Background/Objectives: There is little information on the definition and management of dyslipidemia in patients and survivors of childhood, adolescent and young adult (CAYA) cancer. However, it is known that this population is at higher risk of developing cardiovascular disease (CVD). Dyslipidemia, hypertension, and metabolic syndrome are common among CAYA cancer survivors due to the cancer itself or the treatment received. Therefore, managing dyslipidemia in this population is crucial to mitigate the risk of long-term CVD. The aim of this systematic review was to summarize currently used definitions and cutoffs for dyslipidemia, its prevalence, and management strategies in CAYA cancer survivors. This review further describes reported pharmacological and lifestyle interventions and their impact on lipid levels. Methods: We conducted a systematic literature search in PubMed, including studies published in English, German or French between January 2015 and February 2025. The population included individuals diagnosed with any type of CAYA cancer prior to 25 years of age and either receiving cancer treatment or in follow-up care. We considered all types of publications except for Phase I and II studies. We followed PRISMA guidelines, assessed the quality of the eligible studies according to the respective Joanna Briggs Institute's Critical Appraisal Tools, and reported the results descriptively. Results: Of 575 identified publications, 53 fulfilled the inclusion criteria. Forty-three studies reported on the definitions of abnormal lipid values, 40 stated the prevalence of abnormal lipid values, and 17 studies described management approaches, of which 12 were case reports and small case series. For all three outcomes, the results were very heterogeneous. Using the example of triglycerides (TGs), the cutoff values for high TGs ranged from 5.17 mmol/L to 6.2 mmol/L and the reported prevalence of high TGs ranged from 0% to 75%, with an average of 31%. The only reported intervention to prevent dyslipidemia in CAYA cancer survivors was lifestyle modification. Preventive strategies that started during treatment were lifestyle modifications and fish oil supplements. Conclusions: Our systematic review provides a comprehensive overview of existing definitions, prevalences, and management of abnormal lipid values in CAYA cancer patients and survivors. However, the identified heterogeneities indicate that reported prevalences and results of interventions must be interpreted cautiously. An internationally harmonized approach to defining and reporting lipid values in CAYA cancer survivors is urgently needed to enable tailored screening and treatment strategies.

Background: The impact of cancer therapy on chronic health condition (CHC) burden in childhood cancer survivors is well-established; however, the role of neighborhood-level social determinants of health (SDOH) remains underexplored. Methods: We analyzed 2,508 adult survivors of childhood cancer in the St. Jude Lifetime Cohort Study with ≥2 clinical assessments (2007-2020). SDOH encompassed social vulnerability (the Social Vulnerability Index) and environmental vulnerabilities (e.g., primary care physician [PCP] availability, food inaccessibility), each categorized into quartiles. 177 CHCs were severity-graded (CTCAE v4.03), aggregated into 48 CHC groups, and summarized into global burden. Multivariable logistic regressions examined associations between baseline SDOH and CHC severity progression at global and group levels, adjusting for clinical and personal sociodemographic factors. Interactions of SDOH with personal insurance and educational attainment were examined for effect modification. Findings: Survivors residing in the most SDOH-vulnerable neighborhoods, characterized by low income (OR: 1.83, 95%CI: 1.36-2.46), low education (OR: 1.53, 95%CI: 1.15-2.04), limited PCP availability (OR: 1.30, 95%CI: 1.03-1.64), and food inaccessibility (OR: 1.49, 95%CI: 1.08-2.07), had higher risks of global CHC burden progression than those in the least vulnerable neighborhoods. Living in the most SDOH-vulnerable neighborhoods was associated with higher risks of new-onset/worsening of multiple CHC groups, including low education for peripheral nervous system disorders (OR: 2.69, 95%CI: 1.63-4.43), food inaccessibility for arrhythmias (OR: 4.36, 95%CI: 1.32-14.35), and poor walkability for abnormal glucose metabolism (OR: 4.60, 95%CI: 1.41-15.04), than those in the least vulnerable neighborhoods. Among survivors with public insurance, living in neighborhoods with limited PCP availability and poor walkability amplified peripheral musculoskeletal disorder risk up to 7-fold (OR: 6.11, 95%CI: 2.33-16.04 and OR: 7.37, 95%CI: 2.82-19.27, respectively). Interpretation: SDOH are associated with CHC severity progression among childhood cancer survivors, suggesting the need to integrate multilevel social risk assessment into survivorship care alongside standard clinical management.

As more children with cancer experience improved treatment outcomes across the world, challenges arise with ongoing care needs due to a higher risk of mortality and chronic health conditions compared to the general population. Addressing global pediatric cancer survivorship care, especially in low- and middle-income countries (LMICs), is of growing importance. The current study used the Consolidated Framework for Implementation Research (CFIR) and the Expert Recommendations for Implementing Change (ERIC) to examine the barriers, facilitators, and strategies for implementing childhood cancer survivorship care in LMICs. Using a larger review (PROSPERO registration CRD42021242548), a total of 8,456 articles were considered. The search identified nine eligible articles mentioning determinants of survivorship care across LMICs. Data were extracted from these articles using the CFIR domains of outer setting, inner setting, and individuals. Assigned CFIR constructs were then paired with ERIC strategies using the CFIR–ERIC matching tool. The nine studies were published between 2003 and 2020, representing the following countries: India, Brazil, Turkey, China, and Thailand. Inner setting barriers included lack of available resources—funding, space, materials, and guidelines. Outer setting barriers were related to financing, policies, and laws. Individual patient barriers reported were low health literacy, distance to care centers, and low prioritization of follow-up. No common facilitators were noted. The most feasible ERIC strategies for the barriers identified were accessing new funding, developing and distributing educational materials, developing resource-sharing agreements, and conducting local survivorship care needs assessments. There are limited existing data evaluating childhood cancer survivorship care barriers in LMICs. Of the studies we identified, low resource availability was a frequently reported barrier. As accessing funding can be difficult, resource sharing of contextually adapted guidelines and educational materials can serve as an implementation strategy to improve survivorship care globally. Enhancement of research efforts in resource-limited settings will address key knowledge gaps critical for implementation of global survivorship care and equity throughout the cancer journey.

Survival rates for children and young adults with cancer have significantly improved over recent decades, particularly in high-income countries (HICs), with five-year survival rates exceeding 80%. As a result, the burden of treatment-related late effects has emerged as a major global health challenge. These late sequelae may be progressive, irreversible and life-altering, with profound physical, psychosocial and economic consequences. Despite its association with many of these sequelae, radiotherapy remains a critical component of pediatric cancer care necessitating pediatric-specific evidence to guide safer practice and mitigate short- and long-term toxicity. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative was established to address this need by systematically evaluating dose-volume-risk relationships for normal tissues in children receiving radiotherapy, as impacted by developmental stage and other cancer therapies. PENTEC has produced organ-specific evidence and consensus-based guidelines that are now widely integrated into treatment planning in HICs. However, significant gaps remain including underrepresentation of survivorship endpoints in clinical trials and a paucity of evidence from low- and middle-income countries (LMIC) where survival rates are lower and survivorship infrastructure is less established. This report serves as a statement on the achievements and limitations of the PENTEC initiative, and highlights unique challenges specific to pediatric oncology faced by LMIC across infrastructure, workforce, health systems and sociocultural domains. Finally, it outlines priorities for global collaboration, education, advocacy and LMIC-led research. Broad dissemination and context-appropriate adaptation of PENTEC guidelines offer a cost-effective opportunity to reduce late morbidity and promote more equitable global survivorship outcomes.

10047 Background: Risk for impaired kidney function varies with radiation therapy (RT). We compared different methods for quantifying RT. Methods: Kidney function was graded in 2753 survivors (>10 years post-diagnosis, age ≥18 years) and 806 community controls (CC) per the Kidney Disease International Global Outcomes 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD). Multivariable logistic regression was used to evaluate the associations between grades 3-5 CKD and demographics and treatment exposures. RT was expressed as percentage of total kidney volume treated with 5 Gray (Gy) or more (V5), 10 Gy or more (V10) Gray, Children’s Oncology Group (COG) abdominal RT, or total body irradiation (TBI)/whole abdomen RT (WA). Model discrimination was assessed using area under the receiver operating characteristic curve (AUC). Results: 2.1% of survivors had stages 3 to 5 CKD, compared to 0.12% of CC (Odds Ratio (OR): 17.0 (95% confidence interval (CI) 2.9, 682.8), p < 0.001). Significant associations between higher risks of grades 3-5 CKD and demographic and treatment exposures were identified in separate regression models (Table). AUCs were 0.891, 0.888 and 0.896 for V5, V10, and TBI/WA, models respectively. Conclusions: TBI/WA is a more readily available exposure designation than V5 or V10. These results inform identification of survivors at highest risk for CKD. V5 V10 COG TBI/WA Predictors OR (95%CI) p OR (95%CI) p OR (95%CI) p OR (95%CI) p Race (White vs non-White) 1.68(0.81 – 3.30) 0.144 1.71(0.82 – 3.35) 0.133 1.80(0.89 – 3.44) 0.086 1.71(0.85 – 3.28) 0.116 Age at evaluation 1.09(1.04 – 1.13) <0.001 1.09(1.05 – 1.13) <0.001 1.09(1.05 – 1.13) <0.001 1.10(1.05 – 1.14) <0.001 Hypertension 8.21(4.12 – 17.61) <0.001 8.27(4.15 – 17.71) <0.001 8.61(4.41 – 18.02) <0.001 8.61(4.42 – 17.97) <0.001 Nephrectomy (yes/no) 2.44(0.88 – 6.12) 0.069 2.68(0.97 – 6.72) 0.044 4.23(1.81 – 9.48) 0.001 3.42(1.36 – 8.01) 0.006 Ifosfamide (per 1000 mg/m 2 ) 1.04(1.02 – 1.06) <0.001 1.04(1.02 – 1.05) <0.001 1.04(1.03 – 1.06) <0.001 1.04(1.03 – 1.06) <0.001 Cisplatin (per 100 mg/m 2 ) 1.46(1.26 – 1.68) <0.001 1.46(1.26 – 1.67) <0.001 1.47(1.27 – 1.68) <0.001 1.49(1.29 – 1.70) <0.001 Carboplatin (per 100 mg/m 2 ) 1.03(1.00 – 1.06) 0.024 1.03(1.00 – 1.06) 0.027 1.03(1.00 – 1.06) 0.012 1.03(1.00 – 1.06) 0.012 Calcineurin inhibitor (yes/no) 7.29(1.86 – 26.92) 0.003 7.9(11.94 – 30.52) 0.003 14.79(4.32 – 48.28) <0.001 9.31(2.43 – 33.77) 0.001 Doses Abelcet and/or Ambisome 1.02(0.94 – 1.06) 0.516 1.02(0.94 – 1.06) 0.513 1.02(0.95 – 1.06) 0.469 1.02(0.94 – 1.06) 0.555 Doses amphotericin B 1.00(0.95 – 1.03) 0.990 1.00(0.95 – 1.03) 0.998 1.00(0.96 – 1.03) 0.981 1.00(0.95 – 1.03) 0.936 V5 (per 10%) 1.14(1.04 – 1.24) 0.004 V10 (per 10%) 1.12(1.01 – 1.23) 0.021 COG abdominal radiation therapy (yes/no) 1.49(0.76 – 2.85) 0.235 TBI or WA (yes/no) 2.73(1.08 – 6.61) 0.029

Purpose This study qualitatively explored barriers and facilitators to accessing supportive vision services for childhood cancer survivors with vision deficits and identified current service-delivery contexts from the perspectives of community professionals and caregivers. Methods Participants included caregivers and professionals who completed semi-structured interviews. Provider questions focused on patient identification and assessment, follow-up protocols, and available resources, while caregiver questions addressed navigating survivorship care, academic needs, and goals for their children. Transcripts were thematically analyzed following inductive and deductive coding. Results Six caregivers and 10 professionals completed interviews. Thematic analysis resulted in three contexts for barriers and facilitators: school settings, community organizations, and healthcare settings. Obstacles children and their families may face when navigating the care system include service eligibility, financial barriers, transportation barriers, and geographical barriers. Caregivers described their care navigation experience through the same three contexts. Conclusion Childhood cancer survivors with retinoblastoma face substantial barriers to vision-related support across school, community, and clinical settings. This includes limited access to specialists, inequitable access to resources, and fragmented referral pathways. This study highlights the need for care coordination among healthcare providers, educators, and community agencies to improve functional, academic, and quality-of-life outcomes for this population. Implications for cancer survivors The high survival rate of retinoblastoma leaves a population with vision deficits, yet there remains a lack of integration of interventions for this population to address such deficits. Understanding barriers to vision care in survivorship can inform where to implement future interventions to increase this population's health service utilization.

10010 Background: Childhood cancer survivors face elevated risks for chronic health conditions and premature mortality. Engaging in healthy behaviors may mitigate these risks, yet neighborhood-level vulnerability may constrain survivors’ ability to adopt or sustain them. Methods: Among survivors (n=3,303) and community controls (n=652) in SJLIFE, neighborhood-level vulnerability was measured using census tract level overall and domain-specific (i.e. socioeconomic status, household composition, minority status, housing type and transportation) Social Vulnerability Index (SVI) scores, with higher values indicating higher vulnerability, and the U.S. Department of Agriculture’s persistent poverty measure. Health behaviors, including sedentary time/physical activity, smoking, alcohol, and illicit drug/marijuana use, were categorized as healthy, moderately unhealthy (1-2 unhealthy behaviors), and unhealthy (≥3 unhealthy behaviors). Multinomial logistic regression evaluated associations between neighborhood-level vulnerability at enrollment and health behavior patterns at most recent evaluation among survivors, adjusted for sociodemographic and cancer treatment factors as determined by backward selection. Interaction models compared associations between survivors and controls. Results: Survivors were 53.1% male, 82.5% non-Hispanic White, with a median age of 31.0 years (interquartile range: 23.5 – 38.5) at health behavior assessment. The most common childhood cancer diagnosis was acute lymphoblastic leukemia (28.8%). Survivors in the highest vs. lowest SVI tertile had higher odds of reporting moderately unhealthy (Odds Ratio [OR]: 1.46, 95% Confidence Interval [95% CI]: 1.08 – 1.98) or unhealthy (OR: 1.70, 95% CI: 1.13 – 2.56) behavior patterns, compared to a healthy behavior pattern. Socioeconomic and housing type SVI domains drove these associations, with survivors in the highest tertiles more likely than those in the lowest to have an unhealthy rather than healthy behavior pattern (Socioeconomic OR: 1.55, 95% CI: 1.02 – 2.35; Housing type OR: 1.53, 95% CI: 1.03 – 2.27). Persistent poverty was associated with greater odds of a moderately unhealthy behavior pattern (OR: 1.70, 95% CI: 1.09 – 2.66) in survivors. Housing type vulnerability was associated with disproportionately higher odds of an unhealthy behavior pattern among survivors compared to controls (ratio of ORs: 2.80, 95% CI: 1.19 – 6.60). Conclusions: Neighborhood-level vulnerability was associated with higher likelihood of unhealthy behavior patterns in childhood cancer survivors with housing type vulnerability having a greater impact on health behaviors in survivors compared to controls. Effective interventions to improve survivors’ health behaviors should incorporate neighborhood-level factors.

