Please cite this article in press as: J.-M. Sancho, et al., The long term follow-up of early stage follicular lymphoma treated with radiotherapy, chemotherapy or combined modality treatment, Leuk Res (2015), http://dx.doi.org/10.1016/j.leukres.2015.05.009 ARTICLE IN PRESS G Model LR-5399; No. of Pages 6 Leukemia Research xxx (2015) xxx–xxx Contents lists available at ScienceDirect Leukemia Research journa l h om epage: www.elsevier.com/locate/leukres The long term follow-up of early stage follicular lymphoma treated with radiotherapy, chemotherapy or combined modality treatment Juan-Manuel Sancho a,∗ , Olga García a , Santiago Mercadal b , Helena Pomares b , Rubén Fernández-Alvarez c , Eva González-Barca b , Gustavo Tapia d , Esther González-García c , Miriam Moreno a , Eva Domingo-Domènech b , Marc Sorigué a , José-Tomás Navarro a , Cristina Motlló a , Alberto Fernández-de-Sevilla b , Evarist Feliu a , Josep-Maria Ribera a a Hematology Departments of ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, Badalona, Universitat Autònoma de Barcelona, Spain b ICO-Hospital Duran i Reynals, Barcelona, Spain c Hospital de Cabue˜ nes, Gijón, Spain d Pathology Department, Hospital Germans Trias i Pujol, Spain a r t i c l e i n f o Article history: Received 18 March 2015 Received in revised form 21 May 2015 Accepted 22 May 2015 Available online xxx Keywords: Limited stage Follicular lymphoma Radiotherapy Chemotherapy a b s t r a c t Local (involved-field or recently involved-site) radiotherapy is the standard therapy in limited-stage follicular lymphoma (FL). We retrospectively analyzed the value of chemotherapy in 130 patients with limited-stage FL (46 treated with radiotherapy alone [RT group], 30 with radiotherapy plus chemotherapy [COMBINED group] and 43 with chemotherapy alone [CHEMO group], 11 were managed with observa- tion). Ninety-six percent of patients responded (RT 98%, COMBINED 100%, CHEMO 91%, p = 0.179), and 37% (40/107) of patients in complete response relapsed (RT 42%, COMBINED 27%, CHEMO 41%, p = 0.371). Progression-free survival (PFS) and overall survival (OS) probabilities at 10 years were similar in RT, COMBINED and CHEMO patients (PFS 41%, 61% and 39% [p = 0.167], and OS 77%, 81% and 72% [p = 0.821], respectively), while the COMBINED group showed a trend to better time-to-progression (TTP 43%, 72% and 47% [p = 0.055]). On multivariate analysis, only a FLIPI score ≥2 showed a trend to influence PFS (HR 2.1 [95% confidence interval 0.9–4.6], p = 0.067), and OS (HR 2.4 [0.9–6.5], p = 0.084), while patients treated with radiotherapy plus chemotherapy (COMBINED group) showed a significantly better TTP compared with those receiving only RT (HR 0.3 [0.1–0.8], p = 0.024). In our study no benefit was observed in survival with the use of systemic therapy compared with local radiotherapy. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Follicular lymphoma (FL) is the most frequent low-grade lym- phoma, defined in most cases by an indolent behavior and with a continuous pattern of relapses. Although most of the patients show advanced disease at the time of diagnosis, almost 25–30% are in limited stage [1], encouraging the use of a curative approach. In these cases, radiotherapy constitutes the standard of treatment ∗ Corresponding author at: Hematology Department, Institut Català d’Oncologia, Hospital Germans Trias i Pujol, Jose Carreras Research Institute, Universitat Autònoma de Barcelona, C/Canyet s/n, 08916 Badalona, Spain. Tel.: +34 93 497 89 87; fax: +34 93 497 89 95. E-mail address: jsancho@iconcologia.net (J.-M. Sancho). recommended by most of the published guidelines and reviews [2–7], based on the results of retrospective studies, with overall survival (OS) rates at 10 years ranging between 55% and 70% [8–13] and progression-free survival (PFS) or relapse-free survival rates at 10 years of 44–54% [8,11,13]. However, the dose and field of irra- diation are not well established due to the scarcity of randomized trials [11,14]. In addition, in most of these studies, the main cause of treatment failure is relapse outside the radiation field, although relapses beyond 10 years seem to be infrequent. In retrospective studies systemic therapy has been used in addition to local radio- therapy or after lymphadenectomy with the aim of decreasing the incidence of non-local relapses. Nonetheless, the benefit of this approach remains controversial [15–19]. The objective of this study was to analyze the value of the use of systemic chemotherapy compared with local/locoregional http://dx.doi.org/10.1016/j.leukres.2015.05.009 0145-2126/© 2015 Elsevier Ltd. All rights reserved.