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A cancer diagnosis during adolescence or young adulthood can have a negative impact on long-term physical and mental health. However, little is known about the financial outcomes for survivors of adolescent and young adult (AYA) cancers. A recent study in the Netherlands found that AYA cancer survivors experienced an average decrease of 8.5% in their annual earnings and a decrease in employment levels after diagnosis compared to a control group. The study also highlighted the potential economic consequences for family members who provide informal care and the broader impact on household financial security. While these findings may not be directly applicable to countries like the United States, where access to healthcare and worker protections are different, it is likely that young adult cancer survivors in the US face greater economic challenges. The oncology community is working to identify interventions to reduce the financial burden on AYA cancer survivors, including assessing financial hardship throughout the cancer journey, implementing screening tools, providing financial navigators, and advocating for improved access to affordable cancer care and social safety nets. [Extracted from the article]

Health care systems and providers have a responsibility to ensure that access to cancer clinical trials, opportunities to complete the trial, and access to lifelong survivor care are all thoughtfully examined with an equity lens. This will allow the greatest possible number of pediatric and adolescent and young adult cancer patients to receive the highest quality of care possible, in treatment and beyond. [ABSTRACT FROM AUTHOR]

Cancer treatment exposures and outcomes can often be identified in administrative claims and electronic health record data ([[6], [8]]). Limited availability of data to inform the generation of robust treatment-specific risk estimates for perinatal and maternal outcomes during cancer therapy has been a long-standing barrier to providing accurate risk counseling to inform decision making. [Extracted from the article]

Purpose: Use of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in patients unable to swallow capsules is hindered by the lack of a commercially available oral liquid formulation in many jurisdictions. A stable oral suspension can be extemporaneously prepared using commercially available capsules. We aimed to determine the bioavailability of this aprepitant suspension relative to the capsule. Methods: This two-period crossover study enrolled 17 healthy adult volunteers. Volunteers received a single 125 mg aprepitant dose during each study period. Order of formulation presentation (capsule vs suspension first) was randomized. Thirteen blood samples were collected over a 48-h period. Aprepitant plasma concentrations were determined using liquid chromatography-mass spectroscopy. Relative bioavailability was defined as the geometric least squares mean ratio for area under the concentration versus time curve (AUC) from time zero to infinity of the aprepitant suspension versus the capsule. Bioequivalence, defined as per Health Canada guidelines, was assessed as a secondary aim. Results: Relative bioavailability of the aprepitant suspension was 82.3% (90% CI: 69.09-98.00%). Bioequivalence was not established: geometric least squares mean ratios (suspension/capsule) for AUC time zero to 48 h and maximum concentration were 87.8% (90% CI: 75.48–102.16%) and 86.1% (90% CI: 75.59–98.16%), respectively. No serious adverse events were observed. Conclusions: With a relative bioavailability of 82.3%, the extemporaneous aprepitant oral suspension was well-absorbed relative to the capsule. Though not bioequivalent to the oral capsule, the clinical use of this aprepitant oral suspension in adult and pediatric patients unable to swallow capsules is likely to be effective and safe. [ABSTRACT FROM AUTHOR]

Background: Adolescents with cancer can receive care in pediatric or adult institutions. Survival often differs by locus, but little is known about relative health care utilization and costs. We estimated these in a population-based cohort of adolescents.Methods: All Ontario adolescents (15.0-17.9 years) diagnosed with cancer between 1995 and 2010 were identified from provincial cancer registries. We compared health care resource utilization (hospitalizations, emergency department visits, same-day surgeries, outpatient chemotherapy, radiation, diagnostic/laboratory tests, physician services, home care) and costs (2012 Canadian dollars) during four discrete care phases-prediagnosis (60 days), initial (360 days), continuing (variable), and terminal (360 days)-between adolescents treated in pediatric vs adult institutions, for the whole cohort and within seven diagnostic categories. All statistical tests were two-sided.Results: Of 1356 eligible adolescents, 691 and 665 were treated in adult and pediatric institutions, respectively. Hospitalization rates were higher in pediatric institutions during prediagnosis (14.9% vs 6.9%, P < .001), initial (95.1% vs 73.3%, P < .001), and continuing phases (43.2% vs 34.4%, P = .002), but similar (96.1% vs 96.3%, P = .93) during the terminal phase. Average length of stay was higher at pediatric institutions within most diagnoses and phases. For all diagnoses, median initial phase costs were higher in pediatric than adult institutions (eg, leukemia: $153 926 vs $102 418 per 360 days, P < .001; lymphoma: $65 025 vs $19 846, P < .001, respectively).Conclusions: The costs of caring for adolescents with the same malignancy are considerably higher in pediatric than adult institutions during most phases. Resource utilization, particularly hospitalization, drives much of the cost difference, making these data applicable to other jurisdictions. [ABSTRACT FROM AUTHOR]

The purpose was to describe the incidence and risk factors of congestive heart failure (CHF) among children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). We included 2053 children (≤18 years) with first primary ALL and AML diagnosed 1992-2010 and registered in the Pediatric Oncology Group of Ontario Networked Information System. We identified CHF events through linked administrative databases. At 10 years, the cumulative incidence of CHF was 1.7% in ALL and 7.5% in AML. Factors associated with CHF in ALL were female gender, age <1 year at cancer diagnosis, irradiation and cumulative anthracycline dose ≥250 mg/m2. Irradiation was the only risk factor in AML patients. Of the 23 patients with CHF during active therapy, one developed CHF following treatment completion. Incidence of CHF were 1.7% in ALL and 7.5% in AML. Most with CHF during active therapy did not develop CHF after treatment completion. [ABSTRACT FROM AUTHOR]

Background: The elevated risk for physical late effects in childhood cancer survivors (CCS) is well documented, but their risk for mental health problems is less well described.Methods: The authors assembled a cohort of all 5-year CCS who were diagnosed before age 18 years and treated in an Ontario pediatric cancer center between 1987 and 2008. Patients were matched to population controls and linked to health administration databases. The authors calculated rates of mental health care visits (family physician, psychiatrist, emergency department, hospitalization) and the risk for a severe mental health event (emergency department, hospitalization, suicide). Outcomes were compared using recurrent event and survival analyses.Results: Compared with 20,269 controls, 4117 CCS had a higher rate of mental health visits (adjusted relative rate [RR], 1.34; 95% confidence interval [CI], 1.12-1.52). Higher rates were associated with female gender (RR, 1.39; CI, 1.10-1.75; P = .006) and being diagnosed at ages 15 to 17.9 years (compared with ages 0-4 years: RR, 1.81; 95% CI, 1.17-2.80; P = .008). Cancer type, treatment intensity, and treatments targeting the central nervous system were not significant predictors. Survivors were at increased risk for a severe event compared with controls (adjusted hazard ratio, 1.13; 95% CI, 1.00-1.28; P = .045). CCS who were diagnosed with cancer at age 4 years or younger were at greatest risk: 16.3% (95% CI, 13.2%-19.8%) had experienced a severe event by age 28 years.Conclusions: CCS experienced higher rates of mental health visits and a greater risk for a severe event than the general population. Survivors of adolescent cancer have a higher rate of mental health visits overall, whereas survivors of cancer before age 4 years have a markedly elevated risk of severe events. Cancer 2018;124:2045-57. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Symptom burden in adolescents and young adults (AYA) with cancer is poorly characterized but impacts quality of life. Methods: All Ontario, Canada AYA aged 15-29 years at diagnosis between 2010 and 2018 were linked to population-based healthcare databases, including to Edmonton Symptom Assessment System-revised (ESAS) scores, an 11-point scale routinely obtained at the time of cancer-related outpatient visits and collected provincially. Multistate models estimated mean duration of symptom severity states [none (0) vs. mild (1 vs. 2 vs. 3) vs. moderate (4-6) vs. severe (7-10)], trajectories, and subsequent mortality risk. Variables associated with severe symptoms were also determined. Results: In total, 4296 AYA with =1 ESAS score within a year of diagnosis were included (median age 25 years). Prevalent moderate/severe symptoms included fatigue (59% of AYA) and anxiety (44%). Across symptom type, AYA reporting moderate symptoms were likelier to subsequently experience improvement versus worsening. Risk of death within 6 months increased with increasing symptom burden and was highest in AYA with severe dyspnea (9.0%), pain (8.0%), or drowsiness (7.5%). AYA in the poorest urban neighborhoods were more likely to experience severe symptoms than in the wealthiest areas, with twice the odds of reporting severe depression [adjusted odds ratio (OR) 1.95, 95th confidence interval (95% CI) 1.37-2.78], pain (OR: 1.94, 95% CI: 1.39-2.70), and dyspnea (OR: 1.96, 95% CI: 1.27-3.02). Conclusions: AYA with cancer experience substantial symptom burden. Risk of death increased with symptom severity. Interventions targeting cancer fatigue and anxiety, and targeting AYA in lower-income neighborhoods, are likely to improve quality of life in this population. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To identify and appraise current evidence related to the effectiveness of psychological and physical (nonpharmacologic) pain management modalities for children and young adults with cancer. Data Sources: Electronic searches in MEDLINE®, EMBASE, CINAHL®, PsycINFO, and Web of ScienceTM (from database inception to June 2013) for clinical trials. Data Synthesis: A total of 32 unique studies were identified. Substantial heterogeneity existed across identified studies, precluding meta-analysis. Therefore, a narrative review of included studies is presented. Studies featured psychological and/or physical pain interventions for children and young adults (N = 1,171) aged 1-21 years with a variety of cancer diagnoses. Interventions included aromatherapy, art therapy, distraction, hypnosis, physical activity, physical positioning, touch therapy, and multimodal cognitive-behavior therapy. Twenty-two studies (69%) reported success in preventing or reducing pain intensity. The level of evidence and methodologic quality of studies were generally low. Conclusions: Current nonpharmacologic pain interventions for pediatric and young adult patients with cancer are diverse. Several modalities significantly decreased pain intensity, suggesting that these strategies may be effective methods of pain treatment, particularly in the case of painful medical procedures. Future well-designed, multicenter, randomized, controlled trials are needed to further discern treatment effects on pain and other health outcomes in this population and to compare the relative effectiveness of different modalities. Implications for Nursing: Nurses play a key role in pain assessment and management in pediatric and young adult patients with cancer. The studies included in this review constitute the beginnings of an evidence base that supports the need to implement psychological and physical interventions to improve pain outcomes in pediatric and young adult patients with cancer. [ABSTRACT FROM AUTHOR]

