Feasibility of Intensive Multimodal Therapy in Infants Affected by Rhabdoid Tumors – Experience of the EU-RHAB registry

Abstract

Rhabdoid tumors mainly affect infants and other very young children with a marked vulnerability towards intensive therapy such as invasive surgery, high dose chemotherapy (HDCT) and dose intense radiotherapy. Radiotherapy (RT) is a promising option in rhabdoid tumors but its application in infants remains controversial. Neurocognitive and vascular side effects occur even long after completion of therapy. Therapeutic recommendations suggested by the European Rhabdoid Registry including RT, high dose chemotherapy (HDCT) and methotrexate (MTX) were developed by a consensus committee. Unique to our EU-RHAB database is the ability to analyze data of 64 of 81 registered infants (under one year of age) separate from older children. 20 (age at diagnoses 2–12 months) of these had received radiotherapy. To our knowledge, this is the first report specifically analyzing treatment data of infants suffering from malignant rhabdoid tumors. Our results suggest that radiotherapy significantly increases the mean survival time as well as the 3 year overall survival in infants. We detected a doubling of survival times in infants who received RT. Overall, our results suggest that infants benefit from RT with tolerable acute side effects. Severe long term sequelae likely due to intraventricular MTX and/or RT were reported in 4 patients (leukoencephalopathy). No differences in chemotherapy-related toxicity were observed between infants and children. We suggest that a nihilistic therapeutic approach towards young infants is not warranted and that RT may not be a priori rejected as a therapeutic option in infants.

Zusammenfassung

Rhabdoide Tumoren betreffen hauptsächlich Säuglinge und Kleinkinder. Gerade diese Patientengruppe ist jedoch anfällig für die Nebenwirkungen intensiver Therapien. So können u. a. Hochdosischemotherapie oder Bestrahlung noch lange nach Ende der Behandlung neurokognitive und vaskuläre Schädigungen hervorrufen. Die therapeutischen Empfehlungen der EU-RHAB-Expertengruppe zur Behandlung rhabdoider Tumoren beinhalten Radiotherapie, Hochdosischemotherapie sowie die intraventrikuläre Gabe von Methotrexat (MTX). Die EU-RHAB-Datenbank bietet die einzigartige Möglichkeit, Therapiedaten von Säuglingen (unter 1 Jahr) getrennt von Kindern (über 1 Jahr) analysieren zu können. 64 von 81 registrierten Säuglingen wurden ausgewertet – 20 hiervon erhielten eine Radiotherapie (Alter bei Diagnose: 2–12 Monate). Unsere Ergebnisse zeigen einen signifikanten Anstieg der durchschnittlichen Überlebenszeiten wie auch des 3-Jahre-Überlebens nach einer Radiotherapie. Bei akzeptablen Akutnebenwirkungen sahen wir eine Verdopplung der Überlebenszeit bei Säuglingen, die einer Radiotherapie unterzogen wurden. Schwere neurologische Langzeitnebenwirkungen (Leukoenzephalopathie) wurden bislang bei 4 der mittels Radiotherapie und/oder MTX intraventrikular behandelten Säuglinge registriert. Wir konnten keinerlei Unterschiede im Auftreten von Chemotherapie-bedingten Toxi­zitäten zwischen Säuglingen und Kindern über 1 Jahr feststellen. Wir folgern, dass ein nihilistisches therapeutisches Vorgehen auch im Säug­lingsalter nicht gerechtfertigt ist und gerade die Option einer Radiotherapie in dieser Patientengruppe nicht von vornherein ausgeschlossen werden sollte.

Keywords

rhabdoid tumors - AT/RT - infants - radiotherapy

Schlüsselwörter

rhabdoide Tumoren - AT/RT - Säuglinge - Strahlentherapie

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