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.
"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). "
[Show abstract][Hide abstract] 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.
"In contrast, the risk (RR and EAR) for thyroid cancer after HL did not vary by attained age . 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 . "
[Show abstract][Hide abstract] ABSTRACT: Currently, 17–19% of all new primary malignancies occur in survivors of cancer, causing substantial morbidity and mortality. Research has shown that cancer treatments are important contributors to second malignant neoplasm (SMN) risk.
In this paper we summarise current knowledge with regard to treatment-related SMNs and provide recommendations for future research. We address the risks associated with radiotherapy and systemic treatments, modifying factors of treatment-related risks (genetic susceptibility, lifestyle) and the potential benefits of screening and interventions. Research priorities were identified during a workshop at the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer.
Recently, both systemic cancer treatments and radiotherapy approaches have evolved rapidly, with the carcinogenic potential of new treatments being unknown. Also, little knowledge is available about modifying factors of treatment-associated risk, such as genetic variants and lifestyle. Therefore, large prospective studies with biobanking, high quality treatment data (radiation dose–volume, cumulative drug doses), and data on other cancer risk factors are needed. International collaboration will be essential to have adequate statistical power for such investigations. While screening for SMNs is included in several follow-up guidelines for cancer survivors, its effectiveness in this special population has not been demonstrated. Research into the pathogenesis, tumour characteristics and survival of SMNs is essential, as well as the development of interventions to reduce SMN-related morbidity and mortality. Prediction models for SMN risk are needed to inform initial treatment decisions, balancing chances of cure and SMNs and to identify high-risk subgroups of survivors eligible for screening.
"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. "
[Show abstract][Hide abstract] ABSTRACT: To estimate the risk of radiation induced second cancers after radiotherapy using deep-inspiration breath-hold (DI) technique with three-dimensional conformal (3DCRT) and volumetric arc therapy (VMAT) for patients with Hodgkin's lymphoma (HL).
Early-stage HL with mediastinal and supraclavicular involvement was studied using an Alderson phantom. A whole body CT was performed and all tissues were delineated. The clinical target volumes and planning target volumes (PTV) were determined according to the German Hodgkin study group guidelines. Free-breathing (FB) technique and DI technique were simulated by different safety margins for the PTV definition. In both cases, 30 Gy in 15 fractions was prescribed. Second cancer risk was estimated for various tissues with a second cancer model including fractionation.
When compared with FB-3DCRT, estimated relative life time attributable risk (LAR) of cancer induction after DI-3DCRT was 0.86, 0.76, 0.94 and 0.92 for breast, lung, esophagus and stomach, respectively. With DI-VMAT, the corresponding values were 2.05, 1.29, 1.01, 0.93, respectively. For breast cancer, the LAR observed with DI-VMAT was not substantially distinguishable from the LAR computed for mantle RT with an administered dose of 40 Gy.
This study suggests that DI may reduce the LAR of secondary cancers of all OARs and may be a valuable technique when using 3DCRT. Conversely, VMAT may increase substantially the LAR and should be cautiously implemented in clinical practice.
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