Phase III randomised trial
Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: A randomised phase III trial,☆☆

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Abstract

Purpose

This multicentre, prospective, randomised-controlled trial compared efficacy and toxicity of differing radiotherapy doses in non-Hodgkin lymphoma (NHL).

Patients and methods

Patients with any histological subtype of NHL, requiring radiotherapy for local disease control, whether radical, consolidative or palliative, were included. Three hundred and sixty one sites of indolent NHL (predominantly follicular NHL and marginal zone lymphoma) were randomised to receive 40–45 Gy in 20–23 fractions or 24 Gy in 12 fractions. Six hundred and forty sites of aggressive NHL (predominantly diffuse large B cell lymphoma as part of combined-modality therapy) were randomised to receive 40–45 Gy in 20–23 fractions or 30 Gy in 15 fractions. Patients with all stages of disease, having first-line and subsequent therapies were included; first presentations of early-stage disease predominated.

Results

There was no difference in overall response rate (ORR) between standard and lower-dose arms. In the indolent group, ORR was 93% and 92%, respectively, (p = 0.72); in the aggressive group, ORR was 91% in both arms (p = 0.87). With a median follow-up of 5.6 years, there was no significant difference detected in the rate of within-radiation field progression (HR = 1.09, 95%CI = 0.76–1.56, p = 0.64 in the indolent group; HR = 0.98, 95%CI = 0.68–1.4, p = 0.89 in the aggressive group). There was also no significant difference detected in the progression free or overall survival. There was a trend for reduced toxicities in the low-dose arms; only the reduction in reported erythema reached significance.

Conclusion

In a large, randomised trial, there was no loss of efficacy associated with radiotherapy doses of 24 Gy in indolent NHL and 30 Gy in aggressive NHL, compared with previous standard doses of 40–45 Gy.

Section snippets

Study design

This prospective, randomised study was initiated and supported by the BNLI and subsequently the National Cancer Research Institute (NCRI) Lymphoma and Radiotherapy Clinical Studies Groups. Appropriate ethical approval was obtained, in accordance with the Declaration of Helsinki. Trial execution was overseen by an independent data monitoring committee. The data analysis, preparation of the manuscript, and interpretation were performed independently from the funders.

Eligibility

Consenting patients aged 18 

Results

Between April 1997 and January 2005, 1001(361 indolent, 640 aggressive) randomised treatment allocations were made from 40 treatment centres (998 patients; 3 had 2 separate randomisations) as shown in Consort diagram (Fig. 1). The baseline characteristics were well balanced between arms (Table 1). 83% of patients were to receive radiotherapy as, or as part of, first-line therapy, with the remainder being for relapsed or resistant disease. Of note, the patient population had predominantly

Discussion

This large, randomised trial found no difference in local control of NHL comparing low-dose (24 Gy in indolent NHL; 30 Gy aggressive NHL) with conventional dose (40–45 Gy) radiotherapy. Furthermore, there was no significant difference detected in the in-field progression-free interval, PFS or OS in the low and high dose levels. Importantly the rates of local control were excellent for all radiotherapy doses, with ORR of 93% for indolent lymphoma and 91% for aggressive disease. This is higher than

Acknowledgements

We thank all patients who participated in this trial and research staff at the clinical centres who helped to recruit patients and collect data. We thank the staff of the Haematology Trials Group, CR UK & UCL Cancer Trials Centre, formerly the British National Lymphoma Investigation, for trial and data management. Thanks also to the staff at HMDS for their work obtaining central histological review.

Trial Management Group (TMG): Peter Hoskin (Chief Investigator), David Linch, Paul Smith, Wendi

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    ☆☆

    Preliminary results previously reported orally at the 9th International Conference on Malignant Lymphoma (Annals of Oncology 2005; 16 supp 5:abstract 59).

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