Cancer Causes & Control

, Volume 20, Issue 6, pp 965–980 | Cite as

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

  • Peter Kaatsch
  • Irene Reinisch
  • Claudia Spix
  • Frank Berthold
  • Gritta Janka-Schaub
  • Andreas Mergenthaler
  • Jörg Michaelis
  • Maria Blettner
Original Paper

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.

Keywords

Childhood Cancer Epidemiology Population-based Case–control study Chemotherapy Second cancer 

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)

Abbreviations for chemotherapeutic agents

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

Notes

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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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Peter Kaatsch
    • 1
  • Irene Reinisch
    • 1
  • Claudia Spix
    • 1
  • Frank Berthold
    • 2
  • Gritta Janka-Schaub
    • 3
  • Andreas Mergenthaler
    • 1
  • Jörg Michaelis
    • 4
  • Maria Blettner
    • 4
  1. 1.German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and InformaticsJohannes Gutenberg-University MainzMainzGermany
  2. 2.Paediatric Oncology and HaematologyUniversity Hospital of CologneCologneGermany
  3. 3.Paediatric Haematology and OncologyUniversity Hospital Hamburg-EppendorfHamburgGermany
  4. 4.Institute of Medical Biostatistics, Epidemiology and InformaticsJohannes Gutenberg-University MainzMainzGermany

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