The influence of radiation dose on taste impairment in a prospective observational study cohort of oropharyngeal cancer patients.

BACKGROUND: To analyze the influence of radiation dose on late radiation-associated taste impairment in oropharyngeal cancer (OPC) patients treated with intensity-modulated radiotherapy (IMRT) using the taste bud bearing tongue mucosa as organ at risk. MATERIAL AND METHODS: This study is part of an ongoing, prospective observational study. Cancer-free OPC survivors with at least 24 months from IMRT were included in this analysis. Scores for taste impairment and dry mouth were extracted from the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN) with scores of ≥5 considered as moderate-to-severe symptoms. The mean dose, minimum and maximum dose to the taste bud bearing tongue mucosa, the ipsi- and contralateral parotid and submandibular glands were extracted and analyzed for correlation with moderate-to-severe taste impairment. RESULTS: One hundred sixteen T1-4 OPC patients were included (81% males, median age: 55). The primary tumor was in the tonsil in 92 cases (79%) and in the base of tongue in 21 cases (18%). Patients were treated with 64.2-72.0 Gy; 37 patients (32%) received concurrent chemotherapy and 22 (19%) concurrent targeted therapy. After a median of 58 months from RT (IQR: 43-68) 38 patients (33%) suffered from moderate-to-severe long-term radiation-associated taste impairment. No dose volume parameter of the taste bud bearing tongue mucosa and the salivary glands was significantly associated with moderate-to-severe taste impairment for the whole patient cohort. For patients without concurrent chemotherapy, the minimum and mean dose to the ipsilateral parotid gland, and the maximum dose to the submandibular gland was significantly associated with late taste impairment (all p < 0.05). A significant correlation was found between taste impairment and dry mouth (p < 0.001). CONCLUSION: The dose to the ipsilateral parotid gland seems to play an important role in the development of late taste impairment. The influence of dose to the taste bud bearing tongue mucosa remains unclear and needs further investigation.

Fabrication of an unconventional bolus-type stent for a combined intraoral/extraoral defect treated with proton radiation therapy.

Customized intraoral devices help the radiation oncologist minimize the adverse effects of radiation and maximize the tumor control rate by keeping the anatomic structures in a consistent position during each fraction of radiation treatment. This article illustrates the fabrication of a bolus-type positioning device for a combined intraoral/extraoral defect treated with proton radiation therapy.

Patterns of symptom burden during radiotherapy or concurrent chemoradiotherapy for head and neck cancer: a prospective analysis using the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module.

BACKGROUND: A prospective longitudinal study to profile patient-reported symptoms during radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) for head and neck cancer was performed. The goals were to understand the onset and trajectory of specific symptoms and their severity, identify clusters, and facilitate symptom interventions and clinical trial design. METHODS: Participants in this questionnaire-based study received RT or CCRT. They completed the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module before and weekly during treatment. Symptom scores were compared between treatment groups, and hierarchical cluster analysis was used to depict clustering of symptoms at treatment end. Variables believed to predict symptom severity were assessed using a multivariate mixed model. RESULTS: Among the 149 patients studied, the majority (47%) had oropharyngeal tumors, and nearly one-half received CCRT. Overall symptom severity (P < .001) and symptom interference (P < .0001) became progressively more severe and were more severe for those receiving CCRT. On multivariate analysis, baseline Eastern Cooperative Oncology Group performance status (P < .001) and receipt of CCRT (P < .04) correlated with higher symptom severity. Fatigue, drowsiness, lack of appetite, problem with mouth/throat mucus, and problem tasting food were more severe for those receiving CCRT. Both local and systemic symptom clusters were identified. CONCLUSIONS: The findings from this prospective longitudinal study identified a pattern of local and systemic symptoms, symptom clusters, and symptom interference that was temporally distinct and marked by increased magnitude and a shift in individual symptom rank order during the treatment course. These inform clinicians about symptom intervention needs, and are a benchmark for future symptom intervention clinical trials.

Temporal characterization of acute pain and toxicity kinetics during radiation therapy for head and neck cancer. A retrospective study.

