Doxorubicin and cyclophosphamide increase the risk of subsequent solid malignancies in survivors of childhood cancer, according to results from the Dutch Childhood Cancer Oncology Group LATER study cohort.
“Childhood cancer survivors are at increased risk of developing new malignancies, even decades after treatment has ended,” Jop C. Teepen from Emma Children's Hospital/Academic Medical Center in Amsterdam told Reuters Health by email. “Physicians who take care of survivors of childhood cancer should be aware of a possible increased risk of second malignancies, not only after radiotherapy, but also after certain chemotherapy treatments.”
Childhood cancer survivors who received radiotherapy face an increased risk of subsequent malignant neoplasms (SMNs). Chemotherapy has been linked to an increased risk of acute myeloid leukemia, but its role in the etiology of solid cancers is less clear.
Teepen and colleagues used data from 6,165 five-year childhood cancer survivors to examine the role of specific chemotherapeutic agents in the later development of solid malignancies.
Overall, the risk of any SMN was 5.2-fold higher among childhood cancer survivors than in the general population (an excess of 20.3 cancers per 10,000 person-years), according to the May 22nd Journal of Clinical Oncology online report.
Excess absolute risks of at least 2.0 per 10,000 person-years were observed for female breast, thyroid, soft tissue sarcoma, and CNS malignancies.
The 25-year cumulative incidences were 3.4% for all solid cancers, 1.5% for female breast cancer, and 1.0% for sarcoma.
Doxorubicin was associated with a dose-dependent increased risk of all solid cancers and female breast cancer, whereas cyclophosphamide was associated with a dose-dependent increased risk of sarcoma.
Ifosfamide also appeared to increase the risk of breast cancer and sarcoma, without a clear dose effect.
As in earlier studies, radiotherapy was a significant risk factor for subsequent solid cancers in childhood cancer survivors.
“It is important that survivors who were treated for childhood cancer in the past are regularly seen by a medical team that is familiar with their potential risks of long-term complications to inform them about their risks and to provide medical care for those survivors who are at highest risk of medical problems,” Teepen said.
“To date only women treated with radiotherapy directed to the chest are eligible for breast cancer surveillance additional to population screening efforts,” he said. “The International Guideline Harmonization Group (IGHG) is currently updating their recommendations for breast cancer surveillance among childhood cancer survivors. New evidence from this and other recent studies will be included in the process to reevaluate the pros and cons of surveillance recommendations.”
Dr. Lucie Turcotte from the University of Minnesota Masonic Children's Hospital in Minneapolis, who recently reviewed trends in treatment and subsequent neoplasm risk among five-year survivors of childhood cancer, told Reuters Health by email, "The risk for subsequent solid cancers is not unique to survivors of childhood cancer who were treated with radiation. The evaluation of specific chemotherapeutic agents in subsequent malignancy risk is important, particularly as the use of therapeutic radiation continues to decline. This study sets the stage for additional detailed analyses examining chemotherapy-associated risk.”
“The dose-dependent association between doxorubicin and solid cancer risk, specifically breast cancer risk, is interesting,” she said. “This supports the recent finding from the Childhood Cancer Survivor Study that anthracyclines are associated with increased risk of breast cancer in women not treated with chest irradiation.”
“There are not currently specific guidelines for breast cancer screening in women not treated with chest radiation,” Dr. Turcotte said. “This study demonstrates an at-risk population of women treated with high doses of doxorubicin and suggests the need for closer surveillance of this population.”
J Clin Oncol 2017.