[Show abstract][Hide abstract] ABSTRACT: With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study.
Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire.
Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likely to develop a SPN than expected, where the excess was restricted to 5-24 years post diagnosis. Increased health-care usage and poor health status were also found. Nonetheless, for some psychosocial outcomes survivors were better off than expected.
Up to 25 years after 5-year survival, bone sarcoma survivors are at substantial risk of death and SPNs, but this is greatly reduced thereafter. As 95% of all excess deaths before 25 years follow-up were due to recurrences and SPNs, increased monitoring of survivors could prevent mortality. Furthermore, bone and breast SPNs should be a particular concern. Since there are variations in the magnitude of excess risk depending on the specific adverse outcome under investigation and whether the survivors were initially diagnosed with osteosarcoma or Ewing sarcoma, risks need to be assessed in relation to these factors. These findings should provide useful evidence for risk stratification and updating clinical follow-up guidelines.British Journal of Cancer advance online publication, 19 May 2015; doi:10.1038/bjc.2015.159 www.bjcancer.com.
British Journal of Cancer 05/2015; 112(12). DOI:10.1038/bjc.2015.159 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Childhood cancer is rare but improvements in treatment over the past five decades have resulted in a cohort of more than 30,000 long-term survivors of childhood cancer in the UK with more added annually. These long-term survivors are at risk of late effects of cancer treatment which replace original tumour recurrence as the leading cause of premature death. Second neoplasms are a particular risk and in the central nervous system meningiomas occur increasingly with increased radiation dose to central nervous system tissue and length of time after exposure, resulting in a 500-fold increase above that expected in the normal population by 40 years of follow up. This multidisciplinary author group and others met to discuss the issue. Our pooled information, and consensus that screening should only follow symptoms, was published online by the Royal College of Radiologists in 2013. We outline here the current knowledge and management of these neoplasms secondary to childhood cancer treatment.
[Show abstract][Hide abstract] ABSTRACT: CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain.
The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken.
There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and≥40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed.
The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have reported substantially increased risks of breast cancer among survivors of childhood cancer at 10-20 years posttreatment. Whether these excess risks are sustained beyond 40 years of age when general population incidence of breast cancer begins its steep increase is largely unknown. We quantified the risk of breast cancer in adult female survivors with considerably more survivors followed-up beyond 40 years of age than previously available. Standardized Incidence Ratios (SIR), Excess Absolute Risks (EAR), and cumulative incidence were calculated within a population-based cohort of 8,093 female survivors of childhood cancer. Poisson regression models were used to model SIRs and EARs in a multivariable setting. Eighty-one survivors developed a primary breast cancer, where 37.5 were expected (SIR= 2.2, 95% CI: 1.7-2.7). SIRs decreased significantly with increasing attained age (p(trend) < 0.001) to an SIR of 0.9 (95% CI: 0.5-1.8) at ages beyond 50 years; EARs increased significantly to about 40 years of age (p(trend) < 0.001) but then plateau. Between 30 and 49 years of age survivors experienced approximately 1 extra breast cancer per 1,000 survivors per year. Overall, 3% developed breast cancer by the age of 50. The substantially increased relative risks of breast cancer observed at 10-20 years postdiagnosis are not sustained into ages at which the risk of breast cancer in the general population becomes substantial. Among women who survived to an age of at least 50 years there is currently no evidence of an increased risk of breast cancer.
International Journal of Cancer 11/2008; 123(9):2156-63. DOI:10.1002/ijc.23743 · 5.09 Impact Factor