Cost-effectiveness of weekly adaptive radiotherapy versus standard IMRT in head and neck cancer alongside the ARTIX trial.

BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

Effectiveness of thyme honey in the management of xerostomia in geriatric patients with end-stage renal disease: a randomized controlled clinical trial with a biochemical assessment.

BACKGROUND: Taking into consideration the value of the oral health condition in geriatric people with end-stage renal disease (ESRD) associated with xerostomia and believing that salivary stimulants or substitutes could potentially be used to manage this condition. This study aimed to evaluate the clinical effectiveness of thyme honey as oral rinse in geriatric patients with ESRD using the subjective dry mouth score as a primary objective and to assess the effect of thyme honey on the salivary nitric oxide level, salivary flow rate, and salivary ph in addition to objective dry mouth score as a secondary objective. METHODS: This was a single blinded randomized controlled trial with two equal arms, the interventional arm (thyme honey oral rinse) and the control arm (saline). Twenty-eight geriatric patients with ESRD undergoing hemodialysis complained of xerostomia were recruited from the renal dialysis center. Patients in both arms followed the same administration protocol either with thyme honey oral rinse or saline. The following clinical parameters (the subjective and objective dry mouth scores, salivary flow rate, salivary ph, and salivary nitric oxide (NO) levels) were evaluated for both groups at different intervals (baseline, 1 week, and 1 month). RESULTS: In the current study, it was found that both the subjective and objective dry mouth scores were significantly lower after one month of using thyme honey oral rinse (1.86 ± 0.66B) and (2.21 ± 0.43B) respectively, than the control group (3.07 ± 0.73B) and (3.07 ± 0.83B), respectively with a (p < 0.001). Also, the salivary flow rate was significantly higher after one month of using thyme honey oral rinse (1.56 ± 0.51A), than the control group (0.78 ± 0.27A) with a (p < 0.001). For the NO levels, there was a significant increase in measured value after 1 month in the intervention group (p < 0.001), while for the control group the change was not statistically significant (p = 0.166). CONCLUSIONS: The results of the current study have revealed the efficacy of Thyme honey oral rinse in the management of xerostomia in geriatric patients with ESRD. Trial registration The ClinicalTrials.gov Identifier for this study is NCT05247008.

Prospective assessment of sparing the parotid ducts via MRI sialography for reducing patient reported xerostomia.

PURPOSE: To assess the impact of prospectively sparing the parotid ducts via MRI sialography on patient reported xerostomia for those receiving definitive radiotherapy (RT) for oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS: Thirty-eight patients with oropharynx cancer to be treated with definitive RT underwent pre-treatment MRI sialograms to localize their parotid ducts. The parotid ducts were maximally spared during treatment planning. Patients reported symptoms (PRO-CTCAE and QLQ-H&N35) were collected at 6 and 12 months post-RT and compared to a historical cohort who underwent conventional parotid gland mean dose sparing. Regression models were generated using parotid and submandibular gland doses with and without incorporating the dose to the parotid ducts to determine the impact of parotid duct dose on patient reported xerostomia. RESULTS: At 6 months post-RT, 12/26 (46%) patients reported ≥moderate xerostomia when undergoing parotid ductal sparing compared to 43/61 (70%) in the historical cohort (p = 0.03). At 12 months post-RT, 8/22 (36%) patients reported ≥moderate xerostomia when undergoing parotid ductal sparing compared to 34/68(50%) in the historical cohort (p = 0.08). Using nested logistic regression models, the mean parotid duct dose was found to significantly relate to patient reported xerostomia severity at 6 months post-RT (p = 0.04) and trended towards statistical significance at 12 months post-RT (p = 0.09). At both 6 and 12 months post-RT, the addition of mean parotid duct dose significantly improved model fit (p < 0.05). CONCLUSIONS: MRI sialography guided parotid duct sparing appears to reduce the rates of patient-reported xerostomia. Further, logistic regression analysis found parotid duct dose to be significantly associated with patient reported xerostomia. A significant improvement in model fit was observed when adding mean parotid duct dose compared to models that only contain mean parotid gland dose and mean contralateral submandibular gland dose.

TASTE DISORDERS AND XEROSTOMIA ARE HIGHLY PREVALENT IN PATIENTS WITH COVID-19.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: J. Amorim dos Santos, A.G.C. Normando, R.L.Carvalho da Silva, A.C. Acevedo G. De Luca Canto, N. Sugaya, A.R. Santos-Silva , E.N.S. Guerra (2021). ``Oral Manifestations in Patients with COVID-19: A Living Systematic Review.'' J Dent Res 100(2): 141-154. SOURCE OF FUNDING: Non-profit, Foundations, etc.? National Council for Scientific and Technological Development, Ministry of Education, Brazil and the Department of Research and Innovation, University of Brasilia, Brazil. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

A cross-sectional assessment of long-term effects in adolescent and young adult head and neck cancer survivors treated with radiotherapy.

PURPOSE: Adolescent and young adult (AYA) head and neck (H&N) cancer survivors are at risk of long-term complications. A cross-sectional study of survivors recalled for clinical evaluation was performed to evaluate late effects in this population. METHODS: Surviving patients who had been diagnosed with H&N cancer between the ages of 15 and 39 years and treated with radiation therapy (RT) in British Columbia between 1970 and 2010 were invited to participate in this study. Survivors were assessed in consultation by a radiation oncologist for a complete history and physical exam. Comprehensive data collection of subjective and objective late effects of RT and screening investigations were completed. RESULTS: Of 36 AYA H&N participants, the majority were female (61%), and the most common tumour sites were thyroid (28%), oropharynx (17%), salivary gland (14%) and larynx (14%). Dental extractions post treatment was performed for 33% and dental implants for 17%. The majority (72%) reported xerostomia, 50% had dysphagia to solids and 25% hearing loss. Of the non-thyroid cancer patients who underwent RT to their neck, 45% developed hypothyroidism. There were 28% of participants with asymptomatic carotid stenosis and 27% with thyroid nodules; all were diagnosed after recall screening. CONCLUSIONS: Survivors of AYA H&N cancer treated with RT reported numerous long-term complications. Comprehensive follow-up and screening guidelines should be established for this at-risk population. IMPLICATIONS FOR CANCER SURVIVORS: AYA H&N cancer survivors and their primary care practitioners should be educated on screening recommendations and the risk of late effects.

Quantitative assessment of dry mouth in scrub typhus using salivary scintigraphy.

Scrub typhus is an acute febrile illness caused by the intracellular pathogen Orientia tsutsugamushi. The clinical features include fever, myalgia, lymphadenopathy, and dry mouth. However, no studies have assessed the symptom of dry mouth in patients with scrub typhus. We investigated the pattern of salivary scintigraphy during the acute febrile state and compared it with any changes after treatment. Fourteen patients underwent both pre- and post-treatment salivary scintigraphy. Imaging analysis was conducted using radioactivity in the oral cavity, parotid glands, and submandibular glands. During the acute phase, the radioactivity in the oral cavity markedly decreased, while that in the parotid and submandibular glands was preserved. After treatment, radioactivity in the oral cavity showed a significant increase at 20-min, 40-min, and after wash-out. The ejection fraction (%) of the parotid glands also increased after treatment. In contrast, the radioactivity levels of the parotid and submandibular glands were not statistically different after treatment. Salivary scintigraphy indicated that insufficient saliva excretion from the salivary glands into the oral cavity was one reason for the dry mouth reported by patients with scrub typhus. In the future, salivary scintigraphy imaging could contribute to the evaluation of dry mouth in patients with scrub typhus.

Assessment of Radiation-Induced Xerostomia: Validation of the Xerostomia Questionnaire in Chinese Patients With Head and Neck Cancer.

