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Background: The likelihood of pregnancy and risk of obstetrical or perinatal complications is inadequately documented in female survivors of pediatric cancer.Methods: We assembled a population-based cohort of female survivors of cancer diagnosed at age 21 years and younger in Ontario, Canada, between 1985 and 2012. Survivors were matched 1:5 to women without prior cancer. Multivariable Cox proportional hazards and modified Poisson models assessed the likelihood of a recognized pregnancy and perinatal and maternal complications.Results: A total of 4062 survivors were matched to 20 308 comparisons. Median (interquartile range) age was 11 (4-15) years at cancer diagnosis and 25 (19-31) years at follow-up. By age 30 years, the cumulative incidence of achieving a recognized pregnancy was 22.3% (95% confidence interval [CI] = 20.7% to 23.9%) among survivors vs 26.6% (95% CI = 25.6% to 27.3%) among comparisons (hazard ratio = 0.80, 95% CI = 0.75 to 0.86). A lower likelihood of pregnancy was associated with a brain tumor, alkylator chemotherapy, cranial radiation, and hematopoietic stem cell transplantation. Pregnant survivors were as likely as cancer-free women to carry a pregnancy >20 weeks (relative risk [RR] = 1.01, 95% CI = 0.98 to 1.04). Survivors had a higher relative risk of severe maternal morbidity (RR = 2.31, 95% CI = 1.59 to 3.37), cardiac morbidity (RR = 4.18, 95% CI = 1.89 to 9.24), and preterm birth (RR = 1.57, 95% CI = 1.29 to 1.92). Preterm birth was more likely in survivors treated with hematopoietic stem cell transplantation (allogenic: RR = 8.37, 95% CI = 4.83 to 14.48; autologous: RR = 3.72, 95% CI = 1.66 to 8.35).Conclusions: Survivors of childhood or adolescent cancer are less likely to achieve a pregnancy and, once pregnant, are at higher risk for severe maternal morbidity and preterm birth. [ABSTRACT FROM AUTHOR]

Background: Anthracycline-induced cardiac toxicity is a cause of significant morbidity and early mortality in survivors of childhood cancer. Current strategies for predicting which children are at greatest risk for toxicity are imperfect and diagnosis of cardiac injury is usually made relatively late in the natural history of the disease. This study aims to identify genomic, biomarker and imaging parameters that can be used as predictors of risk or aid in the early diagnosis of cardiotoxicity.Methods: This is a prospective longitudinal cohort study that recruited two cohorts of pediatric cancer patients at six participating centres: (1) an Acute Cohort of children newly diagnosed with cancer prior to starting anthracycline therapy (n = 307); and (2) a Survivor Cohort of long-term survivors of childhood cancer with past exposure to anthracycline (n = 818). The study team consists of three collaborative cores. The Genomics Core is identifying genomic variations in anthracycline metabolism and in myocardial response to injury that predispose children to treatment-related cardiac toxicity. The Biomarker Core is identifying existing and novel biomarkers that allow for early diagnosis and prognosis of anthracycline-induced cardiac toxicity. The Imaging Core is identifying echocardiographic and cardiac magnetic resonance (CMR) imaging parameters that correspond to early signs of cardiac dysfunction and remodeling and precede global dysfunction and clinical symptoms. The data generated by the cores will be combined to create an integrated risk-prediction model aimed at more accurate identification of children who are most susceptible to anthracycline toxicity.Discussion: We aim to identify genomic risk factors that predict risk for anthracycline cardiotoxicity pre-exposure and imaging and biomarkers that facilitate early diagnosis of cardiac injury. This will facilitate a personalized approach to identifying at-risk children with cancer who may benefit from cardio- protective strategies during therapy, and closer surveillance and earlier initiation of medications to preserve heart function after cancer therapy.Trial Registration: NCT01805778 . Registered 28 February 2013; retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Several randomized controlled trials (RCTs) have demonstrated that dexrazoxane reduces