Dr. Levine studied 2,930 female cancer survivors diagnosed at a median age of 6 years between 1979 and 1986 and a median age at follow-up of 34 years, who were compared with 1,399 healthy siblings. Of the survivor cohort, 110 developed NSPM at a median age of 32 years, and the prevalence of NSPM at age 40 years for the entire cohort was 9.1%, giving a relative risk of NSPM of 10.5 compared with siblings, who had a 0.9% NSPM prevalence at age 40.
She found that exposure to alkylating agents and older age at diagnosis put childhood cancer survivors at increased risk of NSPM, which was associated with lower rates of pregnancy and live births after age 31 years. The greatest risk of NSPM occurred if the cyclophosphamide equivalent dose was greater than 6000 mg/m2 (odds ratio = 3.6 compared with no CED); if there had been any radiation to the ovaries (less than 5 Gy: OR = 4.0; 5 Gy or more: OR = 20.4); or if the age at diagnosis was greater than 14 years (OR = 2.3).
Women with NSPM, compared with survivors without NSPM, were less likely ever to be pregnant (OR = 0.41) or to have a live birth after age 30 (OR = 0.35). However, these outcomes were no different between the ages of 21 and 30. Dr. Levine said this information can assist clinicians in counseling their patients about the risk for early menopause and planning for alternative reproductive means, such as oocyte or embryo harvesting and preservation.
Neurocognitive functioning after treatment
Dr. Wei Liu of St. Jude Children’s Research Hospital, Memphis, Tenn., studied the neurocognitive function of long-term survivors of ALL.
Dr. Nathan called ALL “the paradigm for how we’ve sort of learned and adjusted how we treat patients based on late effects.” Early on, the disease was treated with craniospinal radiation and intrathecal chemotherapy, and while patients survived, it became obvious that they suffered neurocognitive and endocrine problems, growth abnormalities, and secondary malignancies. These findings forced a reevaluatuon of treatments, leading to elimination of spinal radiation, reduction of cranial radiation dose, intensification of systemic therapy, including methotrexate, and risk stratification allowing modification of therapies.
Survival was sustained, but long-term outcomes were still based on children treated with radiation. So long-term cognitive consequences in the more modern era of therapy were unknown. Only recently have adult cohorts become available who were treated in the chemotherapy-only era.
Dr. Liu studied 159 ALL survivors who had been treated with chemotherapy alone at a mean age of 9.2 years. The follow-up was at a median of 7.6 years off therapy at a mean age of 13.7 years. At the end of the chemotherapy protocol, patients completed tests of sustained attention, and parents rated survivors’ behavior on standard scales.
She found that for these childhood cancer survivors, sustained attention and behavior functioning at the end of chemotherapy predicted long-term attention and processing speed outcomes. Only exposure to chemotherapy, and not end-of-therapy function, predicted that survivors would have poor executive function of fluency and flexibility at long-term follow up.
Dr. Nathan praised the investigators for their foresight to collect data on the methotrexate area under the curve, number of triple intrathecal therapies (cytarabine, methotrexate, and hydrocortisone), and neurocognitive functioning at the end of chemotherapy. “What’s clear is that chemotherapy alone can lead to neurocognitive late effects,” he said. “But what’s also important is that not all late effects can be predicted by end of therapy assessments.” These late effects appear to evolve over time, so ongoing assessments are needed.
Dr. Turcotte, Dr. Liu, Dr. Levine, and Dr. Nathan each reported no financial disclosures.