Objectives: Pain during Radiation Therapy (RT) for oral cavity/oropharyngeal cancer (OC/OPC) is a clinical challenge due to its multifactorial etiology and variable management. The objective of this study was to define complex pain profiles through temporal characterization of pain descriptors, physiologic state, and RT-induced toxicities for pain trajectories understanding. Materials and methods: Using an electronic health record registry, 351 OC/OPC patients treated with RT from 2013 to 2021 were included. Weekly numeric scale pain scores, pain descriptors, vital signs, physician-reported toxicities, and analgesics were analyzed using linear mixed effect models and Spearman's correlation. Area under the pain curve (AUCpain) was calculated to measure pain burden over time. Results: Median pain scores increased from 0 during the weekly visit (WSV)-1 to 5 during WSV-7. By WSV-7, 60% and 74% of patients reported mouth and throat pain, respectively, with a median pain score of 5. Soreness and burning pain peaked during WSV-6/7 (51%). Median AUCpain was 16% (IQR (9.3-23)), and AUCpain significantly varied based on gender, tumor site, surgery, drug use history, and pre-RT pain. A temporal increase in mucositis and dermatitis, declining mean bodyweight (-7.1%; P < 0.001) and mean arterial pressure (MAP) 6.8 mmHg; P < 0.001 were detected. Pulse rate was positively associated while weight and MAP were negatively associated with pain over time (P < 0.001). Conclusion: This study provides insight on in-depth characterization and associations between dynamic pain, physiologic, and toxicity kinetics. Our findings support further needs of optimized pain control through temporal data-driven clinical decision support systems for acute pain management.

Variable planning margin approach to account for locoregional variations in setup uncertainties.

PURPOSE: To develop a method for creating variable planning margins around a clinical treatment volume (CTV) and to evaluate its application in head and neck cancer radiotherapy in accounting for locoregional variations of nonrigid setup uncertainties. METHODS: Ten computed tomography (CT) images (with a resolution of 0.68 × 0.68 × 2.5 mm(3)) of a head and neck cancer patient were acquired from the first two weeks of treatment for this study. Five rigid structures (the C2, C5, and caudal C7 vertebrae, mandible, and jugular notch) were used as the landmarks for creating variable local margins. At different CTV locations, local margins were calculated as the weighted average of margins determined at different landmark points from previous studies. The weight was determined by a Gaussian falloff function of the distance between the current location and each landmark point. The CTV delineated on the planning CT image, spanning from the upper portion of the mouth to the lower part of the neck, was expanded to form the planning treatment volume (PTV) with either variable or the conventional constant margins. To evaluate the target coverage, the original planning CTV was deformably mapped to each daily treatment CT using a deformable image registration method. We examined the overlap of the deformed CTV and the rigidly aligned PTV for each margin design strategy and compared the efficacy of the variable margin with the constant margin approach. RESULTS: For the variable margin approach with a baseline C2 margin of 2.5 mm in the left-right, anterior-posterior, and superior-inferior directions, an average of 99.2% of the CTV was within the PTV, and for the approach with a constant 2.5 mm margin, an average of 97.9% of the CTV was within the PTV. With a baseline margin of 2.0 mm, the variable margin approach had an average coverage of 97.8%, similar to that of the constant 2.5 mm margin approach. However, its average nonoverlapped PTV proportion was 32.4%, smaller than that of the constant 2.5 mm margin approach (33.7%). Paired t-tests of computations from the ten treatment fractions showed no significant difference in CTV coverage for the variable margin approach with a baseline of 2.0 mm and the constant 2.5 margin approach (p = 0.054), but the nonoverlapped PTV proportion was significantly smaller for the variable margin approach with a baseline of 2.0 mm than for the constant 2.5 mm margin approach (p < 0.0001). The CTV coverage with the variable margin approach was also significantly higher than with the constant margin approach in the lower neck area, where a larger setup error normally occurs. CONCLUSIONS: We implemented a variable margin approach to account for locoregional variations of setup uncertainties for head and neck cancer radiotherapy, and demonstrated the effectiveness of this approach when compared with the conventional global constant margin expansion approach, where the treatment target spreads out to a broad region. As variable margin data become available and more clinical studies are performed, this approach could be applicable to other treatment sites as well.

Development and validation of a contouring guideline for the taste bud bearing tongue mucosa.