BACKGROUND:Ageing survivors of childhood cancer experience pain that substantially affects daily activities and health. We investigated the contribution of pain to frailty development or progression in survivors. METHODS:In this analysis of the St Jude Lifetime Cohort (SJLIFE), adult survivors of childhood cancer treated at a single institution in the USA completed a a baseline assessment including a frailty assessment at cohort entry and a follow-up frailty assessment 4-6 years later. Eligible participants were between ages 18 years and 45 years and were at least 10 years from their childhood cancer diagnosis at cohort entry. Women who were pregnant and participants currently receiving treatment for cancer were not eligible. Criteria for frailty were low lean muscle mass, muscle weakness, poor endurance, slow walking speed, and exhaustion; pre-frailty was defined as meeting two of the criteria, and frailty was defined as meeting three or more. Survivors self-reported pain (bodily pain and headache or migraine pain), pain interference, and health behaviours (including smoking status, alcohol consumption, and sedentary behaviour). Outcomes were analysed in participants who completed clinical assessments at both baseline and follow-up. Multinomial logistic regression examined associations between pain and frailty (odds ratios [ORs] and 95% CIs reported). FINDINGS:1261 adult survivors of childhood cancer recruited for SJLIFE between Jan 1, 2008, and June 30, 2013 completed clinical assessments at baseline (mean age 30·7 years [SD 7·0]; mean time since diagnosis 22·7 years [7·4]) and follow-up (mean time from baseline 5·2 years [0·7]). At baseline, 471 (37·4%) participants reported pain, with 194 (15·4%) also reporting pain interference; 294 (23·3%) participants were pre-frail or frail. From baseline to follow-up, 262 (20·8%) survivors had persistent pain, 211 (16·7%) had increasing pain, and 370 (29·3%) had persistent or progressive frailty. After adjusting for age, sex, race and ethnicity, time since diagnosis, BMI, anxiety, depression, and chronic health conditions, pain with interference was associated with pre-frailty (OR 1·85, 95% CI 1·19-2·88) and frailty (5·66, 2·75-11·68) at baseline and with persistent (3·44, 1·88-6·31) and progressed frailty (2·09, 1·25-3·49). Persistent (1·70, 1·11-2·61) and increasing pain (1·69, 1·09-2·61) from baseline to follow-up were associated with progressed frailty. Physical activity and sedentary behaviour were associated with frailty across models. INTERPRETATION:Pain that interferes with daily functioning is associated with frailty and frailty progression in survivors of childhood cancer, underscoring the need for interventions targeting pain and lifestyle factors to mitigate frailty risk and improve long-term health outcomes. FUNDING:US National Institutes of Health and American Lebanese Syrian Associated Charities.

Background: The impact of cancer therapy on chronic health condition (CHC) burden in childhood cancer survivors is well-established; however, the role of neighborhood-level social determinants of health (SDOH) remains underexplored. Methods: We analyzed 2,508 adult survivors of childhood cancer in the St. Jude Lifetime Cohort Study with ≥2 clinical assessments (2007-2020). SDOH encompassed social vulnerability (the Social Vulnerability Index) and environmental vulnerabilities (government-sourced indicators, e.g., primary care physicians [PCP] availability, food inaccessibility), categorized into quartiles. A total of 177 CHCs were severity-graded (CTCAE v4.03), aggregated into 48 CHC groups, and summarized into global burden. Multivariable logistic regressions examined associations between baseline SDOH and CHC severity progression at global and group levels, adjusting for clinical and personal sociodemographic factors. Interactions of SDOH with personal insurance and educational attainment were examined for effect modification. Findings: Survivors residing in the most SDOH-vulnerable neighborhoods, characterized by low income (OR: 1.83, 95%CI: 1.36-2.46), low education (OR: 1.53, 95%CI: 1.15-2.04), limited PCP availability (OR: 1.30, 95%CI: 1.03-1.64), and food inaccessibility (OR: 1.49, 95%CI: 1.08-2.07), had higher risks of progressive global CHC burden than those in the least vulnerable neighborhoods. Living in the most SDOH-vulnerable neighborhoods, including low education (OR: 2.69, 95%CI: 1.63-4.43 for peripheral nervous system disorders), food inaccessibility (OR: 4.36, 95%CI: 1.32-14.35 for arrhythmias), and poor walkability (OR: 4.60, 95%CI: 1.41-15.04 for abnormal glucose metabolism), was associated with higher risks of new-onset/worsening of multiple CHC groups than in the least vulnerable neighborhoods. SDOH interacted with survivors’ public insurance coverage to amplify CHC burden risk, including limited PCP availability (OR: 6.11, 95%CI: 2.33-16.04) and poor walkability (OR: 7.37, 95%CI: 2.82-19.27) for new-onset/worsening of peripheral musculoskeletal disorders. Interpretation: SDOH are upstream determinants of CHC progression among childhood cancer survivors, necessitating survivorship care that integrates clinical management with community- and policy-level interventions.