The majority of children, adolescents, and young adults diagnosed with cancer will become long-term survivors with many potential years of life ahead of them. Their journey from health through diagnosis and treatment to survivorship involves multiple transitions. Transitional services that should be available throughout this journey include health-related education, health surveillance and screening, management of cancer-related complications, and psychosocial support relevant to their developmental needs. Survivors require lifelong care that focuses not only on the medical risks arising from their cancer therapy, but also the psychosocial, educational, and vocational implications of surviving cancer. Because many community health care providers lack familiarity with the health risks associated with childhood or adolescent/young adult cancer, survivors must have sufficient health knowledge to advocate for risk-based cancer-related follow-up; the provision of a treatment summary and care plan at the conclusion of their cancer therapy is an important tool for facilitating this process. The availability of resources for survivors varies by geography, health care system, and survivor characteristics. Adolescents and young adults who receive their care outside of a pediatric cancer center have particularly limited access. The limitations in cancer center resources (along with survivor preference) strongly suggest that the long-term care of survivors will need to be shared between the cancer centers and primary care providers in survivors' communities. Cancer 2011;117(10 suppl):2335-41. © 2011 American Cancer Society. Survivors of cancer in childhood, adolescence, or young adult life require lifelong care that focuses not only on the medical risks that arise from their cancer therapy but also on the psychosocial, educational, and vocational implications of surviving cancer. Limitations in cancer center resources (along with survivor preference) strongly suggest that this care will need to be shared between cancer centers and primary care providers in survivors' communities. [ABSTRACT FROM AUTHOR]

Existing guidelines for the prevention of antineoplastic chemotherapy-induced nausea and vomiting (CINV) in children are constrained by the lack of robust evidence. Current guidelines recommend the use of a serotonin 5-HT3 receptor antagonist plus a corticosteroid to prevent acute CINV. Consequently, antiemetic agents that are recommended for use in adult cancer patients do not appear in the current pediatric guidelines. In addition, there is no information to guide the selection of alternative antiemetic agents for children who either cannot receive the recommended agents or who do not respond adequately to the treatment. Possible barriers to adherence to the pediatric antiemetic selection guidelines that are currently available are discussed, and published pediatric experience with antiemetic agents recommended in the current adult antiemetic selection guidelines (dolasetron, tropisetron, palonosetron, aprepitant) is summarized in this review. The use of novel and emerging antiemetic therapeutic interventions {metopimazine, diphenhydramine (Benadryl®)-lorazepam (Avitan®)-dexamethasone (Decadron®) [BAD], nabilone, acupuncture, midazolam, olanzapine, mirtazapine, gabapentin, droperidol} in children are explored. [ABSTRACT FROM AUTHOR]

Background: Benefits of prophylactic hematopoietic colony-stimulating factors (CSFs) in adults and children receiving cancer chemotherapy or undergoing stem-cell transplantation (SCT) are unclear. Purpose: To determine whether prophylactic CSFs decrease mortality, infections, and febrile neutropenia more than does placebo or no therapy in patients with cancer and in patients undergoing SCT. Data Sources: Electronic searches of Ovid MEDLINE and EMBASE from inception until April 2007 and of the Cochrane Central Register of Controlled Trials until the second quarter of 2006. Study Selection: We selected 148 trials that were reported in any language that randomly assigned patients to CSFs or to either placebo or no therapy. Prophylactic CSFs were given concurrently with or after initiation of chemotherapy. Data Extraction: Two reviewers independently extracted data onto standardized forms. Data Synthesis: Short-term all-cause mortality appeared to be similar between the prophylactic CSF and the control groups (7.6% vs. 8.0%; relative risk, 0.95 [95% CI, 0.84 to 1.08]; absolute risk reduction, 0.4% [CI, -0.5% to 1.4%]). Risks for infection-related death with CSFs and placebo or no therapy were 3.1% and 3.8%, respectively (relative risk, 0.82 [CI, 0.66 to 1.02]; absolute risk reduction, 0.8% [CI, 0.0% to 1.5%]). Use of CSFs reduced the following more than did placebo or no therapy: documented infections (median rate, 38.9% vs. 43.1%; rate ratio, 0.85 [CI, 0.79 to 0.92]), microbiologically documented infections (median rate, 23.5% vs. 28.6%; rate ratio, 0.86 [CI, 0.77 to 0.96]), and episodes of febrile neutropenia (median rate, 25.3% vs. 44.2%; rate ratio, 0.71 [CI, 0.63 to 0.80]). Limitations: Trial designs, including assessments of infections, and participants were heterogeneous. Estimates of mortality effects were imprecise. Conclusions: Prophylactic CSFs may have little or no effect on mortality but do decrease rates of infection in patients receiving cancer chemotherapy or those undergoing SCT. [ABSTRACT FROM AUTHOR]

Between 1977 and 1991, the Children's Cancer Group and the National Cancer Institute conducted three trials of very high-dose methotrexate (33.6 g/m2; VHD-MTX) in place of cranial radiation (CRT) as central nervous system (CNS) preventive therapy, and assessed efficacy, acute toxicity and long-term neurocognitive outcome. CCG-191P compared VHD-MTX to CRT plus intrathecal methotrexate (IT-MTX) in 181 patients and demonstrated equivalent survival. However, patients treated with CRT had poorer performance on neurocognitive testing over time. CCG-134P evaluated the addition of intensified systemic and intrathecal therapy to VHD-MTX in 128 patients with high-risk acute lymphoblastic leukemia (ALL) and demonstrated reduced CNS relapse compared to the CCG-191P trial, but equivalent survival. CCG-144P compared VHD-MTX to IT-MTX alone in 175 patients with average-risk ALL and demonstrated equivalent survival. VHD-MTX was associated with significant toxicities, particularly neutropenia, transient hepatic dysfunction and sepsis. VHD-MTX achieved similar survival to other CNS-directed therapies without the long-term impact on intelligence, but with substantial acute toxicities. [ABSTRACT FROM AUTHOR]

