Dataset Information

Quantification of very late xerostomia in head and neck cancer patients after irradiation.

ABSTRACT:

Objective

Radiation therapy (RT) for head and neck cancer (HNC) can result in severe xerostomia, or the subjective feeling of dry mouth. Characterizing xerostomia is critical to designing future clinical trials investigating how to improve HNC patients' quality of life (QoL). Few studies have investigated the very late (>5 years post-RT) effects of RT for HNC. We undertook preliminary studies quantifying very late xerostomia.

Methods

Six adults who underwent RT for HNC at least 5 years prior and reported xerostomia were enrolled. Five healthy adults without a self-reported history of HNC or xerostomia were enrolled as controls. All participants completed three validated surveys to measure xerostomia-related QoL. Salivary production rates were measured and compositional analysis of the saliva and oral microbiome was completed.

Results

The QoL survey scores for the HNC participants were significantly worse as compared to the control participants. The HNC participants produced less unstimulated saliva (p = .02) but not less stimulated saliva. The median salivary mucin significantly higher in HNC participants than in control participants (p = .02). There was no significant difference between the pH, amylase, or total protein. Microbiome analysis revealed alpha diversity to be significantly lower in the HNC participants.

Conclusion

In the survivors of HNC who suffer from late toxicities, multiple means of measuring toxicity may be useful. We found that in patients with radiation-induced xerostomia over 5 years after therapy, not only were the QoL surveys significantly worse, as expected, but other measurements such as mucin and oral microbiome diversity were also significantly different.

Level of evidence

SUBMITTER: Blitzer GC

PROVIDER: S-EPMC9392383 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Quantification of very late xerostomia in head and neck cancer patients after irradiation.

Blitzer Grace C GC Rogus-Pulia Nicole M NM Paz Cristina C Nickel Kwangok P KP Cannaday Vanessa L VL Kelm-Nelson Cynthia A CA Sudakaran Sailendharan S Chappell Richard J RJ Glazer Tiffany T Kimple Randall J RJ

Laryngoscope investigative otolaryngology 20220712 4

<h4>Objective</h4>Radiation therapy (RT) for head and neck cancer (HNC) can result in severe xerostomia, or the subjective feeling of dry mouth. Characterizing xerostomia is critical to designing future clinical trials investigating how to improve HNC patients' quality of life (QoL). Few studies have investigated the very late (>5 years post-RT) effects of RT for HNC. We undertook preliminary studies quantifying very late xerostomia.<h4>Methods</h4>Six adults who underwent RT for HNC at least 5 ...[more]

PMID: 36000048

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Project description:AimData from a local quality registry are used to model the risk of late xerostomia after radiotherapy for head and neck cancer (HNC), based on dosimetric- and clinical variables. Strengths and weaknesses of using quality registry data are explored.MethodsHNC patients treated with radiotherapy at the Karolinska University hospital are entered into a quality registry at routine follow up, recording morbidity according to a modified RTOG/LENT-SOMA scale. Other recorded parameters are performance status, age, gender, tumor location, tumor stage, smoking status, chemotherapy and radiotherapy data, including prescribed dose and organ-at-risk (OAR) dose. Most patients are entered at several time points, but at variable times after treatment. Xerostomia was modeled based on follow-up data from January 2014 to October 2018, resulting in 753 patients. Two endpoints were considered: maximum grade ≥2 (XERG≥2) or grade ≥3 (XERG≥3) late xerostomia. Univariate Cox regression was used to select variables for two multivariate models for each endpoint, one based on the mean dose to the total parotid volume (Dtot) and one based on the mean dose to the contralateral parotid (Dcontra). Cox regression allows the estimation of the risk of xerostomia at different time points; models were presented visually as nomograms estimating the risk at 9, 12, and 24 months respectively.ResultsThe toxicity rates were 366/753 (49%) for XERG≥2 and 40/753 (5.3%) for XERG≥3. The multivariate models included several variables for XERG≥2, and dose, concomitant chemotherapy and age were included for XERG≥3. Induction chemotherapy and an increased number of fractions per week were associated with a lower risk of XERG≥2. However, since the causality of these relationships have limited support from previous studies, alternative models without these variables were also presented. The models based on the mean dose to the total parotid volume and the contralateral parotid alone were very similar.ConclusionLate xerostomia after radiotherapy can be modeled with reasonable predictive power based on registry data; models are presented for different endpoints highly relevant in clinical practice. However, the risk of modeling indirect relationships, given the unavoidably heterogeneous registry data, needs to be carefully considered in the interpretation of the results.

Project description:To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands.In a prospective study, 78 patients with Stage III-IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors.Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47-0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points.The PG, SMG, and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo-IMRT, with OC doses remaining significant after adjusting for the PG and SMG doses. These results support efforts to spare all the salivary glands by IMRT, beyond the PGs alone.

Project description:PurposeRadiation-induced xerostomia is one of the most prevalent symptoms during and after head and neck cancer radiation therapy (RT). We aimed to discover the spatial radiation dose-based (voxel dose) importance pattern in the major salivary glands in relation to the recovery of xerostomia 18 months after RT, and to compare the recovery voxel dose importance pattern to the acute incidence (injury) pattern.Methods and materialsThis study included all patients within our database with xerostomia outcomes after completion of curative intensity modulated RT. Common Terminology Criteria for Adverse Events xerostomia grade was used to define recovered versus nonrecovered group at baseline, between end of treatment and 18 months post-RT, and beyond 18 months, respectively. Ridge logistic regression was performed to predict the probability of xerostomia recovery. Voxel doses within geometrically defined parotid glands (PG) and submandibular glands (SMG), demographic characteristics, and clinical factors were included in the algorithm. We plotted the normalized learned weights on the 3-dimensional PG and SMG structures to visualize the voxel dose importance for predicting xerostomia recovery.ResultsA total of 146 head and neck cancer patients from 2008 to 2016 were identified. The superior region of the ipsilateral and contralateral PG was the most influencial for xerostomia recovery. The area under the receiver operating characteristic curve evaluated using 10-fold cross-validation for ridge logistic regression was 0.68 ± 0.07. Compared with injury, the recovery voxel dose importance pattern was more symmetrical and was influenced by lower dose voxels.ConclusionsThe superior portion of the 2 PGs (low dose region) are the most influential on xerostomia recovery and seem to be equal in their contribution. The dissimilarity of the influence pattern between injury and recovery suggests different underlying mechanisms. The importance pattern identified by spatial radiation dose and machine learning methods can improve our understanding of normal tissue toxicities in RT. Further external validation is warranted.

Project description:BackgroundThe aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT).MethodsPrior to RCT, the effect of trehalose (5-20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions.ResultsIn the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05).ConclusionsThe 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

Dataset Information

Quantification of very late xerostomia in head and neck cancer patients after irradiation.

Objective

Methods

Results

Conclusion

Level of evidence

Publications

Quantification of very late xerostomia in head and neck cancer patients after irradiation.

Similar Datasets

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