New evidence on the treatment of early Hodgkin's lymphoma22 Apr 2015
More than 90% of patients with early Hodgkin's lymphoma and negative PET scans after chemotherapy remained free of relapse at 3 years with or without radiation therapy, a randomized trial showed. Despite the statistically negative results, both groups had a good outcome, John Radford, MD, of the University of Manchester in England participating in the trial along other colleagues reported.
Radford and colleagues reported findings from a multicenter, randomized trial to determine whether PET-directed imaging can guide decisions about the need for consolidation radiotherapy. Statistically powered as a noninferiority trial, the study was designed to determine whether using postchemotherapy PET imaging to determine the need for consolidation radiotherapy would lead to an unacceptably high relapse rate.
Clinical trial design
Investigators enrolled 602 patients, and 426 of them had negative PET scans after completing chemotherapy. Subsequently, 420 patients were randomized to consolidation radiotherapy or no further treatment. The primary endpoint was 3-year progression-free survival (PFS).
Patients with stage IA or IIA Hodgkin's lymphoma received three cycles of ABVD chemotherapy, and PET imaging was performed within 2 weeks after completing systemic treatment. Patients who had negative scans were randomized to receive consolidation radiotherapy to the involved field or no further therapy.
Follow-up clinic visits occurred every 3 to 6 months during the first 3 years after completion of treatment and then annually thereafter. Follow-up CT scans occurred at 6, 12, and 24 months.
Initially, the trial design had a 10% absolute difference for the noninferiority margin, meaning the trial would demonstrate noninferiority if patients assigned to no further treatment had a 3-year overall survival that was within a 10% absolute difference of the radiotherapy group. Four years into the trial, new data from clinical trials prompted investigators to change the noninferiority margin to 7%.
After analysis of the results, Radford and his colleagues reported that:
- The 3-year PFS was 94.6% with radiation therapy and 90.8% without.
- However, the statistical confidence intervals associated with the PFS values exceeded the prespecified boundary for demonstrating noninferiority of the chemotherapy-alone group.
- Despite the statistically negative results, both groups had a good outcome.
- Patients with negative PET findings after three cycles of chemotherapy have a very good prognosis, either with or without consolidation radiotherapy. The results suggest that radiotherapy can be avoided for patients with negative PET findings.
- The patient population requires longer follow-up to determine whether PET-directed therapy can reduce the number of second cancers, cardiovascular disease, and deaths as compared with a strategy of administering consolidation radiotherapy to all patients.
- A negative PET scan after completion of chemotherapy might identify patients who could safely omit consolidation radiation therapy and any associated toxicity.
- Analysis of 3-year overall survival, a secondary endpoint, showed a statistically nonsignificant trend favoring the group that received no further treatment.
Statistically negative but important results
Although the British study did not meet the prespecified statistical boundaries, the results inform an important issue in the management of early-stage Hodgkin's lymphoma, said Mitchell Smith, MD, a lymphoma specialist at the Cleveland Clinic.
"We can cure a high percent of people with Hodgkin's lymphoma. The problem is that these tend to be young patients and 15 or 20 years later, they may be having long-term toxicity and even dying from the complications of treatment," Smith commented. "We have to figure out minimal amount of therapy that is required to maintain the high cure rate and minimize chances of long-term damage."
Source: MedPage Today