Background: The optimal consolidation therapy for adults who are in first remission of acute myeloid leukemia after induction chemotherapy and who do not have a histocompatible donor is poorly established. We conducted a meta-analysis to compare the efficacy of autologous bone marrow transplantation with that of non-myeloablative chemotherapy alone (or no further treatment).Methods: Eligible studies were identified by searching electronic databases and by examining the reference lists of relevant studies and review articles. Eligible studies were those that prospectively enrolled adults with acute myeloid leukemia and randomly assigned patients who were in first remission and who did not have a matched sibling donor to one of the two consolidation therapies. Two reviewers independently assessed all studies for relevance and validity. We used a fixed-effects model to calculate the ratio of probabilities for disease-free and overall survival at 48 months or at the nearest recorded assessment point for each study and for all studies combined. All statistical tests were two-sided.Results: We identified 587 potentially relevant studies, 36 of which were retrieved for detailed evaluation. In the six studies eligible for this meta-analysis, a total of 1044 patients were randomly assigned to receive autologous bone marrow transplantation or non-myeloablative chemotherapy (five studies) or autologous bone marrow transplantation or no further treatment (one study). Compared with patients who received chemotherapy or no further treatment, patients who received autologous bone marrow transplantation had a better disease-free survival (ratio of disease-free survival probabilities = 1.24, 95% confidence interval [CI] = 1.06 to 1.44; P =.006) but a similar overall survival (ratio of overall survival probabilities = 1.01, 95% CI = 0.89 to 1.15; P =.86).Conclusion: Our results do not support the routine use of autologous bone marrow transplantation in adult acute myeloid leukemia patients in first remission. [ABSTRACT FROM AUTHOR]

The current standard of care with respect to preventing acute chemotherapy-induced nausea and vomiting (CINV) in children includes the administration of a 5-HT3 antagonist with or without a corticosteroid, depending on the emetogenicity of the chemotherapy to be given. Problems in assessing the emetogenicity of chemotherapy regimens and nausea severity in children may influence the degree of success of CINV prophylaxis. Nevertheless, the majority of children who receive chemotherapy today experience moderate to complete control of acute CINV when given appropriate antiemetic prophylaxis. If children vomit or experience nausea despite appropriate prophylaxis, then measures must be taken to treat these symptoms since these children are likely to go on to experience delayed or anticipatory CINV. However, appropriate selection of interventions to treat acute CINV in children is limited by the lack of rigorous evidence to support one approach over another. Lorazepam is suggested as an immediate agent for the treatment of acute CINV. Doses and frequencies of the 5-HT3 antagonist and corticosteroid administered for initial prophylaxis should also be maximized. Further treatment must be tailored to the circumstances and preferences of each child and family. Options include crossover to another 5-HT3 antagonist, or administration of an adjunctive antiemetic such as metopimazine, low dose metoclopramide, domperidone, alizapride, nabilone, scopolamine, prochlorperazine, or chlorpromazine. Complementary interventions such as acupuncture, hypnosis, counseling, or ginger may also be of benefit. Further study is required to establish optimal antiemetic strategies in children. [ABSTRACT FROM AUTHOR]

Background Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described. Methods Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings. Results Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1]). Conclusion Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes. [ABSTRACT FROM AUTHOR]

To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions. Retrospective cohort study. US administrative database. We identified incident breast, colorectal, and ovarian cancer cases in females aged 15–39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer. Platinum-based chemotherapy. We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries). There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42–0.82) and 0.70 (95% CI 0.51–0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97–1.15) and 1.42 (95% CI 1.31–1.53), respectively. Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors are at increased risk of late mortality (death =5 years after diagnosis) from cancer recurrence and treatment-related late effects. The authors conducted a systematic review and meta-analysis to provide comprehensive estimates of late mortality risk among survivors internationally and to investigate differences in risk across world regions. Methods: Health sciences databases were searched for cohort studies comprised of 5-year childhood cancer survivors in which the risk of mortality was evaluated across multiple cancer types. Eligible studies assessed all-cause mortality risk in survivors relative to the general population using the standardized mortality ratio (SMR). The absolute excess risk (AER) was assessed as a secondary measure to examine excess deaths. Cause-specific mortality risk was also assessed, if reported. SMRs from nonoverlapping cohorts were combined in subgroup meta-analysis, and the effect of world region was tested in univariate meta-regression. Results: Nineteen studies were included, and cohort sizes ranged from 314 to 77,423 survivors. Throughout survivorship, SMRs for all-cause mortality generally declined, whereas AERs increased after 15-20 years from diagnosis in several cohorts. All-cause SMRs were significantly lower overall in North American studies than in European studies (relative SMR, 0.63; 95% confidence interval, 0.49-0.80). SMRs for subsequent malignant neoplasms and for cardiovascular, respiratory, and external causes did not vary significantly between world regions. Conclusions: The current findings suggest that late mortality risk may differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity. Reasons for regional differences remain unclear but may be better elucidated through future analyses of individual-level data. [ABSTRACT FROM AUTHOR]

Background: Siblings of children with cancer may experience adverse household economic consequences, but their financial outcomes in adulthood are unknown. Methods: A total of 880 siblings (aged 18–64 years) of adult‐aged childhood cancer survivors were surveyed to estimate the prevalence of financial hardship by three established domains (behavioral, material, and psychological). For individual financial hardship items matching the contemporaneous National Health Interview Survey or Behavioral Risk Factor Surveillance System, siblings were compared with the general population by calculating adjusted prevalence odds ratios (ORs) to sample‐weighted responses. Multivariable logistic regression models examined associations between sibling characteristics and each hardship domain and between sibling hardship and survivors' cancer/treatment characteristics. Results: Behavioral, material, and psychological hardship was reported by 24%, 35%, and 28%, respectively. Compared with national survey respondents, siblings were more likely to report worries about medical bills (OR, 1.14; 95% confidence interval [CI], 1.06–1.22), difficulty affording nutritious foods (OR, 1.79; 95% CI, 1.54–2.07), and forgoing needed medical care (OR, 1.38; 95% CI, 1.10–1.73), prescription medications (OR, 2.52; 95% CI, 1.99–3.20), and dental care (OR, 1.34; 95% CI, 1.15–1.57) because of cost. Sibling characteristics associated with reporting financial hardship in one or more domains included female sex, older age, chronic health conditions, lower income, not having health insurance, high out‐of‐pocket medical expenditures, and nonmedical/nonhome debt. No survivor cancer/treatment characteristics were associated with sibling financial hardship. Conclusions: Adult siblings of childhood cancer survivors were more likely to experience financial hardship compared with the general population. Childhood cancer may adversely affect entire households, with potentially lasting implications. Adult siblings of long‐term childhood cancer survivors may experience greater aspects of financial hardship compared with the general population. A childhood cancer diagnosis and treatment may adversely affect entire households, with potentially lasting implications. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to establish content validity and assess the psychometric properties of the FACE-Q Craniofacial Module, a patient-reported outcome measure, for use in pediatric and adolescent patients with head and neck cancer (HNC). Methods: To establish content validity (Part 1), between June 2017 and August 2019, cognitive interviews were conducted with survivors of pediatric HNC (n = 15), and input was obtained from clinical experts (n = 21). To examine item and scale performance (Part 2), Rasch Measurement Theory (RMT) analysis was performed using data from two international studies (n = 121). Results: Part 1: Qualitative data from 15 survivors and input from 21 experts provided evidence to support the use of the FACE-Q Craniofacial Module in pediatric HNC. Part 2: The field-test study sample included 121 survivors of pediatric HNC. RMT analysis provided evidence of reliability and validity for 10 FACE-Q scales. Data for each scale fit the RMT model. Scale reliability was high, with Person Separation Index and Cronbach's alpha values ≥0.82 for 9 scales. Mean scores on the Appearance, Psychological, and Social scales were higher for those who liked aspects of their face more. For participants with (vs. without) a facial difference, mean scores were lower for the Face, Jaws, Psychological, and Social scales. Conclusion: The FACE-Q Craniofacial Module evidenced reliability and validity for HNC survivors aged 8–29 years and can be used in research and clinical care to measure quality of life of pediatric survivors with HNC. [ABSTRACT FROM AUTHOR]

