The avoidance of involved-field radiotherapy (IFRT) is an acceptable strategy in patients with early-stage Hodgkin lymphoma who have a negative positron emission tomography (PET) scan after completing 3 cycles of doxorubicin, bleomycin sulfate, vinblastine, and dacarbazine (ABVD), reported John Radford, MD, Professor of Medical Oncology, School of Cancer and Imaging Sciences, University of Manchester, Christie National Health Service Foundation Trust, United Kingdom.
In the United Kingdom’s RAPID trial, a PET-directed approach was a sufficiently robust biomarker of disease elimination, such that IFRT, the current standard of care after abbreviated chemotherapy for patients with stage IA or IIA Hodgkin lymphoma, could be avoided without significantly affecting the patient’s survival.
“A response-adapted approach based on centrally reviewed PET imaging reduces treatment time and costs, improves tolerability, and, most important, removes the burden of early and late toxicity of radiotherapy from the PET-negative population,” said Dr Radford.
Overall, 602 patients with newly diagnosed stage IA or IIA Hodgkin lymphoma underwent PET imaging after 3 courses of ABVD. The PET scan was performed at 1 of 30 quality controlled PET scan centers across the United Kingdom.
Patients with a positive PET scan received an additional course of ABVD followed by IFRT. Patients with a negative PET scan were randomized to further treatment with IFRT applied to disease areas within 6 weeks of the completion of their chemotherapy or to no further treatment.
A positive PET scan was defined as a score of 3, 4, or 5, as assigned at core laboratory review; a PET scan was considered negative if it had a score of 1 or 2. The trial was of a noninferiority design; “some reduction in primary disease control was considered acceptable because of the presumed benefits in terms of reduced late toxicity associated with not radiating everyone,” Dr Radford noted.
Noninferiority was defined as a ≤7% difference in progression-free survival (PFS) from 95% in the arm continuing on to IFRT.
In the trial, 426 (74.7%) PET scans were classified as negative, and 420 patients were randomized to either arm (6 patients with PET-negative scans were not randomized). Of 209 patients randomized to receive IFRT, 25 did not receive it: 19 patients declined after they became aware of the randomization decision, 5 died, and 1 patient developed pneumonia.
In an intent-to-treat analysis, the 3-year PFS was 94.5% in the group that was randomized to IFRT versus 90.8% in the arm that had no further treatment, a hazard ratio of 1.51 in favor of IFRT, which met the criterion for noninferiority for no further treatment. Overall survival was greater in the patients with no further treatment compared with those who received IFRT (99.5% vs 97.1%, respectively).
In a per-protocol analysis of the 392 patients who received their allocated treatment, which included 2 patients in the arm that received no further treatment and who received radiotherapy, 3-year PFS was 97% in those treated with IFRT versus 90.7% in those with no further treatment, which again met the criterion for noninferiority of no further treatment.
“Using PET, it is possible to identify a population of patients with stage IA and IIA Hodgkin lymphoma who have an excellent prognosis after 3 cycles of ABVD,” Dr Radford pointed out.
A longer follow-up is required to establish the impact of a PET-directed approach on 10-year and 20-year survival rates, he said. n