PET-CT for staging & early response: results from 'Response Adapted Therapy in Advanced Hodgkin Lymphoma' (RATHL) (CRUK/07/033).

Abstract

International guidelines recommend PET-CT should replace CT in Hodgkin Lymphoma (HL). The aims of this study were to i) compare PET-CT with CT for staging and ii) measure agreement between expert and local readers, using a five-point scale (Deauville criteria), to adapt treatment in a clinical trial 'Response Adapted Therapy in Advanced Hodgkin Lymphoma' (RATHL) www.cancer.gov/clinicaltrials, reference NCT00678327. Patients were staged for the trial 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 labs. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement amongst 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 characterisation of lesions in the vast majority. Five patients were upstaged by marrow biopsy; 7 by contrast-enhanced CT in bowel and/or liver or spleen. PET2 agreement amongst experts (140 scans) with kappa (95% CI) 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.