Positron-emission tomography (PET)-directed therapy is promising for early-stage Hodgkin lymphoma, according to results of the UK NCRI RAPID trial presented at the 54th Annual Meeting of the American Society of Hematology (ASH).¹ The use of PET scan enabled the identification of a population of patients with early-stage Hodgkin lymphoma (stages IA and IIA) who have an excellent prognosis following three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and who can potentially be spared from having to undergo radiotherapy, avoiding its toxicity.

“In early-stage Hodgkin lymphoma, abbreviated chemotherapy followed by involved-field radiation therapy is standard of care, but some patients are probably cured by chemotherapy alone. We found that the prognosis was excellent without further treatment in the 75% of patients who became PET-negative after three cycles of ABVD,” said John Radford, MD, Professor of Medical Oncology at the University of Manchester, United Kingdom.

Advantages of PET-based Strategy

A PET-directed approach based on centrally reviewed PET images has several advantages, among them reduced treatment time and costs, improved tolerability, and most importantly avoiding late toxicity of radiotherapy, Dr. Radford continued.

“It is crucial with this approach to have experienced reviewers of the PET images,” he stated. “We obtained these results in the setting of quality-controlled PET acquisition, with a central review of PET images at a Core Lab and with a conservative definition of PET-negative. We need longer follow-up to establish the impact of a PET-directed approach on 10- and 20-year survival and cause of death.”

The RAPID study was a noninferiority trial that enrolled 602 patients (321 male and 281 female) with stage IA (33%) and IIA (67%) Hodgkin lymphoma. Sixty-two percent of these patients had a favorable prognosis according to European Organisation for Research and Treatment of Cancer (EORTC) criteria.

Key Findings

Between 2003 to 2010, all patients received three cycles of ABVD. Of these 571 underwent a PET scan. Scans were PET-negative (score of 1 or 2 using the Deauville Criteria for PET scans) in 426 patients (74.7%); 420 were randomly assigned to involved-field radiotherapy or no involved-field radiotherapy. PET-positive patients received a fourth cycle of ABVD plus involved-field radiotherapy.

At a median follow-up of 48.6 months, 194 patients (92.8%) in the PET-negative involved-field radiotherapy arm and 190 (90%) in the PET-negative no-radiotherapy arm were alive with no progressive disease, compared with 125 patients (85.9%) in the PET-positive arm.

In an intent-to-treat analysis of 420 patients assigned to one of the three arms, 3-year progression-free survival was 94.5% in the PET-negative involved-field radiotherapy arm vs 90.8% in the PET-negative no-radiotherapy arm.

A per-protocol analysis excluded 28 patients who did not get allocated involved-field radiotherapy and 2 patients allocated to the no-radiotherapy arm who did get radiotherapy. In this analysis of 392 patients who received allocated treatment, 3-year progression-free survival was 97% for those PET-negative patients treated with involved-field radiotherapy vs 90.7% of those who had no further treatment, and 85.9% for the PET-positive patients.

Survival Analysis

“Both progression-free survival analyses are within the noninferiority margin,” Dr. Radford said, suggesting that PET-negative patients after three cycles of ABVD can be safely treated without involved-field radiotherapy.

Overall survival at 3 years was 97% in the PET-negative group treated with involved-field radiotherapy, 99.5% in the PET-negative group who had no further treatment, and 93.9% in PET-positive patients who got involved-field radiotherapy.

The PET score after three cycles of ABVD, was more predictive than favorable or unfavorable prognosis based on pretreatment risk factors, he told listeners. “In both univariate and multivariate analysis, PET score was highly predictive of outcome.” ■

Disclosure: Dr. Radford reported no potential conflicts of interest.

Reference

1. Radford J, Barrington S, Counsell N, et al: Involved field radiotherapy versus no further treatment in patients with clinical stages IA and IIA Hodgkin lymphoma and a ‘negative’ PET scan after 3 cycles ABVD: Results of the UK NCRI RAPID trial. 2012 Annual Meeting of ASH. Abstract 547. Presented December 10, 2012.