BACKGROUND: Xerostomia is a common complication in patients with head and neck cancer (HNC) during and after radiotherapy. The lack of a simply-administered and well-validated self-reported instrument has hampered the assessment and management of xerostomia for research and clinical purposes in China. OBJECTIVE: This study aimed to evaluate the content validity and psychometric properties of the Xerostomia Questionnaire (XQ) in Chinese patients with HNC undergoing radiotherapy. METHODS: This psychometric evaluation study enrolled 80 patients and was conducted in 2 stages: translation and evaluation of content validity and psychometric evaluation. Cognitive interviews (n = 10) were conducted using the Participant Interview Form. The psychometric evaluation (n = 80) included score distribution, homogeneity (interitem and item-total correlations), factor structure (exploratory factor analysis), internal consistency (Cronbach's α), criterion-related validity (person correlation), and test-retest reliability (intraclass correlations). RESULTS: Content validity was supported by cognitive interviews. The factor analysis resulted in a 1-factor solution with strong factor loadings (0.84-0.91) that explained 75.6% of the total variance. The internal consistency was excellent, with a Cronbach's α of .95. The XQ correlated strongly with other measures of xerostomia (0.70-0.80), which supports criterion-related validity. The test-retest reliability was excellent (intraclass correlation coefficient = 0.92). CONCLUSIONS: The result provides evidence for the validity and reliability of the XQ in a sample of Chinese patients with HNC. IMPLICATIONS FOR PRACTICE: The XQ can be used in both clinical practice and research as a valuable tool to screen for problems with xerostomia, monitor the xerostomia level, and evaluate the effects of treatment and interventions among patients with HNC.

Assessment of saliva and oral candidiasis levels 12, 24 and 36 months after radiotherapy in patients with head and neck cancer.

INTRODUCTION: Hyposalivation is a serious complication during radiotherapy (RT) and it is one of the major risk factors for the presence of candidiasis. The aim of this study was to evaluate the salivary hypofunction during the different stages of RT, analysing its connection with the presence of candidiasis. MATERIAL AND METHODS: A retrospective study was performed in 83 patients who had been diagnosed with head and neck tumours and who were undergoing RT treatment. Their salivary function was clinically analysed throughout the course of the RT treatment (before, during and after treatment) by means of the whole saliva test (WST), both unstimulated (WST-I) and stimulated (WST-II), and its relationship with candidiasis was evaluated using culture-based methods. RESULTS: The WST-I before RT was 37.24±17.36mm and the WST-II was 60.70±30.98mm, with 47% of patients testing positive for candidiasis. The prevalence of candidiasis increased up to 55.8% during RT and it returned to similar pre-RT levels at the end of treatment (45.2%). A statistical significant relationship was found between low WST-I and candidiasis in the 1st (13.58 vs 20.78mm), 3rd (18.06 vs 24.36mm), 6th (16.83 vs 24.5) and 12th (16 vs 28.74mm) months after RT; and this relationship was also detected for WST-II in the 1st (24.73 vs 41.26mm) and 3rd (27.71 vs 39.91mm) months after RT. Female sex was identified as an independent associated risk factor for mild hyposalivation before RT (OR=6.50, CI: 95% 1.77-23.93, p=0.005) and glandular hypofunction (OR=3.01, CI: 95% 1.12-8.10, p=0.029). DISCUSSION: There is a clear relation between hyposalivation and the presence of candidiasis during and after RT. Larger studies must be performed in order to further elucidate this effect.

Prospective assessment of gustatory function after radiotherapy for head and neck cancers.

BACKGROUND: Taste disorders are major causes of morbidity in patients undergoing head and neck irradiation. We quantitatively assessed the gustatory function of patients with head and neck cancers who underwent radiotherapy using recently developed standardised tools for measuring taste. METHODS: Twenty patients undergoing head and neck irradiation responded to a specific questionnaire and were assessed by olfactory and gustatory function tests. To assess changes over time, testing was performed before, immediately after, and at 2- and 4-week intervals following the start of radiotherapy. Concurrently, patients were evaluated for xerostomia from radiotherapy. RESULTS: A decrease in the taste recognition threshold was observed in the second week after the beginning of radiotherapy. The taste detection threshold improved within the 14th-18th week. Most affected patients demonstrated that their gustatory function primarily decreased independent of the olfactory function. Disturbances in taste were exponentially worsened beyond an accumulated dose of 30 Gy and involved all tastants. According to a multivariate analysis, radiation-induced taste impairment was not influenced by the degree of xerostomia. However, there was an association between the dose of irradiation and the severity of taste disturbance. CONCLUSIONS: In this preliminary study, we found that the taste function was worse 2 weeks after the start of radiotherapy and returned to pretreatment levels within 4.5 months. Taste disturbances were exponentially worse beyond an accumulated dose of 20 Gy. Taste dysfunction after radiotherapy was not influenced by the degree of xerostomia, whereas only the dose of irradiation was associated with the severity of taste dysfunction.

Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Frecuencia del síndrome de Sjögren en pacientes con lupus eritematoso del Hospital Central del Instituto de Previsión Social en el año 2017 que acuden a tratamiento odontológico / Frequency of sjögren's syndrome in patients with lupus erythematosus at the Central Hospital of the Social Welfare Institute in 2017 who seek dental treatment

La xerostomía, síndrome de boca seca o síndrome de Sjögren se define como la disminución del flujo salival en condiciones de reposo. El origen de esta endad clínica es mulcausal, pudiendo ser el resultado de una alteración localizada sobre las glándulas productoras de la saliva, o bien el resultado de un desequilibrio o alteración de índole sistémica. La evaluación del grado de disfunción de las glándulas salivares ha constuido un objevo básico por ello el propósito de este estudio fue determinar frecuencia del síndrome de Sjögren en pacientes con lupus eritematoso del hospital central del Instuto de Previsión Social en el año 2017 que acuden a tratamiento odontológico. Se realizó un descripción observacional retrospecvo para lo cual se recurrió a la historial clínico previo permiso del jefe de reumatología para acceder a los datos . Como conclusión general se obtuvo que existe una predominancia de pacientes de entre 46 a 50 años de edad representada por el 39% y de sexo femenino en el 83% de los casos. Se demuestra la frecuencia mencionando que acudieron 74 pacientes y de los cuales 18 (24%) personas presentan lupus eritematoso y síndrome de Sjögren, y entre estos el 78% acude a tratamiento odontológico.

Xerostomia, dry mouth syndrome or Sjögren's syndrome is defined as decreased salivary flow under resng condions. The origin of this clinical enty is mulcausal, and may be the result of an alteraon located on the glands producing saliva, or the result of an imbalance or alteraon of a systemic nature. The evaluaon of the degree of dysfuncon of the salivary glands has been a basic objecve and therefore the purpose of this study was to determine the frequency of Sjögren syndrome in paents with lupus erythematosus from the central hospital of the Social Welfare Instute in 2017 who seek dental treatment. A retrospecve observaonal descripon was made, for which the clinical history was used with the prior permission of the head of rheumatology to access the data. The general conclusion was that there is a predominance of paents between 46 and 50 years of age represented by 39% and female in 83% of cases. The frequency is demonstrated by menoning that 74 paents aended and of which 18 (24%) people present with lupus erythematosus and Sjögren's syndrome, of which 78% aend dental treatment

The Needs and Benefits of Continuous Model Updates on the Accuracy of RT-Induced Toxicity Prediction Models Within a Learning Health System.

PURPOSE: Clinical data collection and development of outcome prediction models by machine learning can form the foundation for a learning health system offering precision radiation therapy. However, changes in clinical practice over time can affect the measures and patient outcomes and, hence, the collected data. We hypothesize that regular prediction model updates and continuous prospective data collection are important to prevent the degradation of a model's predication accuracy. METHODS AND MATERIALS: Clinical and dosimetric data from head and neck patients receiving intensity modulated radiation therapy from 2008 to 2015 were prospectively collected as a routine clinical workflow and anonymized for this analysis. Prediction models for grade ≥2 xerostomia at 3 to 6 months of follow-up were developed by bivariate logistic regression using the dose-volume histogram of parotid and submandibular glands. A baseline prediction model was developed with a training data set from 2008 to 2009. The selected predictor variables and coefficients were updated by 4 different model updating methods. (A) The prediction model was updated by using only recent 2-year data and applied to patients in the following test year. (B) The model was updated by increasing the training data set yearly. (C) The model was updated by increasing the training data set on the condition that the area under the curve (AUC) of the recent test year was less than 0.6. (D) The model was not updated. The AUC of the test data set was compared among the 4 model updating methods. RESULTS: Dose to parotid and submandibular glands and grade of xerostomia showed decreasing trends over the years (2008-2015, 297 patients; P < .001). The AUC of predicting grade ≥2 xerostomia for the initial training data set (2008-2009, 41 patients) was 0.6196. The AUC for the test data set (2010-2015, 256 patients) decreased to 0.5284 when the initial model was not updated (D). However, the AUC was significantly improved by model updates (A: 0.6164; B: 0.6084; P < .05). When the model was conditionally updated, the AUC was 0.6072 (C). CONCLUSIONS: Our preliminary results demonstrate that updating prediction models with prospective data collection is effective for maintaining the performance of xerostomia prediction. This suggests that a machine learning framework can handle the dynamic changes in a radiation oncology clinical practice and may be an important component for the construction of a learning health system.

A Quantitative Clinical Decision-Support Strategy Identifying Which Patients With Oropharyngeal Head and Neck Cancer May Benefit the Most From Proton Radiation Therapy.

PURPOSE: Developing a quantitative decision-support strategy estimating the impact of normal tissue complications from definitive radiation therapy (RT) for head and neck cancer (HNC). We developed this strategy to identify patients with oropharyngeal HNC who may benefit most from receiving proton RT. METHODS AND MATERIALS: Recent normal tissue complication probability (NTCP) models for dysphagia, esophagitis, hypothyroidism, xerostomia, and oral mucositis were used to estimate NTCP for 33 patients with oropharyngeal HNC previously treated with photon intensity modulated radiation therapy (IMRT). Comparative proton therapy plans were generated using clinical protocols for HNC RT at a collaborating proton center. Organ-at-risk (OAR) doses from photon and proton RT plans were used to calculate NTCPs; Monte Carlo sampling 10,000 times was used for each patient to account for model parameter uncertainty. The latency and duration of each complication were modeled from calculated NTCP, accounting for age-, sex-, smoking- and p16-specific conditional survival probability. Complications were then assigned quality-adjustment factors based on severity to calculate quality-adjusted life years (QALYs) lost from each complication. RESULTS: Based on our institutional-delivered photon IMRT doses and the achievable proton therapy doses, the average QALY reduction from all HNC RT complications for photon and proton therapy was 1.52 QALYs versus 1.15 QALYs, with proton therapy sparing 0.37 QALYs on average (composite 95% confidence interval, 0.27-2.53 QALYs). Long-term complications (dysphagia and xerostomia) contributed most to the QALY reduction. The QALYs spared with proton RT varied considerably among patients, ranging from 0.06 to 0.84 QALYs. Younger patients with p16-positive tumors who smoked ≤10 pack-years may benefit most from proton therapy, although this finding should be validated using larger patient series. A sensitivity analysis reducing photon IMRT doses to all OARs by 20% resulted in no overall estimated benefit with proton therapy with -0.02 QALYs spared, although some patients still had an estimated benefit in this scenario, ranging from -0.50 to 0.43 QALYs spared. CONCLUSIONS: This quantitative decision-support strategy allowed us to identify patients with oropharyngeal cancer who might benefit the most from proton RT, although the estimated benefit of proton therapy ultimately depends on the OAR doses achievable with modern photon IMRT solutions. These results can help radiation oncologists and proton therapy centers optimize resource allocation and improve quality of life for patients with HNC.

