title: Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study.
abstract: OBJECTIVE
  Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported.
  
  
  METHODS
  Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m(2), days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients.
  
  
  RESULTS
  At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis.
  
  
  CONCLUSIONS
  This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.
authors.affiliation: Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino, Italy; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Marco
authors.initials: M
authors.lastname: Ruella
authors.affiliation: Department of Oncology, Radiation Oncology, University of Torino, Torino, Italy.
authors.forename: Andrea Riccardo
authors.initials: AR
authors.lastname: Filippi
authors.affiliation: Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bruna
authors.affiliation: Radiation Oncology, Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Russo
authors.affiliation: Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Magni
authors.affiliation: Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Caracciolo
authors.affiliation: Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Passera
authors.affiliation: Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Matteucci
authors.affiliation: Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.affiliation: Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.affiliation: Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Parvis
authors.affiliation: Division of Haematology, Ospedali Riuniti, Ancona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Gini
authors.affiliation: Division of Haematology, Ospedali Riuniti, Ancona, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Olivieri
authors.affiliation: Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.affiliation: Department of Oncology, Radiation Oncology, University of Torino, Torino, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
authors.affiliation: Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino, Italy; Hemato-Oncology Division, European Institute of Oncology, Milano, Italy. Electronic address: corrado.tarella@gmail.com.
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
authors.affiliation: Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Devizzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001853:Bone Marrow / Q000473:pathology; D059248:Chemoradiotherapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000069283:Rituximab