Self-management intervention improves patient adherence to swallowing exercises during radiation for head and neck cancer.

BACKGROUND: While preventive swallowing exercises reduce the risk of radiation-associated dysphagia in patients with head and neck cancer, strategies are needed to improve patient adherence. METHODS: Before radiation, all participants were taught preventive swallowing exercises and randomized to either an adherence intervention or enhanced usual care. During radiation, all participants met twice with a speech pathologist for swallowing assessment and reinforcement of exercises. Intervention participants met weekly with a counselor in-person or by phone. At 6-week post-radiation follow-up, all participants completed a follow-up assessment of self-reported adherence, which was then corroborated with medical record documentation. RESULTS: Newly diagnosed pharyngeal and laryngeal cancer patients without distant metastases were randomized (n = 265; 135 to intervention, and 130 to usual care). Intervention participants were more likely to adhere to exercises during radiation compared to the control group (p < 0.0001). CONCLUSION: The weekly in-person adherence intervention program significantly increased patient's adherence to preventive swallowing exercises during radiation.

Iterative Patient Testing of a Stimuli-Responsive Swallowing Activity Sensor to Promote Extended User Engagement During the First Year After Radiation: Multiphase Remote and In-Person Observational Cohort Study.

BACKGROUND: Frequent sensor-assisted monitoring of changes in swallowing function may help improve detection of radiation-associated dysphagia before it becomes permanent. While our group has prototyped an epidermal strain/surface electromyography sensor that can detect minute changes in swallowing muscle movement, it is unknown whether patients with head and neck cancer would be willing to wear such a device at home after radiation for several months. OBJECTIVE: We iteratively assessed patients' design preferences and perceived barriers to long-term use of the prototype sensor. METHODS: In study 1 (questionnaire only), survivors of pharyngeal cancer who were 3-5 years post treatment and part of a larger prospective study were asked their design preferences for a hypothetical throat sensor and rated their willingness to use the sensor at home during the first year after radiation. In studies 2 and 3 (iterative user testing), patients with and survivors of head and neck cancer attending visits at MD Anderson's Head and Neck Cancer Center were recruited for two rounds of on-throat testing with prototype sensors while completing a series of swallowing tasks. Afterward, participants were asked about their willingness to use the sensor during the first year post radiation. In study 2, patients also rated the sensor's ease of use and comfort, whereas in study 3, preferences were elicited regarding haptic feedback. RESULTS: The majority of respondents in study 1 (116/138, 84%) were willing to wear the sensor 9 months after radiation, and participant willingness rates were similar in studies 2 (10/14, 71.4%) and 3 (12/14, 85.7%). The most prevalent reasons for participants' unwillingness to wear the sensor were 9 months being excessive, unwanted increase in responsibility, and feeling self-conscious. Across all three studies, the sensor's ability to detect developing dysphagia increased willingness the most compared to its appearance and ability to increase adherence to preventive speech pathology exercises. Direct haptic signaling was also rated highly, especially to indicate correct sensor placement and swallowing exercise performance. CONCLUSIONS: Patients and survivors were receptive to the idea of wearing a personalized risk sensor for an extended period during the first year after radiation, although this may have been limited to well-educated non-Hispanic participants. A significant minority of patients expressed concern with various aspects of the sensor's burden and its appearance. TRIAL REGISTRATION: ClinicalTrials.gov NCT03010150; https://clinicaltrials.gov/study/NCT03010150.

Expert Consensus Statement: Management of Dysphagia in Head and Neck Cancer Patients.

OBJECTIVE: To develop an expert consensus statement (ECS) on the management of dysphagia in head and neck cancer (HNC) patients to address controversies and offer opportunities for quality improvement. Dysphagia in HNC was defined as swallowing impairment in patients with cancers of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, or hypopharynx. METHODS: Development group members with expertise in dysphagia followed established guidelines for developing ECS. A professional search strategist systematically reviewed the literature, and the best available evidence was used to compose consensus statements targeted at providers managing dysphagia in adult HNC populations. The development group prioritized topics where there was significant practice variation and topics that would improve the quality of HNC patient care if consensus were possible. RESULTS: The development group identified 60 candidate consensus statements, based on 75 initial proposed topics and questions, that focused on addressing the following high yield topics: (1) risk factors, (2) screening, (3) evaluation, (4) prevention, (5) interventions, and (6) surveillance. After 2 iterations of the Delphi survey and the removal of duplicative statements, 48 statements met the standardized definition for consensus; 12 statements were designated as no consensus. CONCLUSION: Expert consensus was achieved for 48 statements pertaining to risk factors, screening, evaluation, prevention, intervention, and surveillance for dysphagia in HNC patients. Clinicians can use these statements to improve quality of care, inform policy and protocols, and appreciate areas where there is no consensus. Future research, ideally randomized controlled trials, is warranted to address additional controversies related to dysphagia in HNC patients.

