Childhood cancers like leukemia that are treated with higher cumulative doses of chemotherapy like cyclophosphamides and anthracyclines, face an increased risk of developing subsequent/secondary cancers. Secondary/Second Cancers in childhood cancer survivors are a common long term chemotherapy side effect.
Childhood cancers occur in children, teens and young adults. The most common cancer in children is leukemia, a cancer of the blood. Other cancer types such as lymphoma, brain tumors, sarcomas and other solid tumors can also occur. Thanks to improved treatments, there are more than 80% of childhood cancer survivors in the US. Treatments depend on the type of cancer but can include surgery, chemotherapy, radiation therapy and more recently even immunotherapy. However, as per the National Pediatric Cancer Foundation, they estimate that more than 95% of childhood cancer survivors will have a significant health-related issue by the time they are 45 years old, which could be a consequence of their earlier cancer treatment (https://nationalpcf.org/facts-about-childhood-cancer/).
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Second Cancers in Childhood Cancer Survivors
With the presence of a large number of cancer survivors, researchers from the University of Minnesota Medical School examined the association of childhood cancer survivors who were treated with chemotherapy with the incidence of subsequent malignant neoplasm (SMN) as part of the childhood cancer survivor study (Turcotte LM et al, J Clin Oncol., 2019). They evaluated SMNs in survivors who were first diagnosed with cancer when they were less than 21 years old, between 1970-1999. The key details of the study population and findings of their analysis are:
- Median age at diagnosis was 7years and median age at last follow-up was 31.8 years.
- They examined greater than 20,000 childhood survivors who were treated with either chemotherapy alone, chemotherapy along with radiation therapy, radiation therapy alone or neither.
- The childhood survivors treated with chemotherapy alone had a 2.8 fold increased risk of SMN.
- Rate of incidence of SMN was higher in childhood survivors treated with platinum therapy. Additionally, for alkylating agents (Eg. Cyclophosphamide) and anthracyclines (Eg. Doxorubicin), there was a dose response relationship seen between higher doses of these chemotherapy and higher incidence of breast cancer.
Risk of Second Primary Breast Cancer in Leukemia or Sarcoma Survivors
In another earlier analysis as part of the childhood cancer survivor study which included 3,768 female childhood leukemia or sarcoma cancer survivors who were treated with increasing doses of chemotherapy like cyclophosphamide or anthracyclines, it was found that they were significantly associated with risk of developing secondary/second primary breast cancer. There was a 5.3 fold and 4.1 fold increased risk of developing second primary/secondary breast cancer in sarcoma and leukemia survivors respectively. (Henderson TO et al., J Clin Oncol., 2016)
Risk of Secondary Skin Cancers in Childhood Cancer Survivors who once received Radiotherapy
According to the findings from another study called the DCOG-LATER cohort study which included 5843 Dutch childhood cancer survivors who had been diagnosed with various types of cancers between 1963 and 2001, the survivors who were once treated with radiotherapy had an increased risk of secondary skin cancers The study found approximately 30 fold increased risk of basal cell carcinomas in these survivors. This also depended on the extent of skin area exposed during the treatment. (Jop C Teepen et al, J Natl Cancer Inst., 2019)
In summary, childhood cancer survivors who were treated with higher cumulative doses of chemotherapy like cyclophosphamide or anthracyclines for cancers like leukemia face an increased risk of developing subsequent second/secondary cancers (long term chemotherapy side effect). Therefore, risk-benefit analysis of cancer treatment for children and young adults should favor treating with limiting cumulative doses of chemotherapy and consideration of alternative or more targeted therapy options to reduce the risk of developing subsequent malignant cancers in future.
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