Background As proton beam radiation therapy (PBRT) may allow greater normal tissue sparing when compared with intensity-modulated radiation therapy (IMRT), we compared the dosimetry and treatment-related toxicities between patients treated to the ipsilateral head and neck with either PBRT or IMRT. Methods Between 01/2011 and 03/2014, 41 consecutive patients underwent ipsilateral irradiation for major salivary gland cancer or cutaneous squamous cell carcinoma. The availability of PBRT, during this period, resulted in an immediate shift in practice from IMRT to PBRT, without any change in target delineation. Acute toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results Twenty-three (56.1%) patients were treated with IMRT and 18 (43.9%) with PBRT. The groups were balanced in terms of baseline, treatment, and target volume characteristics. IMRT plans had a greater median maximum brainstem (29.7 Gy vs. 0.62 Gy (RBE), P < 0.001), maximum spinal cord (36.3 Gy vs. 1.88 Gy (RBE), P < 0.001), mean oral cavity (20.6 Gy vs. 0.94 Gy (RBE), P < 0.001), mean contralateral parotid (1.4 Gy vs. 0.0 Gy (RBE), P < 0.001), and mean contralateral submandibular (4.1 Gy vs. 0.0 Gy (RBE), P < 0.001) dose when compared to PBRT plans. PBRT had significantly lower rates of grade 2 or greater acute dysgeusia (5.6% vs. 65.2%, P < 0.001), mucositis (16.7% vs. 52.2%, P = 0.019), and nausea (11.1% vs. 56.5%, P = 0.003). Conclusions The unique properties of PBRT allow greater normal tissue sparing without sacrificing target coverage when irradiating the ipsilateral head and neck. This dosimetric advantage seemingly translates into lower rates of acute treatment-related toxicity.

Purpose/Objectives Re-irradiation (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-irradiation, interest in proton beam radiotherapy (PBRT) has increased. Herein, we report the first multi-institutional clinical experience using curative intent PBRT for re-RT in recurrent HNC. Materials/Methods A retrospective analysis of ongoing prospective data registries from 2-hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who had at least one prior course of definitive intent external beam RT were included. Acute and late toxicities were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and by the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial twelve-month freedom from distant metastasis (FFDM) and overall survival (OS) rates were calculated with the Kaplan-Meier method. Results Ninety-two consecutive patients were treated with curative intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months (interquartile range, 5.3-17.5 months). The median time between last RT and PBRT was 34.4 months. There were 76 patients with one prior RT course and 16 with two or more courses. Median PBRT dose was 60.6 Gy (RBE). Eighty-five percent of patients had prior HNC RT for an oropharynx primary and 39% had salvage surgery prior to re-RT. The cumulative incidence of locoregional failure at 12-months, with death as a competing risk, was 25.1%. Actuarial 12-month FFDM and OS were 84.0% and 65.2%, respectively. Acute grade ≥3 toxicities included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was one death during PBRT secondary to disease progression. Grade 3 or greater late skin and dysphagia toxicity were noted in 6 (8.7%) and 4 (7.1%) of patients, respectively. Two patients had grade 5 toxicity secondary to treatment-related bleeding. Conclusions Proton beam re-irradiation of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely secondary to the decreased dose to the surrounding normal, albeit previously irradiated tissue, though longer follow up is needed to confirm these findings.

IMPORTANCE Patients with nonmetastatic nasopharyngeal carcinoma (NPC) are primarily treated by radiotherapy with curative intent with or without chemotherapy and often experience substantial treatment-related toxic effects even with modern radiation techniques, such as intensitymodulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) may improve the toxicity profile; however, there is a paucity of data given the limited availability of IMPT in regions with endemic NPC. OBJECTIVE To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic NPC when treated with IMPT vs IMRT with or without chemotherapy. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study included 77 patients with newly diagnosed nonmetastatic NPC who received curative-intent radiotherapy with IMPT or IMRT at a tertiary academic cancer center from January 1, 2016, to December 31, 2019. Forty-eight patients with Epstein-Barr virus (EBV)-positive tumors were included in a 1:1 propensity score-matched analysis for survival outcomes. The end of the follow-up period was March 31, 2021.EXPOSURES IMPT vs IMRT with or without chemotherapy. MAIN OUTCOMES AND MEASURESThe main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs) and oncologic outcomes, including locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). RESULTSWe identified 77 patients (25 [32.5%] women; 52 [67.5%] men; median [interquartile range] age, 48.7 [42.2-60.3] years), among whom 28 (36.4%) were treated with IMPT and 49(63.6%) were treated with IMRT. Median (interquartile range) follow-up was 30.3 (17.9-41.5) months.On multivariable logistic regression analyses, IMPT was associated with lower likelihood of developing grade 2 or higher acute AEs compared with IMRT (odds ratio [OR], 0.15; 95% CI, 0.03-0.60; P = .01). Only 1 case (3.8%) of a chronic grade 3 or higher AE occurred in the IMPT group compared with 8 cases (16.3%) in the IMRT group (OR, 0.21; 95% CI, 0.01-1.21; P = .15). Propensity score matching generated a balanced cohort of 48 patients (24 IMPT vs 24 IMRT) and found similar PFS in the IMPT and IMRT groups (2-year PFS, 95.7% [95% CI, 87.7%-100%] vs 76.7% [95% CI, 60.7%-97.0%]; hazard ratio [HR], 0.31; 95% CI, 0.07-1.47; P = .14). No locoregional recurrence or death was observed in the IMPT group from the matched cohort. Two-year LRFS was 100% (95% CI, 100%-100%) in the IMPT group and 86.2% (95% CI, 72.8%-100%) in the IMRT group (P = .08).Three-year OS was 100% (95% CI, 100%-100%) in the IMPT group and 94.1% (95% CI, 83.6%-100%) in the IMRT group (P = .42). Smoking history was the only clinical factor significantly (continued) Key Points Question Is intensity-modulated proton therapy (IMPT) associated with fewer treatment-related adverse events and comparable oncologic outcomes for patients with nonmetastatic nasopharyngeal carcinoma (NPC) compared with patients treated with intensity-modulated radiation therapy (IMRT)? Findin...

Objective The purpose of this study is to compare the dosimetric distribution of ipsilateral proton beam radiation therapy (PBRT) to intensity-modulated radiation therapy (IMRT) in the tooth-bearing region of the mandible in patients with head and neck cancer (HNC). Patients and Methods The mandibular dosimetric distribution of HNC patients treated with ≥60 Gy relative biological equivalent (RBE) PBRT were evaluated. The mean radiation doses were calculated in five regions: Ipsilateral molar, ipsilateral premolar, anterior, contralateral premolar and contralateral molar (CM). The CM was used as reference region for comparative analysis. The mandibular dosimetric distribution of patients treated with PBRT was compared to IMRT patients with similar tumor sites and planning target volumes. Results The mean radiation dose to the contralateral regions was lower in patients treated with PBRT compared to IMRT. The average mean radiation dose to the reference region (CM) in patients treated with PBRT (RBE) vs. IMRT: oropharynx [2.2 Gy vs. 23.2 Gy, P <0.00002], parotid [0 Gy vs. 11.8 Gy, P = 0.01] and oral cavity [0.4 Gy vs. 15.6 Gy, P = 0.006]. Conclusion This study demonstrates the effective tissue-sparing capability of PBRT compared to IMRT. Utilization of PBRT could translate to less radiation-related toxicity.

BACKGROUND: Proton therapy (PT) improves outcomes in patients with nasal cavity (NC) and paranasal sinus (PNS) cancers. Herein, the authors have reported to their knowledge the largest series to date using intensity-modulated proton therapy (IMPT) in the treatment of these patients. METHODS: Between 2013 and 2018, a total of 86 consecutive patients (68 of whom were radiation-naive and 18 of whom were reirradiated) received PT to median doses of 70 grays and 67 grays relative biological effectiveness, respectively. Approximately 53% received IMPT. RESULTS: The median follow-up was 23.4 months (range, 1.7-69.3 months) for all patients and 28.1 months (range, 2.3-69.3 months) for surviving patients. The 2-year local control (LC), distant control, disease-free survival, and overall survival rates were 83%, 84%, 74%, and 81%, respectively, for radiation-naive patients and 77%, 80%, 54%, and 66%, respectively for reirradiated patients. Among radiation-naive patients, when compared with 3-dimensional conformal proton technique, IMPT significantly improved LC (91% vs 72%; P < .01) and independently predicted LC (hazard ratio, 0.14; P = .01). Sixteen radiation-naive patients (24%) experienced acute grade 3 toxicities; 4 (6%) experienced late grade 3 toxicities (osteoradionecrosis, vision loss, soft-tissue necrosis, and soft tissue fibrosis) (grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 5.0]). Slightly inferior LC was noted for patients undergoing reirradiation with higher complications: 11% experienced late grade 3 toxicities (facial pain and brain necrosis). Patients treated with reirradiation had more grade 1 to 2 radionecrosis than radiation-naive patients (brain: 33% vs 7% and osteoradionecrosis: 17% vs 3%). CONCLUSIONS: PT achieved remarkable LC for patients with nasal cavity and paranasal sinus cancers with lower grade 3 toxicities relative to historical reports. IMPT has the potential to improve the therapeutic ratio in these malignancies and is worthy of further investigation. Cancer 2020;126:1905-1916.