Optimal Radiotherapy Dose for Follicular and Marginal Zone Lymphomas: 24 vs 4 Gy

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As reported in The Lancet Oncology by Peter Hoskin, MD, and colleagues, 5-year follow-up of the phase III noninferiority FoRT trial showed that radiotherapy at 24 vs 4 Gy continued to be associated with superior freedom from local disease progression in patients with follicular or marginal zone lymphoma.

The initial analysis of the trial, conducted at a median follow-up of 26 months, showed that time to local progression with 4 Gy was not noninferior to 24 Gy (hazard ratio [HR] = 3.42, P < .0001).

Study Details

The open-label multicenter trial included 614 target sites in 548 patients with follicular lymphoma (86% vs 86%) or marginal zone lymphoma (14% vs 14%) requiring radical or palliative radiotherapy. Patients were randomly assigned between April 2006 and June 2011 to receive 24 Gy in 12 fractions (n = 299) or 4 Gy in 2 fractions (n = 315). Patients could have received previous chemotherapy or radiotherapy to another site. The primary endpoint was time to local progression in the irradiated volume based on clinical and radiologic evaluation in the intention-to-treat population.

Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment.
— Peter Hoskin, MD, and colleagues

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Key Findings

Median follow-up was 73.8 months (interquartile range = 61.9–88.0 months).

The 2-year local progression-free rate was 94.1% in the 24-Gy group vs 79.8% in the 4-Gy group, with the difference at 2 years remaining outside the noninferiority margin of 10% at –13.0% (95% confidence interval [CI] = –21.7% to –6.9%). Rates at 5 years were 89.9% vs 70.4% (HR = 3.46, 95% CI = 2.25–5.33, P < .0001).

A total of 155 target sites had further treatment before local progression and use of systemic treatment was similar in both groups. In analysis censoring patients at the time of either additional local treatment to the target site or systemic treatment, proportions of patients without local progression were 94.5% vs 79.2% at 2 years and 89.4% vs 69.0% at 5 years (HR = 3.49, 95% CI = 2.22–5.47, P < .0001).

Local progression-free rates at 5 years were 100% vs 88.0% (HR = not calculable, P = .015) among patients with marginal zone lymphoma and 88.2% vs 67.5% (HR = 3.25, 95% CI = 2.10–5.01, P < .0001) among patients with follicular lymphoma.

No difference in overall survival was observed between groups, with 67 deaths in the 24-Gy group (33 lymphoma, 34 nonlymphoma) and 77 in the 4-Gy group (40 lymphoma, 37 nonlymphoma; HR = 1.03, P = .86). Overall survival at 2 and 5 years was 89.0% vs 90.4% and 75.1% vs 77.6%.

At 12 weeks, grade ≥ 2 adverse events had occurred in 10% vs 4% of patients (P = .0029). From week 12 through 5 years, adverse event rates decreased further, with one grade 3 event occurring in the 24-Gy group. Rates of grade ≥ 2 adverse events were 5% vs 2% at 1 year, 2% vs 0% at 3 years, and 1% vs 0% at 5 years. No treatment-related deaths were reported.

The investigators concluded, “Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment.”

Dr. Hoskin, of Mount Vernon Cancer Centre, Northwood, UK, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Cancer Research UK. For full disclosures of the study authors, visit

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