TROG 99.03

Involved-field radiotherapy alone cures a proportion of stage I and II follicular lymphoma, and the relapses that follow are mostly outside the radiation field. TROG 99.03, run across Australia and New Zealand, tested whether adding systemic treatment after radiotherapy prevents them. 150 patients were randomised between 30 Gy of involved-field radiotherapy alone and the same radiotherapy followed by six cycles of cyclophosphamide, vincristine and prednisolone; from 2006 rituximab was added to the chemotherapy arm, so 31 of the 75 patients in that arm received R-CVP and 44 received CVP.

At a median follow-up of 9.6 years, progression-free survival favoured the combined arm (hazard ratio 0.57, 95 per cent confidence interval 0.34 to 0.95, p = 0.033), with ten-year rates of 59 per cent against 41 per cent. The patients who received R-CVP did markedly better than the contemporaneous radiotherapy-only patients (hazard ratio 0.26, 0.07 to 0.97, p = 0.045). Overall survival was not significantly different, at 95 per cent against 87 per cent at ten years (p = 0.40). Histological transformation occurred in four patients in the combined arm and ten in the radiotherapy arm.

Only 48 per cent of patients were staged with positron emission tomography, which is the trial's main limitation: modern staging reclassifies a proportion of apparent stage I disease as advanced, and that is where some of the radiotherapy-alone failures came from.