Severe Xerostomia Research Articles

Diffusion-weighted imaging as a\xa0follow-up modality for evaluation of major salivary gland function in nasopharyngeal carcinoma patients: a\xa0preliminary study

PurposeTo investigate the value of diffusion-weighted imaging (DWI) in assessing dynamic changes of major salivary gland function during follow-up post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients.Materials and methods31 consecutive patients with pathologically confirmed NPC scheduled for RT underwent six routine follow-up MRI examinations including DWI sequence prior to (pre-RT) and 1, 3, 6, 9, and 12 months post RT. Mean apparent diffusion coefficient (ADC) values of bilateral parotid glands (PGs) and submandibular glands (SMGs) were measured. Objective measurement of salivary flow rate (SFR) under unstimulated (uSFR) and stimulated conditions (sSFR) as well as subjective xerostomia assessment according to a patient-rated questionnaire were conducted before each MRI. Variance analysis was used to evaluate dynamic changes of ADC, SFR and xerostomia questionnaire summary scores (XQ-sum) at different timepoints and the correlation between ADC and XQ-sum. Pearson’s correlation test was used to evaluate the correlations between pre- and post-RT changes of ADC (ΔADC) and SFR (ΔSFR) or mean RT dose.ResultsAt each timepoint, ADCs of PGs were significantly lower than of SMGs, uSFR was significantly lower than sSFR. For both PGs and SMGs, ADCpost-RT were all higher than ADCpre-RT, with significant differences. ADC1m-post-RT initially increased and changed little to ADC3m-post-RT, ADC6m-post-RT, ADC9m-post-RT, and ADC12m-post-RT, then gradually declined over time. The dynamic change trends of SFR were negatively paralleled to those of ADC, while that of XQ-sum was similar. Dose–response relationships were detected between salivary gland mean RT dose and ΔADC. In PGs, negative correlations between ΔsSFR9m-post-RT and ΔADC9m-post-RT, and ΔsSFR12m-post-RT and ΔADC12m-post-RT were detected. In SMGs, negative correlations between ΔsSFR12m-post-RT and ΔADC12m-post-RT, and ΔuSFR12m-post-RT and ΔADC12m-post-RT were also detected. The ADCs of patients with severe subjective xerostomia were significantly higher, while patients with moderate subjective xerostomia presented a tendency toward higher ADCs compared to those with mild xerostomia from 6 to 12 months post RT.ConclusionAs part of routine follow-up MRI in NPC patients, DWI might be a promising modality for follow-up assessing the dynamic changes of major salivary gland function and might be more powerful in the late post-RT period.

Approaches to preventive periodontal care for geriatric patients with somatic disorders

During the last two decades the acute interest in longevity has been kept by the world’s scientific community in relation to quality of health of older adults and prevention of emerging diseases including oral disorders in the old age. This article presents the study of oral conditions in 100 patients between the ages of 60 and 69 who were divided into three groups. This study aims to define approaches to preventive periodontal care for elderly patients with comorbidities. The primary group included patients with periodontal disease (PD) and salivary gland dysfunction: Sjogren’s disease and syndrome, non-insulin dependent diabetes mellitus, chronic pancreatitis. Two experimental groups included patients with normal salivary gland function and PD as well practically healthy persons without PD and normal salivary gland function. A comparative analysis of the results showed spread of dental caries (100%) and periodontal diseases (80%). The clear correlation between periodontium complex inflammation and poor oral hygiene is defined, mostly with men (p<0.05). Structural and optical properties of mixed saliva significantly change subject to periodontium inflammation and xerostomia: severity of xerostomia corresponding to profound hemodynamic and microcirculatory changes causes more intensive structural developmental abnormalities of mixed saliva. The important component of the Periodontal Treatment Protocol is to help older people develop skills and controls of effective thorough tooth brushing.

Relationship among perceived stress, oral health status, stomatitis, and xerostomia in the community during the COVID-19 pandemic: A cross-sectional survey

Aim: The aim of the study was to analyze the relationship between self-reported stress, oral health status, xerostomia, and stomatitis in the community during the COVID-19 pandemic.Materials and Methods: This is a cross-sectional study of 380 community respondents from the city of Bandung, Indonesia, consisting of 82 men and 298 women. Data obtained from online questionnaires using consecutive sampling method showed that the respondents agreed to participate in the study by filling in the informed consent. Furthermore, demographic data including age, education level, occupation, and total income were recorded. The variables measured by a questionnaire are self-reported stress, oral health status, xerostomia inventory, and stomatitis. Data distribution was performed by a descriptive statistic, χ2 test, Phi, and Spearman rank test for correlation analysis.Results: There was a significant correlation between perceived stress scale with oral health status (r’s = 0.135; P = 0.003), with stomatitis (r’s = 0.176; P = 0.015), and with xerostomia (r’s = 0.296; P = 0.022). In addition, age, education level, and total income also showed a significant correlation with stress level.Conclusion: From the findings of this study, it can be concluded that oral health status, xerostomia, and stomatitis were associated with levels of stress. Higher stress indicates poor oral health status, as well as severe xerostomia and stomatitis.

225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience.

