Standard 24 Gy More Effective Than 4 Gy in Radiotherapy for Indolent Lymphoma


Key Points

  • Time to local progression was significantly longer with 24 Gy vs 4 Gy.
  • Response rates were significantly higher with 24 Gy overall and in most subgroups.

Follicular lymphoma has been found to respond to radiotherapy doses as low as 4 Gy. In the phase III FORT trial reported in The Lancet Oncology, Hoskin et al compared radiotherapy with 4 Gy in two fractions vs 24 Gy in 12 fractions in patients with indolent lymphoma, finding that the 24-Gy regimen was more effective.

Study Details

In this unblinded noninferiority trial, patients aged ≥ 18 years with follicular lymphoma or marginal zone lymphoma who had received no treatment for ≥ 1 month and who required local radiotherapy for radical or palliative local control were randomized to receive radiotherapy with 4 Gy in two fractions (n = 315 target sites) or 24 Gy in 12 fractions (n = 299 target sites) at 43 centers in the United Kingdom. Target sites were stratified by histology, palliative or curative treatment intent, and study center. The primary outcome was time to local progression.

The 4-Gy and 24-Gy groups (by target site) were generally balanced for age (mean, 66 years in both), sex (51% and 50% male), diagnosis (86% follicular lymphoma in both, 14% marginal zone lymphoma in both), Karnofsky performance status (normal in 59% and 50%), radiologic stage (IA in 43% and 41%, II in 17% and 18%, III in 18% in both, IV in 10% and 11%), Follicular Lymphoma International Prognostic Index score (51% and 48% low, 22% and 28% intermediate, 17% and 14% high), previous chemotherapy (35% and 32%), and previous radiotherapy (23% and 26%).

Time to Local Progression

After  median follow-up of 26 months, local progression had occurred in 70 sites in the 4-Gy group vs 21 in the 24-Gy group, yielding a hazard ratio (HR) of time to local progression for the 4-Gy group of 3.42 (P < .0001; not noninferior to 24 Gy). Response rates were 81% (complete response in 49%) in the 4-Gy group vs 91% (68% complete response) in the 24-Gy group (P = .0095 for overall response rate), including 80% (48%) vs 91% (67%) in patients with follicular lymphoma (P = .0096), 87% (55%) vs 91% (71%) in those with marginal zone lymphoma (P = .71), 81% (54%) vs 95% (76%) in those with stage I disease (P = .0015), 77% (46%) vs 78% (42%) in those with stage II disease (P = .91), and 82% (54%) vs 95% (75%) in those receiving therapy with curative intent (P = .0053). 

Toxic Effects

Acute grade 3 or 4 toxic effects occurred in 1% of 300 patients in the 4-Gy group vs 3% of 282 in the 24-Gy group, with 1% of patents in each group having late toxic effects. Mucositis occurred in four patients in the 24-Gy group (two acute and two late effects, all grade 3) and in none of the 4-Gy patients. Pain at the irradiation site was the most common acute effect, occurring in two patients in the 4-Gy group and one in the 24-Gy group (all grade 3), and fatigue was the most common late effect, occurring in two patients and one patient, respectively (all grade 3).

The investigators concluded, “24 Gy in 12 fractions is the more effective radiation schedule for indolent lymphoma and should be regarded as the standard of care. However, 4 Gy remains a useful alternative for palliative treatment.”

Peter J. Hoskin, FRCR, of Mount Vernon Cancer Centre, Middlesex, UK, is the corresponding author for the The Lancet Oncology article.

The study was funded by Cancer Research UK. The study authors reported no potential conflicts of interest.

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