Richard T. Hoppe教授

       PET/CT for Hodgkin's lymphoma(HL) Staging and Therapy

        The “Lugano” staging classification system for Hodgkin's lymphoma has been introduced. It retains the I-IV staging breakdown and includes all three B symptoms (fevers, night sweats, weight loss). It requires PET/CT imaging as part of initial staging. It defines bone marrow involvement by PET imaging, rather than bone marrow biopsy. It recommends response assessment at the completion of therapy defined by PET/CT, with the Deauville 5-point scale endorsed as the most effective way for defining a response.

        New concepts of radiation therapy improve its accuracy and safety. These improvements include PET/CT simulation, the reduction in radiation field size (involved node or involved site), adaptive radiation therapy, intensity modulated radiation therapy (IMRT) or volume modulated arc therapy (VMAT), respiratory management by gating or breath hold techniques, particle therapy with protons, image guided therapy, and cone-beam CT treatment verification.

        In limited stage Hodgkin's lymphoma, clinical trials have tested the elimination of radiation therapy based upon the results of an interim PET scan. The EORTC/GELA/IIT HD10 protocol included an interim PET after ABVD×2, and if negative, patients were randomized +/- radiation. They found an excess number of relapses in the chemotherapy alone arm, and concluded that combined modality therapy remains the standard. However, the RAPID trial, conducted in the UK, came to a different conclusion. They performed a PET after ABVD×3 and PET negative patients were randomized +/- radiation. Patients treated with combined modality therapy had a superior freedom from progression that was not significant in the “intent to treat” analysis (p=0.16) ,but was significant in the “as treated” analysis (p=0.02). Based upon these results, the authors recommend chemotherapy alone if the interim PET is negative.

        In advanced disease, ABVD remains the standard for many, however, in Europe, many oncologists use BEACOPP-escalated. Randomized trials show a superiority of BEACOPP escalated for freedom-from-progression, but overall survivals are generally similar. Of concern is the greater toxicity of BEACOPP, including an increased risk for AML/MDS and sterility in most men and many women. Trials have been conducted with dose escalation from ABVD to BEACOPP if the interim PET is positive. Since therapy is not randomized to escalation or no escalation, one must rely on comparison with historic controls. At best, one can only say the early results of this strategy are encouraging.

        Targeted Therapies

        Targeted biologic therapies have been introduced in the management of Hodgkin's lymphoma. The first was brentuximab vedotin, in which a potent anti-tubulin agent (MMAE) is attached to an anti-CD30 monoclonal antibody. This agent showed excellent results in phase 1 and 2 trials. It has proved benefit as a maintenance therapy for patients who are at high risk for relapse after autologous stem cell transplantation (AETHERA trial) and is currently combined with AVD in a prospective randomized comparison with ABVD for patients with advanced disease. Other biologics include the PD-1/PD-L1 inhibitors. Although associated with significant potential toxicity, they achieve responses among patients with previous refractory disease who have failed autologous transplant. (Interviewed by Chunshi Jia)