Prognostic Significance of Mid- and Post-ABVD PET Imaging in Hodgkin's Lymphoma: The Importance of Involved-field Radiotherapy

Abstract and Introduction
Abstract

Background: Although positron emission tomography (PET) response to chemotherapy (CT) has prognostic significance in Hodgkin's lymphoma (HL), it is unclear whether patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)–PET positivity during and/or after CT can be rendered disease free with consolidative involved-field radiotherapy (IFRT).
Methods: Patients with HL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)-based CT and radiotherapy (RT) at our institution from January 2000 to March 2007 were eligible. All patients had either a post-treatment PET or PET–CT before initiation of RT or a negative midtreatment PET or PET–CT. The primary end point was failure-free survival (FFS) for patients with and without residual FDG avidity after ABVD. The treatment outcome of patients with interim PET positivity during CT was also reported.
Results: Seventy-three patients were included in this study. Twenty patients (out of 46) were PET positive on interim PET, and 13 patients (out of 73) were PET positive at the conclusion of CT. At a median follow-up of 3.4 years for surviving patients, the 2-year FFSs for patients PET-negative versus PET-positive disease after ABVD were 95% and 69%, respectively (P < 0.01). On bivariable Cox regression, post-ABVD positivity (hazard ratio 4.8, P = 0.05) was predictive of disease recurrence after controlling for bulky disease. Of the 20 patients with interim PET positivity, three recurred, with a 2-year FFS of 85%. Among the 13 patients with interim PET positivity, but became PET negative at the completion of CT, the 2-year FFS was 92%.
Conclusion: Sixty-nine per cent of patients with residual FDG avidity after ABVD were free of disease after consolidative RT, indicating a majority of patients with persistent lymphoma can be cured by sterilizing this PET-positive disease.
Introduction

The treatment paradigm of Hodgkin's lymphoma (HL) has experienced a dramatic shift over the past 30 years, as combined modality therapy has become the standard of care among patients with early-stage disease.[1] The staging and follow-up of patients have also undergone substantial changes, with functional imaging playing a key role in the management of these patients. Multiple investigators have shown that the presence of residual 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) avidity on positron emission tomography (PET) scan at the completion of CT strongly predicts for subsequent failure.[2–5] In recent years, emerging data are available on the prognostic significance of early PET response in patients receiving CT for HL.[6–9] In one study, early PET response has prognostic significance independent of that of the International Prognostic Score for patients with advanced-stage HL.[9] However, limited data are available on the role of consolidative radiotherapy (RT) in the setting of residual FDG avidity either during or at the conclusion of CT, and it is unclear whether the addition of RT may modify the dismal outcome of patients with residual PET-positive disease.

We have previously shown that a substantial percentage of HL patients with residual gallium positivity during or after adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) CT can be rendered disease free with involved-field radiation therapy (IFRT) alone.[10] Our institution started routinely obtaining mid- and/or postchemotherapy PET imaging in 2000 for patients receiving CT for HL. In this paper, we report the failure-free outcomes of patients with and without postchemotherapy PET positivity treated with consolidative RT, and we also discuss the implications of midtreatment PET positivity in the context of routine postchemotherapy radiation treatment.