title: Phase 1 study of dose escalation in hypofractionated proton beam therapy for non-small cell lung cancer.
abstract: BACKGROUND
  Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control.
  
  
  METHODS
  Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment.
  
  
  RESULTS
  The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT.
  
  
  CONCLUSIONS
  Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA. dgomez@mdanderson.org
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gomez
authors.forename: Michael
authors.initials: M
authors.lastname: Gillin
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Caimiao
authors.initials: C
authors.lastname: Wei
authors.forename: Steven H
authors.initials: SH
authors.lastname: Lin
authors.forename: Cameron
authors.initials: C
authors.lastname: Swanick
authors.forename: Tina
authors.initials: T
authors.lastname: Alvarado
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D000068818:Cetuximab; D019583:Dose Fractionation, Radiation; D004941:Esophagitis / Q000209:etiology / Q000473:pathology; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D015182:Lymphatic Irradiation / Q000379:methods; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D011446:Prospective Studies; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D017564:Radiation Pneumonitis / Q000209:etiology; D012062:Relative Biological Effectiveness
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab