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Klin Padiatr 2014; 226(03): 143-148
DOI: 10.1055/s-0034-1368719
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Intensive Multimodale Therapie bei Säuglingen mit rhabdoiden Tumoren – eine Machbarkeitsanalyse aus dem EU-RHAB-Register
A. Seeringer
1   Swabian Children’s Cancer Center, Children’s Hospital Augsburg, Germany
,
K. Bartelheim
1   Swabian Children’s Cancer Center, Children’s Hospital Augsburg, Germany
,
K. Kerl
2   Hematology and Oncology, University Children’s Hospital Münster, Germany
,
M. Hasselblatt
3   Neuropathology, University Hospital Münster, Germany
,
I. Leuschner
4   Institute of Pathology Christian-Albrechts-University Kiel, Germany
,
S. Rutkowski
5   Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
B. Timmermann
6   Westgerman Protontherapycenter Essen, University Essen, Germany
,
R.-D. Kortmann
7   Radiooncology, University Hospital Leipzig, Germany
,
E. Koscielniak
8   Pediatric Hematology and Oncology, Olgahospital Stuttgart, Germany
,
R. Schneppenheim
5   Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
M. Warmuth-Metz
9   Neuroradiology, University of Würzburg, Germany
,
J. Gerß
10   Institute of Biometry and Clinical Research, University of Münster, Germany
,
R. Siebert
11   Institute of Human Genetics, Christian-Albrechts-University Kiel, Germany
,
N. Graf
12   Pediatric Hematology and Oncology, University Hospital Homburg, Germany
,
J. Boos
2   Hematology and Oncology, University Children’s Hospital Münster, Germany
,
M. C Frühwald
13   Swabian Children’s Cancer Center, Children’s Hospital Augsburg, Germany.
› Author Affiliations
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Publication History

Publication Date:
14 March 2014 (online)

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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
 

  • References

  • 1 Athale UH, Duckworth J, Odame I et al. Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J Pediatr Hematol Oncol 2009; 31: 651-663
    CrossrefPubMedGoogle Scholar
  • 2 Biegel JA, Fogelgren B, Wainwright LM et al. Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Genes Chromosomes Cancer 2000; 28: 31-37
    CrossrefPubMedGoogle Scholar
  • 3 Bourdeaut F, Freneaux P, Thuille B et al. Extra-renal non-cerebral rhabdoid tumours. Pediatr Blood Cancer 2008; 51: 363-368
    CrossrefPubMedGoogle Scholar
  • 4 Buscariollo DL, Park HS, Roberts KB et al. Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis. Cancer 2012; 118: 4212-4219
    CrossrefPubMedGoogle Scholar
  • 5 Duffner PK. Risk factors for cognitive decline in children treated for brain tumors. European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 2010; 14: 106-115
    CrossrefPubMedGoogle Scholar
  • 6 Dufour C, Beaugrand A, Le Deley MC et al. Clinicopathologic prognostic factors in childhood atypical teratoid and rhabdoid tumor of the central nervous system: a multicenter study. Cancer 2012; 118: 3812-3821
    CrossrefPubMedGoogle Scholar
  • 7 Ferrari A, Orbach D, Sultan I et al. Neonatal soft tissue sarcomas. Seminars in fetal & neonatal medicine 2012; 17: 231-238
    CrossrefPubMedGoogle Scholar
  • 8 Grill J, Renaux VK, Bulteau C et al. Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes. International journal of radiation oncology, biology, physics 1999; 45: 137-145
    CrossrefPubMedGoogle Scholar
  • 9 Hilden JM, Meerbaum S, Burger P et al. Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol 2004; 22: 2877-2884
    CrossrefPubMedGoogle Scholar
  • 10 Kearns GL, Abdel-Rahman SM, Alander SW et al. Developmental pharmacology – drug disposition, action, and therapy in infants and children. N Engl J Med 2003; 349: 1157-1167
    CrossrefPubMedGoogle Scholar
  • 11 Lafay-Cousin L, Hawkins C, Carret AS et al. Central nervous system atypical teratoid rhabdoid tumours: the Canadian Paediatric Brain Tumour Consortium experience. European journal of cancer 2012; 48: 353-359
    CrossrefPubMedGoogle Scholar
  • 12 Lakhoo K, Sowerbutts H. Neonatal tumours. Pediatric surgery international 2010; 26: 1159-1168
    CrossrefPubMedGoogle Scholar
  • 13 Morgenstern DA, Gibson S, Brown T et al. Clinical and pathological features of paediatric malignant rhabdoid tumours. Pediatric blood & cancer 2010; 54: 29-34
    CrossrefPubMedGoogle Scholar
  • 14 Packer RJ, Biegel JA, Blaney S et al. Atypical teratoid/rhabdoid tumor of the central nervous system: report on workshop. J Pediatr Hematol Oncol 2002; 24: 337-342
    CrossrefPubMedGoogle Scholar
  • 15 Reinhard H, Reinert J, Beier R et al. Rhabdoid tumors in children: prognostic factors in 70 patients diagnosed in Germany. Oncol Rep 2008; 19: 819-823
    PubMedGoogle Scholar
  • 16 Silber JH, Radcliffe J, Peckham V et al. Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 1992; 10: 1390-1396
    PubMedGoogle Scholar
  • 17 Sultan I, Qaddoumi I, Rodriguez-Galindo C et al. Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors. Pediatric blood & cancer 2010; 54: 35-40
    CrossrefPubMedGoogle Scholar
  • 18 Tekautz TM, Fuller CE, Blaney S et al. Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2005; 23: 1491-1499
    CrossrefPubMedGoogle Scholar
  • 19 Tomlinson GE, Breslow NE, Dome J et al. Rhabdoid tumor of the kidney in the National Wilms’ Tumor Study: age at diagnosis as a prognostic factor. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2005; 23: 7641-7645
    CrossrefPubMedGoogle Scholar
  • 20 von Hoff K, Hinkes B, Gerber NU et al. Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT’91. Eur J Cancer 2009; 45: 1209-1217
    CrossrefPubMedGoogle Scholar
  • 21 Warmann SWNN, Frühwald M, Leuschner I et al. Primary lung metastasis in pediatric malignant non-Wilms renal tumor: Data from SIOP 93-01/GPOH and SIOP 2001/GPOH. Klin Padiatr 2012; 224: 148-152
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Woehrer A, Slavc I, Waldhoer T et al. Incidence of atypical teratoid/rhabdoid tumors in children: a population-based study by the Austrian Brain Tumor Registry, 1996–2006. Cancer 2010; 116: 5725-5732
    CrossrefPubMedGoogle Scholar