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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]

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]

Simple Summary: Survivors of childhood cancer are predisposed to a range of late effects of treatment, including high symptom burden. Symptom burden may vary over time. The aim of this prospective pilot study was to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer using mobile health (mHealth) technology to evaluate symptom fluctuation and associations with future health-related quality of life (HRQOL). The 41 survivors included in this study had high adherence to symptom reporting (83%) and HRQOL reporting (95%). Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Additionally, a higher symptom burden was associated with poorer HRQOL in the future. Daily assessment of symptoms using mHealth technology revealed fluctuations in symptomology and the association between symptom burden and HRQOL. This method of symptom assessment is valuable for improving our understanding of symptom dynamics and sources of variability. Background: Cancer therapies predispose survivors to a high symptom burden. This study utilized mobile health (mHealth) technology to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer to evaluate symptom fluctuation and associations with future health-related quality-of-life (HRQOL). Methods: This prospective study used an mHealth platform to distribute a 20-item cancer-related symptom survey (5 consecutive days each month) and an HRQOL survey (the day after the symptom survey) over 3 consecutive months to participants from the Childhood Cancer Survivor Study. These surveys comprised a PROMIS-29 Profile and Neuro-QOL assessed HRQOL. Daily symptom burden was calculated by summing the severity (mild, moderate, or severe) of 20 symptoms. Univariate linear mixed-effects models were used to analyze total, person-to-person, day-to-day, and month-to-month variability for the burden of 20 individual symptoms. Multivariable linear regression was used to analyze the association between daily symptom burden in the first month and HRQOL in the third month, adjusted for covariates. Results: Out of the 60 survivors invited, 41 participated in this study (68% enrollment rate); 83% reported their symptoms ≥3 times and 95% reported HRQOL in each study week across 3 months. Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Higher first-month symptom burden was associated with poorer HRQOL related to anxiety (regression coefficient: 6.56; 95% CI: 4.10–9.02), depression (6.32; 95% CI: 3.18–9.47), fatigue (7.93; 95% CI: 5.11–10.80), sleep (6.07; 95% CI: 3.43–8.70), pain (5.16; 95% CI: 2.11–8.22), and cognitive function (–6.89; 95% CI: –10.00 to –3.79) in the third month. Conclusions: Daily assessment revealed fluctuations in symptomology, and higher symptom burden was associated with poorer HRQOL in the future. Utilizing mHealth technology for daily symptom assessment improves our understanding of symptom dynamics and sources of variability. [ABSTRACT FROM AUTHOR]

Background The Affordable Care Act (ACA) increased private nonemployer health insurance options, expanded Medicaid eligibility, and provided preexisting health condition protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre- and post-ACA implementation. Methods Using the multicenter Childhood Cancer Survivor Study, we included participants from 2 cross-sectional surveys: pre-ACA (2007-2009; survivors: n = 7505; siblings: n = 2175) and post-ACA (2017-2019; survivors: n = 4030; siblings: n = 987). A subset completed both surveys (1840 survivors; 646 siblings). Multivariable regression models compared post-ACA insurance coverage and type (private, public, uninsured) between survivors and siblings and identified associated demographic and clinical factors. Multinomial models compared gaining and losing insurance vs staying the same among survivors and siblings who participated in both surveys. Results The proportion with insurance was higher post-ACA (survivors pre-ACA 89.1% to post-ACA 92.0% [+2.9%]; siblings pre-ACA 90.9% to post-ACA 95.3% [+4.4%]). Post-ACA insurance increase in coverage was higher among those aged 18-25 years (survivors: +15.8% vs +2.3% or less ages 26 years and older; siblings +17.8% vs +4.2% or less ages 26 years and older). Survivors were more likely to have public insurance than siblings post-ACA (18.4% vs 6.9%; odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.1 to 2.6). Survivors with severe chronic conditions (OR = 4.7, 95% CI = 3.0 to 7.3) and those living in Medicaid expansion states (OR = 2.4, 95% CI = 1.7 to 3.4) had increased odds of public insurance coverage post-ACA. Among the subset completing both surveys, low- and mid-income survivors (<$40 000 and <$60 000, respectively) experienced insurance losses and gains in reference to highest household income survivors (≥$100 000), relative to odds of keeping the same insurance status. Conclusions Post-ACA, more childhood cancer survivors and siblings had health insurance, although disparities remain in coverage. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions Continuity and coordination‐of‐care for childhood cancer survivors with multiple chronic conditions are understudied but critical for appropriate follow‐up care.From April through June 2022, 800 Childhood Cancer Survivor Study participants with two or more chronic conditions (one or more severe/life‐threatening/disabling) were emailed the “Patient Perceived Continuity‐of‐Care from Multiple Clinicians” survey. The survey asked about survivors’ main (takes care of most health care) and coordinating (ensures follow‐up) provider, produced three care‐coordination summary scores (main provider, across multiple providers, patient–provider partnership), and included six discontinuity indicators (e.g., having to organize own care). Discontinuity (yes/no) was defined as poor care on one or more discontinuity item. Chi‐square tests assessed associations between discontinuity and sociodemographics. Modified Poisson regression models estimated prevalence ratios (PRs) for discontinuity risk associated with the specialty and number of years seeing the main and coordinating provider, and PRs associated with better scores on the three care‐coordination summary measures. Inverse probability weights adjusted for survey non‐participation.A total of 377 (47%) survivors responded (mean age 48 years, 68% female, 89% non‐Hispanic White, 78% privately insured, 74% ≥college graduate); 147/373 (39%) reported discontinuity. Younger survivors were more likely to report discontinuity (chi‐square p = .02). Seeing the main provider ≤3 years was associated with more prevalent discontinuity (PR; 95%CI) (1.17; 1.02‐1.34 vs ≥ 10 years). Cancer specialist main providers were associated with less prevalent discontinuity (0.81; 0.66–0.99 vs. primary care). Better scores on all three care‐coordination summary measures were associated with less prevalent discontinuity: main provider (0.73; 0.64–0.83), across multiple providers (0.81; 0.78–0.83), patient–provider partnership (0.85; 0.80–0.89).Care discontinuity among childhood cancer survivors is prevalent and requires intervention. [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]

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]

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]

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: 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]

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: 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]

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]

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]