John Radford, MD
While some patients with Hodgkin lymphoma require radiotherapy, the risks are not necessary for a large portion of patients who can experience long-term disease-free survival with chemotherapy alone, says John Radford, MD, Teenage Cancer Trust Professor of Teenage and Young Adult Cancer at the University of Manchester and Director of Research at the Christie NHS Foundation Trust.
Radiotherapy, which can result in secondary cancers and cardiovascular diseases that undermine long-term survival, is the current standard of care following chemotherapy for patients with early-stage Hodgkin lymphoma.
“Many people believe that a cure is possible for some patients without radiotherapy,” said Radford. “The challenge is identifying those patients.”
The recent RAPID trial, led by Radford and conducted at the UK National Cancer Research Institute, offers a possible solution.
According to study results published in The New England Journal of Medicine
, PET scans immediately following treatment with chemotherapy can predict which patients with early-stage Hodgkin lymphoma will have very good outcomes without additional radiotherapy.
“We’ve shown that people that are PET-negative after three cycles of ABVD chemotherapy have a very good prognosis without further treatment,” said Radford. “The overall results suggest that either with or without radiotherapy the results are very good. There is a marginal increase of progression-free survival by giving radiotherapy but that gain is at the expense of giving everyone radiotherapy, most of whom don’t need it.”
From October 2003 through August 2010, a total of 602 patients were enrolled in the RAPID trial at 94 centers in the United Kingdom. Patients with newly diagnosed stage IA or stage IIA Hodgkin lymphoma received three cycles of ABVD and then underwent PET scanning. Of the patients with negative PET findings, 211 patients received no further treatment, while 209 received standard radiotherapy. The patients with positive PET findings received a fourth cycle of ABVD and radiotherapy.
Survival results were similar across the two groups. The 3-year progression-free survival rate was 94.6% in the radiotherapy group (95% CI, 91.5-97.7) and 90.8% in the group that received no further therapy (95% CI, 86.9-94.8), with an absolute risk difference of −3.8 percentage points (95% CI, −8.8 to 1.3).
The 3-year overall survival rate was 97.1% (95% CI, 94.8-99.4) in the radiotherapy group and 99.0% (95% CI, 97.6-100) in the group with no further therapy. There was a nonsignificant rate ratio of 0.51 (95% CI, 0.15-1.68) in favor of no further therapy (P
At a median of 60 months’ follow-up, there were eight instances of disease progression in the radiotherapy group, and 8 patients had died. Of those 8, only 3 were from patients who received radiotherapy. The other 5 deaths in the radiotherapy group occurred in patients who had been assigned to the radiotherapy group but had not yet received radiotherapy. There were 20 instances of disease progression in the group without radiotherapy, and 4 patients had died, though none died from Hodgkin lymphoma.
The median age was 34 years (range, 16-75), 321 patients (53.3%) were male, and 200 patients (33.2%) had stage IA disease.
These findings, when applied to clinical practice, have the potential to maximize long-term survival in the disease, said Radford.
“For some people, the late toxicities are minimal and won’t be an issue,” said Radford. “But for others, the risks include esophageal cancer, lung cancer, breast cancer, and cardiac disease which can all lead to death. Radiotherapy isn’t a bad thing, but if we can tailor the treatment more precisely to the needs of the patient using PET scans, we may be able to improve overall survival.”
By giving PET scans, therapy can be personalized by age and other risk factors, explained Radford. For patients in their 60s, 70s, or older, where there is concern about relapse and the risks of salvage treatment, radiotherapy may still be the best solution. However, treatment plans should differ for younger patients.
“If a 30-year old has an expectation of 30, 40, or more years of survival, we want to minimize the risks associated with treatment-related toxicities in the future,” said Radford. “Now, we can think a little bit more on a personalized basis and consider what therapy each person should receive.”
Eliminating radiotherapy for those for which it is unnecessary will also reduce the time of treatment and the financial burden, said Radford.
Patients in the study will be reanalyzed at 10 and 15 years and then follow-up will continue every 5 years after. Over the long term, Radford predicts that there could be a more significant difference in survival between the radiotherapy group and the non-radiotherapy group.
However, there are risks with forgoing radiotherapy; follow-up will help explain if those risks are worth the benefit to some patients, he said.
“We know that the relapse rate is a little higher in people that don’t get radiotherapy,” Radford said. “But if you look at the overall survival in the RAPID study, you see that, in both groups, it was excellent. With any de-escalation approach, there are risks. However, I think we need to ask these difficult questions and try and answer them in clinical trials with significant follow-up so that we can make future progress.”
Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma [published online April 23, 2015]. N Engl J Med. doi: 10.1056/NEJMoa1408648.