Background: Adult survivors of childhood cancer are at elevated risk of morbidity and mortality compared to the general population, but their adherence to lifelong periodic surveillance is suboptimal. We aimed to examine adherence to surveillance guidelines for high-yield tests and identify risk factors for nonadherence in adult survivors of childhood cancer. Methods: In this retrospective, population-based cohort study, we used health care administrative data from Ontario, Canada, to identify adult survivors of childhood cancer diagnosed between 1986 and 2014 who were at elevated risk of therapy-related colorectal cancer, breast cancer, or cardiomyopathy. Using a Poisson regression framework, we assessed longitudinal adherence and predictors of adherence to the Children's Oncology Group surveillance guideline. Results: Among 3241 survivors, 327 (10%), 234 (7%), and 3205 (99%) were at elevated risk for colorectal cancer, breast cancer, and cardiomyopathy, respectively. Within these cohorts, only 13%, 6%, and 53% were adherent to recommended surveillance as of February 2020. During a median follow-up of 7.8 years, the proportion of time spent adherent was 14% among survivors at elevated risk for colorectal cancer, 10% for breast cancer, and 43% for cardiomyopathy. Significant predictors of adherence varied across the risk groups, but higher comorbidity was associated with adherence to recommended surveillance. Interpretation: Survivors of childhood cancer in Ontario are rarely up to date for recommended surveillance tests. Tailored interventions beyond specialized clinics are needed to improve surveillance adherence. [ABSTRACT FROM AUTHOR]

Objective: Complementary Health Approaches (CHA) are commonly used by children with cancer; however, a few health care providers (HCPs) inquire about the use of CHA. A standardized questionnaire could facilitate such clinical discussions. We aimed to adapt and determine the face and content validity of the "Which Health Approaches and Treatments are you using?" (WHAT) child and parent-report questionnaires in pediatric oncology. Methods: An electronic Delphi survey that included children with cancer (8–18 years), parents, and HCPs and CHA researchers was conducted to reach consensus on the content of the WHAT questionnaires in pediatric oncology. Children and parents from the Hospital for Sick Children (SickKids), and HCPs and researchers from the International Society of Pediatric Oncology and Pediatric Complementary and Alternative Medicine Research and Education Network completed the survey. To determine the face and content validity of the questionnaires, two iterative cycles of individual interviews were conducted with purposive samples of children (8–18 years), parents, and HCPs from SickKids. Results: Consensus was reached on all domains and items of the original WHAT questionnaires after one Delphi cycle (n = 61). For face and content validity testing, the first cycle of interviews (n = 19) revealed that the questionnaires were mostly comprehensive and relevant. However, the paper-based format of the original WHAT was not user-friendly, and generic items were vague and not aimed at facilitating clinical dialogues about CHA use. The WHAT questionnaires were then modified into electronic cancer-specific self- and proxy-report questionnaires including 13 and 15 items, respectively. The second cycle (n = 21) showed no need for further changes. Conclusions: The modified electronic cancer-specific WHAT questionnaires showed adequate face and content validity. The next step is to determine inter-rater reliability, construct validity, and feasibility of administration of the modified WHAT questionnaires in pediatric oncology. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time. Methods: This is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP's impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants' consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later. The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed. Discussion: The results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population. Trial registration: ClinicalTrials.gov NCT05832138. [ABSTRACT FROM AUTHOR]

Background: A previous multicenter study showed that longitudinal changes in standard cardiac functional parameters were associated with the development of cardiomyopathy in childhood cancer survivors (CCS). Evaluation of the relationship between global longitudinal strain (GLS) changes and cardiomyopathy risk was limited, largely due to lack of quality apical 2‐ and 3‐chamber views in addition to 4‐chamber view. We sought to determine whether apical 4‐chamber longitudinal strain (A4LS) alone can serve as a suitable surrogate for GLS in this population. Methods: A4LS and GLS were measured in echocardiograms with acceptable apical 2‐, 3‐, and 4‐chamber views. Correlation was evaluated using Pearson and Spearman coefficients, and agreement was evaluated with Bland–Altman plots. The ability of A4LS to identify normal and abnormal values compared to GLS as the reference was evaluated. Results: Among a total of 632 reviewed echocardiograms, we identified 130 echocardiograms from 56 patients with adequate views (38% female; mean age at cancer diagnosis 8.3 years; mean follow‐up 9.4 years). Correlation coefficients between A4LS and GLS were.89 (Pearson) and.85 (Spearman), with Bland–Altman plot of GLS—A4LS showing a mean difference of −.71 ± 1.8. Compared with GLS as the gold standard, A4LS had a sensitivity of 86% (95% CI 79%–93%) and specificity of 82% (69%–95%) when using normal range cutoffs and 90% (82%–97%) and 70% (58%–81%) when using ±2 standard deviations. Conclusion: A4LS performs well when compared with GLS in this population. Given the more recent adoption of apical 2‐ and 3‐chamber views in most pediatric echocardiography laboratories, A4LS is a reasonable stand‐alone measurement in retrospective analyses of older study cohorts and echocardiogram biorepositories. [ABSTRACT FROM AUTHOR]

Female survivors of childhood cancer are at risk for primary ovarian insufficiency (POI), defined as the cessation of gonadal function before the age of 40 years. We aimed to develop and validate models to predict age-specific POI risk among long-term survivors of childhood cancer. To develop models to predict age-specific POI risk for the ages of 21–40 years, we used data from the Childhood Cancer Survivor Study (CCSS). Female survivors aged 18 years or older at their latest follow-up, with self-reported menstrual history information and free of subsequent malignant neoplasms within 5 years of diagnosis, were included. We evaluated models that used algorithms based on statistical or machine learning to consider all predictors, including cancer treatments. Cross-validated prediction performance metrics (eg, area under the receiver operating characteristic curve [AUROC]) were compared to select the best-performing models. For external validation of the models, we used data from 5-year survivors in the St Jude Lifetime Cohort (SJLIFE) with ovarian status clinically ascertained using hormone measurements (menopause defined by follicle stimulating hormone >30 mIU/mL and oestradiol <17 pg/mL) and medical chart or questionnaire review. We also evaluated an SJLIFE-based polygenic risk score for POI among 1985 CCSS survivors with genotype data available. 7891 female CCSS survivors (922 with POI) were included in the development of the POI risk prediction model, and 1349 female SJLIFE survivors (101 with POI) were included in the validation study. Median follow-up from cancer diagnosis was 23·7 years (IQR 18·3–30·0) in CCSS and 15·1 years (10·4–22·9) in SJLIFE. Between the ages of 21 and 40 years, POI prevalence increased from 7·9% (95% CI 7·3–8·5) to 18·6% (17·3–20·0) in CCSS and 7·3% (5·8–8·9) to 14·9% (11·6–19·1) in SJLIFE. Age-specific logistic regression models considering ovarian radiation dosimetry or prescribed pelvic and abdominal radiation dose, along with individual chemotherapy predictors, performed well in CCSS. In the SJLIFE validation, the prescribed radiation dose model performed well (AUROC 0·88–0·95), as did a simpler model that considered any exposures to pelvic or abdominal radiotherapy or alkylators (0·82–0·90). Addition of the polygenic risk predictor significantly improved the average positive predictive value (from 0·76 [95% CI 0·63–0·89] to 0·87 [0·80–0·94]; p=0·029) among CCSS survivors treated with ovarian radiation and chemotherapy. POI risk prediction models using treatment information showed robust prediction performance in adult survivors of childhood cancer. Canadian Institutes of Health Research, US National Cancer Institute. [ABSTRACT FROM AUTHOR]

Little is known about infections occurring after childhood cancer treatment. We assessed the risk of severe infection postcancer therapy in survivors of leukemia compared to other cancer types. We performed a population-based cohort study of children <15 years of age diagnosed with cancer (2001–2016), alive and relapse-free 30 days after treatment completion. The risk of severe infection in both groups was estimated using subdistribution proportional hazard regression. We identified 6148 survivors (1960 with leukemia). The cumulative incidence (95% confidence interval) of severe infections at 3 years was 0.70% (0.40–1.2%) in leukemia and 0.51% (0.32–0.79%) in other cancers. The risk of severe infection was not statistically different in leukemia survivors compared to other cancer types in univariate and multivariate analysis (adjusted hazard ratio: 1.40, 95% CI: 0.69–2.85). No significant association was found between a history of leukemia and an increased risk of severe infection after treatment, compared to other cancer types. [ABSTRACT FROM AUTHOR]

