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Background and Purpose: Auto-contouring of complex anatomy in computed tomography (CT) scans is a highly anticipated solution to many problems in radiotherapy. In this study, artificial intelligence (AI)-based auto-contouring models were clinically validated for lymph node levels and structures of swallowing and chewing in the head and neck. Materials and Methods: CT scans of 145 head and neck radiotherapy patients were retrospectively curated. One cohort (n = 47) was used to analyze seven lymph node levels and the other (n = 98) used to analyze 17 swallowing and chewing structures. Separate nnUnet models were trained and validated using the separate cohorts. For the lymph node levels, preference and clinical acceptability of AI vs human contours were scored. For the swallowing and chewing structures, clinical acceptability was scored. Quantitative analyses of the test sets were performed for AI vs human contours for all structures using overlap and distance metrics. Results: Median Dice Similarity Coefficient ranged from 0.77 to 0.89 for lymph node levels and 0.86 to 0.96 for chewing and swallowing structures. The AI contours were superior to or equally preferred to the manual contours at rates ranging from 75% to 91%; there was not a significant difference in clinical acceptability for nodal levels I-V for manual versus AI contours. Across all AI-generated lymph node level contours, 92% were rated as usable with stylistic to no edits. Of the 340 contours in the chewing and swallowing cohort, 4% required minor edits. Conclusions: An accurate approach was developed to auto-contour lymph node levels and chewing and swallowing structures on CT images for patients with intact nodal anatomy. Only a small portion of test set auto-contours required minor edits.

Purpose/Objectives: The purpose of this study was to evaluate patterns of locoregional recurrence (LRR) after surgical salvage and adjuvant reirradiation with IMRT for recurrent head and neck squamous cell cancer (HNSCC). Materials/Methods: Patterns of LRR for 61 patients treated consecutively between 2003 and 2014 who received post-operative IMRT reirradiation to ≥ 60 Gy for recurrent HNSCC were determined by 2 methods: 1) physician classification via visual comparison of post-radiotherapy imaging to reirradiation plans; and 2) using deformable image registration (DIR). Those without evaluable CT planning image data were excluded. All recurrences were verified by biopsy or radiological progression. Failures were defined as in-field, marginal, or out-of-field. Logistic regression analyses were performed to identify predictors for LRR. Results: A total of 55 patients were eligible for analysis and 23 (42 %) had documented LRR after reirradiation. Location of recurrent disease prior to salvage surgery (lymphatic vs. mucosal) was the most significant predictor of LRR after post-operative reirradiation with salvage rate of 67 % for lymphatic vs. 33 % for mucosal sites (p = 0.037). Physician classification of LRR yielded 14 (61 %) in-field failures, 3 (13 %) marginal failures, and 6 (26 %) out-of-field failures, while DIR yielded 10 (44 %) in-field failures, 4 (17 %) marginal failures, and 9 (39 %) out-of-field failures. Most failures (57 %) occurred within the original site of recurrence or first echelon lymphatic drainage. Of patients who had a free flap placed during salvage surgery, 56 % of failures occurred within 1 cm of the surgical flap. Conclusion: Our study highlights the role of DIR in enhancing the accuracy and consistency of POF analysis. Compared to traditional visual inspection, DIR reduces interobserver variability and provides more nuanced insights into dose-specific and spatial parameters of locoregional recurrences. Additionally, the study identifies the location of the initial recurrence as a key predictor of subsequent locoregional recurrence after salvage surgery and re-IMRT.

Objectives: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5 T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort. Methods: Thirty patients with HNSCC who received curative-intent RT at MD Anderson Cancer Center, were included. Baseline and weekly MRI were obtained, and various ADC parameters were extracted from the regions of interest (ROIs). Baseline and weekly ADC parameters were correlated with response during and after RT, and the recurrence using the Mann-Whitney U test. The Wilcoxon signed-rank test was used to compare the weekly ADC versus baseline values. Weekly volumetric changes (Δvolume) for each ROI were correlated with ΔADC using Spearman’s Rho test. Recursive partitioning analysis (RPA) identified the optimal ΔADC threshold associated with different oncologic outcomes. Results: There was a significant rise in all ADC parameters at different time points of RT compared to baseline for both gross primary disease (GTV-P) and gross nodal disease volumes (GTV-N). The increased ADC values for GTV-P were statistically significant only for primary tumors achieving complete remission (CR) during RT. RPA identified GTV-P ΔADC 5th percentile > 13% at the mid-RT as the most significant parameter associated with primary tumors’ CR during RT (p

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy. Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time. Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that can be assessed on MRI, and 31 patients had nodal disease with 46 nodes assessed. Median primary GTV (GTVp) size was 14.1cc. The rate of GTVp shrinkage was highest between pre-treatment and week 4. Patients with T3-T4 tumours had a 3.8-fold decrease in GTVp compared to T1-T2 tumours. The ADC values correlated with residual GTVp. The median nodal volume (GTVn) was 12.4cc. No clinical features were found to correlate with GTVn reduction. The overall change in ADC for GTVn from pre-treatment was significant for 35th–95th percentiles in weeks 1–4 (p < 0.001). Conclusion: A discrepancy in the trajectory of ADC between primary and nodal sites suggested that they exhibit different treatment responses and should be analysed separately in future studies.