Childhood cancer survivors are at increased risk for obesity, which can potentiate treatment-related late effects. The association between bariatric surgery and cardiometabolic outcomes in survivors is unknown. Survivors of childhood cancer enrolled in the St Jude Lifetime Cohort with prior bariatric surgery for obesity (n = 33) and survivors with severe obesity without prior bariatric surgery (n = 542) were included. Body mass index (BMI) change was described. Multivariable logistic regression compared prevalence of cardiometabolic outcomes at follow-up. Mean change in BMI was -11.8 (SD 8.7) kg/m2 and +0.7 (SD 4.2) kg/m2 among survivors with and without bariatric surgery, after median follow-up of 6.1 and 5.3 years, respectively. Survivors with bariatric surgery (compared with those without) had lower odds of dyslipidemia (odds ratio [OR] = 0.3, 95% CI = 0.1 to 0.8) and prediabetes (OR = 0.4, 95% CI = 0.2 to 0.8). Bariatric surgery is associated with sustained BMI reduction and lower risk for cardiometabolic conditions in survivors of childhood cancer.

12114 Background: Survivors of childhood cancer are at high risk for chronic health conditions that may result in disability. However, the prevalence and financial burden of disability, defined using the World Health Organization International Classification of Functioning, Disability and Health (WHO ICF), have not been described in this population. Methods: Disability-related items ascertained using clinical and patient-report data from SJLIFE were classified using standardized WHO ICF childhood cancer components, including impairments in body function or structure (strength, neurocognition, vision, hearing, speech, balance, neuropathy, ataxia, hemiparesis, tone, bowel and bladder, flexibility, gait, posture, pain, fatigue), activity limitations (motor function, communication, personal care), and participation restrictions (physical activity, education, independent living, employment, quality of life). Aggregate disability severity scores (ADSS) were calculated by summing item-level indicators (0 = none/mild; 1 = moderate, severe, or life-threatening disability) across 55 items spanning 3 components (38 body impairments, 5 activity limitations, and 12 participation restrictions). Disability was classified using either age- and sex-specific z-scores derived from 815 community controls (0 = ≥ −1.5; 1 = < −1.5) or NCI Common Terminology Criteria for Adverse Events (CTCAE) grades (0 = < 2; 1 = ≥ 2). Logistic regression evaluated associations between disability and financial burden (cancer-related financial impact), adjusting for sex, race, age at evaluation, and cancer treatment exposures (chemotherapy, cranial radiation, amputation). Results: Among 3,549 survivors (mean age at evaluation 33.6 years; range 18.0–68.9; 52.1% male; 80.7% White non-Hispanic), the most common diagnoses were acute lymphoblastic leukemia (31.9%), central nervous system tumors (14.5%), and Hodgkin lymphoma (10.5%). The point (most recent visit) prevalence (95% CI) of ≥1 item rated as moderate or greater disability was 87.4% (86.3–88.5). Component-specific prevalence was 74.6% (73.2–76.0) for body impairments, 32.9% (31.3–34.4) for activity limitations, and 63.3% (61.7–64.9) for participation restrictions; all were higher than controls (p < 0.001). Higher overall ADSS was associated with greater financial hardship (OR = 2.97; 95% CI 2.05–4.30) with similar associations across all components, including body impairments (OR = 2.67; 95% CI 2.09–3.41), activity limitations (OR = 2.28; 95% CI 1.91–2.72), and participation restrictions (OR = 2.61; 95% CI 2.13–3.21). Conclusions: WHO-defined disability is highly prevalent among adult survivors of childhood cancer and is strongly associated with financial burden. These findings highlight the need for integrated survivorship care that addresses both medical and socioeconomic risk factors.

Childhood cancer survivors are at high risk for treatment-related chronic health conditions. How much of this risk can be attributed to lifestyle is not known. In this study, we assess associations between lifestyle and a range of chronic health conditions and estimate lifestyle-specific population attributable fractions for chronic health conditions in survivors and compare them to those of radiotherapy and chemotherapy. Here we show that unhealthy lifestyle is associated with higher risk for subsequent hypertension, dyslipidemia, diabetes, heart attack, heart failure, valvular disease, joint replacement, anxiety, depression, and impaired physical and mental quality of life. Disease proportions attributed to unhealthy lifestyle exceed those of chemotherapy and radiotherapy for hypertension, diabetes, joint replacement, anxiety, depression, and impaired physical and mental quality of life. Unlike previous cancer treatment exposures, lifestyle can be modified. We need to further develop and implement effective lifestyle interventions in childhood cancer survivors, promoting healthy weight and physical activity.

BACKGROUND:Childhood cancer survivors frequently develop chronic medical conditions long after treatment. Patient-reported symptoms may provide early signals of deteriorating health, but their prognostic value for later disease progression remains unclear. We aim to determine whether symptom patterns and their changes over time are associated with the progression of chronic health conditions in adult survivors of childhood cancer. METHODS:We analyzed 735 survivors enrolled in the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort Study who completed three symptom assessments and repeated standardized clinical evaluations. Symptoms were grouped into physical and emotional dimensions to classify survivors into four clusters from low to high burden. Changes in symptom burden over time were also classified. Progression of total and organ-specific chronic health conditions was determined from clinical assessments. Statistical models evaluated associations between symptom patterns and subsequent disease progression after adjustment for demographic, lifestyle, and treatment factors. RESULTS:Here, we show that survivors with high physical and emotional symptom burden had higher risks of progression of total chronic health conditions and of respiratory, musculoskeletal, neurologic, and endocrine conditions. Survivors with increasing or persistently high symptom burden over time also had greater progression of total and organ-specific conditions, including neurologic, respiratory, endocrine, and reproductive outcomes. CONCLUSIONS:These findings show that symptom patterns provide prognostic information beyond treatment history and identify survivors at elevated risk for worsening health. Integrating routine symptom monitoring into survivorship care may enable earlier detection of disease progression and support more personalized preventive care.

PURPOSESurvival rates for childhood cancer have improved substantially worldwide. Although survivorship begins at cancer diagnosis, the concept of survivorship care often begins 2-5 years from cancer diagnosis. Despite the availability of evidence-based survivorship guidelines, their implementation remains inconsistent, particularly in low- and middle-income countries. This study aimed to characterize clinicians' survivorship care practices, goals, perceived barriers, and tools/needs across variably resourced global settings to inform strategies for sustainable, equitable survivorship care.METHODSWe conducted semistructured interviews with physicians, psychologists, and nurses responsible for childhood cancer survivorship care across diverse health care settings. Participants were recruited across all six WHO regions and represented a range of clinical disciplines and survivorship program maturity levels. Interviews explored care delivery models, survivorship goals, institutional support, and barriers to implementation. Rapid qualitative analysis was performed using a structured matrix approach. Findings were stratified by country income classifications to contextualize resource-related differences.RESULTSThirty-one clinicians from 26 countries participated, representing low- (70.9%), middle- (6.5%), and high-income (22.6%) settings. Survivorship care models varied, ranging from structured, multidisciplinary programs to informal follow-up. Regardless of setting, clinicians shared a common goal of monitoring survivors to optimize long-term health and quality of life. Key barriers included limited funding, workforce shortages, inadequate institutional support, challenges with patient access and follow-up, and difficulties implementing complex survivorship guidelines. Clinicians from lower-resourced settings emphasized the need for adaptable care models and simplified, context-appropriate guidelines, whereas those from higher-income settings reported competing priorities and workforce constraints.CONCLUSIONGlobal childhood cancer survivorship care is highly variable but united by shared goals. Overcoming barriers requires context-adapted guidelines, strengthened institutional support, workforce development, and patient-centered tools. Prioritizing survivorship care everywhere is essential to achieving equitable long-term outcomes for childhood cancer survivors worldwide.