PURPOSE: To introduce a contouring guideline for the taste bud bearing tongue mucosa for head and neck cancer patients receiving radiotherapy. METHODS AND MATERIALS: CT simulation images of oropharyngeal cancer patients were used to delineate both the whole tongue (extrinsic/intrinsic tongue muscles, floor of mouth) and the taste bud bearing tongue mucosa (method A: adaptation of the whole tongue structure; method B: axial adaptation of a mid-sagittal contour). Volumetric and dosimetric parameters of the whole tongue and the two methods of mucosal delineation, spatial overlap between methods A and B, and inter-observer variability for method B were calculated. RESULTS: The study cohort was comprised of 70 patients with T1-4 N0-1 tonsillar (83%) and base of tongue (17%) cancers. Most of the comparative parameters between the whole tongue and mucosa (method A) significantly differed (mean, minimum, and maximum dose, V5-V70, D40-D90). The mean dose calculated for the whole tongue deviated on average 3.77 Gy compared to method A. No significant differences were found between methods A and B of the taste bud bearing tongue mucosa structure, and none of the dosimetric parameters differed more than 1.03 Gy on average. The mean Dice similarity coefficient for both mucosal structures was 0.79 ± 0.05, and 0.63 ± 0.12 for the inter-observer analysis of method B. CONCLUSIONS: We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.

A prospective parallel design study testing non-inferiority of customized oral stents made using 3D printing or manually fabricated methods.

BACKGROUND AND PURPOSE: Customized mouth-opening-tongue-depressing-stents (MOTDs) may reduce toxicity in patients with head and neck cancers (HNC) receiving radiotherapy (RT). However, making MOTDs requires substantial resources, which limits their utilization. Previously, we described a workflow for fabricating customized 3D-printed MOTDs. This study reports the results of a prospective trial testing the non-inferiority of 3D-printed to standard and commercially-available (TruGuard) MOTDs as measured by patient reported outcomes (PROs). MATERIALS AND METHODS: PROs were collected at 3 time points: (t1) simulation, (t2) prior to RT, (t3) between fractions 15-25 of RT. Study participants received a 3D-printed MOTDs (t1, t2, t3), a wax-pattern (t1), an acrylic-MOTDs (t2, t3) and an optional TruGuard (t1, t2, t3). Patients inserted the stents for 5-10 min and completed a PRO-questionnaire covering ease-of-insertion and removal, gagging, jaw-pain, roughness and stability. Inter-incisal opening and tongue-displacement were recorded. With 39 patients, we estimated 90% power to detect a non-inferiority margin of 2 at a significance level of 0.025. Matched pairs and t-test were used for statistics. RESULTS: 41 patients were evaluable. The 3D-printed MOTDs achieved a significantly better overall PRO score compared to the wax-stent (p = 0.0007) and standard-stent (p = 0.0002), but was not significantly different from the TruGuard (p = 0.41). There was no difference between 3D-printed and standard MOTDs in terms of inter-incisal opening (p = 0.4) and position reproducibility (p = 0.98). The average 3D-printed MOTDs turn-around time was 8 vs 48 h for the standard-stent. CONCLUSIONS: 3D-printed stents demonstrated non-inferior PROs compared to TruGuard and standard-stents. Our 3D-printing process may expand utilization of MOTDs.

Automatic detection of contouring errors using convolutional neural networks.

