Assessing Outcomes of Patients Treated With Re-Irradiation Utilizing Proton Pencil-Beam Scanning for Primary or Recurrent Malignancies of the Esophagus and Gastroesophageal Junction

Abstract

Introduction: Re-irradiation (re-RT) for locoregionally recurrent esophageal and gastroesophageal junction (GEJ) cancer and de novo esophageal þ GEJ cancer arising in-field after a course of prior radiation poses considerable treatment challenges given the sensitivity of surrounding organs at risk (OARs). Guidelines for treatment of this presentation are not well established. Pencil-beam scanning (PBS) proton therapy has the ability to decrease radiation dose to OARs relative to photon plans. We present the first published series to date of re-RT with PBS for esophageal þ GEJ malignancies and hypothesize that re-RT with proton PBS will be feasible and improve the safety profile of re-RT for this cohort of patients.Methods: Consecutive esophageal þ GEJ cancers treated with PBS re-RT within a single institution were analyzed. Comparative volumetric-modulated arc therapy photon plans were generated. A total of 17 patients were included for analysis.Results: At a median follow-up of 11.6 months, 1-year local control was 75.3% and overall survival was 68.9%. There were five (27.8%) grade 3 or higher late toxicities. When matched for clinical target volume coverage, proton PBS plans delivered significantly lower doses to the spinal cord, lungs, liver, and heart (all p < 0.05); five volumetricmodulated arc therapy plans would have been undeliverable on the basis of physician-specified OAR constraints.Conclusions: Re-RT for de novo or recurrent malignancies of the esophagus þ GEJ, when delivered with PBS proton therapy, yields high rates of local control with acceptable acute and late toxicities in a high-risk population and decreased radiation dose to OARs relative to comparative photon plans. This is the largest series of proton re-RT for esophageal malignancies and the first that exclusively used PBS.

Executive Summary of Clinical and Technical Guidelines for Esophageal Cancer Proton Beam Therapy From the Particle Therapy Co-Operative Group Thoracic and Gastrointestinal Subcommittees

“…PBT is expected to achieve a potentially large reduction in cumulative doses to critical OARs, including the spinal cord, heart, lungs, proximal bronchial tree, and liver ( 32 – 34 ). Several cohort studies have demonstrated feasibility and encouraging early clinical outcomes with PBT reirradiation for EC ( Table 4 ) ( 31 , 33 , 35 , 36 ). Most recently, DeCesaris et al.…”

“…Another consideration could be superior–inferior posterior oblique beams with the couch at 270°C, which may provide better sparing of normal organs lateral to the target at the expense of delivering higher dose to the spinal cord ( 18 ). Accordingly, most centers treating distal esophagus/GEJ tumors with IMPT have used two to three posterior oriented beams ( 18 , 20 , 33 , 50 ). For treatment of tumors in the cervical and proximal thoracic esophagus, an anterior beam should be considered to reduce lung dose.…”

Reirradiation With Proton Therapy for Recurrent Malignancies of the Esophagus and Gastroesophageal Junction: Results of the Proton Collaborative Group Multi-Institutional Prospective Registry Trial

“…Additionally, a more recent retrospective study of 17 patients described a lower rate of acute grade 3 toxicity (12%) and no acute grade 4 or 5 toxicities. 17 This lower rate of acute toxicities may be because of the use of pencil beam scanning in the latter report versus passive scattering in the former report. However, in that latter study, DeCesaris et al did report higher rates of late toxicities similar to that in Fernandes et al, with 11.1% grade 3, 12.2% grade 4, and 6.6% grade 5 late toxicities.…”

“… 13 , 14 Although proton therapy is increasingly being used in the setting of reirradiation for esophageal cancer, to date, data on outcomes in this patient population are limited to small retrospective 15 and prospective studies, 16 with the largest study reporting outcomes on 17 patients. 17 In this study, we report on outcomes and toxicities from a multi-institutional series of patients with locoregionally recurrent esophageal and GEJ cancers who underwent reRT with PBT.…”

Proton Therapy in the Management of Luminal Gastrointestinal Cancers: Esophagus, Stomach, and Anorectum

“…Of note, all patients but one received protons via the passive scattering technique. Another study generated PBS proton plans for 17 patients with a history of head and neck and thoracic radiation to a median cumulative dose of 104.7 Gy [ 40 ]. The resultant median OS was 19.5 months, with acute and late G3+ toxicity noted in 2 and 5 patients, respectively.…”