# TROG 99.03

Source: https://onco.cc/trials/trog-99-03/  
OnCo record `trog-99-03` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Radiotherapy can cure early follicular lymphoma, but most relapses happen outside the treated area. Adding a short course of drug treatment afterwards halved that risk.

## Summary

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-10-01
- Also known as: TROG 99.03; ALLG NHLLOW5; Radiotherapy with or without systemic therapy in early follicular lymphoma
- Tags: lymphoma-evidence
- Registry id: NCT00115700
- Phase: 3
- Setting: Stage I or II low-grade follicular lymphoma: involved-field radiotherapy alone against radiotherapy followed by six cycles of CVP, with rituximab added from 2006
- Sponsor: Trans Tasman Radiation Oncology Group
- Enrolled: 150
- Result: Ten-year progression-free survival 59 against 41 per cent when systemic therapy followed radiotherapy (hazard ratio 0.57, p = 0.033), with no significant overall survival difference.
- Outcomes: Progression-free survival at 10 years: Radiotherapy then CVP or R-CVP 59% vs Radiotherapy alone 41%, HR 0.57; Overall survival at 10 years: Radiotherapy then CVP or R-CVP 95% vs Radiotherapy alone 87%
- Replication: Consistent with the German MIR study of rituximab with radiotherapy; the FORTplus trial is testing the radiotherapy dose question alongside it.

## Sources

- ClinicalTrials.gov NCT00115700: https://clinicaltrials.gov/study/NCT00115700
- Journal of Clinical Oncology 2018: https://doi.org/10.1200/JCO.2018.77.9892

## Connected records

- cancers: [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Radiation Therapy](https://onco.cc/fronts/radiation/)
- terms: [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/), [Radiotherapy](https://onco.cc/terms/radiotherapy/)
- technologies: [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [PET/CT](https://onco.cc/technologies/pet-ct/)
- drugs: [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Prednisone](https://onco.cc/drugs/prednisone/), [Rituximab](https://onco.cc/drugs/rituximab/), [Vincristine](https://onco.cc/drugs/vincristine/)
- trials: [FORTplus](https://onco.cc/trials/fortplus/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/)
- key papers: [Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03](https://onco.cc/key-papers/paper-trog-99-03-radiotherapy-systemic-therapy-early-follicular-jco-2018/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)

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