Patient-Reported Outcomes after Intensity-Modulated Proton Therapy for Oropharynx Cancer.

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.

Intensity standardization methods in magnetic resonance imaging of head and neck cancer.

BACKGROUND AND PURPOSE: Conventional magnetic resonance imaging (MRI) poses challenges in quantitative analysis because voxel intensity values lack physical meaning. While intensity standardization methods exist, their effects on head and neck MRI have not been investigated. We developed a workflow based on healthy tissue region of interest (ROI) analysis to determine intensity consistency within a patient cohort. Through this workflow, we systematically evaluated intensity standardization methods for MRI of head and neck cancer (HNC) patients. MATERIALS AND METHODS: Two HNC cohorts (30 patients total) were retrospectively analyzed. One cohort was imaged with heterogenous acquisition parameters (HET cohort), whereas the other was imaged with homogenous acquisition parameters (HOM cohort). The standard deviation of cohort-level normalized mean intensity (SD NMIc), a metric of intensity consistency, was calculated across ROIs to determine the effect of five intensity standardization methods on T2-weighted images. For each cohort, a Friedman test followed by a post-hoc Bonferroni-corrected Wilcoxon signed-rank test was conducted to compare SD NMIc among methods. RESULTS: Consistency (SD NMIc across ROIs) between unstandardized images was substantially more impaired in the HET cohort (0.29 ± 0.08) than in the HOM cohort (0.15 ± 0.03). Consequently, corrected p-values for intensity standardization methods with lower SD NMIc compared to unstandardized images were significant in the HET cohort (p < 0.05) but not significant in the HOM cohort (p > 0.05). In both cohorts, differences between methods were often minimal and nonsignificant. CONCLUSIONS: Our findings stress the importance of intensity standardization, either through the utilization of uniform acquisition parameters or specific intensity standardization methods, and the need for testing intensity consistency before performing quantitative analysis of HNC MRI.

The Reality of Randomized Controlled Trials for Assessing the Benefit of Proton Therapy: Critically Examining the Intent-to-Treat Principle in the Presence of Insurance Denial.

PURPOSE: This study hypothesized that insurance denial would lead to bias and loss of statistical power when evaluating the results from an intent-to-treat (ITT), per-protocol, and as-treated analyses using a simulated randomized clinical trial comparing proton therapy to intensity modulated radiation therapy where patients incurred increasing rates of insurance denial. METHODS AND MATERIALS: Simulations used a binary endpoint to assess differences between treatment arms after applying ITT, per-protocol, and as-treated analyses. Two scenarios were developed: 1 with clinical success independent of age and another assuming dependence on age. Insurance denial was assumed possible for patients <65 years. All scenarios considered an age distribution with mean ± standard deviation: 55 ± 15 years, rates of insurance denial ranging from 0%-40%, and a sample of N = 300 patients (150 per arm). Clinical success rates were defined as 70% for proton therapy and 50% for intensity modulated radiation therapy. The average treatment effect, bias, and power were compared after applying 5000 simulations. RESULTS: Increasing rates of insurance denial demonstrated inherent weaknesses among all 3 analytical approaches. With clinical success independent of age, a per-protocol analysis demonstrated the least bias and loss of power. When clinical success was dependent on age, the per-protocol and ITT analyses resulted in a similar trend with respect to bias and loss of power, with both outperforming the as-treated analysis. CONCLUSIONS: Insurance denial leads to misclassification bias in the ITT analysis, a missing data problem in the per-protocol analysis, and covariate imbalance between treatment arms in the as-treated analysis. Moreover, insurance denial forces the critical appraisal of patient features (eg, age) affected by the denial and potentially influencing clinical success. In the presence of insurance denial, our study suggests cautious reporting of ITT and as-treated analyses, and placing primary emphasis on the results of the per-protocol analysis.

Automatic registration of 2D MR cine images for swallowing motion estimation.

