Is there a benefit of 131I-MIBG therapy in the treatment of children with stage 4 neuroblastoma?

M. Schmidt; T. Simon; B. Hero; W. Eschner; M. Dietlein; F. Sudbrock; R. Bongartz; F. Berthold; H. Schicha

doi:10.1055/s-0038-1625111

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2006; 45(04): 145-151
DOI: 10.1055/s-0038-1625111

Original Articles

Schattauer GmbH

Is there a benefit of ¹³¹I-MIBG therapy in the treatment of children with stage 4 neuroblastoma?

A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for the The German Neuroblastoma Trial NB2004Gibt es einen Nutzen durch die ¹³¹I-MIBG-Therapie bei der Behandlung von Kindern mit Neuroblastom Stadium 4?Eine retrospektive Datenanalyse der Deutschen Neuroblastom- Studie NB97 und Auswirkungen auf die Nachfolgestudie NB2004

Authors

M. Schmidt

¹Department of Nuclear Medicine
T. Simon

²Children’s Hospital
B. Hero

²Children’s Hospital
W. Eschner

¹Department of Nuclear Medicine
M. Dietlein

¹Department of Nuclear Medicine
F. Sudbrock

¹Department of Nuclear Medicine
R. Bongartz

³Department of Radiotherapy University of Cologne, Germany
F. Berthold

²Children’s Hospital
H. Schicha

¹Department of Nuclear Medicine

Abstract

Summary

Aim: ¹³¹I-meta-iodobenzylguanidine (¹³¹I-MIBG) therapy has been used in neuroblastoma treatment for many years but its value in high intensive first line treatment protocols is not exactly known. Patients, methods: Stage 4 neuroblastoma patients >1 year with ¹²³I-MIBG positive residual disease (primary tumour and/or metastasis) after complete induction chemotherapy according to the German neuroblastoma trial NB97 were retrospectively analyzed. Results: One-hundred-eleven patients had ¹²³I-MIBG positive residual disease after complete induction chemotherapy. Forty patients received ¹³¹I-MIBG therapy using a median activity of 0.44 GBq/kg body weight. By univariate analysis, patients who underwent ¹³¹I-MIBG therapy had a better 3-year event free survival (3-y-EFS 46±8%) and 3-year overall survival (3-y-OS 58±9%) than 71 patients without ¹³¹I-MIBG therapy (3-y-EFS 19±5%, p=0.003; 3-y-OS 43±6%, p=0.037). However, subgroup analysis of 66 patients who underwent high dose chemotherapy with autologous stem cell transplantation (ASCT) during treatment found a very similar outcome with ¹³¹I-MIBG therapy (3-y-EFS 49±9%, 3-y-OS 59±10%) and without ¹³¹I-MIBG therapy (3-y-EFS 33±9%, p=0.171; 3-y-OS 59±9%, p=0.285) due to the dominating effect of ASCT. By multivariate analysis, ¹³¹I-MIBG therapy had no impact on EFS (p=0.494) and OS (p=0.891). Only ASCT, external beam radiation therapy and MYCN amplification were important for EFS and OS. Conclusions: An independent advantage of I-131-MIBG therapy could not be proven in this retrospective analysis. The ongoing German Neuroblastoma Trial NB2004 will address the influence of ¹³¹I-MIBG therapy with emphasis on tumour dosimetry.

Zusammenfassung

Ziel: Die Therapie mit ¹³¹I-Metaiodbenzylguanidin (¹³¹I-MIBG) wird seit Jahren zur Behandlung des Neuroblastoms praktiziert. Der Wert dieses Therapieelements im Rahmen einer hochintensiven Erstbehandlung ist nicht geklärt. Patienten, Methoden: Stadium-4-Neuroblastompatienten im Alter >1 Jahr, die am Ende der kompletten Induktionschemotherapie der Deutschen Neuroblastom- Studie NB97 noch ¹²³I-MIBG-positives residuelles Tumorgewebe (Primärtumor und/oder Metastasen) hatten, wurden retrospektiv ausgewertet. Ergebnisse: 111 Patienten hatten ¹²³I-MIBG-positives residuelles Tumorgewebe nach abgeschlossener Induktionschemotherapie. 40 Patienten erhielten eine ¹³¹I-MIBG-Therapie unter Verwendung einer medianen Aktivität von 0,44 GBq/kg Körpergewicht. Die univariate Analyse zeigte eine bessere 3-Jahres-Rate für das krankheitsfreie Überleben (3-y-EFS 46±8%) und für das Gesamtüberleben (3-y-OS 58±9%) für die Patienten mit ¹³¹I-MIBG-Therapie verglichen mit 71 Patienten ohne ¹³¹I-MIBG-Therapie (3-y-EFS 19±5%, p=0.003; 3-y-OS 43±6%, p=0.037). Die Subgruppenanalyse der 66 Patienten, die eine Hochdosischemotherapie mit autologer Stammzelltransplantation (ASCT) erhalten hatten, zeigten jedoch eine vergleichbares Überleben mit ¹³¹I-MIBGTherapie (3-y-EFS 49±9%, 3-y-OS 59±10%) und ohne ¹³¹I-MIBG-Therapie (3-y-EFS 33±9%, p=0.171; 3-y-OS 59±9%, p=0.285) wegen des dominierenden Effekts der ASCT. In der multivariaten Analyse hatte ¹³¹I-MIBG keinen Einfluss auf das EFS (p=0,494) oder das OS (p=0,891), wichtig waren ASCT, externe Strahlentherapie und MYCN-Amplifikation. Schlussfolgerungen: Ein unabhängiger Vorteil der ¹³¹I-MIBG-Therapie konnte in dieser retrospektiven Analyse nicht bewiesen werden. Die laufende Deutsche Neuroblastom-Studie NB2004 wird den Einfluss der ¹³¹I-MIBG-Therapie untersuchen, wobei der Tumordosimetrie ein besonderer Stellenwert zukommt.

Keywords

High risk neuroblastoma - stage 4 neuroblastoma - ¹³¹I-MIBG therapy

Schlüsselwörter

Hochrisiko-Neuroblastom - Neuroblastom Stadium 4 - ¹³¹I-MIBG-Therapie

Full Text

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