Up to 30% of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) never respond or develop resistance to 177Lu-labeled PSMA-targeted radioligand monotherapy. Single-agent PSMA-targeted radioligand therapy (PRLT) with the alpha-emitter 225Ac showed promise against mCRPC but may cause severe and/or persistent xerostomia, which may substantially impair patients' quality-of-life. We hypothesized that when 177Lu-PSMA ligand alone is ineffective, tandem therapy with low-activity 225Ac-PSMA ligand plus full activity of the beta emitter may enhance efficacy while minimizing xerostomia severity. We retrospectively analyzed pilot experience with 1 course of 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy in our first 20 patients with mCRPC receiving this intervention after insufficiently responding to 177Lu-PSMA-617 monotherapy. This cohort had late-stage/end-stage disease with high baseline prostate-specific antigen (PSA) concentration (median 215 ng/mL), heavy pre-treatment (abiraterone and/or enzalutamide, and 177Lu-PRLT [median cumulative activity, 26.3 GBq] in 20/20 patients, 100%; docetaxel and/or cabazitaxel in 13/20 patients, 65%), and frequent Eastern Cooperative Oncology Group performance status of 2 (8/20 patients, 40%). Median (minimum-maximum) administered activities were 225Ac-PSMA-617, 5.3 (1.5-7.9) MBq, and 177Lu-PSMA-617, 6.9 (5.0-11.6) GBq. Significant responders to tandem therapy received 177Lu-PSMA-617 monotherapy as maintenance (median [minimum-maximum]: 1 [0-5] cycle). After a median (minimum-maximum) 22 (14-63) weeks' follow-up, 13/20 patients (65%) had as best biochemical response a PSA decline > 50%. Median (95% confidence interval) progression-free survival was 19 (12-26) weeks, and overall survival was 48 (4-92) weeks post-tandem therapy administration. Xerostomia was reported as grade 1 (very mild) in 8/20 patients (40%), grade 2 (mild) in 5/20 (25%), and grade 3/4 in 0/20. Our results suggest that a single course of tandem therapy with low-activity 225Ac-PSMA-617/full-activity 177Lu-PSMA-617 may safely enhance response to PRLT in men with late-stage/end-stage mCRPC while minimizing xerostomia severity. Formal study of this combination is warranted.

Oral Health-Related Quality of Life Among Publicly Insured Mental Health Service Outpatients With Serious Mental Illness.

The study investigated factors associated with unmet need for dental care and oral health-related quality of life (OHQoL) among individuals with serious mental illness receiving outpatient care in a public mental health program serving a largely low-income population, mostly from racial-ethnic minority groups. Cross-sectional interview data were collected from a convenience sample (N=150) of outpatients. Adjusted risk ratios (ARRs) and adjusted risk differences (ARDs) were estimated by logistic regression models to examine the independent contribution of sociodemographic and clinical factors to low OHQoL and past-year unmet dental need, defined as inability to obtain all needed dental care. More than half of participants reported low OHQoL (54%) and a past-year dental visit (61%). Over one-third (39%) had past-year unmet dental need. Financial barriers (ARR=3.16) and nonfinancial barriers (ARR=2.18) were associated with greater risk for past-year unmet dental need after control for age, gender, high dental anxiety, and limited English proficiency. ARDs for financial and nonfinancial barriers indicated absolute differences of 40 and 27 percentage points, respectively. Unmet dental need (ARR=1.31), xerostomia severity (ARR=1.20), and a schizophrenia spectrum diagnosis (ARR=1.33) were associated with low OHQoL, after control for age and current smoking, with ARDs ranging from 11 to 15 percentage points. Improving oral health promotion, oral health service access, and the integration of the mental and oral health systems may help reduce the high prevalence of low OHQoL in this population, given that low OHQoL is partly driven by unmet dental need.

NTCP Modeling of Patient Reported Xerostomia after De-Intensified Chemoradiotherapy for HPV Associated Oropharynx Cancer

Patients with head & neck tumors are commonly treated with external radiation therapy. Due to the proximity of the parotids to the tumor they often receive high doses to a portion of their volume. We prospectively enrolled patients on an IRB-approved clinical trial to estimate the correlation between different normal tissue complication probability (NTCP) models and dosimetric indices of the parotid and submandibular glands with the patient reported severity of xerostomia 12 months post de-intensified chemoradiotherapy. 120 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma were treated with de-intensified chemoradiotherapy. 60Gy delivered with intensity modulated radiotherapy was prescribed to all patients, who also received concurrent weekly intravenous cancer-treating drugs (30 mg/m2). The dose constraints for contralateral parotid and submandibular glands were mean dose <26 and <35, respectively. The status of xerostomia was reported pre- and post-treatment using the patient reported outcome version of the CTCAE (PRO-CTCAE): none/mild/moderate/severe/very severe. We correlated individual patient dosimetric data from the contralateral parotid and contralateral glands (parotid and submandibular glands combined) with the changes in the severity of xerostomia at 12 month post-treatment. A change in severity (from baseline) of ≥ 2 was considered clinically meaningful. The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models. Xerostomia increased in 40 patients (33%). Median mean doses to the contralateral parotid and combined glands were 23Gy (range: 5.1-47.1Gy) and 28Gy (range: 6-50Gy), respectively. For both structures, the V15Gy and mean doses correlated best with the subsequent xerostomia (AUC = 0.68-0.70). The values for the D50, m and n parameters of the Lyman-Kutcher-Burman model are 67Gy, 0.58 and 0.01 for the contralateral parotid and 56Gy, 0.56 and 0.12 for the combined glands. The values for the D50, γ and s parameters of the Relative Seriality model are 31.0Gy, 0.46 and 1.0 for the contralateral parotid and 39Gy, 0.48 and 1.0 for the combined glands. The AUC values for the two NTCP models for the contralateral parotid and combined glands and were similar 0.65 and 0.64, respectively. A statistically significant Odds Ratio of 5.7 (95%CI: 2.0-16.1Gy) was found for the contralateral parotid at V15Gy ≤ 53% and 7.8 (95%CI: 2.2-27.5Gy) for the combined glands at V15Gy ≤ 61%. The dosimetric thresholds V15Gy ≤ 53% to the contralateral parotid and V15Gy ≤ 61% to the combined parotid and submandibular glands were found to significantly reduce the risk for xerostomia. The dose-response curve of xerostomia could be determined by fitting the clinical data with the LKB and RS NTCP models. These models can provide constraints, which can be very useful in prospective treatment plan optimization and evaluation.

The Radiation Dose Received By the Parotid Gland Stem Cell Region Based on Mid-Treatment Imaging Can Predict Patient-Reported Xerostomia

To determine whether the radiation dose to the parotid gland stem cell (SC) region is associated with long-term patient-reported xerostomia after definitive head and neck cancer (HNC) radiation therapy (RT), and whether mid-treatment dose assessment improves the association. The SC region of the parotid gland, defined as being located next to the dorsal edge of the mandible, near the Stensen’s duct at the anterior border based on pre-clinical investigations, was delineated on CT scans with a 0.5 cm isotropic margin for 65 HNC patients that had undergone definitive RT between 2009 and 2014. Prospectively collected EORTC QLQ-H&N35 quality-of-life questionnaires with minimum 9 months follow-up were used to score xerostomia on a 4-grade scale, where grade 3 and 4 was considered severe xerostomia in this analysis. The SC regions were delineated on pre-treatment as well as mid-treatment CT scans to determine the best model for predicting xerostomia. The association between the mean dose to the spared parotid gland or SC region of the spared parotid and the risk of severe xerostomia was examined using logistic regression and receiver operating characteristics (ROC). Increasing radiation dose to either whole parotid or the SC region was associated with an increased risk of patient-reported xerostomia (p=0.003 and p=0.005). Importantly, the mid-treatment analysis showed that the dose to the SC region was more predictive of xerostomia than that of the pre-treatment or using the whole parotid dose, as per the ROC areas under the curve (AUCs) in Table 1. For every 1 Gy increase in radiation dose to the SC region evaluated at mid-treatment, we observed an 8% increase in the odds of xerostomia. We furthermore found that the parotid volume of patients with xerostomia was on average 27% reduced at mid-treatment, compared to only 15% for patients without xerostomia. We found that increased radiation dose to the SC region of the spared parotid gland was associated with an increased risk of patient-reported xerostomia, especially when evaluated at mid-treatment. This supports the hypothesis that targeting the SC region reduces regenerative capacity of the gland, which is also supported by the large reduction in parotid size. These results can assist clinicians in adapting RT to optimize efficacy while improving patients’ post treatment quality-of-life.Abstract 2985; Table 1Logistic regression models predicting patient-reported xerostomia.OR per Gy (95% CI)p-valueROC AUC (95% CI)Spared parotid mean dose pre-treatment1.08 (1.03, 1.13)0.0030.72 (0.60, 0.85)Spared parotid SC mean dose pre-treatment1.07 (1.02, 1.12)0.0050.70 (0.57, 0.83)Spared parotid mean dose mid-treatment1.07 (1.01, 1.13)0.0260.72 (0.54, 0.90)Spared parotid SC mean dose mid-treatment1.08 (1.02, 1.14)0.0120.76 (0.60, 0.93) Open table in a new tab

Predicting Xerostomia Using Diffusion Weighted Imaging in Head and Neck Cancer

Diffusion weighted imaging is an MRI technique that is sensitive to cell density, and has been shown to be predictive of response and outcome in head and neck cancer (HNC). Its role in xerostomia prediction in HNC has been limited. ADC maps have been shown to be correlated to cellularity and have the potential to be used to better understand the physiological meaning of MR derived radiomics. We hypothesized that combining salivary gland ADC with MR image features significantly improves xerostomia prediction compared to MR features alone. Baseline images and xerostomia (NCI CTCAE v4.0) at 3 month follow-up were prospectively collected in HNC patients treated at our institution with radiotherapy (RT) from 2015-2018. Moderate to severe xerostomia was defined as grade ≥ 2. Prior to treatment, T1-weighted images with a turbo spin echo sequence post-Gd and multiple-b (b=0, 100, 600, 1000s/mm2) diffusion weighted images were acquired on a 1.5T MRI scanner. Ipsilateral/contralateral parotid and submandibular glands (iPG, cPG, iSG, cSG) contoured on the CT images were propagated onto the MR images. MR images were normalized using relative intensity based on the mean subcutaneous fat at the level of the salivary glands. 429 MR radiomic features were extracted. Features were pre-selected by examining the predictor-outcome association by removing predictors based on the p-value of the correlation (p>0.05). A shrinkage regression analysis of pre-selected features was performed using least absolute shrinkage and selection operator (LASSO). To address the imbalance of patients with xerostomia, we applied a synthetic minority over-sampling technique to create a balanced set. ADC maps were determined using a voxel-by-voxel basis by evaluating the signal loss after subsequent diffusion sensitizing gradients using the exponential fit S(b)=S(0)e(-ADC×b). Prediction modeling was performed using generalized linear model with ten-fold cross validation. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Standardized beta coefficients were determined (β). Ninety-two HNC patients were evaluated, with (n=25, 61±11yr) and without severe xerostomia (n=67, 59±11yr). The AUC/sensitivity/specificity for the models containing T1-MR features, mean PG ADC, and T1-MR+PG-ADC, were 0.70/0.65/0.67, 0.65/0.74/0.58, and 0.76/0.65/0.67. In the T1-MR+ADC model, cPG ADC (β=4.16, p=0.004) significantly contributed to the model and there was a trend towards significance for iPG ADC (β=-1.27, p=0.06). These results suggest that increased diffusivity (suggesting decreased cellularity) of the cPG prior to RT is related to increased risk of xerostomia. In a small cohort of HNC patients, combining T1 features with ADC improved the xerostomia prediction model. This work suggests that diffusivity of the parotid glands may influence RT-induced xerostomia. Future work is required in larger cohort to generalize these findings.

Predicting Late Radiation-Induced Xerostomia with Parotid PET Biomarkers and Dose Metrics

Xerostomia is a common long-term toxicity from head and neck radiotherapy that is only partially predicted by delivered dose to salivary glands. Associations between parotid gland imaging biomarkers and late radiation-induced xerostomia have recently been shown. The aim of this study was to assess predictive models for late xerostomia incorporating pre-treatment parotid PET biomarkers compared to a base model using parotid dose alone in a homogeneous group of patients treated for orophangeal cancer. 47 patients with p16+ oropharyngeal squamous cell carcinoma were treated on two prospective institutional protocols with 70 Gy IMRT and concurrent carboplatin/paclitaxel. The 90th percentile of standardized uptake value (SUV-P90) was generated from each parotid gland on pre and 3-month post-RT PET scans. Late xerostomia (12-months post-RT) was defined by the patient-reported University of Michigan Xerostomia Questionnaire (XQ), and parotid-specific salivary flow rate (SFR). XQ outcomes included both the summary score (XQ-sum12m) and the most variable eating-related item as determined by principal component analysis: frequency of sipping fluids to aid in swallowing food (XQ-sip12m). Univariate analysis was applied to dose and SUV-P90 features as predictors of late xerostomia using both continuous and discrete scales. Multivariate analysis was applied for dose only and combined dose and SUV-P90 using penalized logistic regression for feature selection and model prediction based on the LASSO technique. Mean parotid dose and SUV-P90 from both pre and post-RT PET scans were significantly associated with patient-reported xerostomia and stimulated SFR (Stim12m) but not unstimulated SFR. Associations were stronger for SUV-P90 from the contralateral parotid (SUV-P90CL) than the ipsilateral parotid, and from 3-month PET scans relative to pre-treatment scans. On multivariate analysis, the addition of pre-treatment SUV-P90CL and an interaction term for dose and SUV to the model significantly improved the prediction for late moderate or severe xerostomia compared to the base model, from AUC = 0.70 to 0.74 for XQ-sum12m and from 0.74 to 0.84 for XQ-sip12m. The improvements remained statistically significant upon cross-validation. The addition of pre-treatment parotid PET biomarkers significantly improved a predictive model for late patient-reported xerostomia over a model based on parotid dose alone. The improvement was greatest for the single eating-related item with the largest inter-patient variability (XQ-sip12m). Correlation between SUV-P90 from 3-month post-RT PET scans and late xerostomia was even higher than those from pre-treatment scans, suggesting that mid-treatment scans should be further explored for a potential role in adaptive radiotherapy.Abstract 121; Table 1SUV-P90CL (3m)Mean XQ-Sum12mMean XQ-Sip12mMean Stim12m< 1.551.37.50.171.5 - 2.029.04.40.392.0 - 2.521.92.80.48> 2.510.81.30.80 Open table in a new tab

Physical and Radiobiological Evaluation of Accelerated Intensity Modulated Radiotherapy for Locally Advanced Head and Neck Cancer and Comparison with Short-Term Clinical Outcomes.

Objective:The present study aims to evaluate the accelerated intensity modulated radiotherapy (IMRT) of head and neck (HandN) treatments using physical indices and radiobiological models with its clinical correlation using histogram analysis in radiation therapy (HART). The radiobiological evaluation in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP) indices were compared with acute toxicity. Materials and Methods:A total of twenty patients with stage III and IV of HandN cases treated with accelerated IMRT using 6MV photons were chosen for the study. Using HART software, physical indices of the IMRT plans have been defined by universal plan indices (UPI’s) which summarize the various recognized plan indices. The overall quality factor (QF) of a plan was determined by a linear combination of all indices in UPI set. The clinical outcomes in terms of the acute toxicity like dysphagia and xerostomia were compared with NTCP values of the OAR calculated from HART software. Results:The mean QF and the mean Poisson TCP index was found to be 0.993±0.02 and 0.86 ±0.02 respectively. The mean JT Lyman NTCP index for bilateral parotid, constrictors, and larynx were found to be 0.23±0.14, 0.30±0.17 and 0.22±0.15 respectively. The acute toxicities in terms of severity of xerostomia and dysphagia have shown a moderate correlation with NTCP values of bilateral parotids, constrictors, and larynx, respectively. Conclusion:The mean QF based on UPI was found to be close to unity, which correlates with being a better IMRT plan. The present study suggested the existence of a moderate correlation between the calculated NTCP values and their respective severities of the organ at risk (OAR’s). Accelerated IMRT with chemotherapy is a clinically feasible option in the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) with encouraging initial tumor response and acceptable acute toxicities.

