International Validation Study for Interim PET in ABVD-Treated, Advanced-Stage Hodgkin Lymphoma: Interpretation Criteria and Concordance Rate Among Reviewers

At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates. Methods: A cohort of advanced-stage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score. Results: Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1–3) or positive (score of 4–5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET–positive scans were true-positive, and 12 were false-positive. Two hundred three interim PET–negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET–positive and –negative patients, respectively (P < 0.0001). The agreement between pairs of reviewers was good or very good, ranging from 0.69 to 0.84 as measured with the Cohen kappa. Overall agreement was good at 0.76 as measured with the Krippendorf α. Conclusion: The 5-point score proposed at Deauville for reviewing interim PET scans in advanced Hodgkin lymphoma is accurate and reproducible enough to be accepted as a standard reporting criterion in clinical practice and for clinical trials.

[1]  Sigrid Stroobants,et al.  Revised response criteria for malignant lymphoma. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  M. Baccarani,et al.  Early interim 18F-FDG PET in Hodgkin’s lymphoma: evaluation on 304 patients , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[3]  Klaus Krippendorff,et al.  Answering the Call for a Standard Reliability Measure for Coding Data , 2007 .

[4]  J. Raemaekers,et al.  Development and application of a real-time on-line blinded independent central review of interim PET scans to determine treatment allocation in lymphoma trials. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Michel Meignan,et al.  Report on the First International Workshop on interim-PET scan in lymphoma , 2009, Leukemia & lymphoma.

[6]  R. Advani,et al.  Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. , 2010, Blood.

[7]  Jacob Cohen A Coefficient of Agreement for Nominal Scales , 1960 .

[8]  W. Oyen,et al.  FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0 , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[9]  F. d'Amore,et al.  Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from a joint Italian-Danish study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Martin Hutchings,et al.  FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. , 2006, Blood.

[11]  A. Levis,et al.  The predictive value of positron emission tomography scanning performed after two courses of standard therapy on treatment outcome in advanced stage Hodgkin's disease. , 2006, Haematologica.

[12]  T. Nihashi,et al.  Fluorine-18-fluorodeoxyglucose positron emission tomography for interim response assessment of advanced-stage Hodgkin's lymphoma and diffuse large B-cell lymphoma: a systematic review. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[14]  J. R. Landis,et al.  The measurement of observer agreement for categorical data. , 1977, Biometrics.

[15]  J. S. Júnior,et al.  18F-FDG PET After 2 Cycles of ABVD Predicts Event-Free Survival in Early and Advanced Hodgkin Lymphoma , 2010, The Journal of Nuclear Medicine.

[16]  J. Leonard,et al.  FDG‐PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease , 2006, Cancer.

[17]  J. Radford,et al.  Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma , 2010, European Journal of Nuclear Medicine and Molecular Imaging.