Involved-field radiotherapy (IFRT) followed by rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) improved progression-free survival (PFS) and the rate of relapse outside of radiation fields among patients with follicular lymphoma (FL) compared with IFRT alone, according to a study published in the Journal of Clinical Oncology.1

IFRT leads to disease control in more than 90% of patients with localized, stage I/II disease, and is potentially a curative treatment. The risk of relapse is high, however, particularly outside the irradiated fields, and approximately half of patients experience disease progression after 10 years. Evidence from previous studies has demonstrated that combined modality therapy (CMT) with chemotherapy and RT may improve long-term outcomes in this patient population.

For this study ( Identifier: NCT00115700), researchers randomly assigned 150 patients with stage I/II low-grade FL to receive 30 Gy IFRT alone or IFRT plus 6 cycles of chemotherapy between 2000 and 2012; in the chemotherapy arm, 44 patients received CVP and from 2006, 31 received R-CVP. 18F-labeled fluorodeoxyglucose-positron emission tomography (PET) was not required. At baseline, 75% of patients had stage I disease, median age was 57 years, and 48% were PET-staged. The median follow-up was 9.6 years.

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Results showed that the PFS was superior among patients treated with IFRT plus chemotherapy (hazard ratio [HR], 0.57; 95% CI, 0.34-0.95; P = .033). Patients who received chemotherapy plus IFRT had a 10-year PFS rate of 59% (95% CI, 46-74) compared with 41% (95% CI, 30-57) among patients treated with IFRT alone.

Patients who received IFRT plus R-CVP had a significantly superior PFS compared with contemporaneous patients treated with IFRT alone (HR, 0.26; 95% CI, 0.07-0.97; P = .045). Factors associated with an improved PFS were fewer involved regions (P = .047) and PET staging (P = .056).

Histologic transformation occurred in 4 patients in the CMT arm compared with 10 patients who were treated with IFRT alone (P = .1), and while there were 10 deaths in the IFRT-alone arm compared with 5 in the CMT arm, there was no significant difference in overall survival between cohorts.

The authors concluded that “for patients with stage I to II FL who are treated with curative intent, we recommend treatment with IFRT followed by chemoimmunotherapy as a reasonable evidence-based choice for the standard of care. The combination of RT with more effective or less toxic systemic therapy regimens could potentially achieve superior results.”


  1. MacManus M, Fisher R, Roos D, et al. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03 [published online July 5, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.77.9892