PURPOSE: To develop a head and neck normal structures autocontouring tool that could be used to automatically detect the errors in autocontours from a clinically validated autocontouring tool. METHODS: An autocontouring tool based on convolutional neural networks (CNN) was developed for 16 normal structures of the head and neck and tested to identify the contour errors from a clinically validated multiatlas-based autocontouring system (MACS). The computed tomography (CT) scans and clinical contours from 3495 patients were semiautomatically curated and used to train and validate the CNN-based autocontouring tool. The final accuracy of the tool was evaluated by calculating the Sørensen-Dice similarity coefficients (DSC) and Hausdorff distances between the automatically generated contours and physician-drawn contours on 174 internal and 24 external CT scans. Lastly, the CNN-based tool was evaluated on 60 patients' CT scans to investigate the possibility to detect contouring failures. The contouring failures on these patients were classified as either minor or major errors. The criteria to detect contouring errors were determined by analyzing the DSC between the CNN- and MACS-based contours under two independent scenarios: (a) contours with minor errors are clinically acceptable and (b) contours with minor errors are clinically unacceptable. RESULTS: The average DSC and Hausdorff distance of our CNN-based tool was 98.4%/1.23 cm for brain, 89.1%/0.42 cm for eyes, 86.8%/1.28 cm for mandible, 86.4%/0.88 cm for brainstem, 83.4%/0.71 cm for spinal cord, 82.7%/1.37 cm for parotids, 80.7%/1.08 cm for esophagus, 71.7%/0.39 cm for lenses, 68.6%/0.72 for optic nerves, 66.4%/0.46 cm for cochleas, and 40.7%/0.96 cm for optic chiasm. With the error detection tool, the proportions of the clinically unacceptable MACS contours that were correctly detected were 0.99/0.80 on average except for the optic chiasm, when contours with minor errors are clinically acceptable/unacceptable, respectively. The proportions of the clinically acceptable MACS contours that were correctly detected were 0.81/0.60 on average except for the optic chiasm, when contours with minor errors are clinically acceptable/unacceptable, respectively. CONCLUSION: Our CNN-based autocontouring tool performed well on both the publically available and the internal datasets. Furthermore, our results show that CNN-based algorithms are able to identify ill-defined contours from a clinically validated and used multiatlas-based autocontouring tool. Therefore, our CNN-based tool can effectively perform automatic verification of MACS contours.

Creating customized oral stents for head and neck radiotherapy using 3D scanning and printing.

BACKGROUND: To evaluate and establish a digital workflow for the custom designing and 3D printing of mouth opening tongue-depressing (MOTD) stents for patients receiving radiotherapy for head and neck cancer. METHODS: We retrospectively identified 3 patients who received radiation therapy (RT) for primary head and neck cancers with MOTD stents. We compared two methods for obtaining the digital impressions of patients' teeth. The first method involved segmentation from computed tomography (CT) scans, as previously established by our group, and the second method used 3D scanning of the patients' articulated stone models that were made during the conventional stent fabrication process. Three independent observers repeated the process to obtain digital impressions which provided data to design customized MOTD stents. For each method, we evaluated the time efficiency, dice similarity coefficient (DSC) for reproducibility, and the 3D printed stents' accuracy. For the 3D scanning method, we evaluated the registration process using manual and automatic approaches. RESULTS: For all patients, the 3D scanning method demonstrated a significant advantage over the CT scanning method in terms of time efficiency with over 60% reduction in time consumed (p < 0.0001) and reproducibility with significantly higher DSC (p < 0.001). The printed stents were tested over the articulated dental stone models, and the trueness of fit and accuracy of dental anatomy was found to be significantly better for MOTD stents made using the 3D scanning method. The automated registration showed higher accuracy with errors < 0.001 mm compared to manual registration. CONCLUSIONS: We developed an efficient workflow for custom designing and 3D-printing MOTD radiation stents. This workflow represents a considerable improvement over the CT-derived segmentation method. The application of this rapid and efficient digital workflow into radiation oncology practices can expand the use of these toxicity sparing devices to practices that do not currently have the support to make them.

Psychosocial and economic impact of cancer.

This article explores the psychosocial and economic implications of cancer and their relevance to the clinician. After a general overview of the topic, the authors focus on aspects of particular importance to the dental professional, including the psychosocial and economic implications of the oral complications of cancer and its therapy, head and neck cancers, and special issues among children with cancer and cancer survivors.

Salivary flow rates measured during radiation therapy in head and neck cancer patients: a pilot study assessing salivary sediment formation.

STATEMENT OF PROBLEM: Xerostomia often occurs in patients being managed for head and neck cancer who receive radiation therapy. Although accurate salivary sampling can be therapeutically important to measure during radiation, sampling errors can occur because of salivary sediments. Determining the impact that salivary sediments have on measured salivary flow rates during radiation is important for management of patients. PURPOSE: The purpose of this study was to assess the magnitude of error associated with the inclusion of nonsalivary components (sediment) in the calculation of whole stimulated saliva flow rates prior to and during radiation therapy (SS and SSR) in patients with head and neck cancer. MATERIAL AND METHODS: Whole paraffin-stimulated saliva was collected in large-mouth centrifuge tubes from 20 patients with head and neck cancer prior to and during the third week of radiation therapy. Gravimetric methods were used to calculate the flow rates at g/5 min. After centrifugation, supernatant saliva was removed and the sediment was oven-dried to remove residual moisture. Sediment weight was subtracted from the original weight of saliva specimens and flow rates were recalculated. Means and standard deviations were determined and flow rate differences before (BC) and after (AC) sediment correction were evaluated statistically with the paired t test (alpha=.05). A nonparametric analysis of the flow rate data with the Wilcoxon matched-pairs signed-ranks test was also used to examine the magnitude and direction of the intrapair (BC-AC) differences (alpha=.05). RESULTS: On average, salivary sediment contributed less than 1% of the total uncorrected weight of saliva prior to radiation therapy. In specimens collected during radiation therapy, sediment contributed an average of 14% of the total uncorrected weight and as high as 95.4% in 1 patient. Sediment percentages were 20% and higher in 4 patients. In the Wilcoxon analysis, 19 out of 20 paired BC and AC flow rates were higher in the BC group in the SS and SSR samples. CONCLUSIONS: The error associated with the inclusion of salivary sediment in the calculation of saliva flow rates prior to radiation treatment was small, but statistically significant. The magnitude of the sediment effect was more pronounced in specimens taken during radiotherapy and was significant, as determined by the Wilcoxon test, but the mean paired differences were not significantly different according to the t test.

Patient reported dry mouth: Instrument comparison and model performance for correlation with quality of life in head and neck cancer survivors.

PURPOSE: To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). METHODS: Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size. RESULTS: Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p < 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5). CONCLUSION: The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.

Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia.

PURPOSE: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. METHODS AND MATERIALS: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). RESULTS: Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). CONCLUSIONS: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.

Erratum to "Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 2: Phase I study".

Radiation-induced xerostomia can result in the rapid onset and progression of dental caries in head and neck cancer patients. Topically applied fluorides have been successfully used to inhibit the formation of dental caries in this population. However, because intensive daily self-application is required, compliance is an issue. The intraoral fluoride-releasing system (IFRS) containing a sodium fluoride core is a newly developed, sustained-release, passive drug delivery system that does not require patient involvement except for periodic replacement, thus reducing the effect of patient compliance on its effectiveness in dental caries prevention. Twenty-two head and neck cancer patients from U. T. M. D. Anderson Cancer Center, with radiation-induced xerostomia, were entered into a pilot study to contrast the daily home use of a 0.4% stannous fluoride-gel-containing tray (control group) to IFRS (study group) with respect to tolerability and adherence, and to obtain information on relative caries preventive efficacy. Participants were stratified on the basis of radiation exposure and randomly assigned to treatment with either IFRS or stannous fluoride gel. Patients in both groups were fitted with two IFRS retainers and also were instructed to use a 1100-ppm fluoride conventional sodium fluoride dentifrice twice daily. The study was conducted as a single-blinded, parallel-cell trial. Pre-existing carious lesions were restored prior to the beginning of the study. The efficacy variable was determined by the mean number of new or recurrent decayed surfaces. Patients were examined for caries 4, 8, 12, 24, 36, and 48 weeks after initiation of treatment. Reports of adverse reactions were based on information volunteered by patients and that were elicited during interviews. At baseline, the resting and stimulated salivary flow rates (g/5min) were significantly greater in the control group than in the study group (p<0.05). Patients in the control group had received significantly more radiation than those in the test group (68Gy vs. 60Gy; p=0.047). No marked differences in follow-up new and recurrent caries were found between the stannous fluoride gel control and IFRS groups during the study period. The rate of new or recurrent carious lesions in the group treated with the fluoride gel was slightly lower than in the IFRS group, based on carious lesions at the baseline examination (Poisson mean number of new or recurrent carious lesions for the control group=0.55 per year vs. 0.83 per year for the study group, p=0.705; odds ratio of the occurrence of any new or recurrent caries during follow-up for control group vs. the study group=0.80; p=0.781). This pilot study revealed that the IFRS was well-tolerated and safe in this study population associated with minimal complications during the duration of this study and was comparable in efficacy to a SnF(2) gel in preventing caries development. The IFRS provided similar rates of control for caries formation to a fluoride-gel-containing tray. The IFRS is designed to release a daily dose of 0.12mg of sodium fluoride, which can be evenly distributed throughout the oral cavity for a single application of 4 months. It would be more convenient than the daily home application of a tray of 0.4% stannous fluoride or 1.1% sodium fluoride gel, and avoids the problem of variable patient compliance.

