Salvage Treatment and Survival for Relapsed Follicular Lymphoma Following Primary Radiation Therapy: A Collaborative Study on Behalf of ILROG

Michael S Binkley, Jessica L Brady, Carla Hajj, Monica Chelius, Karen Chau, Alex Balogh, Mario Levis, Andrea Riccardo Filippi, Michael Jones, Sameera Ahmed, Michael MacManus, Andrew Wirth, Masahiko Oguchi, Anders Krog Vistisen, Therese Youssef Andraos, Andrea K Ng, Berthe M P Aleman, Seo Hee Choi, Youlia M Kirova, Sara HardyGabriele Reinartz, Hans T Eich, Scott V Bratman, Louis S Constine, Chang-Ok Suh, Bouthaina Dabaja, Tarec C El-Galaly, David C Hodgson, Umberto Ricardi, Joachim Yahalom, N George Mikhaeel, Richard T Hoppe

Research output: Contribution to journalArticlepeer-review


PURPOSE: We previously reported that ∼30% of patients with localized follicular lymphoma (FL) staged by (18)F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed. METHODS AND MATERIALS: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. RESULTS: Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%. CONCLUSIONS: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (
Original languageEnglish
Pages (from-to)522-529
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number3
Publication statusPublished - Jul 1 2019


  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived/administration & dosage
  • Antineoplastic Agents, Immunological/therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols/administration & dosage/therapeutic use
  • Cyclophosphamide/administration & dosage
  • Doxorubicin/administration & dosage
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Follicular/diagnostic imaging/*mortality/pathology/*radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Positron Emission Tomography Computed Tomography
  • Prednisone/administration & dosage
  • Progression-Free Survival
  • Radiopharmaceuticals
  • Recurrence
  • Retrospective Studies
  • Rituximab/therapeutic use
  • *Salvage Therapy
  • Time Factors
  • Vincristine/administration & dosage
  • Watchful Waiting
  • Young Adult


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