PURPOSE: To automate the estimation of swallowing motion from 2D MR cine images using deformable registration for future applications of personalized margin reduction in head and neck radiotherapy and outcome assessment of radiation-associated dysphagia. METHODS: Twenty-one patients with serial 2D FSPGR-MR cine scans of the head and neck conducted through the course of definitive radiotherapy for oropharyngeal cancer. Included patients had at least one cine scan before, during, or after radiotherapy, with a total of 52 cine scans. Contours of 7 swallowing related regions-of-interest (ROIs), including pharyngeal constrictor, epiglottis, base of tongue, geniohyoid, hyoid, soft palate, and larynx, were manually delineated from consecutive frames of the cine scan covering at least one swallowing cycle. We applied a modified thin-plate-spline robust-point-matching algorithm to register the point sets of each ROI automatically over frames. The deformation vector fields from the registration were then used to estimate the motion during swallowing for each ROI. Registration errors were estimated by comparing the deformed contours with the manual contours. RESULTS: On average 22 frames of each cine scan were contoured. The registration for one cine scan (7 ROIs over 22 frames) on average took roughly 22 minutes. A number of 8018 registrations were successfully batch processed without human interaction after the contours were drawn. The average registration error for all ROIs and all patients was 0.36 mm (range: 0.06 mm- 2.06 mm). Larynx had the average largest motion in superior direction of all structures under consideration (range: 0.0 mm- 58.7 mm). Geniohyoid had the smallest overall motion of all ROIs under consideration and the superior-inferior motion was larger than the anterior-posterior motion for all ROIs. CONCLUSION: We developed and validated a deformable registration framework to automate the estimation of swallowing motion from 2D MR cine scans.

Transoral laser microsurgery for glottic cancer in the elderly: Efficacy and safety.

BACKGROUND: Data about the results of transoral laser microsurgery (TLM) in elderly patients are limited. METHODS: A retrospective study of 72 consecutive cases of glottic carcinoma (63 pT1 and 9 pT2 cases) in elderly patients (≥70 years old, mean 76 years) treated with TLM was made. A systematic review of the literature was performed. RESULTS: Six patients (8%) had postoperative complications, but no treatment-related deaths were observed. Local recurrences occurred in 12 patients (16.5%): nine with pT1 (14%) and three with pT2 (33%) tumors. Five-year disease-specific survival (DSS), overall survival, and laryngectomy-free survival were 95%, 68%, and 88%, respectively. The literature review indicated that TLM is safe and effective treatment for these patients, with few complications and good local control (>85%) and DSS (>90%) rates. CONCLUSIONS: Our results and the information from the literature show that TLM for glottic cancer in elderly patients can lead to satisfactory treatment results.

Patient-reported outcomes of symptom burden in patients receiving surgical or nonsurgical treatment for low-intermediate risk oropharyngeal squamous cell carcinoma: A comparative analysis of a prospective registry.

PURPOSE: To explore treatment-related changes in symptom burden and quality of life (QOL) in oropharyngeal squamous cell cancer (OPSCC) patients treated surgically and non-surgically. PATIENTS AND METHODS: Eighty-six patients with human papillomavirus-associated OPSCC treated at the Head and Neck Center at The University of Texas MD Anderson Cancer Center were recruited to a prospective registry study between 2014 and 2016 and completed the core, head and neck-specific, and symptom interference sections of the MD Anderson symptom inventory (MDASI) multi-symptom questionnaire and the EQ-5D health status assessment as a measure of QOL at four time points. RESULTS: Longitudinal improvements from post-treatment nadir were observed across all groups. For patients treated with single modality, symptom interference, but not core and head and neck specific, MDASI scores were significantly better at 6 months in patients treated with surgery than radiation (P = 0.04). For patients treated with multiple modalities, scores for each of the three domains (i.e., core, head and neck -specific, and interference MDASI) were significantly better in the surgical group than the nonsurgical group at treatment completion (P = 0.0003, P = 0.0006 and P = 0.02) and 6 weeks (P = 0.001, P = 0.05 and P = 0.04), but not 6 months (P = 0.11, P = 0.16 and P = 0.040). No significant differences in EQ5D health status were observed between groups at any time point, reflecting similar overall QOL in all groups. CONCLUSION: Symptom burden and QOL improves after treatment in OPSCC survivors over time regardless of whether primary surgical or nonsurgical treatment is used, although acute symptom profiles may differ.

The Current Role of Salvage Surgery in Recurrent Head and Neck Squamous Cell Carcinoma.