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues.The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. Discussion: The PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk.Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021.Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021.

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed and Google Scholar were searched to identify original research articles describing the incidence, mechanism, dosimetry, treatment, or prevention of radiation-related hypothyroidism for adults receiving RT for the treatment of head and neck cancers. The snowball method was used to identify additional articles. For identified articles, we tabulated several datapoints, including publication date, patient sample size, estimated hypothyroidism incidence, cancer site/type, follow-up period, radiation modality and technique, use of multimodality therapy, method of thyroid function evaluation, and proposed dosimetric predictors of hypothyroidism. (3) Results: One hundred and eleven articles met inclusion criteria, reflecting a range of head and neck cancer subtypes. There was a large variation in the estimated incidence of RT-related hypothyroidism, with a median estimate of 36% (range 3% to 79%). Reported incidence increased in later publication dates, which was likely related to improved screening and longer follow up. There were a wide variety of predictive metrics used to identify patients at high risk of hypothyroidism, the most common of which were volumetric and mean dosimetrics related to the thyroid gland (Vxx%, Dmean). More recently, there has been increasing evidence to suggest that the thyroid gland volume itself and the volume of the thyroid gland spared from high-dose radiation (VSxx) may better predict thyroid function after RT. There were no identified studies investigating the role of advanced radiotherapeutic techniques such as MRI-guided RT or particle therapy to decrease RT-related hypothyroidism. Conclusions: Hypothyroidism is a common toxicity resulting from therapeutic radiation for head and neck cancer with recent estimates suggesting 40–50% of patients may experience hypothyroidism after treatment. Dosimetric predictive models are increasingly able to accurately identify patients at risk of hypothyroidism, especially those utilizing thyroid VS metrics. Further investigation regarding the potential for advanced radiotherapeutic therapies to decrease RT-induced thyroid dysfunction is needed.

Pain from radiation-therapy-induced oral mucositis during head-neck cancer treatment is aggravated by concurrent chemotherapy and commonly fails traditional treatments. To explore safe and sustainable alternatives, we investigated methylene blue oral rinse to reduce radiation-therapy-related oral mucositis pain. For this, we conducted a retrospective observational cohort study in a tertiary-care academic care cancer center including 85 patients with refractory oral mucositis pain during radiation therapy for head-neck cancer. Changes in pain (scale 0–10), oral function burden (scale 0–6) and requirement for percutaneous endoscopic gastrostomy tube placement were measured. Among 58 patients, 60% received radiation therapy alone and 40% received concurrent chemotherapy-radiation therapy. Methylene blue oral rinse (MBOR) significantly decreased oral mucositis pain for at least 6.2 h (median + SD 8 ± 1.68 before vs. 2 ± 2.20 after; p < 0.0001) and oral function burden (3.5 ± 1.33 before vs. 0 ± 0.86 after; p < 0.0001). Eleven patients (19%) had percutaneous endoscopic gastrostomy tubes placed before using methylene blue oral rinse; subsequently, four (36%) resumed oral alimentation after methylene blue oral rinse. Two patients (3%) required percutaneous endoscopic gastrostomy tubes despite methylene blue oral rinse. Minimal adverse events were reported (n = 9, 15%). Our study showed that methylene blue oral rinse was an effective and safe topical treatment for opioid-refractory oral pain from oral mucositis associated with radiation therapy for head-neck cancer.

Purpose: An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies patients with head and neck squamous cell carcinoma (HNSCC) bearing TP53 missense mutations as high-risk, associated with poor outcomes, or low-risk, with similar outcomes as TP53 wild-type, and has been validated as a reliable prognostic marker. We performed this study to further validate prior findings demonstrating that EAp53 is a prognostic marker for patients with locally advanced HNSCC and explored its predictive value for treatment outcomes to adjuvant bio-chemoradiotherapy. Methods and Materials: Eighty-one resection samples from patients treated surgically for stage III or IV human papillomavirus-negative HNSCC with high-risk pathologic features, who received either radiation therapy + cetuximab + cisplatin (cisplatin) or radiation therapy + cetuximab + docetaxel (docetaxel) as adjuvant treatment in a phase 2 study were subjected to TP53 targeted sequencing and EAp53 scoring to correlate with clinical outcomes. Due to the limited sample size, patients were combined into 2 EAp53 groups: (1) wild-type or low-risk; and (2) high-risk or other. Results: At a median follow-up of 9.8 years, there was a significant interaction between EAp53 group and treatment for overall survival (P = .008), disease-free survival (P = .05), and distant metastasis (DM; P = .004). In wild-type or low-risk group, the docetaxel arm showed significantly better overall survival (hazard ratio [HR] 0.11, [0.03-0.36]), disease-free survival (HR 0.24, [0.09-0.61]), and less DM (HR 0.04, [0.01-0.31]) than the cisplatin arm. In high-risk or other group, differences between treatments were not statistically significant. Conclusions: The docetaxel arm was associated with better survival than the cisplatin arm for patients with wild-type or low-risk EAp53. These benefits appear to be largely driven by a reduction in DM.

Purpose: The objective was to identify clinical and epidemiological factors associated with utilization of a complex oral treatment device (COTD), which may decrease toxicity in patients undergoing radiation therapy for head and neck cancer (HNC). Materials and Methods: We retrospectively reviewed data from 1992 to 2013 in the Surveillance, Epidemiology, and End Results (SEER)-Medicare databases to analyze COTD usage during intensity-modulated radiation therapy (IMRT) for patients diagnosed with cancer of the tongue, floor of mouth, nasopharynx, tonsil, or oropharynx. Patients with a radiation simulation and complex treatment device code within 4 weeks before the first IMRT claim were identified as meeting COTD usage criteria. Demographic, regional, tumor, and treatment data were analyzed. Results: Out of 4511 patients who met eligibility criteria, 1932 patients (42.8%) did not utilize a COTD while 2579 (57.2%) met usage criteria. COTD utilization increased over time (36.36% usage in 1992 vs. 67.44% usage in 2013, p

Purpose: Head and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury. Methods: Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18FDG-PET-CT scans, and physician-reported xerostomia assessment at 3–6 months post-RT (Xero 3–6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0–5 Gy, 5–10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT. Results: 432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3–6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10–50 Gy (p

Purpose: To report patient-reported outcomes (PROs) derived from the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) tool, in patients with oropharynx cancer (OPC) treated with intensity-modulated proton therapy (IMPT) in the context of first-course irradiation. Materials and Methods: Patients with locally advanced OPC treated with radical IMPT between 2011 and 2018 were included in a prospective registry. FACT-HN scores were measured serially during and 24 months following IMPT. PRO changes in the FACT-HN scores over time were assessed with mixed-model analysis. Results: Fifty-seven patients met inclusion criteria. Median age was 60 years (range, 41-84), and 91% had human papillomavirus-associated disease. In total, 28% received induction chemotherapy and 68% had concurrent chemotherapy. Compliance to FACT-HN questionnaire completion was 59%, 48%, and 42% at 6, 12, and 24 months after treatment, respectively. The mean FACT-General (G), FACT-Total, and FACT-Trial Outcome Index (TOI) score changes were statistically and clinically significant relative to baseline from week 3 of treatment up to week 2 after treatment. Nadir was reached at week 6 of treatment for all scores, with maximum scores dropping by 15%, 20%, and 39% compared to baseline for FACT-G, FACT-Total, and FACT-TOI, respectively. Subdomain scores of physical well-being, functional well-being, and head and neck additional concerns decreased from baseline during treatment and returned to baseline at week 4 after treatment. Conclusions: IMPT was associated with a favorable PRO trajectory, characterized by an acute decline followed by rapid recovery to baseline. This study establishes the expected acute, subacute, and chronic trajectory of PROs for patients undergoing IMPT for OPC.

Purpose: To report clinical outcomes in terms of disease control and toxicity in patients with major salivary gland cancers (SGCs) treated with proton beam therapy. Materials and Methods: Clinical and dosimetric characteristics of patients with SGCs treated from August 2011 to February 2020 on an observational, prospective, single-institution protocol were abstracted. Local control and overall survival were calculated by the Kaplan-Meier method. During radiation, weekly assessments of toxicity were obtained, and for patients with ≥ 90 days of follow-up, late toxicity was assessed. Results: Seventy-two patients were identified. Median age was 54 years (range, 23-87 years). Sixty-three patients (88%) received postoperative therapy, and nine patients (12%) were treated definitively. Twenty-six patients (36%) received concurrent chemotherapy. Nine patients (12%) had received prior radiation. All (99%) but one patient received unilateral treatment with a median dose of 64 GyRBE (relative biological effectiveness) (interquartile range [IQR], 60-66), and 53 patients (74%) received intensity-modulated proton therapy with either single-field or multifield optimization. The median follow-up time was 30 months. Two-year local control and overall survival rates were 96% (95% confidence interval [CI] 85%-99%) and 89% (95% CI 76%-95%], respectively. Radiation dermatitis was the predominant grade-3 toxicity (seen in 21% [n = 15] of the patients), and grade ≥ 2 mucositis was rare (14%; n = 10 patients). No late-grade ≥ 3 toxicities were reported. Conclusion: Proton beam therapy for treatment of major SGCs manifests in low rates of acute mucosal toxicity. In addition, the current data suggest a high rate of local control and minimal late toxicity.