Clinical and dosimetric predictors of physician and patient reported xerostomia following intensity modulated radiotherapy for nasopharyngeal cancer – A prospective cohort analysis

Background and purposeTo compare physician and patient reported xerostomia and correlate xerostomia with dosimetric and clinical parameters for nasopharyngeal cancer (NPC) patients treated with intensity modulated radiotherapy (IMRT) and chemotherapy. Patients and methodsWe analyzed the data of 172 patients with locally advanced NPC. Xerostomia was evaluated via physician-rated xerostomia based on RTOG morbidity score (E1), patient-rated dry mouth (E2) and patient-rated sticky saliva (E3) based on EORTC QLQ-HN35 questionnaire. Primary endpoint was the presence of moderate to severe xerostomia at 2-year after completion of IMRT. ResultsThe levels of physician reported xerostomia (E1) were consistently lower than patient reported dry mouth (E2) over time. The incidence of patients with xerostomia at 3-month post RT was 58% based on E1, 70% based on E2, and 51% based on E3. The corresponding incidence rates at 2-year post RT was 26% (E1), 36% (E2) and 21% (E3). The incidence of patients with xerostomia at 1-year post RT was close to that at 2-year post RT for all the 3 endpoints. The average Dmean of parotid glands was 41.5 Gy (range: 31.0 Gy-65.9 Gy, median: 40.7 Gy). No dosimetric parameters were significantly associated with xerostomia. ConclusionSignificant proportion of patients still experienced long term xerostomia with IMRT. Dose-effect relationships between xerostomia and the parotid glands were not observed in this study.

Normal Tissue Complication Probability (NTCP) modeling and validation of quantitative analysis of normal tissue effects in the clinic (QUANTEC) guideline using quality of life questionnaire for parotid gland during head and neck radiotherapy

Introduction: Radiation therapy is the main treatment method for head and neck cancers, which comprise 3–5% of all cancers. A major side effect of this treatment is complication of the parotid glands, i.e. xerostomia, which occurs at relatively low doses. This complication leads to mouth dryness which is the most common problem for head and neck cancer survivors. There are different grades of xerostomia and severe xerostomia is defined as a long-term reduction in the function of salivary gland to less than 25% relative to the pre-radiotherapy baseline value. The grading of xerostomia is usually assessed by patient self-reports carried out by the quality of life questionnaire (QoL), designed based on indigenous criteria and internationally recognized protocols. In recent years several studies have focused on normal tissue complication probability (NTCP) modeling of xerostomia using quality of life questionnaires with or without functional analysis based on various standard model parameters. Lyman (LKB) model is commonly used to predict the normal tissue complication probability (NTCP). This model uses the patient’s calculated dose volume histogram of (DVH) of an organ at risk (OAR) and the dose response curve parameters. The quantitative analysis of normal tissue effects in the clinic (QUANTEC) effort is to refine the guidelines based on 3D dose/volume and outcome data. According to QUANTEC guideline to limit the severity of xerostomia, maximum dose received by one or both of parotid glands should be 20 Gy and 25 Gy (20/25 Gy), respectively. The aim of this study was to evaluate the NTCP model parameters for all grades of acute parotid complications using the LKB model during head and neck conformal radiotherapy treatment and using a QoL questionnaire. Materials and Methods: 50 patients with head and neck cancer who have been referred for radiotherapy to Milad Hospital in Isfahan, Iran, were selected. QoL questionnaire datasets of patients with squamous cell carcinoma and lymph node cancers beside the parotids were within the radiation field were analyzed. The European organization for research and treatment of cancer (EORTC) QLQ HN35 was used in three stages (before, during and at the end of treatment). Prescribed dose per fraction was modified to 2 Gy/fraction equivalent dose for each patients. The LKB model with DVH reduction to form the equivalent uniform dose (EUD), known as LEUD was used. The model parameters of TD50 (Tolerance Dose 50%) and m was assessed by fitting the patient reported complication data to the normal tissue complication probability (NTCP) curve. Results: One patient (2%) at stage 2 and 5 patients (10%) at stage 3 experienced grade 3 xerostomia. The dose-response curves (LKB model) for occurrence of xerostomia was fitted to the QoL data which were collected at stages 2 and 3. These parameters were TD50 =23.3Gy, m =1 and TD50 =21.6 Gy, m =1 at stage 2 and stage 3, respectively. Conclusion: The agreement between the NTCP modeling based on QoL questionnaire data and the QUANTEC guidelines, confirms the cutoff values of 20/25 Gy to spare the parotid gland.

Long-term effects of radioiodine treatment on salivary gland function in adult survivors of pediatric differentiated thyroid carcinoma.

Pediatric differentiated thyroid cancer (DTC) is a rare disease. Initial treatment of DTC consists of a (near) total thyroidectomy and radioactive iodine (131I) therapy. Previous studies in adults showed that 131I treatment may result in a reduced salivary gland function. Studies regarding salivary gland function in children treated for DTC are sparse. Our aim was to assess long-term effects of 131I treatment on salivary gland function in survivors of pediatric DTC. Methods: In a nationwide cross-sectional study, salivary gland function of patients treated for pediatric DTC between 1970 and 2013 (>5 years after diagnosis, ≥18 years old at time of evaluation) was studied. Salivary gland function was assessed by sialometry, sialochemistry and a xerostomia inventory. Salivary gland dysfunction was defined as unstimulated whole saliva flow ≤0.2mL/min and/or a stimulated whole saliva flow ≤0.7 mL/min. Results: Sixty-five patients (median age at evaluation 33 [IQR, 25-40] years, 86.2% female, median follow-up period 11 [IQR, 6-22] years) underwent 131I treatment. Median cumulative 131I activity was 5.88 [IQR, 2.92-12.95] GBq, 47.7% underwent multiple 131I administrations. Salivary gland dysfunction was present in 30 (47.6%) patients. Levels of amylase and total protein in saliva were reduced. Moderate to severe xerostomia was present in 22 (35.5%) patients. Stimulated salivary secretion was lower and severity of xerostomia complaints higher in patients treated with higher cumulative 131I activity. Conclusion: In survivors of pediatric DTC, clinically significant salivary gland dysfunction was found in 35.5% and was related to the cumulative 131I activity of the treatment.

Intra-patient and inter-patient comparisons of DNA damage response biomarkers in Nasopharynx Cancer (NPC): analysis of NCC0901 randomised controlled trial of induction chemotherapy in locally advanced NPC

BackgroundInter-patient heterogeneity in radiation-induced DNA damage responses is proposed to reflect intrinsic variations in tumour and normal tissue radiation sensitivity, but the prediction of phenotype by a molecular biomarker is influenced by clinical confounders and assay reproducibility. Here, we characterised the intrapatient and inter-patient heterogeneity in biomarkers of DNA damage and repair and radiation-induced apoptosis.MethodsWe enrolled 85 of 172 patients with locally advanced nasopharynx cancer from a randomised controlled phase II/III trial of induction chemotherapy added to chemo-radiotherapy. G0 blood lymphocytes were harvested from these patients, and irradiated with 1, 4, and 8 Gy ex vivo. DNA damage induction (1 Gy 0.5 h) and repair (4 Gy 24 h) were assessed by duplicate γH2AX foci assays in 50–100 cells. Duplicate FLICA assays performed at 48 h post-8 Gy were employed as surrogate of radiation-induced apoptosis; %FLICA-positive cells were quantified by flow cytometry.ResultsWe observed limited intrapatient variation in γH2AX foci and %FLICA readouts; median difference of duplicate foci scores was − 0.37 (IQR = − 1.256-0.800) for 1 Gy 0.5 h and 0.09 (IQR = − 0.685-0.792) for 4 Gy 24 h; ICC of ≥0.80 was observed for duplicate %FLICA0Gy and %FLICA8Gy assays of CD4+ and CD8+ T lymphocytes. As expected, we observed wide inter-patient heterogeneity in both assays that was independent of intrapatient variation and clinical covariates, with the exception of age, which was inversely correlated with %FLICAbackground-corrected (Spearman R = − 0.406, P < 0.001 [CD4+]; R = − 0.220, P = 0.04 [CD8+]). Lastly, an exploratory case-control analysis indicates increased levels of γH2AX foci at 4 Gy 24 h in patients with severe late radiotherapy-induced xerostomia (P = 0.05).ConclusionHere, we confirmed the technical reproducibility of DNA damage response assays for clinical implementation as biomarkers of clinical radiosensitivity in nasopharynx cancer patients.

Dose-Volume Histogram (DVH) Patterns within the Salivary Glands and Clinical Parameters Predict Xerostomia in Head and Neck Cancer (HNC) Patients, from Injury to Recovery

NCI-CTCAE-graded xerostomia is routinely captured in our analytic database demonstrating that its maximum severity and prevalence occurs within 18 mos after RT (injury), with the prevalence decreasing (recovery) where a lower rate of decreasing prevalence can be observed thereafter. Studies have indicated that the spatial distribution of radiation to the salivary glands differentially affects the risk of xerostomia. We sought to characterize the spatial dosimetry to the salivary glands and the oral cavity as it related to the risk of maximum xerostomia injury and its recovery as defined above while controlling for clinical parameters. HNC patients treated from 2007 to 2017 in our institution with CTCAE graded xerostomia available for at least 18 mos of follow-up were evaluated. Patients with moderate to severe xerostomia (CTCAE grade ≥ 2) before RT were excluded. 22 spatial zones were geometrically created from the parotid glands (PG), submandibular glands (SMG) and oral cavity (OC) for each patient. DVH features (D10-D90) for each zone as well as clinical parameters were used to predict xerostomia injury (CTCAE grade ≥ 2) within 18 mos post-RT, and recovery (grade decrease to < 2) after 18 mos of follow-up. A total of 217 HNC patients were identified with 146 developing moderate to severe xerostomia (CTCAE grade ≥ 2) within 18 mos of follow-up. The dataset was randomly split into a training and test dataset at the ratio of 7:3 for each outcome. Ridge logistic regression with 10-fold cross-validation was applied to predict xerostomia injury and recovery respectively in the training datasets. The critical zones associated xerostomia injury was the medial inferior portion of the ipsilateral PG (relative to the primary tumor) and the superior portion of the ipsilateral PG for recovery. The dose – recovery pattern was significantly influenced by the low - dose bath (D80-D90) across the superior portion of ipsilateral PG. The area under the receiver operating characteristic curve (AUC) was 0.78 and 0.74 for xerostomia injury and recovery respectively in validation datasets. The AUC for injury and recovery are 0.72 and 0.70 respectively in test datasets. Our data science methodology demonstrated that different spatial-dose patterns for xerostomia injury vs. recovery and highlighted the strength of this analytic technique along with the importance of assessing xerostomia during follow-up. These observations if validated provide insights into new strategies for RT deintensification. This work was supported by the Radiation Oncology Institute.

