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.

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.

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.

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.

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.

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.

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.

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.