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

Importance: Whole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial. Objective: To assess whether xerostomia is a toxic effect of WBRT. Design, Setting, and Participants: This observational cohort study enrolled patients from November 2, 2015, to March 20, 2018, at 1 academic center (University of North Carolina Hospitals) and 2 affiliated community hospitals (High Point Regional Hospital and University of North Carolina Rex Hospital). Adult patients (n = 100) receiving WBRT for the treatment or prophylaxis of brain metastases were enrolled. Patients who had substantial baseline xerostomia or did not complete WBRT or at least 1 postbaseline questionnaire were prospectively excluded from analysis and follow-up. Patients received 3-dimensional WBRT using opposed lateral fields covering the skull and the C1 or C2 vertebra. Per standard practice, the parotid glands were not prospectively delineated. Main Outcomes and Measures: Patients completed the University of Michigan Xerostomia Questionnaire and a 4-point bother score at baseline, immediately after WBRT, at 1 month, at 3 months, and at 6 months. The primary end point was the 1-month xerostomia score, with a hypothesized worsening score of 10 points from baseline. Results: Of the 100 patients enrolled, 73 (73%) were eligible for analysis and 55 (55%) were evaluable at 1 month. The 73 patients included 43 women (59%) and 30 men (41%) with a median (range) age of 61 (23-88) years. The median volume of parotid receiving at least 20 Gy (V20Gy) was 47%. The mean xerostomia score was 7 points at baseline and was statistically significantly higher at each assessment period, including 21 points immediately after WBRT (95% CI, 16-26; P < .001), 23 points (95% CI, 16-30; P < .001) at 1 month, 21 points (95% CI, 13-28; P < .001) at 3 months, and 14 points (95% CI, 7-21; P = .03) at 6 months. At 1 month, the xerostomia score increased by 20 points or more in 19 patients (35%). The xerostomia score at 1 month was associated with parotid dose as a continuous variable and was 35 points in patients with parotid V20Gy of 47% or greater, compared with only 9 points in patients with parotid V20Gy less than 47% (P < .001). The proportion of patients who self-reported to be bothered quite a bit or bothered very much by xerostomia at 1 month was 50% in those with parotid V20Gy of 47% or greater, compared with only 4% in those with parotid V20Gy less than 47% (P < .001). At 3 months, this difference was 50% vs 0% (P = .001). Xerostomia was not associated with medication use. Conclusions and Relevance: Clinically significant xerostomia occurred by the end of WBRT, appeared to be persistent, and appeared to be associated with parotid dose. The findings from this study suggest that the parotid glands should be delineated for avoidance to minimize these toxic effects in patients who undergo WBRT and often do not survive long enough for salivary recovery.

Objective and subjective assessment of xerostomia in patients of locally advanced head-and-neck cancers treated by intensity-modulated radiotherapy.

BACKGROUND: Parotid-sparing intensity-modulated radiotherapy (IMRT) effectively reduces xerostomia in head-and-neck cancer (HNC). Changes in the salivary output at 1 year were studied and correlation with quality of life (QOL) changes in patients of locally advanced HNC (LAHNC) was drawn. MATERIALS AND METHODS: Between October 2009 and October 2011, 20 patients of LAHNC were treated with IMRT using simultaneous integrated boost technique. High-risk clinical target volume (CTV) was given a dose of 66 Gy/30 fr, intermediate-risk CTV 60 Gy/30 fr, and low-risk CTV 54 Gy/30 fr. The saliva flow rate was estimated for 5 min at rest (unstimulated) and after using lemon drops (stimulated) for the next 5 min, at baseline (pretreatment), and 3, 6, and 12 months following treatment. Evaluation of patients' perception of dry mouth was done using EORTC-QLQ-C30 and HN35 questionnaires at the same time points. RESULTS: Baseline unstimulated and stimulated salivary flow rates were 0.659 ml/min and 1.69 ml/min, respectively. At 3 months, a significant reduction in unstimulated (0.346 ml/min) and stimulated (0.80 ml/min) flow rate was observed. Unstimulated flow rate continued to decrease further till 6 months (0.295 ml/min), but slight improvement was seen in stimulated flow rate (0.91 ml/min). At 12 months, minimal recovery was observed in both unstimulated (0.362 ml/min) and stimulated flow rates (1.09 ml/min). EORTC-QOL questionnaire mean scores for dryness and stickiness of saliva were 10 and 15 at baseline and increased to 36 and 25, respectively, at 3 months. At 6 months, symptom score for dryness further increased to 45 and then decreased to 33 at 12 months. Stickiness score remained static from 3 to 12 months. Salivary flow rate correlated well with dry mouth (P < 0.05) but not with the perception of sticky saliva (P = 0.82) at 6 months and beyond. CONCLUSIONS: Both salivary flow rate and xerostomia-related questions worsened at 3 months even with IMRT and showed a similar pattern of recovery.

Intensity-modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) for head and neck cancer: cost-effectiveness analysis.

BACKGROUND: A cost-effectiveness analysis of IMRT compared to 3D-CRT for head and neck cancer patients (HNCPs) was conducted in the Brazilian Public Health System. METHODS: A Markov model was used to simulate radiation therapy-induced dysphagia and xerostomia in HNCPs. Data from the PARSPORT trial and the quality-of-life study were used as parameters. The incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained were calculated. RESULTS: At 2 years, IMRT was associated with an incremental benefit of 0.16 QALYs gained per person, resulting in an ICER of BRL 31,579 per QALY gained. IMRT was considered cost-effective when using the guideline proposed by the World Health Organization (WHO) of three times the national gross domestic product (GDP) per capita (BRL 72,195). Regarding life expectancy (15 years), the incremental benefit of IMRT was 1.16 QALYs gained per person, with an ICER of BRL 4,341. IMRT was also cost-effective using the WHO definition, which states that the maximum cost is equal to the GDP per capita (BRL 24,065). CONCLUSIONS: IMRT was considered cost-effective from the perspective of the Brazilian public health system.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus Proton Therapy for Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: To compared the cost-effectiveness of intensity modulated proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) in the management of stage III-IVB oropharynx cancer (OPC). METHODS AND MATERIALS: A Markov model was constructed to compare IMRT with PBT for a 65-year-old patient with stage IVA OPSCC. We assumed PBT led to a 25% reduction in long-term xerostomia, short-term dysgeusia, and the need for gastrostomy tube. Fewer dental complications were also expected with PBT. Incremental cost-effectiveness ratios (ICERs) were calculated, and value of information analyses were performed. The societal willingness-to-pay was defined as $100K per quality-adjusted life year (QALY). RESULTS: The ICERs for PBT for favorable human papillomavirus (HPV)-positive OPC were $288,000/QALY and $390,000/QALY in the payer perspective (PP) and societal perspective, respectively. Under nearly every scenario, PBT was not cost-effective, with ICERs above $150,000/QALY in the PP. The ICERs for HPV-negative OPC were typically greater than $250K/QALY in both perspectives. For HPV-positive patients, the ICER was less than $100,000/QALY in the PP only in younger patients who experienced a 50% reduction in both xerostomia and gastrostomy use. On probabilistic sensitivity analyses, there were 0% and 0.4% probabilities that PBT was cost-effective for 65- and 55-year old patients, respectively. The value of information was zero or negligible for all ages and perspectives at willingness-to-pay of $100,000/QALY and only meaningful in the PP for younger patients at a willingness-to-pay of $150,000/QALY. CONCLUSIONS: Intensity modulated proton beam therapy was only cost-effective in the PP if assumed to achieve profound reductions in long-term morbidity for younger patients; it was never cost-effective in the societal perspective. Prospective data are needed (and may be valuable) to better characterize the comparative toxicities of these treatments but are unlikely to change this calculation, except potentially in the most favorable cohort of patients.