Role of Imaging in Predicting Radiation Induced Xerostomia

The development of predictive biomarkers for radiation toxicities (e.g. xerostomia) may better identify head and neck cancer (HNC) patients suitable for treatment intensification. Radiomics is a promising approach to identify image-based biomarkers. We hypothesize that baseline salivary gland structure-function evaluated using computed tomography (CT) and magnetic resonance imaging (MRI) based radiomics can be used for predicting radiation induced xerostomia. HNC patients treated between 2009 and 2015 at our institution with xerostomia graded by NCI-CTCAE at 3-month follow up were included. For each patient, contours of the parotid and submandibular glands on baseline planning CT (non-contrast enhanced) were prospectively collected. CT images were corrected for metal artifact reduction to minimize the effect of dental artifacts in radiomic feature computation. Baseline MR images were acquired post-contrast using a T1-weighted pulse sequence. CT images and corresponding contours were registered to MR images using rigid or deformable registration with commercially available software. In each patient, 5744 CT and MR features were extracted for ipsilateral(IL)/contralateral(CL) salivary glands. The dataset was randomly partitioned into training and validation sets using an 80/20 split. Features from the training set were first ranked in univariate analysis by likelihood for predicting severe xerostomia (grade ≥2). Features correlated with xerostomia (p<0.1) were further reduced using a maximum relevance minimum redundancy method. The final set of image features was selected using LASSO logistic regression. A Random Forest model with leave-one-out cross-validation was applied to predict radiation induced xerostomia. Three models were developed with image features extracted from (1) CT only, (2) MR only, and (3) CT+MR. Area under the receiver operator curve (AUC) was compared across models. The training dataset (n=112) revealed 11 CT and 6 MR image features. CT features included: CL parotid Gray Level Size Zone matrix (GLSZM) gray level non-uniformity (consistent with parotid gland heterogeneity) and Gray Level Co-occurrence Matrix (GLCM) correlation; IL submandibular GLCM entropy and total energy. MR features included: CL parotid Short Run High Gray Level Emphasis and total energy features. The cross-validated AUCs for the training data for CT only/MR only/CT+MR was 0.72/0.60/0.74 in xerostomia prediction. The AUC for the validation data (n=28) for CT only/MR only/CT+MR features was 0.82/0.68/0.73. In this cohort of HNC patients, these results suggest that CT image features may be used to predispose patients susceptible to radiation induced xerostomia. Further investigation with a larger cohort is required.

Effect of a gel-type denture adhesive on unstimulated whole saliva and minor salivary gland flow rates and on subjective orofacial sicca symptoms

To determine whether the continuous use of gel-type denture adhesives influence the unstimulated whole saliva, the palatal and labial saliva flow rates, and to assess the possible changes of subjective orofacial sicca symptoms. 28 maxillary complete denture wearing patients (average age: 70 ± 10 years) were investigated. A gel-type denture adhesive was administered to the patients for regular use during the 3 weeks of examination. A questionnaire of 16 questions was used to evaluate subjective orofacial sicca symptoms. Unstimulated whole saliva was determined by the spitting method, palatal and labial saliva flow rates were measured by the Periotron® device with filter paper discs at the initial, first, second and third weeks. The following tests were used: subjective values - χ2-test; flow rates - ANOVA, paired Student's t-test. According to the questionnaire, the ratio or severity of xerostomia did not change. A significant increase in the subjective feeling of "saliva thickness" could be detected (p = 0.027), but the other subjective parameters remained unchanged. Palatal saliva flow rates decreased significantly by week 3 (week 0: 4.21 ± 3.96 µl/cm2/min; week 3: 2.21 ± 2.30 µl/cm2/min; p = 0.024). On the other hand, there was no significant change in the unstimulated whole saliva (week 0: 0.37 ± 0.36 ml/min; week 3: 0.39 ± 0.35 ml/min) and labial saliva (week 0: 3.99 ± 3.75 µl/cm2/min; week 3: 2.58 ± 3.39 µl/cm2/min) flow rates. The regular use of denture adhesives did not influence xerostomia and the majority of subjective orofacial sicca symptoms, but may cause a subjective feeling of "increased saliva thickness" and reduce palatal minor salivary gland flow rates among complete maxillary denture wearers. Orv Hetil. 2018; 159(40): 1637-1644.