Intensity-modulated proton therapy and osteoradionecrosis in oropharyngeal cancer.

PURPOSE: We compared mandibular doses and osteoradionecrosis in patients with oropharyngeal cancer after intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT). METHODS AND MATERIALS: We identified 584 patients who received definitive radiotherapy for oropharyngeal cancer from January 2011 through June 2014 at MD Anderson Cancer Center (534 IMRT and 50 IMPT). The dosimetric variables and osteoradionecrosis were compared with Chi-square test or Fisher's exact test. RESULTS: Median follow-up time for all patients (534 IMRT and IMPT) was 33.8months (33.8months IMRT vs. 34.6months IMPT, P=0.854), and median time to osteoradionecrosis was 11.4months (range 6.74-16.1months). Mandibular doses were lower for patients treated with IMPT (minimum 0.8 vs. 7.3Gy; mean 25.6 vs. 41.2Gy; P<0.001), and osteoradionecrosis rates were lower as well: 2% IMPT (1 grade 1), 7.7% IMRT (12 grade 4, 5 grade 3, 1 grade 2 and 23 grade 1). Osteoradionecrosis location depended on the primary tumor site and high-dose field in the mandible. CONCLUSIONS: Osteoradionecrosis events were significantly associated with higher dose irradiation to mandibular. Use of IMPT minimized excess irradiation of the mandible and consequently reduced the risk of osteoradionecrosis for oropharyngeal cancer.

Design and fabrication of a 3D-printed oral stent for head and neck radiotherapy from routine diagnostic imaging.

BACKGROUND: Oral stents have been shown to reduce the deleterious effects of head and neck radiotherapy through the displacement of normal tissues away from the areas of high dose irradiation. While these stents are commonly used in the treatment of patients with head and neck cancer at many large academic cancer centers, their use is much more limited outside of these institutions due to the time and expertise required for their fabrication. RESULTS: In the study, we describe a novel method to design and manufacture oral stents from routine computed tomography (CT) imaging studies through the use of 3D printing technologies. CONCLUSION: Our proposed method may help to greatly expand access to these beneficial devices for patients undergoing radiation treatment at centers without access to dental and oral/maxillofacial specialists.

Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old.

BACKGROUND: Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation therapy (RT) for oropharyngeal cancer (OPC). METHODS: Cancer-free head and neck cancer survivors (>6 months since treatment completion) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those patients ≥65 years old at treatment for OPC with definitive RT were included. Individual and overall symptom severity and clinical variables were analyzed. RESULTS: Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at RT was 71 yrs. (range: 65-85); median time from RT to MDASI-HN was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0-10 scale) were dry mouth (3.48 ± 2.95), taste (2.81 ± 3.29), swallowing (2.59 ± 2.96), mucus in mouth/throat (2.04 ± 2.68), and choking (1.30 ± 2.38) reported at moderate-severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1-4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchical cluster analysis resulted in 3 patient groups: 1) ~65% with ranging from none to moderate symptom burden, 2) ~35% with moderate-severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallowing) and 3) 2 pts. with severe ratings of most items. CONCLUSIONS: The overall long-term symptom burden seen in this older OPC cohort treated with modern standard therapy was largely favorable, yet a higher symptom group (~35%) with a distinct pattern of mostly local and classically RT-related symptoms was identified.

Multiple regions-of-interest analysis of setup uncertainties for head-and-neck cancer radiotherapy.

