UK Trial of PET-Directed Therapy Suggests That No Radiotherapy May Be an Option in PET-Negative Early-Stage Hodgkin Lymphoma


Key Points

  • No further treatment was not noninferior to radiotherapy in PET-negative patients with early-stage Hodgkin lymphoma.
  • The prognosis was good with or without radiotherapy.

In a UK phase III RAPID trial reported in The New England Journal of Medicine, Radford et al compared no further treatment vs involved-field radiotherapy in patients with early-stage Hodgkin lymphoma who had negative positron emission tomography (PET) findings after 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The difference in 3-year progression-free survival in the no-radiotherapy group vs the radiotherapy group did not meet the prespecified noninferiority criterion; however, as stated by the investigators, “[P]atients in this study…had a very good prognosis either with or without consolidation radiotherapy.”

Study Details

In the study, 602 patients (median age, 34 years; 53% male) with newly diagnosed stage IA or IIA Hodgkin lymphoma received 3 cycles of ABVD, with 571 then undergoing PET scanning. A total of 426 patients (75%) had negative PET findings. Of them, 420 were randomly assigned to receive no further treatment (n = 211) or involved-field radiotherapy (n = 209). Demonstration of noninferiority of no further treatment had to exclude a difference in the 3-year progression-free survival rate of ≥ 7 percentage points from the assumed 95% progression-free survival rate in the radiotherapy group.

Disease Progression Rates

At a median follow-up of 60 months, 88.6% of the no-radiotherapy group and 92.3% of the radiotherapy group were alive without disease progression. Episodes of disease progression had occurred in 20 patients (9.5%) in the no-radiotherapy group vs 8 patients (3.8%) in the radiotherapy group, death after disease progression had occurred in 2 (0.9%) vs 3 patients (1.4%), and death without disease progression had occurred in 2 (0.9%) vs 5 patients (2.4%). In the radiotherapy group, five of the deaths occurred in patients who had not received radiotherapy.

Three-year progression-free survival was 90.8% (95% confidence interval [CI] = 86.9%–94.8%) in the no-radiotherapy group vs 94.6% (95% CI = 91.5%–97.7%) in the radiotherapy group, yielding an absolute risk difference of −3.8 percentage points and a 95% CI of −8.8 to 1.3.

The investigators concluded: “In stage IA and stage IIA Hodgkin’s lymphoma with no mediastinal bulk, patients with negative PET findings after three cycles of ABVD have a very good prognosis either with or without consolidation radiotherapy. Although the noninferiority margin was exceeded in this study, the results suggest that radiotherapy can be avoided for patients with negative PET findings. A longer follow-up period is required to determine whether the response-adapted approach used in RAPID leads to fewer second cancers, less cardiovascular disease, and improved overall survival, as compared with a strategy incorporating radiotherapy for all patients.”

John Radford, MD, of the University of Manchester and the Christie NHS Foundation Trust, is the corresponding author of The New England Journal of Medicine article.

The study was funded by Leukaemia and Lymphoma Research, Lymphoma Research Trust, Teenage Cancer Trust, and UK Department of Health. For full disclosures of the study authors, visit

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