Summary: We leveraged population‐based clinical and healthcare data to identify treatment patterns and long‐term outcomes among adolescents and young adults (AYA) with nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL). All Ontario, Canada, AYA aged 15–21 years at diagnosis with NLPHL between 1992 and 2012 were identified, and their detailed clinical data were collected. Linkage to healthcare databases identified additional events (subsequent malignant neoplasms [SMN], relapses and deaths). Event‐free survival (EFS) and overall survival (OS) were compared by locus of care (adult vs. paediatric) and predictors of outcomes determined. Of 1014 AYA with Hodgkin lymphoma, 54 (5.3%) had NLPHL; 15 (27.8%) were treated at a paediatric centre. No paediatric centre patient received radiation only versus 16 (41.0%) of adult centre patients. Excision only was more common in paediatric centres (p < 0.001). The 20‐year EFS and OS rates were 82.9% ± 5.2% and 100% respectively. Advanced stage (hazard ratio: 4.9, 95% CI: 1.3–18.4; p = 0.02) was associated with inferior EFS. Although the 25‐year cumulative incidence of SMN was 19.3% ± 9.6% for the entire cohort, there were no SMN among the patients treated with excision only. AYA with NLPHL have outstanding long‐term survival. Resection alone was rare outside of paediatric institutions but associated with excellent outcomes. Given substantial SMN risks, chemotherapy‐sparing and radiation‐sparing strategies for appropriate subsets of patients are warranted. [ABSTRACT FROM AUTHOR]

5-year survival after childhood cancer does not fully describe life-years lost due to childhood cancer because there are a large number of deaths occurring beyond 5-years (late mortality) related to cancer and cancer treatment. Specific causes of health-related (non-recurrence, non-external) late mortality and risk reduction through modifiable lifestyle and cardiovascular risk factors are not well described. Through using a well-characterised cohort of 5-year survivors of the most common childhood cancers, we evaluated specific health-related causes of late mortality and excess deaths compared with the general US population and identified targets to reduce future risk. In this multi-institutional, hospital-based, retrospective cohort study, late mortality (death ≥5 years from diagnosis) and specific causes of death were evaluated in 34 230 5-year survivors of childhood cancer diagnosed at an age younger than 21 years from 1970 to 1999 at 31 institutions in the USA and Canada; median follow-up from diagnosis was 29 years (range 5–48) in the Childhood Cancer Survivor Study. Demographic, self-reported modifiable lifestyle (ie, smoking, alcohol, physical activity, and BMI) and cardiovascular risk factors (ie, hypertension, diabetes, and dyslipidaemia) associated with health-related mortality (which excludes death from primary cancer and external causes and includes death from late effects of cancer therapy) were evaluated. 40-year cumulative all-cause mortality was 23·3% (95% CI 22·7–24·0), with 3061 (51·2%) of 5916 deaths from health-related causes. Survivors 40 years or more from diagnosis experienced 131 excess health-related deaths per 10 000 person-years (95% CI 111–163), including those due to the top three causes of health-related death in the general population: cancer (absolute excess risk per 10 000 person-years 54, 95% CI 41–68), heart disease (27, 18–38), and cerebrovascular disease (10, 5–17). Healthy lifestyle and absence of hypertension and diabetes were each associated with a 20–30% reduction in health-related mortality independent of other factors (all p values ≤0·002). Survivors of childhood cancer are at excess risk of late mortality even 40 years from diagnosis, due to many of the leading causes of death in the US population. Modifiable lifestyle and cardiovascular risk factors associated with reduced risk for late mortality should be part of future interventions. US National Cancer Institute and the American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor to respond to a comment on the authors' article regarding the use of autologous bone marrow transplantation in adult acute myeloid leukemia patients

Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the heart was exposed, are at increased risk of cardiomyopathy. Symptomatic cardiomyopathy is typically preceded by a series of gradually progressive, asymptomatic changes in structure and function of the heart that can be ameliorated with treatment, prompting specialist organisations to endorse guidelines on cardiac surveillance in at-risk survivors of cancer. In 2015, the International Late Effects of Childhood Cancer Guideline Harmonization Group compiled these guidelines into a uniform set of recommendations applicable to a broad spectrum of clinical environments with varying resource availabilities. Since then, additional studies have provided insight into dose thresholds associated with a risk of asymptomatic and symptomatic cardiomyopathy, have characterised risk over time, and have established the cost-effectiveness of different surveillance strategies. This systematic Review and guideline provides updated recommendations based on the evidence published up to September, 2020. [ABSTRACT FROM AUTHOR]

Background: With improved survival among children after transplantation, our understanding of the risk for developing other comorbidities is improving, yet little is known about the long-term risk of cardiovascular events and mortality after solid organ transplantation. Methods: In a cohort study using health administrative data, we compared cardiovascular events in children (n = 615) with liver, lung, kidney, small bowel, or multi-organ transplant at the Hospital for Sick Children, Toronto, Canada, with asthmatic children (n = 481,697) between 1996 and 2014. Outcomes included non-fatal cardiovascular events, cardiovascular death, all-cause mortality, and a composite of non-fatal and fatal cardiovascular events. Time-stratified Cox proportional hazards models were used. Results: Among 615 children, 317 (52%) were recipients of kidneys, 253 (41%) of livers, and the remaining 45 (7%) had lung, small bowel, or multi-organ transplants. Median follow-up was 12.1 [7.2, 16.7] years. Non-fatal incident cardiovascular events were 34 times higher among solid organ transplant recipients than non-transplanted children (incidence rate ratio (IRR) 34.4, 95% CI: 25.5, 46.4). Among transplant recipients, the cumulative incidence of non-fatal and fatal cardiovascular events was 2.3% and 13.0%, 5 and 15 years after transplantation, respectively. Conclusions: Increased rate of cardiovascular events in children after transplantation highlights the need for surveillance during transition into adulthood and beyond. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Summary: Childhood cancer survivors are at risk for development of subsequent neoplasms of the CNS. Better understanding of the rates, risk factors, and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer could lead to more informed screening guidelines. Two investigators independently did a systematic search of Medline and Embase (from January, 1966, through March, 2012) for studies examining subsequent neoplasms of the CNS among survivors of childhood cancer. Articles were selected to answer three questions: what is the risk of CNS tumours after radiation to the cranium for a paediatric cancer, compared with the risk in the general population; what are the outcomes in children with subsequent neoplasms of the CNS who received CNS-directed radiation for a paediatric cancer; and, are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 were included in this Review. These studies reported that childhood cancer survivors have an 8·1–52·3-times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation, and some studies showed a correlation between radiation dose and risk of subsequent CNS tumours. 5-year survival ranged from 0–19·5% for subsequent high-grade gliomas and 57·3–100% for meningiomas, which are similar rates to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up, and small sample sizes. We conclude that survivors of childhood cancer who received cranial radiation therapy have an increased risk for subsequent CNS neoplasms. The current literature is insufficient to comment about the potential harms and benefits of routine screening for subsequent CNS neoplasms. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the patient-, cancer-, and treatment-related factors related to cancer worry in adolescent and young adult (AYA) survivors of cancer in childhood in the U.S. through the use of the Cancer Worry Scale (CWS).

Background: Cancer survivors treated with any dose of radiation to the abdomen, pelvis, spine, or total body irradiation (TBI) are at increased risk for developing colorectal cancer (CRC) compared to the general population. Since earlier detection of CRC is strongly associated with improved survival, the Children's Oncology Group (COG) Long-Term Follow-Up Guidelines recommend that these high-risk cancer survivors begin CRC screening via a colonoscopy or a multitarget stool DNA test at the age of 30 years or 5 years following the radiation treatment (whichever occurs last). However, only 37% (95% CI 34.1-39.9%) of high-risk survivors adhere to CRC surveillance. The Activating cancer Survivors and their Primary care providers (PCP) to Increase colorectal cancer Screening (ASPIRES) study is designed to assess the efficacy of an intervention to increase the rate of CRC screening among high-risk cancer survivors through interactive, educational text-messages and resources provided to participants, and CRC screening resources provided to their PCPs.Methods: ASPIRES is a three-arm, hybrid type II effectiveness and implementation study designed to simultaneously evaluate the efficacy of an intervention and assess the implementation process among participants in the Childhood Cancer Survivor Study (CCSS), a North American longitudinal cohort of childhood cancer survivors. The Control (C) arm participants receive electronic resources, participants in Treatment arm 1 receive electronic resources as well as interactive text messages, and participants in Treatment arm 2 receive electronic educational resources, interactive text messages, and their PCP's receive faxed materials. We describe our plan to collect quantitative (questionnaires, medical records, study logs, CCSS data) and qualitative (semi-structured interviews) intervention outcome data as well as quantitative (questionnaires) and qualitative (interviews) data on the implementation process.Discussion: There is a critical need to increase the rate of CRC screening among high-risk cancer survivors. This hybrid effectiveness-implementation study will evaluate the effectiveness and implementation of an mHealth intervention consisting of interactive text-messages, electronic tools, and primary care provider resources. Findings from this research will advance CRC prevention efforts by enhancing understanding of the effectiveness of an mHealth intervention and highlighting factors that determine the successful implementation of this intervention within the high-risk cancer survivor population.Trial Registration: This protocol was registered at clinicaltrials.gov (identifier NCT05084833 ) on October 20, 2021. [ABSTRACT FROM AUTHOR]

Objective: To compare antimüllerian hormone (AMH) patterns by cancer status and treatment exposures across 6 years after incident breast cancer using administrative data.Design: In a cross-sectional design, AMH levels in patients who developed incident breast cancer between ages 15-39 years during 2005-2019 were matched 1:10 to levels in females without cancer in the OptumLabs Data Warehouse. Modeled AMH patterns were compared among cyclophosphamide-based chemotherapy, non-cyclophosphamide-based chemotherapy, no chemotherapy, and no breast cancer groups.Setting: Commercially insured females in the United States.Patient(s): Females with and without breast cancer.Exposure(s): Breast cancer, cyclophosphamide- and non-cyclophosphamide-based chemotherapy.Main Outcome Measure(s): AMH levels.Result(s): A total of 233 patients with breast cancer (mean age, 34 years; standard deviation, 3.7 years) contributed 278 AMH levels over a median of 2 years (range, 0-6.7 years) after diagnosis; 52% received cyclophosphamide-based chemotherapy, 17% received non-cyclophosphamide-based chemotherapy (80% platinum-based), and 31% received no chemotherapy. A total of 2,777 matched females without cancer contributed 2,780 AMH levels. The pattern of AMH levels differed among the 4 groups. Among females without cancer and breast cancer survivors who did not undergo chemotherapy, AMH declined linearly over time. In contrast, among those who received cyclophosphamide-based and noncyclophosphamide-based chemotherapy, a nonlinear pattern of AMH level of initial fall during chemotherapy, followed by an increase over 2-4 years, and then by a plateau over 1-2 years before a decline was observed.Conclusion(s): In breast cancer survivors, AMH levels from administrative data supported ovarian toxicity of non-cyclophosphamide-based chemotherapy in breast cancer and efficiently depicted the timing and duration of changes in ovarian reserve to reflect the residual reproductive lifespan. [ABSTRACT FROM AUTHOR]

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: Children with leukemia and Down syndrome (DS) are at higher risk of acute treatment toxicities than those without DS. Whether late toxicity risks are also elevated is unknown. Methods: The authors identified all patients diagnosed with leukemia before the age of 18 years in Ontario, Canada between 1987 and 2013 and who survived greater than 5 years since their last pediatric cancer event. Survivors were divided into those with and without DS, matched by birth year, sex, leukemia type, and receipt of radiation. DS survivors were matched to individuals with DS without childhood cancer (DS controls) in a 1:10 ratio. Outcomes were identified through linkage to population‐based health services databases. Results: DS survivors (n = 79) experienced inferior overall survival compared to non‐DS survivors (n = 231) (20‐year overall survival, 81.7% ± 6.8% vs 98.3% ± 1.2%; hazard ratio [HR], 12.8; P <.0001) and to DS controls (n = 790; 96.3% ± 1.2%; HR, 5.4 P <.0001). Pulmonary and infectious deaths were noted among DS survivors. There was no difference in the incidence of congestive heart failure between DS survivors and either control cohort, nor of hearing loss or dementia between DS survivors and DS controls. Conclusions: DS survivors were at substantially higher risk of late mortality than non‐DS survivors or DS controls. This excess risk was not attributable to cardiac‐ or subsequent malignant neoplasm‐related late effects, historically main causes of premature death among non‐DS survivors. Chronic morbidities associated with DS were not increased compared to DS controls. DS‐specific surveillance guidelines may be warranted. Although children with leukemia who have Down syndrome (DS) are more likely to experience acute treatment toxicities than those without DS, whether they are also at higher risk for late mortality and morbidity is unknown. In this population‐based study, 5‐year survivors with DS are more than 12 times as likely to die as non‐DS survivors and more than 5 times as likely to die as DS individuals without cancer; this is not due to an elevated risk for cardiac morbidity or second cancers but rather is due to pulmonary and infectious causes. [ABSTRACT FROM AUTHOR]

Background: Early initiation of breast cancer screening is recommended for high-risk women, including survivors of childhood cancer treated with chest radiation. Recent studies suggest that female survivors of childhood leukemia or sarcoma treated without chest radiation are also at elevated early onset breast cancer risk. However, the potential clinical benefits and cost-effectiveness of early breast cancer screening among these women are uncertain.Methods: Using data from the Childhood Cancer Survivor Study, we adapted 2 Cancer Intervention and Surveillance Modeling Network simulation models to reflect the elevated risks of breast cancer and competing mortality among leukemia and sarcoma survivors. Costs and utility weights were based on published studies and databases. Outcomes included breast cancer deaths averted, false-positive screening results, benign biopsies, and incremental cost-effectiveness ratios.Results: In the absence of screening, the lifetime risk of dying from breast cancer among survivors was 6.8% to 7.0% across models. Early initiation of annual mammography with breast magnetic resonance imaging screening between ages 25 and 40 years would avert 52.6% to 64.3% of breast cancer deaths. When costs and quality-of-life impacts were considered, screening starting at age 40 years was the only strategy with an incremental cost-effectiveness ratio below the $100 000 per quality-adjusted life-year (QALY) gained cost-effectiveness threshold ($27 680 to $44 380 per QALY gained across models).Conclusions: Among survivors of childhood leukemia or sarcoma, early initiation of breast cancer screening at age 40 years may reduce breast cancer deaths by half and is cost-effective. These findings could help inform screening guidelines for survivors treated without chest radiation. [ABSTRACT FROM AUTHOR]

