Interim PET response criteria in paediatric non-Hodgkin’s lymphoma

Summary

Aim: To evaluate the use and reliability of the PET-based response criteria for interim PET (iPET) in terms of interobserver variability in pediatric and adolescent patients suffering from non-Hodgkin´s lymphoma (NHL). Particular attention was given to the identification of visual cutoff to separate patients with a favourable outcome. Patients, methods: Retrospective analysis of PET-datasets of 18 children and adolescents suffering from NHL who underwent iPET after two cycles of chemotherapy for response assessment. Data sets were evaluated and rated in three independent review centers (RC) (blindedread, intra-center consensus) using a visual 5-point response scale. Ratings were compared to clinical outcome. Pairwise interobserver agreement was analysed with Cohen’s kappa-test (k). Overall agreement (between attended RCs) was assessed with Fleiss’ k-test. Results: Four patients suffered relapse (early, n = 2; late, n = 2). Per region analyses on interobserver variability revealed a “substantial” agreement (Fleiss’ k = 0.618). Per patient analyses revealed concordant iPETratings in eight patients: iPET-negative (iPET–), n = 5; iPET-positive (iPET+), n = 2; iPET-inconclusive (iPET±), n = 1. Discordant ratings were found in the remaining patients. Patients with early relapse were concordantly identified using mediastinal blood pool structures (MBPS, score ≥ 3) as visual cutoff between iPET+ or iPET–, respectively. However, patients with late relapse were not concordantly identified taking the MBPS as visual cutoff. Conclusion: The iPET interpretation using a dedicated PET-based response scale assured a low interobserver variability in per-region but not in per-patient analyses in a multicenter read. Using a sensitive read out (iPET+, score ≥ 3) a reliable identification of patients suffering relapse was limited to those with early relapse.

Zusammenfassung

Ziel: Evaluation der Reliabilität der PETbasierten, visuellen Kriterien für die Beurteilung des Ansprechens auf die Therapie bei Kindern und Jugendlichen mit Non-Hodgkin-Lymphom (NHL) zum Interim-Zeitpunkt (iPET). Ferner Versuch der Identifizierung eines visuellen Schwellenwertes, mit dem eine Trennung von Patienten mit sehr guter Prognose möglich sein soll. Patienten, Methoden: Retrospektive Auswertung der iPET-Datensätze von 18 Kindern und Jugendlichen mit NHL-Erkrankung nach Abschluss von zwei Zyklen Chemotherapie. Die Datensätze wurden verblindet in drei voneinander unabhängigen Zentren (je 2 Auswerter, Intrazenterkonsensus) unter Verwendung einer 5-stufigen Beurteilungsskala ausgewertet und dem klinischen Verlauf gegenübergestellt. Der paarweise Vergleich der Interobserver-Variabilität erfolgte mittels Cohen-kappa(k)-Test. Die Übereinstimmung zwischen den Zentren wurde durch den Fleiss-k-Test bestimmt. Ergebnisse: Vier Patienten erlitten ein Rezidiv (früh, n = 2; spät, n = 2). Die Region-bezogene Analyse erbrachte ein Fleiss k von 0,618 (beachtliche Übereinstimmung). In der Patienten-basierten Analyse wurden acht Patienten konkordant beurteilt: iPET negativ (iPET–), n = 5; iPET positiv (iPET+), n = 2; iPET uneindeutig (iPET±), n = 1. Die verbleibenden Patienten wurden diskordant befundet. Unter Annahme, dass eine Traceraufnahme in residuelle Läsionen größer oder gleich dem der mediastinalen Strukturen (≥ Score 3) als visueller Schwellenwert zwischen den Befunden iPET+ und iPET–dient, wurden die Patienten mit frühem Rezidiv konkordant iPET+ bewertet. Patienten mit spätem Rezidiv wurden nicht iPET+ bzw. nicht konkordant positiv bewertet. Schlussfolgerungen: Unter Verwendung einer dedizierten, visuellen Skala zur Beurteilung der iPET konnte in einer multizentrischen Auswertung „beachtliche Übereinstimmung” nur in der Läsions -, aber nicht in der Patienten-basierten Auswertung erreicht werden. Die sensitive Beurteilung der iPET (iPET+, ≥ Score 3) erlaubte eine sichere Detektion von Patienten mit Frührezidiv. Patienten mit Spätrezidiv konnten auch mit Hilfe der sensitiven Be urteilung nicht sicher detektiert werden.

Keywords

FDG-PET - non-Hodgkin lymphoma - response assessment - response criteria - therapy monitoring - children

Schlüsselwörter

FDG-PET - Non-Hodgkin-Lymphom - Therapiekontrolle - Beurteilungskriterien - Therapie-Monitoring - Kinder