PENERAPAN PEMBERIAN PERMEN KARET XYLITOL UNTUK XEROSTOMIA PADA PASIEN PENYAKIT GINJAL KRONIS DI RUMAH SAKIT TK. III 04.06.02 BHAKTI WIRA TAMTAMA SEMARANG

Hemodialysis is an action used in kidney failure patients to remove and clean up metabolic waste substances and other toxic substances. So you have to undergo hemodialysispatients undergoing hemodialysis must be limited to administration of fluids. The consequences of fluid restriction can lead to complaints of thirst and xerostomia. Giving xylitol gum can stimulate saliva to overcome xerostomia. The purpose of this case study is to describe the application of xylitol gum to reduce xerostomia in patients. The method used in this study is Quasy Experiment. The instrument used was SXI-D (Summated Xersotomia Inventory-Dutch Version). Subjects of 2 people over the age of 30 years. The intervention was done in the form of chewing 2 grains of xylitol gum 3 times a day after a large meal and brushing his teeth for 2 consecutive weeks. The results of case studies on subject 1 showed a decrease in xerostomia before being given the first hemodialysis measurement intervention, namely 23 severe xerostomia, on the last day of intervention, 7 mild xerostomia. In subject 2 there was a decrease in xerostomia before the first. gum administration is recommended as a nursing intervention in the management of patients with hemodialysis measurement intervention was given, 23 severe xerostomia, on the last day of intervention, 10 mild xerostomia. The application of xylitol xerostomia.

Systematic review and meta-analyses of intensity-modulated radiation therapy versus conventional two-dimensional and/or or three-dimensional radiotherapy in curative-intent management of head and neck squamous cell carcinoma.

IntroductionTechnological advancements in treatment planning and delivery have propelled the use of intensity-modulated radiation therapy (IMRT) in head and neck squamous cell carcinoma (HNSCC). This review compares IMRT with conventional two-dimensional (2D) and/or three-dimensional (3D) radiotherapy (RT) in curative-intent management of HNSCC.MethodsOnly randomized controlled trials (RCTs) offering curative-intent RT in patients with non-metastatic HNSCC were included. Outcome data was extracted independently by two reviewers, pooled using the Cochrane methodology, and expressed as risk ratio (RR) or hazard ratio (HR) as appropriate with 95% confidence intervals (CIs). Xerostomia was the primary outcome of interest whereas loco-regional control, overall survival and quality-of-life (QOL) were secondary endpoints.ResultsSeven RCTs involving 1155 patients directly comparing IMRT with 2D/3D-RT in HNSCC were included. The primary objective in five of seven index RCTs was reduction in xerostomia, with only one trial each using loco-regional control and overall survival as primary endpoints for sample size calculation. The use of IMRT was associated with a 36% relative risk reduction in ≥grade 2 acute xerostomia (RR = 0.64, 95%CI = 0.49–0.84; p = 0.001) compared to 2D/3D-RT. More importantly, IMRT significantly reduced the risk of ≥grade 2 late xerostomia (RR = 0.44, 95%CI = 0.34–0.57; p = 0.00001) compared to non-IMRT techniques at all time-points. Within the limitations of inadequate sample size and low statistical power, IMRT also resulted in 24% relative reduction in the risk of loco-regional relapse (HR = 0.76, 0.57–1.01; p = 0.06) and 30% relative reduction in risk of death (HR = 0.70, 95%CI = 0.57–0.88; p = 0.002) compared to 2D/3D-RT. However, this benefit of IMRT for loco-regional control and overall survival was limited to nasopharyngeal cancer patients alone, with no significant difference in efficacy between the two techniques in patients with cancers of the laryngo-pharynx in this analysis, highlighting the inconsistency in results of subgroup analyses stratified by primary site. Inadequate reporting of data precluded statistically pooling of results for QOL outcomes.ConclusionsThere is consistent moderate-quality evidence that IMRT significantly reduces the risk of moderate to severe acute and late xerostomia compared to 2D/3D-RT in curative-intent radiotherapeutic management of HNSCC. However, the quality of evidence regarding the superiority of IMRT over conventional techniques for disease-related endpoints is rather low due to relative lack of power and inconsistency of results precluding robust conclusions.

Dietary Intake, Body Composition, and Oral Health Parameters among Female Patients with Primary Sjögren’s Syndrome

There is limited knowledge about dietary intake and body composition among patients with primary Sjögren’s syndrome. We assessed dietary intakes with 24-h recalls and body composition with anthropometry and bioelectrical impedance in 20 female patients. Various scoring tools were used to assess oral health. The patients had a lower energy percentage (E%) from carbohydrates (p = 0.02) and a higher E% from fat (p = 0.01) compared to a reference group. The lower intake of carbohydrates was due to a lower bread intake (p = 0.04), while the higher intake of fat was due to a higher intake of butter, margarine, and oil (p = 0.01). The patients ate more than twice (p = 0.02) as much fish as the reference group. The compliance to recommended intakes of macro- and micronutrients was good. Forty-percent of the patients were overweight/obese. Increased intake of beverages was observed in patients with severe xerostomia and/or low oral health-related quality of life, whereas reduced fat intake was found in hyposmic patients. In conclusion, the dietary intake among the patients was not much different from the reference group and complied with recommendations. Most oral health parameters were not associated with nutrient intakes. Specific dietary guidelines are probably not needed to ensure adequate nutrition among such patients.