Patients with early-stage Hodgkin’s lymphoma who receive negative findings on PET following three cycles of chemotherapy have a very good prognosis whether or not they received follow up radiotherapy, according to the U.K.-based RAPID trial.
The findings, published April 23 in the New England Journal of Medicine, suggest taking an individualized approach to treating early-stage Hodgkin’s lymphoma and could reduce the number of patients receiving radiotherapy and the associated late toxic effects.
While chemotherapy is often followed by radiotherapy in the treatment of Hodgkin’s lymphoma, radiotherapy itself is a potential cause of second cancers and cardiovascular disease. Lead author John Radford, MD, of the University of Manchester and the Christie National Health Service Foundation Trust, and colleagues aimed to determine the necessity of this follow up therapy with the RAPID (Randomized Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease) trial.
Specifically, the study sought patients with newly diagnosed stage IA or stage IIA Hodgkin’s lymphoma who had received three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A total of 602 patients were recruited, with 426 undergoing PET and receiving negative results. Researchers randomly assigned 420 of these patients to either receive radiotherapy or no further therapy.
Radford and colleagues acknowledged that progression-free survival was likely to be lower in the group receiving no further therapy because the negative predictive value of PET is not perfect, though they saw this as acceptable since the likely benefits in overall survival would be seen in a lower incidence of side effects from radiation. The trial was designed to exclude a difference in three-year progression-free survival rate of 7 percentage points or more from an assumed 95 percent progression-free survival rate in the radiotherapy group.
“Whether −7 percentage points is an appropriate margin of noninferiority is a value judgment, but it represents an attempt to balance the effects of treatment on disease control and late toxic effects,” wrote the authors.
After a median 60 months of follow-up, the three-year progression-free survival rate was 94.6 percent in the radiotherapy group and 90.8 percent in the no further therapy group. This absolute risk difference of -3.8 percentage points had a 95 percent confidence interval that included a possible difference of up to 8.8 percentage points.
There were eight instances of disease progression in the radiotherapy group and 20 in the no further therapy group. Eight patients in the radiotherapy group died, one from Hodgkin’s lymphoma, however no deaths from Hodgkin’s lymphoma were observed in patients with negative PET findings who were randomly assigned to receive no further therapy.
While noting that the noninferiority margin was exceeded in the study, Radford and colleagues said the results still suggested radiotherapy could be avoided in patient with negative PET findings. Modest improvements in survival rates are “bought at the expense of exposing all patients to radiation, most of whom will not benefit and some of whom will be harmed,” they wrote. “In fact, for patients cured with chemotherapy, the addition of radiotherapy can only contribute additional toxic effects.”