Background
TROG 99.03: multicenter phase III RCT of 150 patients with stage I-II low-grade follicular lymphoma, randomized to involved-field radiotherapy alone vs radiotherapy plus systemic therapy, enrolled 2000-2012.
Interventions and follow up
Arm A: 30 Gy involved-field radiotherapy (IFRT) alone
Arm B: IFRT + 6 cycles CVP (cyclophosphamide, vincristine, prednisolone); rituximab added to CVP after 2006
Primary endpoint: PFS
mFollow up: 9.6yr
Arm B: IFRT + 6 cycles CVP (cyclophosphamide, vincristine, prednisolone); rituximab added to CVP after 2006
Primary endpoint: PFS
mFollow up: 9.6yr
Results
10yr PFS: 41% (IFRT) vs 59% (IFRT+systemic); HR 0.57, 95% CI 0.33–0.95, P=.033
10yr OS: 86% vs 95%; HR 0.62, P=.40
10yr OS: 86% vs 95%; HR 0.62, P=.40
Adverse events
Deaths: 5 in IFRT arm (1 neutropenia after salvage chemo) vs 5 in IFRT+systemic arm (1 lymphoma)
Tolerability: combined-modality therapy was generally well tolerated with manageable hematologic toxicity from the systemic component
Tolerability: combined-modality therapy was generally well tolerated with manageable hematologic toxicity from the systemic component
Conclusions
In early-stage low-grade follicular lymphoma, adding systemic (chemo)immunotherapy to involved-field radiotherapy significantly improved PFS over radiotherapy alone, without an OS benefit on long-term follow-up.
Key Limitations
Small (n=150), with regimen evolving mid-study (rituximab added in 2006), so the systemic arm is heterogeneous. Underpowered for OS. Older CVP backbone differs from contemporary bendamustine-rituximab.
Clinical Context
Supports consideration of adding systemic therapy to radiotherapy in selected early-stage FL, though IFRT alone remains a standard option per ESMO and ASCO given the lack of OS benefit. Further data with modern regimens are needed.