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Case–control study on the therapy of childhood cancer and the occurrence of second malignant neoplasms in Germany

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Abstract

We report on a nested case–control study with 328 cases with second malignant neoplasm (SMN) following childhood cancer and 639 matched controls based on the German Childhood Cancer Registry. In the adjusted overall analysis, the odds ratio (OR) for SMN following any radiotherapy or chemotherapy is 2.1 [95% confidence interval (CI): 1.8–3.3] and 1.8 (95% CI: 0.98–3.1), respectively. The strongest effect is seen for alkylating agents (OR=2.0, 95% CI: 1.2–3.3). The risk of SMN after leukemia is pronounced for antimetabolites (OR=17.2, 95% CI: 1.7–177) and asparaginase (OR=4.3, 95% CI: 1.7–11.0). Following solid tumors, the greatest effect is seen for platinum derivatives (OR=4.1, 95% CI: 1.7–10.1). For anthracyclines, a decreased risk is observed (OR=0.3, 95% CI: 0.1–0.6). Secondary solid tumors are mainly associated with radiotherapy (OR=4.5, 95% CI: 2.5–8.0), especially secondary carcinomas. Secondary acute myeloid leukemia and myelodysplastic syndrome are mainly associated with alkylating agents (OR=8.5, 95% CI: 0.97–74.8), asparaginase (OR=6.8, 95% CI: 2.3–20.6), and platinum derivatives (OR=4.5, 95% CI: 1.5–13.6). The observed risks are in many instances lower than the ones published in previous studies relating to earlier treatment eras of the primary diseases. These differences may be attributed to less toxic but still effective treatment regimes but also to differences in the length of follow-up.

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Abbreviations

ALL:

Acute lymphoid leukemia

AML:

Acute myeloid leukemia

CI:

Confidence interval

CNS:

Central nervous system

GCCR:

German Childhood Cancer Registry

GPOH:

Gesellschaft für Pädiatrische Onkologie und Hämatologie (Society of Pediatric Oncology and Hematology)

MDS:

Myelodysplastic syndrome

OR:

Odds ratio

SMN:

Second malignant neoplasm

TOS:

Therapy optimization study (cooperative clinical trial for optimization of therapy)

ACTD:

Actinomycin D

ADR:

Doxorubicin

ARAC:

Cytarabine

ASP:

l-Asparaginase

BLE:

Bleomycin sulfate

CAR:

Carboplatin

CCNU:

Lomustine

CP:

Cyclophosphamide

DDP:

Cisplatin

DNR:

Daunorubicin

DTIC:

Dacarbazine

IFO:

Ifosfamide

MEL:

Melphalan

MITO:

Mitoxantrone

MP:

Mercaptopurine

MTX:

Methotrexate

PRO:

Procarbazine

TG:

Thioguanine

VCR:

Vincristine

VDS:

Vindesine

VIN:

Vinblastin

VM26:

Teniposide

VP16:

Etoposide

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Acknowledgments

The authors also gratefully acknowledge the contribution by the German Society for Pediatric Oncology and Hematology (GPOH) and the associated Therapy Optimization Trials who provided data. For qualified discussion, we would like to thank especially the pediatric oncologists Prof. V. Gerein and Prof. B. Kornhuber. The authors also are grateful to the former research associates (MD) of the project (U. Derichs, G. Klein, U. Mendelssohn, B. Schulz, R. Wibbing) as well as to members of our staff (M. Decher-Neff, B. Hillebrecht, I. Kerenyi, M. Lückel) for preparing data and to I. Jung for helping with the analyses.

Financial support

The project was funded by the Federal Ministry for Education and Research in the framework of the Competence Network in Paediatric Oncology and Haematology (Funding No. 01GI0419). For ongoing financial support of the registry’s work, the authors would like to thank the Federal Ministry for Health and Social Security and the 16 ministries of health of the German states, particularly of Rhineland-Palatinate.

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Authors and Affiliations

  1. German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 69, 55101, Mainz, Germany

    Peter Kaatsch, Irene Reinisch, Claudia Spix & Andreas Mergenthaler

  2. Paediatric Oncology and Haematology, University Hospital of Cologne, Cologne, Germany

    Frank Berthold

  3. Paediatric Haematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Gritta Janka-Schaub

  4. Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz, Mainz, Germany

    Jörg Michaelis & Maria Blettner

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  1. Peter Kaatsch
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  2. Irene Reinisch
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  3. Claudia Spix
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Correspondence to Peter Kaatsch.

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Institution in which the work was performed: German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz

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Kaatsch, P., Reinisch, I., Spix, C. et al. Case–control study on the therapy of childhood cancer and the occurrence of second malignant neoplasms in Germany. Cancer Causes Control 20, 965–980 (2009). https://doi.org/10.1007/s10552-009-9315-1

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