anthracycline cardiotoxicity in adults, but use in children has been hindered by lack of direct evidence of cardioprotection and concerns regarding second malignant neoplasms (SMNs). This study aimed to systematically review the evidence regarding dexrazoxane in children.Methods: We searched Medline, Embase, the Cochrane Library, and abstracts for RCTs and nonrandomized studies (NRSs) that compared dexrazoxane to no cardioprotection among children. We combined findings using random-effects models. All statistical tests were two-sided.Results: Eleven eligible publications reported results from five RCTs (1254 patients), and 15 publications reported results from 12 NRSs (3385 patients). Dexrazoxane did not impact clinical cardiotoxicity in RCTs because of a low cardiotoxic event rate (three events among all patients) but was associated with a reduction in subclinical cardiotoxicity. Among NRSs, dexrazoxane was associated with a reduction in clinical cardiotoxicity (relative risk (RR) = 0.29, P = .001) and clinical+subclinical cardiotoxicity (RR = 0.43, P < .001). Among RCTs, 17 of 635 (2.7%) patients treated with dexrazoxane developed an SMN compared with seven of 619 (1.1%) who did not receive dexrazoxane (RR = 2.37, P = .06). Two RCTs that used concurrent etoposide reported an increased risk of acute myeloid leukemia, while one that used cranial radiation reported an increased risk of brain tumors. Event-free survival did not differ (P = .91).Conclusion: Dexrazoxane is associated with a statistically significant risk reduction for most cardiotoxic outcomes. Dexrazoxane is associated with a statistically borderline increase in SMNs, possibly because of an interaction with concurrent cancer therapies. The decision to use dexrazoxane in children should balance the risks of cardiotoxicity and SMNs specific to each treatment protocol. [ABSTRACT FROM AUTHOR]

Simple Summary: It is unclear what the risk of negative health outcomes is after cancer during adolescence and young adulthood. We conducted a review to understand the risk of second cancers, chronic conditions, and death in adolescent and young adult (AYA) cancer survivors and found factors that increase the risk. In total, 652 studies were identified, of which 106 were included in the review: 23 for second cancers, 34 for chronic conditions, and 54 for deaths. The number of included studies increased over time, from four studies in 2010 to 17 in 2020. The studies found that AYA cancer survivors are at an increased risk of second cancers, chronic conditions, and deaths. In particular, the following factors increased risk: radiation exposure for second cancers; younger attained age and earlier calendar period of diagnosis for chronic conditions; and non-Hispanic Black or Hispanic, low socioeconomic status, and earlier calendar period of diagnosis for deaths. Risk factors associated with late effects in survivors of adolescent and young adult (AYA) cancer are poorly understood. We conducted a systematic scoping review to identify cohort studies published in English from 2010–2020 that included: (1) cancer survivors who were AYAs (age 15–39 years) at diagnosis and (2) outcomes of subsequent malignant neoplasms (SMNs), chronic conditions, and/or late mortality (>5 years postdiagnosis). There were 652 abstracts identified and, ultimately, 106 unique studies were included, of which 23, 34, and 54 studies related to the risk of SMNs, chronic conditions, and mortality, respectively. Studies investigating late effects among survivors of any primary cancer reported that AYA cancer survivors were at higher risk of SMN, chronic conditions, and all-cause mortality compared to controls. There was an indication that the following factors increased risk: radiation exposure (n = 3) for SMNs; younger attained age (n = 4) and earlier calendar period of diagnosis (n = 3) for chronic conditions; and non-Hispanic Black or Hispanic (n = 5), low socioeconomic status (n = 3), and earlier calendar period of diagnosis (n = 4) for late mortality. More studies including the full AYA age spectrum, treatment data, and results stratified by age, sex, and cancer type are needed to advance knowledge about late effects in AYA cancer survivors. [ABSTRACT FROM AUTHOR]