Summary: Survival disparities by locus of care (LOC; paediatric versus adult) among adolescents and young adults (AYA) with acute lymphoblastic leukaemia (ALL) are well documented. Whether similar disparities exist among AYA with aggressive mature B‐cell non‐Hodgkin lymphoma (B‐NHL) is unknown. We identified all Ontario, Canada AYA aged 15–21 years at diagnosis of B‐NHL between 1992 and 2012. Demographic, disease, treatment and outcome data were chart abstracted. The impact of LOC on event‐free (EFS) and overall survival (OS) were determined, adjusted for patient and disease covariates. Among 176 AYA with B‐NHL, 62 (35·2%) received therapy at paediatric centres. The 5‐year EFS and OS [± standard error (SE)] for the overall cohort were 72·2 [3·4]% and 76·1 [3·2]% respectively. Both EFS and OS were superior among paediatric centre AYA [EFS (± SE) 82·2 (4·9)% vs. 66·7 (4·4)%, P = 0·02; OS 85·5 (4·5)% vs. 71·1 (4·3)%, P = 0·03]. Adjusted for histology, stage and time period, adult centre AYA had inferior EFS [hazard ratio (HR) 2·4, 95% confidence interval (CI) 1·1–4·9, P = 0·02] and OS (HR 2·5, 95% CI 1·1–5·7, P = 0·03). Sensitivity analyses restricted to the latest time period, when most adult centre AYA received rituximab, demonstrated similar disparities. Similar to AYA with ALL, AYA with B‐NHL may benefit from being treated with paediatric protocols. Studies prospectively validating these results are warranted. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults (AYAs) with cancer may experience elevated rates of high‐intensity end‐of‐life (HI‐EOL) care. Locus‐of‐care (LOC) disparities (pediatric vs adult) in AYA end‐of‐life (EOL) care are unstudied. Methods: A decedent population‐based cohort of Ontario AYAs diagnosed between 1992 and 2012 at the ages of 15 to 21 years was linked to administrative data. The authors determined the prevalence and associations of a composite outcome of HI‐EOL care that included any of the following: intravenous chemotherapy within 14 days of death, more than 1 emergency department visit, more than 1 hospitalization, or an intensive care unit (ICU) admission within 30 days of death. Secondary outcomes included measures of the most invasive EOL care (ventilation within 14 days of death and ICU death) and in‐hospital death. Results: There were 483 decedents: 60.5% experienced HI‐EOL care, 20.3% were ventilated, and 22.8% died in the ICU. Compared with patients with solid tumors, patients with hematological malignancies had the greatest odds of HI‐EOL care (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.5‐3.4), ventilation (OR, 4.7; 95% CI, 2.7‐8.3), and ICU death (OR, 4.4; 95% CI, 2.6‐4.4). Subjects treated in pediatric centers versus adult centers near death (OR, 2.4; 95% CI, 1.2‐4.8) and those living in rural areas (OR, 2.1; 95% CI, 1.1‐3.9) were more likely to experience ICU death. Conclusions: AYAs with cancer experience high rates of HI‐EOL care, with patients in pediatric centers and those living in rural areas having the highest odds of ICU death. This study is the first to identify LOC‐based disparities in EOL care for AYAs, and it highlights the need to explore the mechanisms underlying these disparities. In this population‐based linkage study of adolescent and young adult cancer decedents, patients treated in pediatric settings near death experience disproportionate rates of intensive end‐of‐life care in comparison with adult settings. Other risk factors are hematological malignancies and rural living. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)‐associated subsequent malignant neoplasms (SMNHPV) in childhood cancer survivors are poorly understood. Methods: The cumulative risk of SMNHPV was assessed among 24,363 Childhood Cancer Survivor Study participants. Standardized incidence ratios (SIRs) and absolute excess risk were calculated using age‐matched, sex‐matched, and calendar year rates from the Surveillance, Epidemiology, and End Results program. Poisson regression models identified SMNHPV risk factors, evaluating relative SIRs (rSIR) and 95% confidence intervals (95% CIs). Results: In total, 46 survivors developed an SMNHPV (median age, 31 years [range, 10‐56 years]; median time from primary cancer, 21 years [range, 9‐35 years]). SMNHPV sites included oropharynx (N = 44), anorectum (N = 6), uterine cervix (N = 2), and vulva (N = 2). The 33‐year cumulative incidence was 0.3% (95% CI, 0.2%‐0.4%), and the SIR was nearly 3‐fold that of the general population (SIR, 2.86; 95% CI, 2.05‐4.00). Female survivors were not at increased risk of cervical or vulvar cancers compared with the general population. All survivors had an elevated risk of oropharyngeal SMNHPV (males: SIR, 4.06; 95% CI, 2.37‐6.97; females: SIR, 8.44; 95% CI 4.88‐14.61) and anorectal SMNHPV (males: SIR, 13.56; 95% CI, 5.09‐36.13; females: SIR, 9.15; 95% CI, 2.29‐36.61). Males (vs females: rSIR, 1.99; 95% CI, 1.00‐3.94); head, neck, and pelvic radiotherapy doses >3000 centigray (vs none: rSIR, 2.35; 95% CI, 1.11‐4.97); and cisplatin‐equivalent doses >400 mg/m2 (vs none: rSIR, 4.51; 95% CI, 1.78‐11.43) were associated with increased SMNHPV SIRs in multivariable analysis. Conclusions: Childhood cancer survivors are at increased risk for SMN in sites susceptible to HPV‐associated malignancies. Further research examining HPV in the etiology of SMN and the promotion of HPV vaccination and surveillance guidelines for SMNHPV in cancer survivors is warranted. Childhood cancer survivors are at increased risk for subsequent malignant neoplasms in anatomic sites associated with human papillomavirus infection. The promotion of prevention and surveillance strategies for these subsequent malignancies is warranted in this population. [ABSTRACT FROM AUTHOR]

Background: Medical financial burden includes material, behavioral, and psychological hardship and has been underinvestigated among adult survivors of childhood cancer. Methods: A survey from 698 survivors and 210 siblings from the Childhood Cancer Survivor Study was analyzed. The intensity of financial hardship was estimated across 3 domains: 1) material, including conditions that arise from medical expenses; 2) behavioral, including coping behaviors to manage medical expenses; and 3) psychological hardship resulting from worries about medical expenses and insurance, as measured by the number of instances of each type of financial hardship (0, 1‐2, and ≥3 instances). Multivariable logistic regressions were conducted to examine the clinical and sociodemographic predictors of experiencing financial hardship (0‐2 vs ≥3 instances). Results: The intensity of financial hardship did not significantly differ between survivors and siblings. Survivors reported more instances of material hardship than siblings (1‐2 instances: 27.2% of survivors vs 22.6% of siblings; ≥3 instances: 15.9% of survivors vs 11.4% siblings; overall P =.03). In multivariable regressions, insurance was protective against all domains of financial hardship (behavioral odds ratio [OR], 0.12; 95% confidence interval [CI], 0.06‐0.22; material OR, 0.37; 95% CI, 0.19‐0.71; psychological OR, 0.10; 95% CI, 0.05‐0.21). Survivors who were older at diagnosis, female, and with chronic health conditions generally had higher levels of hardship. Brain radiation and alkylating agents were associated with higher levels of hardship. Conclusions: Material, behavioral, and psychological financial burden among survivors of childhood cancer is common. Survivors of childhood cancer are at risk for economic consequences of their cancer treatment that manifest through the domains of material, behavioral, and psychological hardship. A high intensity of medical financial hardship is common among survivors of long‐term childhood cancer. [ABSTRACT FROM AUTHOR]

Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute–funded cancer centers. This consortium has regularly held topic-focused biannual face-to-face symposiums. These meetings are a place to review cancer informatics and data science priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues that we faced at our respective institutions and cancer centers. Here, we provide meeting highlights from the latest CI4CC Symposium, which was delayed from its original April 2020 schedule because of the COVID-19 pandemic and held virtually over three days (September 24, October 1, and October 8) in the fall of 2020. In addition to the content presented, we found that holding this event virtually once a week for 6 hours was a great way to keep the kind of deep engagement that a face-to-face meeting engenders. This is the second such publication of CI4CC Symposium highlights, the first covering the meeting that took place in Napa, California, from October 14-16, 2019. We conclude with some thoughts about using data science to learn from every child with cancer, focusing on emerging activities of the National Cancer Institute's Childhood Cancer Data Initiative. [ABSTRACT FROM AUTHOR]

Background: Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the United States.Methods: We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material [eg, problems paying bills], psychological [eg, distress], and behavioral [eg, forgoing care due to cost]) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately.Results: A total of 2588 AYA cancer survivors (median = 31 [interquartile range = 26-35] years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior.Conclusions: Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors' health, and multifaceted interventions are necessary to address underlying causes. [ABSTRACT FROM AUTHOR]

Purpose: Adolescent and young adult cancer survivors require lifelong healthcare to address the late effects of therapy. We examined the impact of different provider models of long‐term follow‐up (LTFU) care on adherence to recommended surveillance. Methods: We conducted a retrospective cohort study using administrative health databases in Ontario, Canada. Five‐year survivors were identified from IMPACT, a database of patients aged 15–20.9 years at diagnosis of six cancers between 1992 and 2010. We defined three models of LTFU care hierarchically: specialized survivor clinics (SCCs), general cancer clinics (GCCs), and family physician (FP). We assessed adherence to the Children's Oncology Group surveillance guidelines for cardiomyopathy and breast cancer. Multistate models assessed adherence transitions and impacts of LTFU attendance. Results: A total of 1574 survivors were followed for a mean of 9.2 years (range 4.3–13.9 years) from index (5‐year survival). The highest level of LTFU attended in the first 2‐years post‐index was a GCC (47%); only 16.7% attended a SCC. By the end of study, 72% no longer attended any of the models of care and only 2% still attended an SCC. Among 188 survivors requiring breast cancer surveillance, 6.9% were adherent to their first required surveillance testing. Attendance at a SCC in the previous year and higher cumulative FP or GCC visits increased the rate of subsequently becoming adherent. Among 857 survivors requiring cardiomyopathy surveillance, 11% were adherent at study entry. Each subsequent SCC visit led to an 11.3% (95% CI: 1.05–1.18) increase in the rate of becoming adherent. Conclusion: LTFU attendance and surveillance adherence are sub‐optimal. SCC follow‐up is associated with greater adherence, but few survivors receive such care, and this proportion diminished over time. Interventions are needed to improve LTFU attendance and promote surveillance adherence. [ABSTRACT FROM AUTHOR]

