Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy

Abstract

BackgroundTo evaluate acute toxicity endpoints in a cohort of patients receiving head and neck radiation with proton therapy or intensity modulated radiation therapy (IMRT).MethodsForty patients received comprehensive head and neck radiation including bilateral cervical nodal radiation, given with or without chemotherapy, for tumors of the nasopharynx, nasal cavity or paranasal sinuses, any T stage, N0-2. Fourteen received comprehensive treatment with proton therapy, and 26 were treated with IMRT, either comprehensively or matched to proton therapy delivered to the primary tumor site. Toxicity endpoints assessed included g-tube dependence at the completion of radiation and at 3 months after radiation, opioid pain medication requirement compared to pretreatment normalized as equivalent morphine dose (EMD) at completion of treatment, and at 1 and 3 months after radiation.ResultsIn a multivariable model including confounding variables of concurrent chemotherapy and involved nodal disease, comprehensive head and neck radiation therapy using proton therapy was associated with a lower opioid pain requirement at the completion of radiation and a lower rate of gastrostomy tube dependence by the completion of radiation therapy and at 3 months after radiation compared to IMRT. Proton therapy was associated with statistically significant lower mean doses to the oral cavity, esophagus, larynx, and parotid glands. In subgroup analysis of 32 patients receiving concurrent chemotherapy, there was a statistically significant correlation with a greater opioid pain medication requirement at the completion of radiation and both increasing mean dose to the oral cavity and to the esophagus.ConclusionsProton therapy was associated with significantly reduced radiation dose to assessed non-target normal tissues and a reduced rate of gastrostomy tube dependence and opioid pain medication requirements. This warrants further evaluation in larger studies, ideally with patient-reported toxicity outcomes and quality of life endpoints.

Outcomes and toxicities of definitive radiotherapy and reirradiation using 3‐dimensional conformal or intensity‐modulated (pencil beam) proton therapy for patients with nasal cavity and paranasal sinus malignancies

“…Without IMPT to treat skin as an avoidance structure, it will receive the full prescription dose, resulting in higher cutaneous toxicity in patients treated with proton‐based versus photon‐based treatments. Prior studies also have reported decreased acute toxicity with PT compared with IMRT . Late grade 3 toxicities were seen in only 6 patients (7% of our entire cohort), and included vision loss, osteonecrosis with soft tissue necrosis requiring surgical debridement and flap reconstruction, brain necrosis, soft tissue fibrosis, and severe facial pain requiring hospitalization.…”

Intensity-modulated proton therapy and osteoradionecrosis in oropharyngeal cancer

“…One comparison of 3D and IMRT approaches showed that IMRT for oral cancer could reduce the volumes of mandible that received >50 Gy, >55 Gy, and >60 Gy, in addition to producing fewer hot spots and a lower maximum dose to the mandible [10]. More recently, numerous reports have been published documenting the theoretical advantages of proton therapy over photon therapy for head and neck cancer [23–25]. The first use of multi-field optimization for IMPT was reported in 2014 for head and neck malignancies [16]; indeed, IMPT (as opposed to passively scattered proton therapy) has been shown in treatment-planning comparisons to be the most effective in reducing the doses to the spinal cord, parotid, and brainstem [13, 26].…”

Biological Model for Predicting Toxicity in Head and Neck Cancer Patients Receiving Proton Therapy

“…A recent MD Anderson Cancer Center series compared intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy using photons for nasopharyngeal cancer and found a 3-fold reduction in the rate of gastrostomy tube placement for patients receiving protons, which was attributed to decreased oral cavity toxicity [2]. Additional studies evaluating the use of protons in head and neck cancer have yielded similar conclusions [3][4][5][6].…”