title: Involved-node proton therapy in combined modality therapy for Hodgkin lymphoma: results of a phase 2 study.
abstract: OBJECTIVE
  This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement.
  
  
  METHODS
  Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis.
  
  
  RESULTS
  The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed.
  
  
  CONCLUSIONS
  Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to those of conventional photon therapy.
authors.affiliation: Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida. Electronic address: bhoppe@floridaproton.org.
authors.forename: Bradford S
authors.initials: BS
authors.lastname: Hoppe
authors.affiliation: Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Stella
authors.initials: S
authors.lastname: Flampouri
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Robert
authors.initials: R
authors.lastname: Zaiden
authors.affiliation: Department of Pediatrics, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: William
authors.initials: W
authors.lastname: Slayton
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology Nemours Children's Clinic, Jacksonville, Florida.
authors.forename: Eric
authors.initials: E
authors.lastname: Sandler
authors.affiliation: Department of Radiology, Division of Functional and Molecular Imaging, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Savas
authors.initials: S
authors.lastname: Ozdemir
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: James W
authors.initials: JW
authors.lastname: Lynch
authors.affiliation: Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Zuofeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.affiliation: Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Mendenhall
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D015182:Lymphatic Irradiation / Q000379:methods*; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D011446:Prospective Studies; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011832:Radiation Injuries / Q000517:prevention & control; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult