PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study

Sally Barrington ,Karin Hjorthaug,Stefano Luminari,Eva Brun,John Radford,Massimo Federico,Helén Almquist,Judith Trotman,Lindsey Stevens,Leanne Berkahn,Thomas H Roberts,Francesco D’Amore,Alexander Fosså,Antonella Franceschetto,Donald A R Sinclair ,Daniël Molin ,Amy A Kirkwood ,Z Viney ,Michael Fulham ,Paul J Smith ,Michael O’doherty ,Lucy Pike ,Peter Johnson

doi:10.1182/blood-2015-11-679407

Abstract

AbstractInternational guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

Highlights

Positron Emission Tomography (PET) and PET-CT, using 2-deoxy-2-[fluorine-18]fluoro-Dglucose (FDG), has been extensively used for imaging patients with Hodgkin Lymphoma (HL)
In RATHL the outcome for patients with a ‘negative’ scan was not influenced by the PET2 score and our observations suggest that the liver is likely to be a more reproducible threshold, readers may possibly have paid closer attention to the decision to assign a score of 4 rather than 3, knowing this would result in treatment escalation
Staging of HL patients in this large prospective study confirms that an important proportion will be staged differently using PET-CT compared to clinical assessment, CT and bone marrow biopsy

Summary

Introduction

. International guidelines recently recommended that PET-CT be used for routine staging of FDG-avid lymphomas and for response assessment using a five-point scale (5-PS), the socalled ‘Deauville criteria’. PET-CT was preferred for staging due to improved accuracy compared with CT and as a baseline for subsequent response assessment. Contrast enhanced CT (ceCT) may be required if accurate nodal measurement is needed e.g. in clinical trials, assessment of bowel involvement, compression/thrombosis of central vessels and for radiation planning. . Further, changes in FDG uptake are more relevant than changes in nodal size for response assessment. Changes in FDG uptake are more relevant than changes in nodal size for response assessment Both ceCT and PET-CT are frequently performed at diagnosis, with added cost and radiation exposure

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