title: A Prospective Study of Proton Beam Reirradiation for Esophageal Cancer.
abstract: OBJECTIVE
  Reirradiation to the esophagus carries a significant risk of complications. Proton therapy may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of previously radiated normal tissues.
  
  
  METHODS
  Between June 2010 and February 2014, 14 patients with a history of thoracic radiation and newly diagnosed or locally recurrent esophageal cancer began proton beam reirradiation on a prospective trial. Primary endpoints were feasibility and acute toxicity. Toxicity was graded according Common Toxicity Criteria version 4.0.
  
  
  RESULTS
  The median follow-up was 10 months (2-25 months) from the start of reirradiation. Eleven patients received concurrent chemotherapy. The median interval between radiation courses was 32 months (10-307 months). The median reirradiation prescription dose was 54.0 Gy (relative biological effectiveness [RBE]) (50.4-61.2 Gy[RBE]), and the median cumulative prescription dose was 109.8 Gy (76-129.4 Gy). Of the 10 patients who presented with symptomatic disease, 4 patients had complete resolution of symptoms, and 4 had diminished or stable symptoms. Two patients had progressive symptoms. The median time to symptom recurrence was 10 months. Maximum acute nonhematologic toxicity attributable to radiation was grade 2 (64%, N=9), 3 (29%, N=4), 4 (0%), and 5 (7%, N=1). The acute grade 5 toxicity was an esophagopleural fistula more likely related to tumor progression than radiation. Grade 3 nonhematologic acute toxicities included dysphagia, dehydration, and pneumonia. There was 1 late grade 5 esophageal ulcer more likely related to tumor progression than radiation. There were 4 late grade 3 toxicities: heart failure, esophageal stenosis requiring dilation, esophageal ulceration from tumor, and percutaneous endoscopic gastrostomy tube dependence. The median time to local failure was 10 months, and the median overall survival was 14 months.
  
  
  CONCLUSIONS
  Our data demonstrate that proton reirradiation is feasible, with an encouraging symptom control rate, modest radiation-related toxicity, and favorable survival in this high-risk population.
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: Annemarie.fernandes@gmail.com.
authors: Annemarie
authors: A
authors: Fernandes
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Abigail T
authors: AT
authors: Berman
authors: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Rosemarie
authors: R
authors: Mick
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Stefan
authors: S
authors: Both
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Kristi
authors: K
authors: Lelionis
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: John N
authors: JN
authors: Lukens
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Edgar
authors: E
authors: Ben-Josef
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: James M
authors: JM
authors: Metz
authors: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: John P
authors: JP
authors: Plastaras
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D004935:Esophageal Diseases / Q000209:etiology; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D004947:Esophagus / Q000528:radiation effects; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy*; D011446:Prospective Studies; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods; D011832:Radiation Injuries / Q000150:complications; D011879:Radiotherapy Dosage; D000069475:Re-Irradiation / Q000009:adverse effects* / Q000379:methods; D012062:Relative Biological Effectiveness; D014456:Ulcer / Q000209:etiology