The Pediatric Hodgkin Consortium (PHC) hypothesized that increasing chemotherapeutic dose-density for Hodgkin lymphoma (HL) they could increase the complete response rate among favorable risk patients with HL after 8 weeks of Stanford V compared to 8 weeks of VAMP. This would translate to a decrease in patients who required radiation therapy (RT) to achieve a cure. HOD08 (NCT00846742) was a phase II multicenter investigator-initiated single- arm trial for patients ≤ 21 years of age with previously untreated stage IA or IIA HL without mediastinal bulk or extranodal disease extension and fewer than three sites of disease. Treatment consisted of a modified 8-week Stanford V regimen (vinblastine, doxorubicin, vincristine, bleomycin, mechlorethamine, etoposide and prednisone). Modified tailored field RT was administered only to disease sites achieving less than a CR. The primary objective was to increase CR rate after 8 weeks of chemotherapy by at least 20% (from an estimated 44% to 64%) compared to patients treated on a previous trial (HOD99). HOD08 enrolled 85 patients with HL and 72 were evaluable for the primary objective of whom 55 (76.4%) achieved a CR at all sites and did not receive RT. The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 87.4% (95% confidence interval (CI) 80.4%-95.0%) and 98.7% (95% CI 96.2%-100%), respectively. A dose-dense modified Stanford V regimen reduced the proportion of low-risk pediatric patients with HL who received RT while maintaining excellent outcomes. NCT00846742

BACKGROUND:Adult survivors of childhood cancer are at higher risk of premature aging compared to their cancer-free peers due to the cancer and its treatments. However, little is known about the effect of adherence to healthy dietary patterns on aging in childhood cancer survivors. METHODS:A cross-sectional analysis was conducted of 3322 participants (mean age, 30.5 years; standard deviation [SD], 8.4) from the St. Jude Lifetime Cohort Study. Diet was measured by a food frequency questionnaire and used to assess the Healthy Eating Index (HEI)-2015 and alternate Mediterranean diet (aMED) scores. Premature aging was assessed by the deficit accumulation index and categorized into low, medium, and high risk. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) with 95% confidence intervlas (CIs). RESULTS:The mean (SD) HEI-2015 score was 60.0 (10.9) of 100, and the aMED score was 4.2 (2.0) of 9. Twenty percent and 8% of survivors were in the medium and high deficit accumulation index categories, respectively. Higher adherence to HEI-2015 (ORhigh vs. low = 0.80; 95% CI, 0.69-0.93 per 10-point increment) and aMED (ORhigh vs. low = 0.91; 95% CI, 0.84-0.98 per 1-point increment) were associated with a lower risk of premature aging. The associations remained consistent among survivors who received radiation or chemotherapy. CONCLUSION:Adherence to a healthy diet may contribute to reducing the premature aging risk in adult survivors of childhood cancer. Interventions that support healthy eating in this population could potentially have benefits for long-term health outcomes.

PURPOSE:With new evidence emerging about breast cancer risk following anthracycline chemotherapy, the International Late Effects of Childhood Cancer Guideline Harmonization Group updated the evidence and breast cancer surveillance recommendations for female childhood, adolescent, and young adult (CAYA) cancer survivors. METHODS:The Grading of Recommendations Assessment, Development, and Evaluation methodology was used to incorporate new knowledge and refine breast cancer surveillance recommendations. The guideline panel updated the systematic literature review and revised recommendations based on new evidence, clinical judgment, and assessments of benefits and harms of surveillance, ensuring adaptability across various health care systems. RESULTS:The literature update revealed new findings on the effects of anthracyclines on breast cancer risk in female CAYA cancer survivors. Moderate-quality evidence shows no significant association between doxorubicin doses <100 mg/m2 and breast cancer risk. High-quality evidence indicates a statistically significant but weak association between breast cancer risk and 100-199 mg/m2 doxorubicin (relative risk, <2) and a moderate breast cancer risk (relative risk, 2-4) for those treated with ≥200 mg/m2 in the absence of radiotherapy exposing breast tissue (chest radiation). Routine breast cancer surveillance after ≥200 mg/m2 doxorubicin in the absence of chest radiation is reasonable from age 30 years onward or ≥8 years from exposure (whichever occurs last). Due to inconclusive evidence, no recommendation could be formulated for routine breast cancer surveillance after daunorubicin, epirubicin, or idarubicin, in the absence of chest radiation. CONCLUSION:The newly identified evidence on breast cancer risk after anthracyclines supports changes in the 2019 recommendations regarding breast cancer surveillance for survivors treated with ≥200 mg/m2 doxorubicin without chest radiation.

Supplementary Table S2 shows the results of bivariate analyses between individual-level participant variables and frailty status