title: PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.
abstract: International 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.
authors.affiliation: PET Imaging Centre, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom;
authors.forename: Sally F
authors.initials: SF
authors.lastname: Barrington
authors.affiliation: Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom;
authors.forename: Amy A
authors.initials: AA
authors.lastname: Kirkwood
authors.affiliation: Department of Nuclear Medicine, University of Modena and Reggio Emilia, Modena, Italy;
authors.forename: Antonella
authors.initials: A
authors.lastname: Franceschetto
authors.affiliation: Department of Molecular Imaging (PET-CT), Royal Prince Alfred Hospital, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fulham
authors.affiliation: Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom;
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Roberts
authors.affiliation: Department of Medical Imaging and Physiology and.
authors.forename: Helén
authors.initials: H
authors.lastname: Almquist
authors.affiliation: Department of Oncology and Radiation Physics, Skane University Hospital, Lund University, Lund, Sweden;
authors.forename: Eva
authors.initials: E
authors.lastname: Brun
authors.affiliation: Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark;
authors.forename: Karin
authors.initials: K
authors.lastname: Hjorthaug
authors.affiliation: Department of Radiology, Guy's and St. Thomas' National Health Service (NHS) Foundation Trust, London, United Kingdom;
authors.forename: Zaid N
authors.initials: ZN
authors.lastname: Viney
authors.affiliation: PET Imaging Centre, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom;
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Pike
authors.affiliation: Oncology Unit, Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy;
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.affiliation: Oncology Unit, Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy;
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.affiliation: The University of Manchester and the Christie NHS Foundation Trust, Manchester, United Kingdom;
authors.forename: John
authors.initials: J
authors.lastname: Radford
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Concord, Repatriation General Hospital, Sydney, Australia;
authors.forename: Judith
authors.initials: J
authors.lastname: Trotman
authors.affiliation: Department of Oncology, Norwegian Radium Hospital, Oslo, Norway;
authors.forename: Alexander
authors.initials: A
authors.lastname: Fosså
authors.affiliation: Haematology, Auckland City Hospital, Auckland, New Zealand;
authors.forename: Leanne
authors.initials: L
authors.lastname: Berkahn
authors.affiliation: Department of Genetics and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden;
authors.forename: Daniel
authors.initials: D
authors.lastname: Molin
authors.affiliation: Haematology, Aarhus University, Aarhus, Denmark; and.
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Amore
authors.affiliation: PET Imaging Centre, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom;
authors.forename: Donald A
authors.initials: DA
authors.lastname: Sinclair
authors.affiliation: Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
authors.affiliation: PET Imaging Centre, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Doherty
authors.affiliation: Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom;
authors.forename: Lindsey
authors.initials: L
authors.lastname: Stevens
authors.affiliation: Cancer Research UK Centre, University of Southampton, Southampton, United Kingdom.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Johnson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D001761:Bleomycin / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D003606:Dacarbazine / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000032:analysis; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000032:analysis; D014747:Vinblastine / Q000627:therapeutic use
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin