Karen Wasilewski-Masker

Bone Mineral Density Deficits in Survivors of Childhood Cancer: Long-term Follow-up Guidelines and Review of the Literature

The development of curative therapy for most pediatric malignancies has produced a growing population of childhood cancer survivors who are at increased risk for a variety of health problems resulting from their cancer or its treatment. Because of the fact that many treatment-related sequelae may not become clinically apparent until the survivor attains maturity or begins to age, the ability of primary care providers to anticipate late effects of treatment is essential for providing timely interventions that prevent or correct these sequelae and their adverse effects on quality of life. Altered bone metabolism during treatment for childhood cancer may interfere with attainment of peak bone mass, potentially predisposing to premature onset of and more severe complications related to osteopenia and osteoporosis. Bone mineral deficits have been reported after treatment for a variety of pediatric malignancies and represent morbidity that can be reduced or prevented through lifestyle changes and attention to other common cancer-related sequelae such as hypogonadism. The Childrens Oncology Group long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers provide risk-based surveillance recommendations that are based on expert opinion and review of the scientific literature for potential late effects of pediatric cancer therapy including osteopenia. This review summarizes the existing literature that has defined characteristics of cancer survivors at risk for bone mineral deficits and contributed to the surveillance and counseling recommendations outlined in the Childrens Oncology group long-term follow-up guidelines.

Osteonecrosis in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

PURPOSEnOsteonecrosis (ON) is a potentially serious complication of therapy in survivors of childhood cancer. Our goals were to describe the incidence of ON and identify patient and treatment characteristics associated with elevated risk.nnnPATIENTS AND METHODSnThe rate of self-reported ON was determined for 9,261 patients enrolled onto the Childhood Cancer Survivor Study, a cohort of 5-year survivors of childhood cancer diagnosed from 1970 to 1986, and compared with the rate in a random sample of 2,872 siblings of survivors. Survivors with positive responses were reinterviewed to confirm the diagnosis.nnnRESULTSnFifty-two cancer survivors reported ON in 78 joints, yielding 20-year cumulative incidence of 0.43% and a rate ratio (RR) of 6.2 (95% CI, 2.3 to 17.2) compared with siblings, adjusted for age and sex; 44% developed ON in a previous radiation field. The RR was greatest among survivors of stem-cell transplantation for acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (RR = 26.9, 66.5, and 93.1, respectively). Nontransplantation patients with ALL (RR = 6.5; 95% CI, 2.2 to 19.4), AML (RR = 11.2; 95% CI, 2.1 to 61.2), and bone sarcoma (RR = 7.3; 95% CI, 2.0 to 26.2) were at higher risk for ON. Older age at diagnosis, shorter elapsed time, older treatment era, exposure to dexamethasone (+/- prednisone), and gonadal and nongonadal radiation were independently associated with ON.nnnCONCLUSIONnON among long-term survivors of childhood cancer is rare. However, compared with siblings, childhood cancer survivors have a significantly increased relative rate of ON, particularly those who were older at diagnosis and who received dexamethasone or radiation therapy. Future studies are needed to better delineate our findings, particularly the increased risk after gonadal radiation.

Late Recurrence in Pediatric Cancer: A Report From the Childhood Cancer Survivor Study

BACKGROUNDnAn increasing percentage of childhood cancer patients are surviving their disease, but there is limited research on late recurrence. We sought to estimate late recurrence rates for the most common pediatric cancers and to determine risk factors for late recurrence.nnnMETHODSnThe incidence of late recurrences, or first recurrences that occurred more than 5 years after diagnosis, was analyzed for the most common pediatric cancers using data from the Childhood Cancer Survivor Study, a retrospective cohort of 5-year survivors of childhood and adolescent cancers who were diagnosed between 1970 and 1986. A total of 12,795 survivors with no history of recurrence within 5 years after their original cancer diagnosis were included in the analysis, with a total of 217,127 person-years of follow-up. Cumulative incidence of late recurrence at 5, 10, 15, and 20 years after diagnosis was calculated using death as a competing risk. Adjusted relative rates of late recurrence were obtained using multivariable Poisson regression. All statistical tests were two-sided.nnnRESULTSnOverall, 5-year survivors of pediatric cancers experienced a cumulative incidence of recurrent disease of 4.4%, 5.6%, and 6.2% at 10, 15, and 20 years, respectively. Cumulative incidence varied by diagnosis: Survivors of Ewing sarcoma and astrocytoma had the highest 20-year cumulative incidences at 13.0% (95% confidence interval [CI] = 9.4 to 16.5) and 14.4% (95% CI = 12.3 to 16.6), respectively. In multivariable analysis, the greatest risk factors for late recurrence included diagnosis, combination treatment with chemotherapy and radiation, earlier treatment era, and fewer years since diagnosis (P < .001 for all).nnnCONCLUSIONnLate recurrence is a risk for some pediatric cancers. By understanding diagnosis-specific risks, patients, families, and their medical providers can be better informed of the probability of cure.

Prevalence and Predictors of Sperm Banking in Adolescents Newly Diagnosed With Cancer: Examination of Adolescent, Parent, and Provider Factors Influencing Fertility Preservation Outcomes

Purpose To estimate the prevalence of sperm banking among adolescent males newly diagnosed with cancer and to identify factors associated with banking outcomes. Patients and Methods A prospective, single-group, observational study design was used to test the contribution of sociodemographic, medical, psychological/health belief, communication, and developmental factors to fertility preservation outcomes. At-risk adolescent males (N = 146; age 13.00 to 21.99 years; Tanner stage ≥ 3), their parents, and medical providers from eight leading pediatric oncology centers across the United States and Canada completed self-report questionnaires within 1 week of treatment initiation. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs for specified banking outcomes (collection attempt v no attempt and successful completion of banking v no banking). Results Among adolescents (mean age, 16.49 years; standard deviation, 2.02 years), 53.4% (78 of 146) made a collection attempt, with 43.8% (64 of 146) successfully banking sperm (82.1% of attempters). The overall attempt model revealed adolescent consultation with a fertility specialist (OR, 29.96; 95% CI, 2.48 to 361.41; P = .007), parent recommendation to bank (OR, 12.30; 95% CI, 2.01 to 75.94; P = .007), and higher Tanner stage (OR, 5.42; 95% CI, 1.75 to 16.78; P = .003) were associated with an increased likelihood of a collection attempt. Adolescent history of masturbation (OR, 5.99; 95% CI, 1.25 to 28.50; P = .025), banking self-efficacy (OR, 1.23; 95% CI, 1.05 to 1.45; P = .012), and parent (OR, 4.62; 95% CI, 1.46 to 14.73; P = .010) or medical team (OR, 4.26; 95% CI, 1.45 to 12.43; P = .008) recommendation to bank were associated with increased likelihood of sperm banking completion. Conclusion Although findings suggest that banking is underutilized, modifiable adolescent, parent, and provider factors associated with banking outcomes were identified and should be targeted in future intervention efforts.

Human Papillomavirus Vaccination Rates in Young Cancer Survivors

Purpose Cancer survivors are at high risk for human papillomavirus (HPV)-related morbidities; we estimated the prevalence of HPV vaccine initiation in cancer survivors versus the US population and examined predictors of noninitiation. Methods Participants included 982 cancer survivors (9 to 26 years of age; 1 to 5 years postcompletion of therapy); we assessed HPV vaccine initiation, sociodemographic and clinical characteristics, and vaccine-specific health beliefs; age-, sex-, and year-matched US population comparisons were from the National Immunization Survey-Teen and the National Health Interview Survey (2012-2015). Results The mean age at the time of the study was 16.3 ± 4.7 years; the mean time off therapy was 2.7 ± 1.2 years; participants were 55% male and 66% non-Hispanic white; 59% had leukemia/lymphoma. Vaccine initiation rates were significantly lower in cancer survivors versus the general population (23.8%; 95% CI, 20.6% to 27.0% v 40.5%; 95% CI, 40.2% to 40.7%; P < .001); survivors were more likely to be HPV vaccine-naïve than general population peers (odds ratio [OR], 1.72; 95% CI, 1.41 to 2.09; P < .001). Initiation in adolescent survivors (ages 13 to 17 years) was 22.0% (95% CI, 17.3% to 26.7%), significantly lower than population peers (42.5%; 95% CI, 42.2% to 42.8%; P < .001). Initiation in young adult survivors and peers (ages 18 to 26 years) was comparably low (25.3%; 95% CI, 20.9% to 29.7% v 24.2%; 95% CI, 23.6% to 24.9%). Predictors of noninitiation included lack of provider recommendation (OR, 10.8; 95% CI, 6.5 to 18.0; P < .001), survivors perceived lack of insurance coverage for HPV vaccine (OR, 6.6; 95% CI, 3.9 to 11.0; P < .001), male sex (OR, 2.9; 95% CI, 1.7 to 4.8; P < .001), endorsement of vaccine-related barriers (OR, 2.7; 95% CI, 1.6 to 4.6; P < .001), and younger age (9 to 12 years; OR, 3.7; 95% CI, 1.8-7.6; P < .001; comparison, 13 to 17 years). Conclusion HPV vaccine initiation rates in cancer survivors are low. Lack of provider recommendation and barriers to vaccine receipt should be targeted in vaccine promotion efforts.

Low Anti-Müllerian Hormone in Pediatric Cancer Survivors in the Early Years after Gonadotoxic Therapy.

STUDY OBJECTIVEnTo obtain anti-Müllerian hormone (AMH) levels in female childhood cancer survivors and determine the association of therapeutic exposures with diminished ovarian reserve (DOR).nnnDESIGNnCross-sectional study.nnnSETTINGnAcademic medical center.nnnPARTICIPANTSnForty-nine survivors (mean agexa0=xa014.9xa0years, SDxa0=xa03.3xa0years; mean time without therapyxa0=xa07.5xa0years, SDxa0=xa03.6xa0years) who received alkylator/heavy metal chemotherapy, and/or radiation exposure to the ovaries with 2 or more years without therapy were recruited.nnnINTERVENTIONSnNone.nnnMAIN OUTCOME MEASURESnAMH, follicle stimulating hormone (FSH) levels (random), and therapeutic characteristics such as cyclophosphamide equivalent dose (CED), heavy metal exposure, and bilateral ovarian radiation exposure were determined for each subject. DOR was defined as a low AMH (less than the fifth percentile for age-matched controls), and premature ovarian insufficiency as an FSH greater than 40 IU/L with AMH less than the fifth percentile.nnnRESULTSnFourteen subjects (28.6%) had DOR, and 5 (10.2%) had premature ovarian insufficiency. Those with a low AMH were more likely exposed to a higher CED (Pxa0=xa0.001) and/or bilateral ovarian radiation exposure (Pxa0=xa0.048). In the multivariate model of DOR adjusted for age at diagnosis, DOR was associated with bilateral radiation (odds ratioxa0=xa039.9; 95% confidence interval 2.1-759.7; Pxa0=xa0.04). There was a nonsignificant trend with increasing odds of low AMH with increased CED.nnnCONCLUSIONnDOR, defined by an AMH less than the fifth percentile, was observed in more than one-quarter of pediatric cancer survivors exposed to gonadotoxic cancer therapy and was significantly associated with bilateral ovarian irradiation. Identifying risk factors for low AMH prompts AMH and FSH surveillance in the early years after cancer therapy and, if needed, early referral to a reproductive specialist.