PURPOSE: To analyze three-dimensional setup uncertainties for multiple regions of interest (ROIs) in head-and-neck region. METHODS AND MATERIALS: In-room computed tomography (CT) scans were acquired using a CT-on-rails system for 14 patients. Three separate bony ROIs were defined: C2 and C6 vertebral bodies and the palatine process of the maxilla. Translational shifts of 3 ROIs were calculated relative to the marked isocenter on the immobilization mask. RESULTS: The shifts for all 3 ROIs were highly correlated. However, noticeable differences on the order of 2-6 mm existed between any 2 ROIs, indicating the flexibility and/or rotational effect in the head-and-neck region. The palatine process of the maxilla had the smallest right-left shifts because of the tight lateral fit in the face mask, but the largest superior-inferior movement because of in-plane rotation and variations in jaw positions. The neck region (C6) had the largest right-left shifts. The positioning mouthpiece was found effective in reducing variations in the superior-inferior direction. There was no statistically significant improvement for using the S-board (8 out of 14 patients) vs. the short face mask. CONCLUSIONS: We found variability in setup corrections for different regions of head-and-neck anatomy. These relative positional variations should be considered when making setup corrections or designing treatment margins.

Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 1: Fluorides.

Radiation-induced xerostomia results in significant changes in the oral cavity particularly oral microbial changes, which include a marked increase in the number of cariogenic organisms, notably Streptococcus mutans and lactobacillus species. This loss of the capacity to secrete saliva creates or promotes the rapid onset and progression of rampant dental caries. In this 2-part series, the benefit of fluoride in reducing caries activity is presented. Part 1 discusses the historical and currently available fluoride preparations and Part 2 presents data of a recently completed trial investigating the benefit of an intraoral sodium fluoride releasing system.

Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 2: Phase I study.

Radiation-induced xerostomia can result in the rapid onset and progression of dental caries in head and neck cancer patients. Topically applied fluorides have been successfully used to inhibit the formation of dental caries in this population. However, because intensive daily self-application is required, compliance is an issue. The intraoral fluoride-releasing system (IFRS) containing a sodium fluoride core is a newly developed, sustained-release, passive drug delivery system that does not require patient involvement except for periodic replacement, thus reducing the effect of patient compliance on its effectiveness in dental caries prevention. Twenty-two head and neck cancer patients from U. T. M. D. Anderson Cancer Center, with radiation-induced xerostomia, were entered into a pilot study to contrast the daily home use of a 0.4% stannous fluoride-gel-containing tray (control group) to IFRS (study group) with respect to tolerability and adherence, and to obtain information on relative caries preventive efficacy. Participants were stratified on the basis of radiation exposure and randomly assigned to treatment with either IFRS or stannous fluoride gel. Patients in both groups were fitted with two IFRS retainers and also were instructed to use a 1100-ppm fluoride conventional sodium fluoride dentifrice twice daily. The study was conducted as a single-blinded, parallel-cell trial. Pre-existing carious lesions were restored prior to the beginning of the study. The efficacy variable was determined by the mean number of new or recurrent decayed surfaces. Patients were examined for caries 4, 8, 12, 24, 36, and 48 weeks after initiation of treatment. Reports of adverse reactions were based on information volunteered by patients and that were elicited during interviews. At baseline, the resting and stimulated salivary flow rates (g/5min) were significantly greater in the control group than in the study group (p<0.05). Patients in the control group had received significantly more radiation than those in the test group (68Gy vs. 60Gy; p=0.047). No marked differences in follow-up new and recurrent caries were found between the stannous fluoride gel control and IFRS groups during the study period. The rate of new or recurrent carious lesions in the group treated with the fluoride gel was slightly lower than in the IFRS group, based on carious lesions at the baseline examination (Poisson mean number of new or recurrent carious lesions for the control group=0.55 per year vs. 0.83 per year for the study group, p=0.705; odds ratio of the occurrence of any new or recurrent caries during follow-up for control group vs. the study group=0.80; p=0.781). This pilot study revealed that the IFRS was well-tolerated and safe in this study population associated with minimal complications during the duration of this study and was comparable in efficacy to a SnF(2) gel in preventing caries development. The IFRS provided similar rates of control for caries formation to a fluoride-gel-containing tray. The IFRS is designed to release a daily dose of 0.12mg of sodium fluoride, which can be evenly distributed throughout the oral cavity for a single application of 4 months. It would be more convenient than the daily home application of a tray of 0.4% stannous fluoride or 1.1% sodium fluoride gel, and avoids the problem of variable patient compliance.