Intensity-modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) for head and neck cancer: cost-effectiveness analysis

SUMMARY BACKGROUND: A cost-effectiveness analysis of IMRT compared to 3D-CRT for head and neck cancer patients (HNCPs) was conducted in the Brazilian Public Health System. METHODS: A Markov model was used to simulate radiation therapy-induced dysphagia and xerostomia in HNCPs. Data from the PARSPORT trial and the quality-of-life study were used as parameters. The incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained were calculated. RESULTS: At 2 years, IMRT was associated with an incremental benefit of 0.16 QALYs gained per person, resulting in an ICER of BRL 31,579 per QALY gained. IMRT was considered cost-effective when using the guideline proposed by the World Health Organization (WHO) of three times the national gross domestic product (GDP) per capita (BRL 72,195). Regarding life expectancy (15 years), the incremental benefit of IMRT was 1.16 QALYs gained per person, with an ICER of BRL 4,341. IMRT was also cost-effective using the WHO definition, which states that the maximum cost is equal to the GDP per capita (BRL 24,065). CONCLUSIONS: IMRT was considered cost-effective from the perspective of the Brazilian public health system.

RESUMO INTRODUÇÃO: Foi realizada uma análise de custo-efetividade da radioterapia com intensidade modulada de feixe (IMRT) comparada com a radioterapia conformada para pacientes com câncer de cabeça e pescoço (CCP) no contexto do Sistema Único de Saúde (SUS). MÉTODOS: Foi elaborado um modelo de Markov para comparar os custos médicos diretos e os desfechos de saúde relacionados à qualidade de vida do paciente pós-intervenção radioterápica sofrendo de xerostomia e disfagia. Com essa finalidade, foram usados os dados do estudo PARSPORT e parâmetros de qualidade de vida. Os resultados comparativos das estratégias alternativas de tratamento foram medidos pela razão de custo-efetividade incremental (RCEI). O desfecho analisado foi o de anos de vida ajustados à qualidade (QALY). RESULTADOS: Em um horizonte de tempo de dois anos, a IMRT foi associada com um benefício incremental de ganho de 0,16 QALYs por indivíduo, resultando em um RCEI de R$ 31.579 por QALY ganhado. A IMRT foi custo-efetivo, adotando-se o limite máximo de disposição a pagar, proposto pela OMS, de três vezes o PIB per capita nacional, equivalente a R$ 72.195. No horizonte de tempo de 15 anos, o benefício incremental de ganho foi de 1,16 QALYs por indivíduo, com um RCEI de R$ 4.341. A IMRT foi custo-efetivo, adotando-se o limite de disposição a pagar, proposto pela OMS, de uma vez o PIB per capita nacional, equivalente a R$ 24.065. CONCLUSÃO: A IMRT foi considerada um tratamento custo-efetivo na perspectiva do SUS.

Randomized Controlled Trial of Rituximab and Cost-Effectiveness Analysis in Treating Fatigue and Oral Dryness in Primary Sjögren's Syndrome.

OBJECTIVE: To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS). METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro-positive patients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness. RESULTS: All 133 patients who were randomized to receive placebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group). CONCLUSION: The results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population.

The price of robustness; impact of worst-case optimization on organ-at-risk dose and complication probability in intensity-modulated proton therapy for oropharyngeal cancer patients.

PURPOSE: To quantify the impact of the degree of robustness against setup errors and range errors on organ-at-risk (OAR) dose and normal tissue complication probabilities (NTCPs) in intensity-modulated proton therapy for oropharyngeal cancer patients. MATERIAL AND METHODS: For 20 oropharyngeal cases (10 unilateral and 10 bilateral), robust treatment plans were generated using 'minimax' worst-case optimization. We varied the robustness against setup errors ('setup robustness') from 1 to 7mm and the robustness against range errors ('range robustness') from 1% to 7% (+1mm). We evaluated OAR doses and NTCP-values for xerostomia, dysphagia and larynx edema. RESULTS: Varying the degree of setup robustness was found to have a considerably larger impact than varying the range robustness. Increasing setup robustness from 1mm to 3, 5, and 7mm resulted in average NTCP-values to increase by 1.9, 4.4 and 7.5 percentage point, whereas they increased by only 0.4, 0.8 and 1.2 percentage point when increasing range robustness from 1% to 3%, 5% and 7%. The degree of setup robustness was observed to have a clinically significant impact in bilateral cases in particular. CONCLUSIONS: For oropharyngeal cancer patients, minimizing setup errors should be given a higher priority than minimizing range errors.