Hodgkin Lymphoma

RATHL: Phase III Randomized Study of Response-Adapted Therapy Using Fludeoxyglucose F18(FDG)-PET/CT Imaging in Patients With Newly Diagnosed Stage II-IV Hodgkin Lymphoma

NCT00678327

 The UK National Cancer Research Institute Lymphoma Clinical Studies Group through the Cancer Research UK/UCL Trials Office, London. In collaboration with the Gruppo Italiano per lo Studio dei Linfomi, the Australasian Leukaemia and Lymphoma Group, the All Ireland Cooperative Oncology Research Group, and Centres in the Nordic Countries.

Exactly 1,200 patients will be registered in the trial after full staging including FDG-PET imaging. All patients receive two courses of full-dose ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) chemotherapy and then undergo a repeat FDG-PET scan. Patients who become PET-negative are randomized between ABVD and AVD, the omission of bleomycin aiming to reduce lung toxicity while achieving an equivalent outcome. Those who remain PET-positive undergo treatment escalation with the BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine, procarbazine, prednisone) regimen, thereby attempting to improve remission rates.

Advanced Hodgkin lymphoma is often curable, but with standard ABVD chemotherapy initial treatment still fails in around one-quarter of patients, and, in those who are cured, late toxicity remains a significant problem. Cure rates might be increased using more intensive initial treatment, but the resulting toxicity would be unacceptable if those with a good chance of cure using standard therapy were subjected to the high-dose regimen. Baseline clinicopathologic characteristics are poor discriminators in this respect, but there is increasing evidence that FDG-PET functional imaging can give accurate prognostic information if performed early during the course of treatment. The aim of this trial is to prospectively evaluate the use of FDG-PET in early assessment of treatment response. The imaging information will guide selective escalation of therapy for those with a poor prognosis and provide the basis for testing de-escalation of treatment to minimize long-term toxicity for those with a good initial response.

 An important issue for PET scanning that has not been adequately addressed in publications to date is that of reproducibility. The interpretation of FDG-PET scans is an evolving field with person-to-person and center-to-center variation. This study uses a standardized approach to the central reporting of PET scan results, validated by using them to guide subsequent therapy. This trial is an important test of the prospective use of FDG-PET scanning to modulate the intensity of treatment for advanced Hodgkin lymphoma. The study will provide a high level of statistical power for the randomized question and will also give information on a large cohort of patients treated with intensification following a positive CT-PET scan. Because there will be some cross-over between the randomized arms, mainly with reduction of bleomycin dose for patients developing pulmonary toxicity, the power of the analysis may be slightly reduced.