Addition of rituximab to involved-field radiation therapy prolongs progression-free survival in stage I-II follicular lymphoma: Results of a multicenter study

Marco Ruella, Andrea Riccardo Filippi, Riccardo Bruna, A. Di Russo, M. Magni, D. Caracciolo, R. Passera, P. Matteucci, M. Di Nicola, P. Corradini, Guido Parvis, G. Gini, A. Olivieri, Marco Ladetto, Umberto Ricardi, C. Tarella, L. Devizzi

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Purpose 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 and Materials 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/m2, 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. © 2016 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)783-791
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
Publication statusPublished - 2016


  • Diagnosis
  • Multivariant analysis
  • Oncology
  • Radiotherapy
  • Regression analysis
  • Risk assessment
  • Cox regression analysis
  • Disease monitoring
  • Follicular lymphoma
  • Involved-field radiation therapy
  • Methods and materials
  • Multi variate analysis
  • Observational study
  • Progression free survival
  • Patient treatment
  • cyclophosphamide
  • doxorubicin
  • prednisone
  • rituximab
  • vincristine
  • antineoplastic agent
  • adult
  • age
  • aged
  • Article
  • cancer radiotherapy
  • cancer recurrence
  • cohort analysis
  • controlled study
  • female
  • follicular lymphoma
  • Follicular Lymphoma International Prognostic Index
  • follow up
  • human
  • hypothyroidism
  • involved field radiation therapy
  • large cell lymphoma
  • lymphocytopenia
  • major clinical study
  • male
  • molecular probe
  • mucosa inflammation
  • multicenter study
  • neutropenia
  • observational study
  • overall survival
  • polymerase chain reaction
  • priority journal
  • progression free survival
  • radiation field
  • radiation injury
  • smoking
  • very elderly
  • xerostomia
  • bone marrow
  • chemoradiotherapy
  • clinical trial
  • disease free survival
  • Lymphoma, Follicular
  • middle aged
  • mortality
  • pathology
  • procedures
  • retrospective study
  • survival analysis
  • time factor
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents
  • Bone Marrow
  • Chemoradiotherapy
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Rituximab
  • Survival Analysis
  • Time Factors


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