Long-term solid cancer risk among 5-year survivors of Hodgkin's lymphoma
ABSTRACT 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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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
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ABSTRACT: To evaluate the impact of reduced radiation and combined modality therapy (CMT) in the treatment of Hodgkin lymphoma, we assessed the risk of second malignant neoplasms (SMNs) in patients who received extended-field radiotherapy only and patients who underwent CMT. Among 404 patients treated at Yale during 1970-2004, the risk of solid SMNs was elevated in the radiotherapy only group (n = 198, median follow-up = 21·1 years) compared to the general population, with a standardized incidence ratio (SIR) of 1·85 [95% confidence interval (CI): 1·17-2·78]. No increase was observed in the CMT group (n = 206, median follow-up = 14·3 years), although potential differences in SMN risk were indicated across the age spectrum in subgroup analysis. Patients who received mustard-containing regimens had increased risks for haematological SMNs (SIR = 8·74) and all SMNs (SIR = 1·85). When the analysis was stratified by age at diagnosis, children (0-20 years) had a significantly higher risk of SMNs (SIR = 5·24, 95% CI: 2·26-10·33), regardless of the treatment received. These findings suggest that recent treatment options utilizing lower dose radiation and less intense alkylator chemotherapy might be associated with lower incidences of SMNs among adults but not necessarily children.British Journal of Haematology 07/2012; 158(5):615-25. DOI:10.1111/j.1365-2141.2012.09211.x
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ABSTRACT: The Nottinghamshire Lymphoma Registry contains the details of all the patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a population of 1.1 million. It was therefore possible to study the outcome of treatment for Hodgkin's disease for three 10-year cohorts (1973-1982, 1983-1992 and 1993-2002).The aims of the study were to compare survival time among the three patient cohorts, to identify prognostic factors and to estimate relative survival. A total of 745 patients diagnosed between 1973 and 2002 were analysed for survival. Survivorship was estimated by the Kaplan-Meier method and parametric survival models. An accelerated failure-time regression was used for multivariate analysis. Overall, patients were observed for 9.8 (0.3-34.82) years (median(range)), on average. One, five and fifteen-year disease-specific survival was found to be 87% (85-90%), 77% (74-80%) and 70% (67-74%), respectively. For those for diagnosed between 1973 and 1982, the 15-year survival was found to be 57%; for 1983-1992, it was 74% and for 1993-2002, it was 83% (P<0.001). The difference remained significant after adjusting for prognostic factors. The actuarial risk of developing a second malignancy at 20 years was for the 1973-1982 cohort, 12.4%, and for the 1983-1992 cohort, 18.8%. Treatment advances and effective management of toxicities of treatment over time, have resulted in a significantly longer survival for patients with Hodgkin's disease diagnosed within a defined population.British Journal of Cancer 06/2012; 107(3):531-6. DOI:10.1038/bjc.2012.228