Background
Phase II randomized trial (FoRT — Follicular lymphoma Radiotherapy Trial). 614 sites of disease in 205 patients with advanced or relapsed indolent NHL (predominantly follicular lymphoma) requiring palliative local radiotherapy. Compared ultra-low-dose 4 Gy vs standard-dose 24 Gy local RT to individual sites. Co-primary endpoints: local progression-free rate and toxicity.
Interventions and follow up
Arm A: 24 Gy in 12 fractions (standard palliative dose) (n=309 sites)
Arm B: 4 Gy in 2 fractions × 2 Gy (ultra-low-dose) (n=305 sites)
Primary endpoint: Local progression-free rate at 2 year
mFollow up: 28 month
Arm B: 4 Gy in 2 fractions × 2 Gy (ultra-low-dose) (n=305 sites)
Primary endpoint: Local progression-free rate at 2 year
mFollow up: 28 month
Results
Overall response rate (24 Gy): 89% (CR 61%)
Overall response rate (4 Gy): 76% (CR 40%)
Local PFS at 2 years (24 Gy): 81%
Local PFS at 2 years (4 Gy): 57%
Grade ≥3 toxicity: Low in both arms
Overall response rate (4 Gy): 76% (CR 40%)
Local PFS at 2 years (24 Gy): 81%
Local PFS at 2 years (4 Gy): 57%
Grade ≥3 toxicity: Low in both arms
Adverse events
Main adverse events: Grade ≥3 acute toxicity uncommon in both arms. Late grade ≥3 toxicity rare. Acute skin reactions and fatigue more common with 24 Gy. No significant difference in quality of life between arms.
Conclusions
Both 4 Gy and 24 Gy achieve useful palliation for symptomatic indolent NHL lesions. 24 Gy provides significantly better local control and higher complete response rates. 4 Gy is a valid option when preserving normal tissue or minimizing treatment burden is prioritized, or for re-irradiation scenarios.
Key Limitations
Key Limitations: Lesion-level (not patient-level) randomization limits interpretation of patient outcomes. Sites were randomized independently, so patients could receive both doses to different sites. Not a curative-intent trial — palliation only. 24 Gy is still suboptimal vs curative 24 Gy ISRT for limited-stage FL.
Clinical Context
FoRT is the key evidence base for ultra-low-dose RT (2×2 Gy = 4 Gy) as a palliative option in follicular lymphoma. ILROG guidelines (Brady Blood 2019) now formally recommend 2×2 Gy for palliation and 24 Gy for curative-intent limited-stage FL. This approach is particularly useful for patients with multiply relapsed disease requiring repeated local treatment.
References