Long-Term Solid Cancer Risk Among 5-Year Survivors of Hodgkin's Lymphoma

Princess Margaret Hospital, University Health Network, and the Department of Radiation Oncology, University of Toronto, Canada.
Journal of Clinical Oncology (Impact Factor: 18.43). 05/2007; 25(12):1489-97. DOI: 10.1200/JCO.2006.09.0936
Source: PubMed


Hodgkin's lymphoma (HL) survivors are known to be at substantially increased risk of solid cancers (SC). However, no investigation has used multivariate modeling to estimate the relative risk (RR), excess absolute risk (EAR), and cumulative incidence for specific attained ages and ages at HL diagnosis.
We identified 18,862 5-year HL survivors from 13 population-based cancer registries in North America and Europe. Poisson regression was used to evaluate the effects of age at diagnosis, attained age, latency, sex, treatment, and year of diagnosis on the RR and EAR of SC.
Among 1,490 identified SC, 850 were estimated to be in excess. For most cancer sites, both RR and EAR decreased with age at HL diagnosis and showed strong dependencies on attained age. For a patient diagnosed at age 30 years and survived to > or = 40 years, modeled risks were significantly elevated for cancers of the breast (RR = 6.1), other supradiaphragmatic sites (RR = 6.0), and infradiaphragmatic sites (RR = 3.7); the largest RR (20-fold) was observed for malignant mesothelioma. Thirty-year cumulative risks of SC for men and women diagnosed at 30 years were 18% and 26%, respectively, compared with 7% and 9%, respectively, in the general population. For young HL patients, risks of breast and colorectal cancers were elevated 10 to 25 years before the age when routine screening would be recommended in the general population.
Multivariable modeling demonstrates for the first time temporal changes in SC risk not evident in unadjusted analyses, and can facilitate the development of individualized risk assessment and the creation of screening strategies for early detection.

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    • "Some authors studied the efficacy of dose escalation on secondary cancer induction(Manem et al, 2014b)(Schneider et al, 2007). It has also been noted that the latency period is typically between 10 to 20 years for solid tumors, and around 5 years for leukemia post irradiation (Zhang et al, 2012)(Wang et al, 2014)(Schneider et al, 2014)(van Leeuwen et al, 2003)(Yeoh and Mikhaeel, 2010)(Yahalom, 2009)(Hodgson et al, 2007a). As a result of increasing prevalence of secondary malignancies, it is clearly of great importance to investigate the risks associated with different treatment regimens as well as their possible variation with age (by incorporating age at exposure and time since exposure)(Hodgson et al, 2007b). "
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    ABSTRACT: Although the survival rate of cancer patients has significantly increased due to advances in anti-cancer therapeutics, one of the major side effects of these therapies, particularly radiotherapy, is the potential manifestation of radiation-induced secondary malignancies. In this work, a novel evolutionary stochastic model is introduced that couples short-term formalism (during radiotherapy) and long-term formalism (post treatment). This framework is used to estimate the risks of second cancer as a function of spontaneous background and radiation-induced mutation rates of normal and pre-malignant cells. By fitting the model to available clinical data for spontaneous background risk together with data of Hodgkins lymphoma survivors (for various organs), the second cancer mutation rate is estimated. The model predicts a significant increase in mutation rate for some cancer types, which may be a sign of genomic instability. Finally, it is shown that the model results are in agreement with the measured results for excess relative risk (ERR) as a function of exposure age, and that the model predicts a negative correlation of ERR with increase in attained age. This novel approach can be used to analyze several radiotherapy protocols in current clinical practice, and to forecast the second cancer risks over time for individual patients.
    Biophysik 10/2014; DOI:10.1007/s00411-014-0576-z · 1.53 Impact Factor
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    • "In contrast, the risk (RR and EAR) for thyroid cancer after HL did not vary by attained age [20]. Because most cancer rates in the general population increase substantially with increasing age, even steady or declining RRs with increasing age can be associated with strikingly increasing EARs, such as the pattern described above for breast cancer after HL [20]. "
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    • "Late toxicities, especially radiation induced second cancers, are of major concern in patients treated for Hodgkin’s lymphoma [22,24]. To reduce the incidence of second cancer induction after radiation therapy, two possibilities can be explored: reducing the total radiation dose and reducing the volume (i.e. "
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