C. David Fuller

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.

Toward a model-based patient selection strategy for proton therapy: External validation of photon-derived normal tissue complication probability models in a head and neck proton therapy cohort

OBJECTIVE To externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT). METHODS This prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve. RESULTS 192 patients were included. The most prevalent tumor site was oropharynx (n=86, 45%), followed by sinonasal (n=28), nasopharyngeal (n=27) or parotid (n=27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6months after PBT; 0.70 versus 0.68 for dry mouth 6months after PBT; and 0.73 versus 0.85 for hypothyroidism 12months after PBT. CONCLUSION Although a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC.

Proton Therapy Reduces Treatment-Related Toxicities for Patients with Nasopharyngeal Cancer: A Case-Match Control Study of Intensity-Modulated Proton Therapy and Intensity-Modulated Photon Therapy

Abstract Purpose: The physical properties of proton therapy allow for decreased dose delivery to nontarget structures. The purpose of this study was to determine if this translates into a clinical benefit by comparing acute and chronic morbidity between patients with nasopharyngeal carcinoma who are treated with intensity-modulated proton therapy (IMPT) and those treated with intensity-modulated radiation therapy (IMRT). Materials and Methods: Patients receiving IMPT for nasopharyngeal cancer from 2011-13 were matched in a 2:1 IMPT to IMRT ratio. Matching criteria were, in order, T-stage, N-stage, radiation dose, chemotherapy type, World Health Organization classification, sex, and age. Results: Ten patients treated with IMPT and 20 matched patients treated with IMRT were included. By the end of treatment, 2 IMPT-treated patients (20%) and 13 IMRT-treated patients (65%) required gastrostomy tube (GT) insertion (P = .020). Patients receiving IMPT had significantly lower mean doses to the oral cavity, brain...

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.

Definitive proton radiation therapy and concurrent cisplatin for unresectable head and neck adenoid cystic carcinoma: A series of 9 cases and a critical review of the literature

The primary treatment for head and neck adenoid cystic carcinoma (ACC) is surgery. Infrequently, however, ACCs propensity for perineural and base of skull invasion can preclude definitive surgical management. We present our experience with proton radiation therapy (RT) and concurrent platinum‐based chemotherapy.

Intensity-modulated proton therapy and osteoradionecrosis in oropharyngeal cancer

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

A Multidisciplinary Orbit-Sparing Treatment Approach That Includes Proton Therapy for Epithelial Tumors of the Orbit and Ocular Adnexa

PURPOSE Postoperative radiation is often indicated in the treatment of malignant epithelial tumors of the orbit and ocular adnexa. We present details of radiation technique and toxicity data after orbit-sparing surgery followed by adjuvant proton radiation therapy. METHODS AND MATERIALS Twenty patients underwent orbit-sparing surgery followed by proton therapy for newly diagnosed malignant epithelial tumors of the lacrimal gland (n=7), lacrimal sac/nasolacrimal duct (n=10), or eyelid (n=3). Tumor characteristics, treatment details, and visual outcomes were obtained from medical records. Acute and chronic toxicity were prospectively scored using Common Terminology Criteria for Adverse Events version 4.0. RESULTS The median radiation dose was 60 Gy(RBE) (relative biological effectiveness; [range 50-70 Gy]); 11 patients received concurrent chemotherapy. Dose to ipsilateral anterior optic structures was reduced in 13 patients by having them gaze away from the target during treatment. At a median follow-up time of 27.1 months (range 2.6-77.2 months), no patient had experienced local recurrence; 1 had regional and 1 had distant recurrence. Three patients developed chronic grade 3 epiphora, and 3 developed grade 3 exposure keratopathy. Four patients experienced a decrease in visual acuity from baseline but maintained vision sufficient to perform all activities of daily living without difficulty. Patients with grade ≥3 chronic ocular toxicity had higher maximum dose to the ipsilateral cornea (median 46.3 Gy[RBE], range 36.6-52.7 Gy[RBE] vs median 37.4 Gy[RBE], range 9.0-47.3 Gy(RBE); P=.017). CONCLUSIONS Orbit-sparing surgery for epithelial tumors of the orbit and ocular adnexa followed by proton therapy successfully achieved disease control and was well tolerated. No patient required orbital exenteration or enucleation. Chronic grade 3 toxicity was associated with high maximum dose to the cornea. An eye-deviation technique can be used to limit the maximum corneal dose to <35 Gy(RBE).

Predicting two-year longitudinal MD Anderson Dysphagia Inventory outcomes after intensity modulated radiotherapy for locoregionally advanced oropharyngeal carcinoma.

To determine the factors associated with longitudinal patient‐reported dysphagia as measured by the MD Anderson Dysphagia Inventory (MDADI) in locoregionally advanced oropharyngeal carcinoma (OPC) survivors treated with split‐field intensity modulated radiotherapy (IMRT).

Symptom burden as a driver of decisional regret in long‐term oropharyngeal carcinoma survivors

The purpose of this study was to characterize decisional regret and its association with symptom burden in a large cohort of oropharyngeal carcinoma (OPC) survivors.

Outcomes for olfactory neuroblastoma treated with induction chemotherapy

Oncologic outcomes for induction chemotherapy and its role in patients with advanced olfactory neuroblastoma (ONB) remain unclear.