Originally published as JCO Early Release 10.1200/JCO.2007.14.6068 on March 17 2008

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Risk of Subsequent Solid Tumors After Non-Hodgkin's Lymphoma: Effect of Diagnostic Age and Time Since Diagnosis

Kari Hemminki, Per Lenner, Jan Sundquist, Justo Lorenzo Bermejo

From the Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Family and Community Medicine, Karolinska Institute, Huddinge; and the Norrlands University Hospital, Umea, Sweden

Corresponding author: Kari Hemminki, MD, PhD, German Cancer Research Centre,Im Neuenheimer Feld 580, Heidelberg, Germany 69120; e-mail: k.hemminki{at}dkfz.de

Purpose: Quantitative data on subsequent cancers after primary cancers provide information on treatment-related risks on second cancers, with implications for therapeutic adverse effects and human susceptibility in general. Quantitative data on solid tumors are limited. We focus on survivors of non-Hodgkin's lymphoma (NHL) because the disease is diagnosed at a wide range of ages and treated uniformly primarily with chemotherapy.

Patients and Methods: The nationwide Swedish Family-Cancer Database included 11.5 million individuals whose cancers were retrieved from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent neoplasms among 28,131 patients with NHL.

Results: The SIR for solid tumors after NHL was 1.65 (2,290 patients) and that for lymphohematopoietic neoplasms was 5.36 (369 patients). Among the 25 most common solid tumors, the SIRs were increased for all but nine sites; the highest SIR (40.8) was observed for spinal meningioma. The SIRs for solid tumors declined in an age-dependent manner from 4.52 in diagnostic age younger than 20 years to 1.12 in diagnostic age 70+ years. In the most common patient groups, the SIRs for solid tumors increased up to 30 years after NHL diagnosis. Because of the high incidence of solid tumors in these age groups, they contributed the largest numbers of therapy-related cases.

Conclusion: These data indicate that age at treatment determines both the magnitude of the initial relative risk and the time-dependent modulation of the response. Therapy-related damage persists at least 30 years and its toll of solid tumors is largest 21 to 30 years after diagnosis.

published online ahead of print at www.jco.org on March 17, 2008.

Supported by the Deutsche Krebshilfe, the Swedish Cancer Society, the Swedish Council for Working Life and Social Research, and European Union Grants No. LSHC-LT-2004-503465 and Food-CT-2005-016320.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.