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

Purpose: We previously reported that ∼30% of patients with localized follicular lymphoma (FL)staged by 18F-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 18F-fluorodeoxyglucose (18F-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 (<12 months)have inferior survival compared with those with longer disease-free interval.