Chemoradiotherapy has emerged as a gold standard in advanced squamous cell carcinoma of the head and neck (SCCHN). Because 50% of advanced stage patients relapse after nonsurgical primary treatment, the role of salvage surgery (SS) is critical because surgery is generally regarded as the best treatment option in patients with recurrent resectable SCCHN. Surgeons are increasingly confronted with considering operation among patients with significant effects of failed non-surgical primary treatment. Wide local excision to achieve clear margins must be balanced with the morbidity of the procedure, the functional consequences of organ mutilation, and the likelihood of success. Accurate selection of patients suitable for surgery is a major issue. It is essential to establish objective criteria based on functional and oncologic outcomes to select the best candidates for SS. The authors propose first to understand preoperative prognostic factors influencing survival. Predictive modeling based on preoperative information is now available to better select patients having a good chance to be successfully treated with surgery. Patients with a high comorbidity index, advanced oropharyngeal or hypopharyngeal primary tumors, and both local and regional recurrence have a very limited likelihood of success with salvage surgery and should be strongly considered for other treatments. Following SS, identifying patients with postoperative prognostic factors predicting high risk of recurrence is essential because those patients could benefit of adjuvant treatment or be included in clinical trials. Finally, defining HPV tumor status is needed in future studies including recurrent oropharyngeal SCC patients.

Head and Neck Cancer: A Review of the Impact of Treatment Delay on Outcome.

Delay between the initial symptoms, diagnosis, and the definitive treatment of head and neck cancers is associated with tumor progression and upstaging. These delays may lead to poor outcomes and may mandate more aggressive treatments with unnecessary morbidity and even mortality. The multidisciplinary team approach for the treatment of patients with head and neck cancers has improved organization of standard clinical guidelines, but this development has yet to translate into a demonstrable impact on survival. We review the association between waiting times (time between diagnosis and initiation of treatment) and clinical outcomes in patients with head and neck squamous cell carcinoma (HNSCC).

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.

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 <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. DISCUSSION: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.

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.

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

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

Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma.

PURPOSE: A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer. METHODS AND MATERIALS: Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration. RESULTS: Fifty patients with OPC treated from March 3, 2011, to July 2014 formed the cohort. Eighty-four percent were male, 50% had never smoked, 98% had stage III/IV disease, 64% received concurrent therapy, and 35% received induction chemotherapy. Forty-four of 45 tumors (98%) tested for p16 were positive. All patients received IMPT (multifield optimization to n=46; single-field optimization to n=4). No Common Terminology Criteria for Adverse Events grade 4 or 5 toxicities were observed. The most common grade 3 toxicities were acute mucositis in 58% of patients and late dysphagia in 12%. Eleven patients had a gastrostomy (feeding) tube placed during therapy, but none had a feeding tube at last follow-up. At a median follow-up time of 29 months, 5 patients had disease recurrence: local in 1, local and regional in 1, regional in 2, and distant in 1. The 2-year actuarial overall and progression-free survival rates were 94.5% and 88.6%. CONCLUSIONS: The oncologic, toxicity, and functional outcomes after IMPT for OPC are encouraging and provide the basis for ongoing and future clinical studies.

Reirradiation of Head and Neck Cancers With Proton Therapy: Outcomes and Analyses.

PURPOSE: Reirradiation of head and neck (H&N) cancer is a clinical challenge. Proton radiation therapy (PRT) offers dosimetric advantages for normal tissue sparing and may benefit previously irradiated patients. Here, we report our initial experience with the use of PRT for H&N reirradiation, with focus on clinical outcomes and toxicity. METHODS AND MATERIALS: We retrospectively reviewed the records of patients who received H&N reirradiation with PRT from April 2011 through June 2015. Patients reirradiated with palliative intent or without prior documentation of H&N radiation therapy were excluded. Radiation-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: The conditions of 60 patients were evaluated, with a median follow-up time of 13.6 months. Fifteen patients (25%) received passive scatter proton therapy (PSPT), and 45 (75%) received intensity modulated proton therapy (IMPT). Thirty-five patients (58%) received upfront surgery, and 44 (73%) received concurrent chemotherapy. The 1-year rates of locoregional failure-free survival, overall survival, progression-free survival, and distant metastasis-free survival were 68.4%, 83.8%, 60.1%, and 74.9%, respectively. Eighteen patients (30%) experienced acute grade 3 (G3) toxicity, and 13 (22%) required a feeding tube at the end of PRT. The 1-year rates of late G3 toxicity and feeding tube independence were 16.7% and 2.0%, respectively. Three patients may have died of reirradiation-related effects (1 acute and 2 late). CONCLUSIONS: Proton beam therapy can be a safe and effective curative reirradiation strategy, with acceptable rates of toxicity and durable disease control.

Disease control and toxicity outcomes for T4 carcinoma of the nasopharynx treated with intensity-modulated radiotherapy.

