nausea and vomiting. Failure to control these symptoms can adversely affect the patient's ability to complete their treatment regimen. Although there are many promising new treatments in the area of symptom management for this patient population, a review of the literature reflects the need for more research.

A pragmatic contouring guideline for salivary gland structures in head and neck radiation oncology: the MOIST target.

OBJECTIVES: One of the main normal tissue toxicities in head and neck radiation oncology is xerostomia. In several studies, reduced radiation dose to the salivary glands has been shown to diminish the effects of gland dysfunction. However, no clear guidelines exist to define the anatomic location of the involved glands on cross-sectional imaging in a pragmatic manner. This study presents an anatomic, computed tomography (CT)-based definition of the major and minor salivary glands. METHODS: On the basis of information from normal structure anatomy, the location of major and minor salivary glands was identified and translated into a cross-sectional CT-based description of the salivary glands. RESULTS: The major salivary glands include the parotids and submandibular glands. The minor salivary glands are presented as a part of a surrogate structure (the Minor Oral Including Sublingual Salivary Tissue target), including the minor glands located in the oral mucosa of the tongue, hard and soft palate, buccal mucosa, and inner surface of the lips. CONCLUSIONS: Clinical implementation of CT-based delineations of the salivary glands according to the proposed guideline should reduce interobserver variability. This may lead to an improved understanding of the relationship between radiation dose and volume and effects on salivary function.

Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues.

Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed.