Radiotherapy Compared to Other Strategies in the Treatment of Stage I/II Follicular Lymphoma: A Study of 404 Patients with a Median Follow-Up of 15 Years

PLoS One. 2015 Jul 6;10(7):e0131158. doi: 10.1371/journal.pone.0131158. eCollection 2015.

Abstract

Purpose: To investigate outcome for patients with follicular lymphoma (FL) stage I-II treated at a population-based referral institution with a median follow-up of 15 years. Overall and cause-specific survival was compared to that of a sex, age and residency matched individuals from normal population.

Material and methods: 404 patients with early stage FL treated between 1980 and 2005 were retrospectively analyzed. Two of three patients had stage I disease. Based on clinical characteristics, first line treatments were radiotherapy (RT) (48% of patients), chemotherapy (CT) (16%), combined chemo-and radiotherapy (CRT) (16%) or observation (OBS) (15%). Survival was modeled with Kaplan-Meier methodology. Multivariate analyses were performed with the Cox model.

Results: Fifteen years overall survival (OS), progression free survival (PFS) and time to next treatment (TNT) were 50% (95% confidence interval [CI]: 45-55), 42% (95% CI: 36-47) and 48% (95% CI, 42-54), respectively. For patients treated with RT 97% achieved a complete remission, and 15 year OS, PFS and TNT were 57% (95% CI, 50-64), 46% (95% CI, 39-54) and 49% (95% CI, 42-57), respectively. Relapse rate after RT and CRT was 49% and 36%, respectively. Only 2% of patients who received RT or CRT relapsed inside the radiation field and 5% had isolated near-field relapse. No statistical differences were found between treatment groups regarding death from cardiovascular disease or incidence of second cancer. Compared to a matched normal population, non-lymphoma cancer mortality was higher among patients given RT, hazard ratio 1.66 (95% CI: 1.14-2.42; P<0.01). Compared to other treatment modalities, patients selected for observation without treatment did not have inferior outcome.

Conclusions: A differentiated treatment strategy in early stage FL results in long term survival for the majority of patients. OBS is a valid initial choice for selected patients without lymphoma-related symptoms.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cardiovascular Diseases / mortality
  • Chemoradiotherapy
  • Chlorambucil / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Follicular / mortality
  • Lymphoma, Follicular / pathology
  • Lymphoma, Follicular / radiotherapy*
  • Lymphoma, Follicular / therapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Second Primary / epidemiology
  • Norway / epidemiology
  • Prednisolone / administration & dosage
  • Registries
  • Rituximab / administration & dosage
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Watchful Waiting
  • Young Adult

Substances

  • Chlorambucil
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisolone

Supplementary concepts

  • VAP-cyclo protocol

Grants and funding

Dlawer Abdulla Barzenje has been supported with grants from Østfold Hospital Trust, Fredrikstad, Norway. Arne Kolstad and Harald Holte have both received a research grant from Norwegian Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.