Purpose: To characterize our experience and the disease control and toxicity of proton therapy (PT) for patients with head and neck cancer (HNC). Patients and Methods: Clinical outcomes for patients with HNC treated with PT at our institution were prospectively collected in 2 institutional review board–approved prospective studies. Descriptive statistics were used to summarize patient characteristics and outcomes. Overall survival, local-regional control, and disease-free survival were estimated by the Kaplan-Meier method. Treatment-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events (version 4.03) scale. Results: The cohort consisted of 573 patients treated from February 2006 to June 2018. Median patient age was 61 years. Oropharynx (33.3%; n = 191), paranasal sinus (11%; n = 63), and periorbital tissues (11%; n = 62) were the most common primary sites. Patients with T3/T4 or recurrent disease comprised 46% (n = 262) of the cohort. The intent of PT was definitive in 53% (n = 303), postoperative in 37% (n = 211), and reirradiation in 10% (n = 59). Median dose was 66 Gy (radiobiological equivalent). Regarding systemic therapy, 43% had received concurrent (n = 244), 3% induction (n = 19), and 15% (n = 86) had both. At a median follow-up of 2.4 years, 88 patients (15%) had died and 127 (22%) developed disease recurrence. The overall survival, local-regional control, and disease-free survival at 2 and 5 years were, respectively, 87% and 75%, 87% and 78%, and 74% and 63%. Maximum toxicity (acute or late) was grade 3 in 293 patients (51%), grade 2 in 234 patients (41%), and grade 1 in 31 patients (5%). There were 381 acute grade 3 and 190 late grade 3 unique toxicities across 212 (37%) and 150 (26%) patients, respectively. There were 3 late-grade 4 events across 2 patients (0.3%), 2 (0.3%) acute-grade 5, and no (0%) late-grade 5 events. Conclusions: The overall results from this prospective study of our initial decade of experience with PT for HNC show favorable disease control and toxicity outcomes in a multidisease-site cohort and provide a reference benchmark for future comparison and study.

Purpose: We compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT). Patients and Methods: In 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores. Results: Patient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P = 0.05; and at 2 years, P = 0.04) and composite work impairment scores (at 1 year, P = 0.04; and at 2 years, P = 0.04) were seen in patients treated with IMPT versus those treated with IMRT. Conclusion: In patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.

Purpose: Proton radiation therapy (PRT) may offer dosimetric and clinical benefit in the treatment of head and neck carcinoma of unknown primary (HNCUP). We sought to describe toxicity and quality of life (QOL) in patients with HNCUP treated with PRT. Patients and Methods: Toxicity and QOL were prospectively tracked in patients with HNCUP from 2011 to 2019 after institutional review board approval. Patients received PRT to the mucosa of the nasopharynx, oropharynx, and bilateral cervical lymph nodes with sparing of the larynx and hypopharynx. Patient-reported outcomes were tracked with the MD Anderson Symptom Inventory–Head and Neck Module, the Functional Assessment of Cancer Therapy–Head and Neck, the MD Anderson Dysphagia Inventory, and the Xerostomia-Related QOL Scale. Primary study endpoints were the incidence of grade ≥ 3 (G3) toxicity and QOL patterns. Results: Fourteen patients (median follow-up, 2 years) were evaluated. Most patients presented with human papillomavirus–positive disease (n = 12, 86%). Rates of G3 oral mucositis, xerostomia, and dermatitis were 7% (n = 1), 21% (n = 3), and 36% (n = 5), respectively. None required a gastrostomy. During PRT, QOL was reduced relative to baseline and recovered shortly after PRT. At 2 years after PRT, the local regional control, disease-free survival, and overall survival were 100% (among 7 patients at risk), 79% (among 6 patients at risk), and 90% (among 7 patients at risk), respectively. Conclusion: Therefore, PRT for HNCUP was associated with highly favorable dosimetric and clinical outcomes, including minimal oral mucositis, xerostomia, and dysphagia. Toxicity and QOL may be superior with PRT compared with conventional radiation therapy and PRT maintains equivalent oncologic control. Further prospective studies are needed to evaluate late effects and cost-effectiveness.

Abstract Background Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. Methods One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. Discussion This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. Trial registration ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018

Background: A prior phase III, multicenter (United States and China), clinical trial found true acupuncture (TA) resulted in lower xerostomia scores 12 months after radiotherapy than that of a standard care control group. This small pilot study examined brain function changes comparing TA to sham acupuncture (SA) in US and Fudan patients undergoing head and neck radiotherapy. Methods: To determine cerebral activity during TA versus SA acupuncture, patients underwent electroencephalogram evaluation (EEG) immediately prior, during and after both conditions. Acupuncture occurred during weeks 3 to 5 of radiotherapy, with patients receiving either TA or SA, followed 2 to 3 days later by the other treatment in a counterbalanced manner. Results: In the TA minus SA condition (N = 14 Fudan; N = 13 US), most changes were in the delta (0.5-3.5 Hz) and alpha (8-12 Hz) bandwidths. Delta was present in the frontal gyrus and parahippocampal gyrus. Alpha was present in the anterior and posterior cingulate, lingual gyrus, amygdala, precuneus, medial frontal gyrus, fusiform gyrus, and superior frontal gyrus. Maximal cortical differences in the Fudan cohort between TA and SA were in areas previously shown to be associated with (TA). In the US cohort, maximal differences between TA and SA were associated with areas which are usually decreased in TA conditions. Conclusions: There were distinct differences in brain function between those receiving TA and SA and there were clear differences between cultures, helping to explain the lack of placebo effect in the Fudan participants and strong placebo effect in the US patients.

Purpose: To describe the baseline and serial tumor microbiome in HPV-associated oropharynx cancer (OPC) over the course of radiotherapy (RT). Methods: Patients with newly diagnosed HPV-associated OPC treated with definitive radiotherapy +/− concurrent chemotherapy were enrolled in this prospective study. Using 16S rRNA gene sequencing, dynamic changes in the tumor site microbiome during RT were investigated. Surface tumor samples were obtained before RT and at week 1, 3 and 5 of RT. Radiological primary tumor response at mid-treatment was categorized as complete (CR) or partial (PR). Results: Ten patients were enrolled, but 9 patients were included in the final analysis. Mean age was 62 years (range: 51–71). As per AJCC 8th Ed, 56%, 22% and 22% of patients had stage I, II and III, respectively. At 4-weeks, 6 patients had CR and 3 patients had PR; at follow-up imaging post treatment, all patients had CR. The baseline diversity of the tumoral versus buccal microbiome was not statistically different. For the entire cohort, alpha diversity was significantly decreased over the course of treatment (p = 0.04). There was a significant alteration in the bacterial community within the first week of radiation. Baseline tumor alpha diversity of patients with CR was significantly higher than those with PR (p = 0.03). While patients with CR had significant reduction in diversity over the course of radiation (p = 0.01), the diversity remained unchanged in patients with PR. Patients with history of smoking had significantly increased abundance of Kingella (0.05) and lower abundance of Stomatobaculum (p = 0.03) compared to never smokers. Conclusions: The tumor microbiome of HPV-associated OPC exhibits reduced alpha diversity and altered taxa abundance over the course of radiotherapy. The baseline bacterial profiles of smokers vs. non-smokers were inherently different. Baseline tumor alpha diversity of patients with CR was higher than patients with PR, suggesting that the microbiome deserves further investigation as a biomarker of radiation response.

Objectives: To evaluate whether the use of oral stents during intensity modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC) is associated with long-term patient reported symptoms. Materials and methods: Data was obtained from a prospective observational study of disease-free head and neck cancer survivors. Radiation-associated patient reported symptoms were assessed using the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN). Scores of ≥5 (11-point Likert scale, 0-10) were considered moderate/severe. Stratification was performed regarding IMRT volume (uni- versus bilateral neck) and stent utilization, with non-parametric analyses between groups. Results: 462 OPC survivors formed the cohort (54% tonsil, 46% base of tongue primaries). A tongue-deviating stent was used in 17%, tongue-depressing stent in 46%, and no stent in 37%. Median prescribed dose to the high dose clinical target volume was 66.0 Gy. Median follow-up from RT to MDASI-HN assessment was 68 months. Twenty percent had received unilateral neck RT (all had tonsil primaries), in whom a significant improvement in the proportion of patients with moderate/severe taste impairment (2% vs. 15%, p = 0.047) and lack of appetite (0% vs. 9%, p = 0.019) was associated with the use of tongue-deviating stents compared to no oral stent. In those who had received bilateral neck RT, a significant improvement in the proportion of patients with moderate/severe difficulty swallowing/chewing was associated with use of a tongue-depressing stent (21% vs. 31% without oral stent, p = 0.013). Conclusion: Disease-site specific select use of oral stents during IMRT was associated with reduced long-term patient reported symptoms in OPC survivors.

Abstract Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-virally mediated OPSCC, this effect is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. Methods We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002–2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p 30 PY patients didn’t differ significantly from HPV- patients (p = 0.72, p = 0.27, respectively). HPV+ > 30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p = 0.03, 76% vs 88.3%; p = 0.07, and 52.3% vs 74%; p = 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively. Conclusions Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV + OPSCC smokers should be avoided.

Purpose: We evaluated the geometric and dosimetric-based distribution of mucosal and nodal recurrences in patients with metastatic head and neck squamous cell carcinoma to cervical lymph nodes of unknown primary after intensity modulated radiation therapy using validated typology-indicative taxonomy. Methods and Materials: We reviewed the data of 260 patients who were irradiated between 2000 and 2015 and had a median follow-up time for surviving patients of 61 months. The mucosal and nodal recurrences were manually delineated on computed tomography images demonstrating the recurrences. The images were overlaid on the treatment plan using deformable image registration. The locations of the recurrences were determined relative to the original planning target volumes and doses using centroid-based approaches. Subsequently, the pattern of failures were classified into 5 types based on combined spatial and dosimetric criteria: A (central high dose), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose). For patients with type A failure with simultaneous nontype A lesions, the overall pattern of failures was defined as type A. Results: Thirty-two patients had mucosal or nodal recurrences. The most common clinical nodal stage was N2b (66%). Preradiation therapy neck dissections were performed in 6 patients. The median dose delivered to clinical tumor volume 1 was 66 Gy. The majority (84%) had total/partial pharyngeal mucosa elective irradiation. Twenty-three patients had nodal recurrences, 8 had mucosal recurrences, and 1 had both nodal and mucosal recurrences. Twenty-one patients (91%) had type A nodal failure, and 7 of the mucosal failures (89%) were type C. Conclusions: The majority of nodal recurrences occurred within the high-dose area, demanding the need for identification of radioresistant areas within malignant nodes. Future studies should focus on either dose escalation of high-risk volumes or novel radiosensitizers.

Background and purpose: Taste impairment is a common radiation-induced toxicity in head and neck cancer (HNC) patients acutely. However, data on the potential for recovery and the time dependent course of late taste impairment are limited. Materials and methods: As part of an IRB-approved observational prospective study, HNC patients underwent serial surveys including the MD Anderson Symptom Inventory - Head and Neck module (MDASI-HN). For our analysis, we extracted MDASI-HN taste item results from oropharyngeal cancer patients treated with intensity-modulated radiotherapy or volumetric modulated arc therapy and at least two taste assessments after ≥1 year from end of radiotherapy (RT). Results: 1214 MDASI taste items from 326 patients between 1 and 13 years post-RT were included. Median prescribed dose to the high-dose clinical target volume (CTV1) was 66.0 Gy, with 180 patients (55%) receiving chemotherapy. Taste markedly improved in the first years from end of RT, but plateaued after year 5. In patients with taste assessment in subsequent years, a significant reduction in taste impairment was found from the second to the third year (p = 0.001) and tended towards significance from the third to the fourth year (p = 0.058). Multivariate analysis revealed treatment site as significant factor in the sixth year from RT and CTV1 dose and age in the seventh year. Conclusion: Radiation-induced taste impairment may improve over an extended time interval, but becomes relatively stable from year 5 post-RT. Direct characterization of RT-induced taste impairment and the calculation of normal tissue complication probability should include consideration of the time-dependent course in taste recovery. Keywords: Taste, Radiotherapy, Oropharyngeal cancer, Quality of life, Recovery of function

In treatment planning, multiple imaging modalities can be employed to improve the accuracy of tumor delineation but this can be costly. This study aimed to compare the interobserver consistency of using dual energy computed tomography (DECT) versus magnetic resonance imaging (MRI) for delineating tumors in the head and neck cancer (HNC) re-irradiation scenario. Twenty-three patients with recurrent HNC and had planning DECT and MRI were identified. Contoured tumor volumes by seven radiation oncologists were compared. Overall, T1c MRI performed the best with median DSC of 0.58 (0–0.91) for T1c. T1c MRI provided higher interobserver agreement for skull base sites and 60 kV DECT provided higher interobserver agreement for non-skull base sites.

Introduction Medical students often lack training in advanced communication skills encompassing emotionally fraught situations and those in which an intense emotional response is expected. Such skills are required for clinical situations encountered during residency. We created and evaluated an advanced communication skills workshop (ACSW) using standardized patients for senior medical students. The workshop emphasized communication skills for four scenarios—strong emotion, goals of care, medical error, and palliative care assessment—and utilized formative peer assessment and feedback. Methods We created the four ACSW cases with case-specific communication behavior checklists and a common modified Master Interview Rating Scale in a Capstone Course for senior medical students. In groups of three, students rotated through three of four stations. Each student conducted one of the interviews while the other two completed the checklists and provided verbal feedback. We performed one-way analyses of variance on Likert responses and content analysis on open responses on a post-ACSW survey. Results Ninety-one students completed the ACSW and survey. Students assigned high value to all four ACSW student roles: interviewer, observer, feedback recipient, and feedback provider. Students rated the experience above average to excellent on nearly all survey items. Open-response themes included “liked the opportunity to give or receive peer feedback” (46%) and “found the checklists helpful” (45%). Discussion Feasible and well received by senior medical students, our ACSW offers an opportunity to practice and observe advanced communication skills and peer feedback. A peer-assisted, formative learning model, the ACSW efficiently addresses a key aspect of residency preparation.

Objectives: We sought to model chronic radiation-associated dysphagia (RAD) in patients given intensity-modulated radiation therapy (IMRT) for oropharyngeal squamous cell cancer (OPSCC) as a function of age and dose to non-target swallowing muscles. Methods: We reviewed 300 patients with T1-T4 N0-3 M0 OPSCC given definitive IMRT with concurrent chemotherapy. Chronic RAD was defined as aspiration or stricture on videoflouroscopy/endoscopy, gastrostomy tube, or aspiration pneumonia at ≥12 months after IMRT. Doses to autosegmented regions of interest (ROIs; inferior, middle and superior constrictors, anterior and posterior digastrics, mylo/geniohyoid complex, intrinsic tongue, and gengioglossus) were obtained from DICOM-RT plans and dose-volume histograms. The probability of chronic RAD as a function of mean ROI dose, stratified by age (

Abstract 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

Background and purpose: Minimizing radiation dose exposure to nearby organs is key to limiting clinical toxicities associated with radiotherapy. Several treatment modalities such as split- or whole-field intensity-modulated radiotherapy (SF-IMRT, WF-IMRT) and volumetric modulated arc therapy (VMAT) are being used to treat tonsillar cancer patients with unilateral neck radiotherapy. Herein, we provide a modern dosimetric comparison of all three techniques. Materials and methods: Forty patients with tonsillar cancer treated with definitive, ipsilateral neck SF-IMRT were evaluated. Each patient was re-planned with WF-IMRT and VMAT techniques, and doses to selected organs-at-risk (OARs) including the larynx, esophagus, and brainstem were compared. Results: No significant differences in target coverage existed between plans; however, the heterogeneity index improved using WF-IMRT and VMAT relative to SF-IMRT. Compared to SF-IMRT, WF-IMRT and VMAT plans had significantly lower mean doses to the supraglottic larynx (31 Gy, 18.5 Gy, 17 Gy; p

Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients’ quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image – guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient’s plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). Methods: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node

