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

 

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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.

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