title: What is the optimal management of early-stage low-grade follicular lymphoma in the modern era?
abstract: BACKGROUND
  Despite international practice guidelines endorsing radiotherapy (RT) as the preferred initial therapy, treatment approaches vary for patients with early-stage follicular lymphoma. The authors engaged the National Cancer Data Base to analyze patterns of care and survival outcomes for patients with early-stage follicular lymphoma in the era of modern therapy.
  
  
  METHODS
  A National Cancer Data Base retrospective cohort study was conducted of 35,961 patients with lymph node and extranodal, American Joint Committee on Cancer stage I to II, WHO grade 1 to 2 follicular lymphoma who were diagnosed between 1998 and 2012. Univariate and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics that were predictive of overall survival (OS) and treatment use. Propensity score-adjusted Cox proportional hazards ratios for survival in patients treated for follicular lymphoma were used.
  
  
  RESULTS
  Of the 35,961 patients with follicular lymphoma included in the current study, 63% had stage I disease, 79% were without extranodal disease, and 61% were aged >60 years. RT use decreased from 37% in 1999 to 24% in 2012 (P<.0001), with corresponding significant increases in observation and single-agent chemotherapy. Patients who received RT had 5-year and 10-year OS rates of 86% and 68%, respectively, compared with 74% and 54%, respectively, for those who did not receive RT (P<.0001). On multivariable survival analysis, including a propensity score to account for potential uncaptured confounding variables due to a lack of randomization, upfront RT remained independently associated with improved OS (hazard ratio of death, 0.54; 95% confidence interval, 0.47-0.63 [P<.0001]).
  
  
  CONCLUSIONS
  RT is an increasingly underused treatment approach in the era of modern therapy for patients with early-stage follicular lymphoma. The use of RT appears to improve OS and should remain standard practice as encouraged by clinical practice guidelines.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: John A
authors.initials: JA
authors.lastname: Vargo
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Beant S
authors.initials: BS
authors.lastname: Gill
authors.affiliation: Department of Epidemiology, Epidemiology Data Center, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
authors.forename: Goundappa K
authors.initials: GK
authors.lastname: Balasubramani
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Sushil
authors.initials: S
authors.lastname: Beriwal
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011878:Radiotherapy; D012189:Retrospective Studies; D057832:Watchful Waiting
chemical_list: D000970:Antineoplastic Agents
keywords: National Cancer Data Base (NCDB); National LymphoCare Study; follicular lymphoma; radiotherapy; rituximab