Abstract Background Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity. Methods The proposed study is designed as a prospective observational study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR imaging during RT and post treatment CT, MRI and PET/CT images. In addition, blood sample will be collected for biomarker analysis at those time intervals. CTC assessments will be performed on the CellSave tube using the FDA-approved CellSearch® Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from the EDTA blood samples will be collected, labeled with a de-identifying number, and stored at − 80 °C for future analyses. Discussion The primary objective of the study is to evaluate the prognostic value and correlation of weekly tumor response kinetics (gross tumor volume and MR signal changes) and circulating tumor cells of mucosal head and neck cancers during radiation therapy using MRI in predicting treatment response and clinical outcomes. This study will provide landmark information as to the utility of CTCs (‘liquid biopsy) and tumor-specific functional quantitative imaging changes during treatment to guide personalization of treatment for future patients. Combining the biological information from CTCs and the structural information from MRI may provide more information than either modality alone. In addition, this study could potentially allow us to determine the optimal time to obtain MR imaging and/ or CTCs during radiotherapy to assess tumor response and provide guidance for patient selection and stratification for future dose escalation or de-escalation strategies. Trial registration Clinicaltrials.gov (NCT03491176). Date of registration: 9th April 2018. (retrospectively registered). Date of enrolment of the first participant: 30th May 2017.

Purpose: We aim to determine the feasibility and dosimetric benefits of a novel MRI-guided IMRT dose-adaption strategy for human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC). Materials/methods: Patients with locally advanced HPV+ OPC underwent pre-treatment and in-treatment MRIs every two weeks using RT immobilization setup. For each patient, two IMRT plans were created (i.e. standard and adaptive). The prescription dose for the standard plans was 2.12 Gy/fx for 33 fractions to the initial PTV. For adaptive plans, a new PTVadaptive was generated based on serial MRIs in case of detectable tumor shrinkage. Prescription dose to PTVadaptive was 2.12 Gy/fx to allow for maximum dose to the residual disease. Any previously involved volumes received minimally a floor dose of 50.16 Gy. Uninvolved elective nodal volumes were prescribed 50.16 Gy in 1.52 Gy/fx. Dosimetric parameters of organs at risk (OARs) were recorded for standard vs. adaptive plans. Normal tissue complication probability (NTCP) for toxicity endpoints was calculated using literature-derived multivariate logistic regression models. Results: Five patients were included in this pilot study, 3 men and 2 women. Median age was 58 years (range 45–69). Three tumors originated at the tonsillar fossa and two at the base of tongue. The average dose to 95% of initial PTV volume was 70.7 Gy (SD,0.3) for standard plans vs. 58.5 Gy (SD,2.0) for adaptive plans. The majority of OARs showed decrease in dosimetric parameters using adaptive plans vs. standard plans, particularly swallowing related structures. The average reduction in the probability of developing dysphagia ≥ grade2, feeding tube persistence at 6-month post-treatment and hypothyroidism at 1-year post-treatment was 11%, 4%, and 5%, respectively. The probability of xerostomia at 6-month was only reduced by 1% for adaptive plans vs. standard IMRT. Conclusion: These in silico results showed that the proposed MRI-guided adaptive approach is technically feasible and advantageous in reducing dose to OARs, especially swallowing musculature. Keywords: MRI-guided radiotherapy, Dose adaptation, IMRT, Human papillomavirus positive oropharyngeal cancer, Head and neck cancer, Dysphagia, Normal tissue complication probability

Introduction: Peripheral blood count components are accessible and evidently predictive in other cancers but have not been explored in oropharyngeal carcinoma. We examine if there is an association between the use of intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) and lymphopenia, as well as if there is an association between baseline neutrophilia, baseline leukocytosis and lymphocyte nadir in oropharyngeal cancer. Materials and Methods: Analysis started with 150 patients from a previous case to case study design, which retrospectively identified adults with oropharyngeal carcinoma, 100 treated with IMRT in 2010-2012 and 50 treated with IMPT in 2011â2014. Pretreatment leukocyte, neutrophil, lymphocyte, and hemoglobin levels were extracted, as were neutrophil and lymphocyte nadir levels during radiotherapy. We retained 137 patients with recorded pre-treatment leukocyte and neutrophil levels for associated analysis and 114 patients with recorded lymphocyte levels during radiation and associated analysis. Multivariate survival analyses were done with Cox regression. Results: The radiotherapy type (IMRT vs. IMPT) was not associated with lymphopenia (grade 3 Pâ¯>â¯.99; grade 4 Pâ¯=â¯.55). In univariate analyses, poor overall survival was associated with pretreatment neutrophilia (hazard ratio [HR] 5.58, 95% confidence interval [CI] 1.99â15.7, Pâ¯=â¯.001), pretreatment leukocytosis (HR 4.85, 95% CI 1.73â13.6, Pâ¯=â¯.003), grade 4 lymphopenia during radiotherapy (HR 3.28, 95% CI 1.14â9.44, Pâ¯=â¯.03), and possibly smoking status >10 pack-years (HR 2.88, 95% CI 1.01â8.18, Pâ¯=â¯.05), but only T status was possibly significant in multivariate analysis (HR 2.64, 95% CI 0.99â7.00, Pâ¯=â¯.05). Poor progression-free survival was associated with pretreatment leukocytosis and T status in univariate analysis, and pretreatment neutrophilia and advanced age on multivariate analysis. Conclusions: Treatment modality did not affect blood counts during radiotherapy. Pretreatment neutrophilia, pretreatment leukocytosis, and grade 4 lymphopenia during radiotherapy were associated with worse outcomes after, but establishing causality will require additional work with increased statistical power. Keywords: Head and neck cancer, Radiotherapy, Proton therapy, Leukocytosis, Lymphopenia

