# Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03

Source: https://onco.cc/key-papers/paper-trog-99-03-radiotherapy-systemic-therapy-early-follicular-jco-2018/  
OnCo record `paper-trog-99-03-radiotherapy-systemic-therapy-early-follicular-jco-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding six cycles of drug treatment after radiotherapy for early follicular lymphoma cut relapses outside the treated area and improved ten-year freedom from progression from 41 to 59 per cent.

## Summary

A multicentre randomised controlled trial enrolling patients with stage I to II low-grade follicular lymphoma after computed tomography staging and bone marrow biopsy; positron emission tomography was not mandatory. Patients were randomised to 30 Gy of involved-field radiotherapy alone, or the same radiotherapy followed by six cycles of cyclophosphamide, vincristine and prednisolone. From 2006 rituximab was added to the systemic arm.

Between 2000 and 2012, 150 patients were enrolled, 75 per arm; of the 75 in the systemic arm, 44 received CVP and 31 R-CVP. At randomisation 75 per cent had stage I disease, median age was 57, 52 per cent were male and 48 per cent had positron emission tomography staging. At a median follow-up of 9.6 years (range 3.1 to 15.8), progression-free survival favoured the systemic 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 (46 to 74) against 41 per cent (30 to 57).

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: TROG 99.03; MacManus 2018; ALLG NHLLOW5
- Tags: lymphoma-evidence
- Journal: Journal of Clinical Oncology
- Year: 2018
- DOI: 10.1200/JCO.2018.77.9892
- Authors: MacManus M, Fisher R, Roos D, et al.
- Findings: Ten-year progression-free survival was 59 per cent (95 per cent confidence interval 46 to 74) with radiotherapy followed by systemic therapy against 41 per cent (30 to 57) with radiotherapy alone (hazard ratio 0.57, 0.34 to 0.95, p = 0.033).; Patients who received R-CVP did markedly better than 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 (p = 0.1).; Fewer involved regions (p = 0.047) and positron emission tomography staging (p = 0.056) were associated with better progression-free survival.
- What it means: The evidence that early follicular lymphoma is less often confined to the radiation field than staging suggests, and that a short course of systemic treatment after radiotherapy reduces relapse. It is also the reason modern practice stages this disease with positron emission tomography.
- Caveats: 150 patients recruited over twelve years, which is small and slow, and gives wide confidence intervals.; Only 48 per cent had positron emission tomography staging, so some apparent stage I disease was probably advanced.; The systemic arm changed mid-trial when rituximab was added, so the two chemotherapy regimens are not separately randomised.; No overall survival difference, in a disease where ten-year survival exceeds 87 per cent in both arms.

## Sources

- Journal of Clinical Oncology 2018: https://doi.org/10.1200/JCO.2018.77.9892
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29975623/
- Europe PMC: https://europepmc.org/article/MED/29975623

## Connected records

- 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/)
- 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: [Radiotherapy](https://onco.cc/terms/radiotherapy/)
- technologies: [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/), [TROG 99.03](https://onco.cc/trials/trog-99-03/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- key papers: [FoRT long-term follow-up: 4 Gy versus 24 Gy for follicular and marginal zone lymphoma](https://onco.cc/key-papers/paper-fort-long-term-follow-up-hoskin-lancet-oncol-2021/)

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