Background: Individuals diagnosed with acute lymphoblastic leukemia (ALL) between the ages of 22 and 39 years experience worse outcomes than those diagnosed when they are 21 years old or younger. Treatment at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) mitigates these disparities but may be associated with higher expenditures.Methods: Using deidentified administrative claims data (OptumLabs Data Warehouse), the cancer-related expenditures were examined among patients with ALL diagnosed between 2001 and 2014. Multivariable generalized linear model with log-link modeled average monthly health-plan-paid (HPP) expenditures and amount owed by the patient (out-of-pocket [OOP]). Cost ratios were used to calculate excess expenditures (CCC vs non-CCC). Incidence rate ratios (IRRs) compared CCC and non-CCC monthly visit rates. Models adjusted for sociodemographics, comorbidities, adverse events, and months enrolled.Results: Clinical and sociodemographic characteristics were comparable between CCC (n = 160) and non-CCC (n = 139) patients. Higher monthly outpatient expenditures in CCC patients ($15,792 vs $6404; P < .001) were driven by outpatient hospital HPP expenditures. Monthly visit rates and per visit expenditures for nonchemotherapy visits (IRR = 1.6; P = .001; CCC = $8247, non-CCC = $1191) drove higher outpatient hospital expenditures among CCCs. Monthly OOP expenditures were higher at CCCs for outpatient care (P = .02). Inpatient HPP expenditures were significantly higher at CCCs ($25,918 vs $13,881; ꞵ = 0.9; P < .001) before accounting for adverse events but were no longer significant after adjusting for adverse events (ꞵ = 0.4; P = .1). Hospitalizations and length of stay were comparable.Conclusions: Young adults with ALL at CCCs have higher expenditures, likely reflecting differences in facility structure, billing practices, and comprehensive patient care. It would be reasonable to consider CCCs comparable to the oncology care model and incentivize the framework to achieve superior outcomes and long-term cost savings.Lay Summary: Health care expenditures in young adults (aged 22-39 years) with acute lymphoblastic leukemia (ALL) are higher among patients at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) than those at non-CCCs. The CCC/non-CCC differences are significant among outpatient expenditures, which are driven by higher rates of outpatient hospital visits and outpatient hospital expenditures per visit at CCCs. Higher expenditures and visit rates of outpatient hospital visits among CCCs may also reflect how facility structure and billing patterns influence spending or comprehensive care. Young adults at CCCs face higher inpatient HPP expenditures; these are driven by serious adverse events. [ABSTRACT FROM AUTHOR]

Background: Retrospective multicenter research using echocardiograms obtained for routine clinical care can be hampered by issues of individual center quality. We sought to evaluate imaging and patient characteristics associated with poorer quality of archived echocardiograms from a cohort of childhood cancer survivors. Methods: A single blinded reviewer at a central core laboratory graded quality of clinical echocardiograms from five centers focusing on images to derive 2D and M‐mode fractional shortening (FS), biplane Simpson's ejection fraction (EF), myocardial performance index (MPI), tissue Doppler imaging (TDI)–derived velocities, and global longitudinal strain (GLS). Results: Of 535 studies analyzed in 102 subjects from 2004 to 2017, all measures of cardiac function could be assessed in only 7%. While FS by 2D or M‐mode, MPI, and septal E/E′ could be measured in >80% studies, mitral E/E′ was less consistent (69%), but better than EF (52%) and GLS (10%). 66% of studies had ≥1 issue, with technical issues (eg, lung artifact, poor endocardial definition) being the most common (33%). Lack of 2‐ and 3‐chamber views was associated with the performing center. Patient age <5 years had a higher chance of apex cutoff in 4‐chamber views compared with 16‐35 years old. Overall, for any quality issue, earlier era of echo and center were the only significant risk factors. Conclusion: Assessment of cardiac function using pooled multicenter archived echocardiograms was significantly limited. Efforts to standardize clinical echocardiographic protocols to include apical 2‐ and 3‐chamber views and TDI will improve the ability to quantitate LV function. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is a common adolescent and young adult (AYA) cancer. While outcome disparities between pediatric vs. adult centers [locus of care (LOC)] have been demonstrated in other AYA cancers such as acute lymphoblastic leukemia, they have not been well studied in HL. We therefore compared population‐based treatment patterns and outcomes in AYA HL by LOC. The IMPACT Cohort includes data on all Ontario, Canada AYA (15‐21 years) diagnosed with HL between 1992 and 2012. Linkage to population‐based health administrative data identified late effects. We examined LOC‐based differences in treatment modalities, cumulative doses, event‐free survival (EFS), overall survival (OS), and late effects. Among 954 AYA, 711 (74.5%) received therapy at adult centers. Pediatric center AYA experienced higher rates of radiation therapy but lower cumulative doses of doxorubicin and bleomycin. 10‐year EFS did not differ between pediatric vs. adult cancer vs. community centers (83.8% ± 2.4% vs. 82.8% ± 1.6% vs. 82.7%±3.0%; P =.71); LOC was not significantly associated with either EFS or OS in multivariable analyses. Higher incidences of second malignancies in pediatric center AYA and of cardiovascular events in adult center AYA were observed, but were not significant. In conclusion, while pediatric and adult centers used different treatment strategies, outcomes were equivalent. Differences in treatment exposures are however likely to result in different late‐effect risks. Protocol choice should be guided by individual late‐effect risk. [ABSTRACT FROM AUTHOR]

Background: Cancer treatment can cause gonadal impairment. Acute ovarian failure is defined as the permanent loss of ovarian function within 5 years of cancer diagnosis. We aimed to develop and validate risk prediction tools to provide accurate clinical guidance for paediatric patients with cancer.Methods: In this cohort study, prediction models of acute ovarian failure risk were developed using eligible female US and Canadian participants in the Childhood Cancer Survivor Study (CCSS) cohort and validated in the St Jude Lifetime Cohort (SJLIFE) Study. 5-year survivors from the CCSS cohort were included if they were at least 18 years old at their most recent follow-up and had complete treatment exposure and adequate menstrual history (including age at menarche, current menstrual status, age at last menstruation, and menopausal aetiology) information available. Participants in the SJLIFE cohort were at least 10-year survivors. Participants were excluded from the prediction analysis if they had an ovarian hormone deficiency, had missing exposure information, or had indeterminate ovarian status. The outcome of acute ovarian failure was defined as permanent loss of ovarian function within 5 years of cancer diagnosis or no menarche after cancer treatment by the age of 18 years. Logistic regression, random forest, and support vector machines were used as candidate methods to develop the risk prediction models in the CCSS cohort. Prediction performance was evaluated internally (in the CCSS cohort) and externally (in the SJLIFE cohort) using the areas under the receiver operating characteristic curve (AUC) and the precision-recall curve (average precision [AP; average positive predictive value]).Findings: Data from the CCSS cohort were collected for participants followed up between Nov 3, 1992, and Nov 25, 2016, and from the SJLIFE cohort for participants followed up between Oct 17, 2007, and April 16, 2012. Of 11 336 female CCSS participants, 5886 (51·9%) met all inclusion criteria for analysis. 1644 participants were identified from the SJLIFE cohort, of whom 875 (53·2%) were eligible for analysis. 353 (6·0%) of analysed CCSS participants and 50 (5·7%) of analysed SJLIFE participants had acute ovarian failure. The overall median follow-up for the CCSS cohort was 23·9 years (IQR 20·4-27·9), and for SJLIFE it was 23·9 years (19·0-30·0). The three candidate methods (logistic regression, random forest, and support vector machines) yielded similar results, and a prescribed dose model with abdominal and pelvic radiation doses and an ovarian dose model with ovarian radiation dosimetry using logistic regression were selected. Common predictors in both models were history of haematopoietic stem-cell transplantation, cumulative alkylating drug dose, and an interaction between age at cancer diagnosis and haematopoietic stem-cell transplant. External validation of the model in the SJLIFE cohort produced an estimated AUC of 0·94 (95% CI 0·90-0·98) and AP of 0·68 (95% CI 0·53-0·81) for the ovarian dose model, and AUC of 0·96 (0·94-0·97) and AP of 0·46 (0·34-0·61) for the prescribed dose model. Based on these models, an online risk calculator has been developed for clinical use.Interpretation: Both acute ovarian failure risk prediction models performed well. The ovarian dose model is preferred if ovarian radiation dosimetry is available. The models, along with the online risk calculator, could help clinical discussions regarding the need for fertility preservation interventions in girls and young women newly diagnosed with cancer.Funding: Canadian Institutes of Health Research, Women and Children's Health Research Institute, National Cancer Institute, and American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]