Purpose: Uncertainties related to geometric distortion are a major obstacle for effectively utilizing MRI in radiation oncology. We aim to quantify the geometric distortion in patient images by comparing their in-treatment position MRIs with the corresponding planning CTs, using CT as the non-distorted gold standard. Methods: Twenty-one head and neck cancer patients were imaged with MRI as part of a prospective Institutional Review Board approved study. MR images were acquired with a T2 SE sequence (0.5 Ã 0.5 Ã 2.5 mm voxel size) in the same immobilization position as in the CTs. MRI to CT rigid registration was then done and geometric distortion comparison was assessed by measuring the corresponding anatomical landmarks on both the MRI and the CT images. Several landmark measurements were obtained including; skin to skin (STS), bone to bone, and soft tissue to soft tissue at specific levels in horizontal and vertical planes of both scans. Inter-observer variability was assessed and interclass correlation (ICC) was calculated. Results: A total of 430 landmark measurements were obtained. The median distortion for all landmarks in all scans was 1.06 mm (IQR 0.6â1.98). For each patient 48% of the measurements were done in the right-left direction and 52% were done in the anteroposterior direction. The measured geometric distortion was not statistically different in the right-left direction compared to the anteroposterior direction (1.5 ± 1.6 vs. 1.6 ± 1.7 mm, respectively, p = 0.4). The magnitude of distortion was higher in the STS peripheral landmarks compared to the more central landmarks (2.0 ± 1.9 vs. 1.2 ± 1.3 mm, pÂ

Abstract 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.

Abstract 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.

Abstract Background We sought to identify spatial/dosimetric patterns of failure for oral cavity cancer patients receiving post-operative IMRT (PO-IMRT). Methods Two hundred eighty-nine OCC patients receiving PO-IMRT were retrospectively reviewed from 2000 to 2012. Diagnostic CT documenting recurrence (rCT) was co-registered with planning CT (pCT) using a validated deformable image registration software. Manually segmented recurrent gross disease (rGTV) was deformed to co-registered pCTs. Mapped rGTVs were compared dosimetrically to planned dose and spatially to planning target volumes using centroid-based approaches. Failures types were classified using combined spatial/dosimetric criteria: A (central high-dose), B (peripheral high-dose), C (central intermediate/low-dose), D (peripheral intermediate/low-dose), and E (extraneous-dose). Results Fifty-four patients with recurrence were analyzed; 26 local recurrence, 19 regional recurrence, and 9 both local and regional recurrence. Median time to recurrence was 4 months (range 0–71). Median rGTVs volume was 3.7 cm3 (IQR 1.4–10.6). For spatial and dosimetric analysis of the patterns of failure, 30 patients (55.5%) were classified as type A (central high-dose). Non-central high dose failures were distributed as follows: 2 (3.7%) type B, 10 (18.5%) type C, 1 (1.8%) type D, and 9 (16.7%) type E. Non-IMRT failure in the matching low-neck field was seen in two patients. No failures were noted at the IMRT-supraclavicular field match-line. Conclusions Approximately half of patients with local/regional failure had non-central high dose recurrence. Peripheral high dose misses were uncommon reflecting adequate delineation and dose delivery. Future strategies are needed to reduce types C and E failures.

Background: The use of patient symptom reports with frequent symptom assessment may be preferred over the more commonly used health-related quality of life questionnaires. Aims: We sought to linguistically validate the Turkish version of the M.D. Anderson Symptom Inventory-Head and Neck module (MDASI-HN) patient reported outcome questionnaire. Study Design: Validation study. Methods: Following standard forward and backward translation of the original and previously validated English MDASI-HN into a Turkish version (T-MDASI-HN), it was administered to patients with head and neck cancer able to read and understand Turkish. Patients were then cognitively debriefed to evaluate their understanding and comprehension of the T-MDASI-HN. Individual and group responses are presented using descriptive statistics. Results: Twenty-six participants with head and neck cancer completed the T-MDASIHN and accompanying cognitive debriefing. Overall, 97 percent of the individual TMDASI-HN items were completed. Average recorded time to complete the 28 item TMDASI-HN questionnaire was 5.4 minutes (range 2-10). Average overall ease of completion, understandability, and acceptability were favorably rated at 1.0, 1.1, and 0.2, respectively, on scales from 0 to 10. Only 5 of the 26 of participants reported trouble completing any single questionnaire items, namely the “difficulty remembering” item for 3 individuals. Conclusion: The T-MDASI-HN is linguistically valid with ease of completion, relevance, comprehensibility, and applicability and it can be a useful clinical and research tool.

Abstract In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.