• References

• 1 Amthauer H, Furth C, Denecke T. et al. FDG-PET in 10 children with non-Hodgkin's lymphoma: initial experience in staging and follow-up. Klin Padiatr 2005; 217: 327-333.
• 2 Bakhshi S, Radhakrishnan V, Sharma P. et al. Pediatric nonlymphomblastic non-Hodgkin lymphoma: Baseline, interim, and posttreatment PET/CT versus contrast-enhanced CT for evaluation – A prospective study. Radiology 2012; 262: 956-968.
• 3 Broyde A, Boycov O, Strenov Y. et al. Role and prognostic significance of the Ki-67 index in non-Hodgkin’s lymphoma. Am J Hematol 2009; 84: 338-343.
• 4 Campo E, Swerdlow SH, Harris NL. et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 2011; 117: 5019-5032.
• 5 Casasnovas RO, Meignan M, Berriolo-Riedinger A. et al. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood 2011; 118: 37-43.
• 6 Cox MC, Ambrogi V, Lanni V. et al. Use of interim [¹⁸F]fluorodeoxyglucose-positron emission tomography is not justified in diffuse large B-cell lymphoma during first-line immunochemotherapy. Leuk Lymphoma 2012; 53: 263-269.
• 7 Depas G, De Barsy C, Jerusalem G. et al. ¹⁸F-FDG PET in children with lymphomas. Eur J Nucl Med Mol Imaging 2005; 32: 31-38.
• 8 Edeline V, Bonardel G, Brisse H. et al. Prospective study of ¹⁸F-FDG PET in pediatric mediastinal lymphoma: a single center experience. Leuk Lymphoma 2007; 48: 823-826.
• 9 Furth C, Steffen IG, Amthauer H. et al. Early and late therapy response assessment with [¹⁸F]fluor-odeoxyglucose positron emission tomography in pediatric Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol 2009; 27: 4385-4391.
• 10 Furth C, Amthauer H, Hautzel H. et al. Evaluation of interim PET response criteria in paediatric Hodgkin’s lymphoma – results for dedicated assessment criteria in a blinded dual-centre read. Ann Oncol 2011; 22: 1198-1208.
• 11 Furth C, Meseck RM, Steffen IG. et al. SUV-measurements and patient-specific corrections thereof in pediatric Hodgkin-lymphoma: Is there a benefit for PPV in early response assessment by FDG-PET?. Pediatr Blood Cancer 2012; 59: 475-480.
• 12 Hermann S, Wormanns D, Pixberg M. et al. Staging in childhood lymphoma: differences between FDG-PET and CT. Nuklearmedizin 2005; 44: 1-7.
• 13 Hernandez-Pampaloni M, Takalkar A. et al. F-18 FDG-PET imaging and correlation with CT in staging and follow-up of pediatric lymphomas. Pediatr Radiol 2006; 36: 524-531.
• 14 Horning SJ, Juweid ME, Schöder H. et al. Interim Positron emission tomography (PET) scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. Blood 2010; 28: 775-777.
• 15 Kaatsch P, Spix C. Registry - Annual Report 2008. Technischer Bericht. Universität Mainz; 2008. www.kinderkrebsregister.de/extern/veroeffentlichungen/jahresberichte/jb2008/index.html
• 16 Kluge R, Körholz D. Role of FDG-PET in Staging and therapy of children with Hodgkin lymphoma. Klin Padiatr 221: 315-319.
• 17 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159-174.
• 18 Lin C, Itti E, Haioun C, Petegnief Y. et al. Early ¹⁸F-FDG PET for prediction of prognosis in patients with diffuse large B-cell lymphoma: SUV-based assessment versus visual analysis. J Nucl Med 2007; 10: 1626-1632.
• 19 London K, Cross S, Onikul E. et al. ¹⁸F-FDG PET/ CT in paediatric lymphoma: comparison with conventional imaging. Eur J Nucl Med Mol Imaging 2011; 38: 274-284.
• 20 Lopci E, Burnelli R, Ambrosini V. et al. ¹⁸F-FDG PET in pediatric lymphomas: a comparison with conventional imaging. Cancer Biother Radiopharm 2008; 6: 681-689.
• 21 Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on interim-PET scan in lymphoma. Leuk Lymphoma 2009; 50: 1257-1260.
• 22 Meignan M, Itti E, Gallamini A. et al. Interim ¹⁸F-fluorodeoxyglucose positron emission tomography in diffuse large B-cell lymphoma: qualitative or quantitative interpretation–where do we stand?. Leuk Lymphoma 2009; 50: 1753-1756.
• 23 Meignan M, Gallamini A, Itti E. et al. Report on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 26–27 September 2011 and Menton 2011 consensus. Leuk Lymphoma 2012; 53: 1876-1881.
• 24 Miller E, Metser U, Avrahami G. et al. Role of ¹⁸F-FDG PET/CT in staging and follow-up of lymphoma in pediatric and young adult patients. J Comput Assist Tomogr 2006; 30: 689-694.
• 25 Montravers F, McNamara D, Landman-Parker J. et al. ¹⁸F-FDG in childhood lymphoma: clinical utility and impact on management. Eur J Nucl Med Mol Imaging 2002; 29: 1155-1165.
• 26 Moskowitz CH, Schöder H, Teruya-Feldstein J. et al. Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in advanced-stage diffuse large B-Cell lymphoma. J Clin Oncol 2010; 28: 1896-1903.
• 27 Reiter A, Schrappe M, Parwaresch R. et al. Non-Hodgkin’s lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage–a report of the Berlin-Frankfurt-Munster Group. J Clin Oncol 1995; 13: 359-372.
• 28 Pregno P, Chiappella A, Bello M. et al. Interim ¹⁸FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood 2012; 119: 2066-2073.
• 29 Reiter A. Diagnosis and treatment of childhood non-hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2007: 285-296.
• 30 Riad R, Omar W, Kotb M. et al. Role of PET/CT in malignant pediatric lymphoma. Eur J Nucl Med Mol Imaging 2010; 2: 319-329.
• 31 Safar V, Dupuis J, Itti E. et al. Interim [¹⁸F]fluoro-deoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with an- thracycline-based chemotherapy plus rituximab. J Clin Oncol 2012; 30: 184-190.
• 32 Van Waas M, Neggers SJ, Te Winkel ML. et al. Endocrine late sequelae in long-term survivors of childhood non-Hodgkin lymphoma. Ann Oncol 2012; 23: 1626-1632.