BACKGROUND: Treatment of T4 nasopharyngeal carcinoma (NPC) is challenging because of the proximity of the tumor to the central nervous system. The purpose of this study was to present our evaluation of disease control and toxicity outcomes for patients with T4 NPC treated with intensity-modulated radiation therapy (IMRT) and chemotherapy. METHODS: The medical records of 66 patients with T4 NPC treated from 2002 to 2012 with IMRT were reviewed. Endpoints included tumor control and toxicity outcomes (Common Terminology Criteria for Adverse Events [CTCAE v4.0]). RESULTS: Median follow-up was 38 months. Five-year rates of locoregional control, distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) were 80%, 62%, 57%, and 69%, respectively. Nodal involvement was associated with worse PFS (p = .015). Gross target volume (GTV) volume >100 cm and planning target volume (PTV) volume >400 cm were associated with worse OS (p = .038 and p = .004, respectively). Four patients had significant cognitive impairment, and 9 had MRI evidence of brain necrosis. CONCLUSION: For patients with T4 NPC treated with IMRT and chemotherapy, survival and locoregional disease control rates have improved; however, late treatment toxicity remains a concern. © 2015 Wiley Periodicals, Inc. Head Neck 38: E925-E933, 2016.

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis.

BACKGROUND: Owing to its physical properties, intensity-modulated proton therapy (IMPT) used for patients with oropharyngeal carcinoma has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities. METHODS: We performed a 1:2 matching of IMPT to IMRT patients. Our study cohort consisted of IMPT patients from a prospective quality of life study and consecutive IMRT patients treated at a single institution during the period 2010-2014. Patients were matched on unilateral/bilateral treatment, disease site, human papillomavirus status, T and N status, smoking status, and receipt of concomitant chemotherapy. Survival analyzes were performed using a Cox model and binary toxicity endpoints using a logistic regression analysis. RESULTS: Fifty IMPT and 100 IMRT patients were included. The median follow-up time was 32months. There were no imbalances in patient/tumor characteristics except for age (mean age 56.8years for IMRT patients and 61.1years for IMPT patients, p-value=0.010). Statistically significant differences were not observed in overall survival (hazard ratio (HR)=0.55; 95% confidence interval (CI): 0.12-2.50, p-value=0.44) or in progression-free survival (HR=1.02; 95% CI: 0.41-2.54; p-value=0.96). The age-adjusted odds ratio (OR) for the presence of a gastrostomy (G)-tube during treatment for IMPT vs IMRT were OR=0.53; 95% CI: 0.24-1.15; p-value=0.11 and OR=0.43; 95% CI: 0.16-1.17; p-value=0.10 at 3months after treatment. When considering the pre-planned composite endpoint of grade 3 weight loss or G-tube presence, the ORs were OR=0.44; 95% CI: 0.19-1.0; p-value=0.05 at 3months after treatment and OR=0.23; 95% CI: 0.07-0.73; p-value=0.01 at 1year after treatment. CONCLUSION: Our results suggest that IMPT is associated with reduced rates of feeding tube dependency and severe weight loss without jeopardizing outcome. Prospective multicenter randomized trials are needed to validate such findings.

Favorable patient reported outcomes following IMRT for early carcinomas of the tonsillar fossa: Results from a symptom assessment study.

BACKGROUND: A questionnaire-based study was conducted to assess long-term patient reported outcomes (PROs) following definitive IMRT-based treatment for early stage carcinomas of the tonsillar fossa. METHODS: Participants had received IMRT with or without systemic therapy for squamous carcinoma of the tonsillar fossa (T1-2 and N0-2b) with a minimum follow-up of 2years. Patients completed a validated head and neck cancer-specific PRO instrument, the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Symptoms were compared between treatment groups of interest and overall symptom burden was evaluated. RESULTS: Of 139 participants analyzed, 51% had received ipsilateral neck IMRT, and 62% single modality IMRT alone (no systemic therapy). There were no differences in mean severity ratings for the top-ranked individual symptoms or symptom interference for those treated with bilateral versus ipsilateral neck IMRT alone. However, 40% of those treated with bilateral versus 25% of those treated with ipsilateral neck RT alone reported moderate-to-severe levels of dry mouth (p=0.03). Fatigue, numbness/tingling, and constipation were rated more severe for those who had received systemic therapy (p<0.05 for each), but absolute differences were small. Overall, 51% had no more than mild symptom ratings across all 22 symptoms assessed. CONCLUSIONS: The long-term patient reported symptom profile in this cohort of tonsil cancer survivors treated with definitive IMRT-based treatment showed a majority of patients with no more than mild symptoms, low symptom interference, and provides an opportunity for future comparison studies with other treatment approaches.