BACKGROUND:Colorectal cancer (CRC) risk is increased in childhood cancer survivors (CCS). In France, fecal immunochemical testing (FIT) is recommended every 2 years for those aged 50-74 years, although no specific CRC-screening programs are dedicated to CCS. METHODS:We investigated the participation rate in CRC screening by using the national health data system to identify FIT in the French Childhood Cancer Survivor Study cohort, across three two-year periods-2016-17, 2018-19, and 2020-21-to compare it to the general population via indirect standardization and used multivariable logistic regression to investigate factors influencing CCS participation. RESULTS:In 2016-17, 2018-19, and 2020-21, respectively, 20.0%, 21.8%, and 23.2% participated in screening, which is lower than the rate for the general population [standardized incidence ratios (95% CI) = 0.62 (0.49-0.78), 0.72 (0.59-0.87), and 0.70 (0.59-0.83), respectively]. Demographic, clinical, therapeutic, and socio-economic determinants were not associated with CRC-screening participation. Although these patterns were not consistently observed across all subgroups, survivors with severe long-term complications tended to have higher participation [odds ratio (95% CI) = 1.64 (1.07-2.53)], whereas higher medical expenses were associated with lower participation (P < .01). CONCLUSION:Despite an increased risk of CRC after childhood cancer, participation in CRC-screening programs remains low in CCS. Survivors and their physicians require educational initiatives to promote CRC screening and provide risk-adapted surveillance guidelines.

Most previous studies aimed to establish etiological signatures of thyroid tumors compared sporadic papillary thyroid carcinomas (sPTC) and PTC that develop in individuals exposed to ionizing radiation during childhood. However, such approaches may lead to a biased signature combining exposure markers independent of the carcinogenic process and markers of radiation-induced carcinogenesis. We analyzed the miRNome (Affymetrix) and transcriptome (RNA sequencing) of a series of normal thyroid tissues and PTC from Ukrainian individuals contaminated with iodine-131 released by the Chornobyl Nuclear Power Plant in 1986 at high (> 0.5 Gy; N = 9) or low (< 50 mGy; N = 12) thyroid radiation doses, and from unexposed Ukrainian individuals (N = 28). First, the six sample groups were analyzed jointly using partial least squares discriminant analysis (sPLS-DA) to assess whether normal tissues and PTC shared common multi-omic signatures associated with exposure history, independent of carcinogenesis. Next, we applied a multiblock sPLS-DA (DIABLO) to isolate markers associated with exposure in the three normal tissue groups. Then, using the remaining miR and genes from the datasets not associated with exposure, we searched for a multi-omics signature associated with a difference in the carcinogenic process. sPLS-DA analysis of the six sample groups showed that normal tissues and PTC from exposed individuals shared a common multi-omics signature (58 miR/snoRNA, 50 genes) compared to unexposed samples. Our DIABLO analysis identified 44 miR/snoRNA and 45 genes exposure signatures distinguishing exposed from unexposed normal tissues. These signatures, when applied to PTC groups, supported that PTC developed after radiation exposure exibited exposure markers independent of any carcinogenic process. In addition to this exposure signature, we identified 39 miR/snoRNA and 64 genes signatures that identified the PTC developed after radiation exposure which deviated significantly from the sPTC profile. Normal tissues and PTC from exposed individuals exhibit a common molecular long-term memory of exposure history. Furthermore, PTC developed after radiation exposure display dose-dependent molecular specificities compared to sPTC. As PTC associated with low doses are mainly subclinical sPTC revealed by screening in the post-Chornobyl population, the proposed multi-omic signature could be attributable to sPTC developed in an exposed thyroid gland.

Table S4 presents the quality control results using the q-genie scale for each article included in this review.

Fatigue is a prevalent and late effect among childhood cancer survivors (CCSs). Few large studies have comprehensively evaluated its prevalence and determinants. Identifying risk factors for fatigue and severe fatigue (SF) is crucial to improving survivorship care. This study assessed the prevalence of fatigue and SF, as well as demographic, clinical, and treatment-related predictors in the French Childhood Cancer Survivor Study (FCCSS). This cross-sectional analysis included adult 5-year CCSs diagnosed before age 21 (1946–2000) in the FCCSS cohort. Fatigue was measured using the French Multidimensional Fatigue Inventory (MFI-20); SF was defined as a total score > 60. Associations with sex, age, cancer type, treatment, and social deprivation were estimated using multivariable regressions. Analyses were stratified by central nervous system (CNS) vs. non-CNS tumors and compared to general population norms. Among 3170 CCSs, fatigue scores exceeded population norms from age 30, with women affected earlier and more severely. General (10.0 ± 4.2) and physical fatigue (9.6 ± 4.2) were the most pronounced dimensions, increasing with age and peaking at ≥ 50 years. Higher fatigue scores were independently associated with female sex, obesity, older age, and CNS tumor history. SF affected 16

Table S1 displays all the keywords used to search articles in the Pubmed database.

PURPOSE:Accurate dose estimation to the heart and lungs is essential for assessing cardiopulmonary toxicity in women treated with radiotherapy (RT). However, DICOM-RT datasets often lack reliable dose information for organs located partly or entirely outside the beam path, limiting large-scale dose-response studies. We introduce an approach that supplements native DICOM-RT dose data with publicly available out-of-field (OOF) dose profiles to improve dose estimation in these regions, and apply it to breast cancer RT. METHODS:Dose-volume histogram (DVH) metrics for the heart and lungs were evaluated in 149 patients. Voxels inside the beam path were assigned TPS doses from RT-Dose. Outside, a percent-depth-dose (PDD) and off-axis-ratio formalism was used to re-estimate voxel dose. Extended off-axis-ratio values were derived from empirical OOF-dose datasets. Geometric beam parameters for patient-specific 3D dose reconstruction were obtained from DICOM-RT files. Paired DVH metrics from TPS and re-evaluated doses were compared using the Wilcoxon signed-rank test. RESULTS:For volumetric-modulated arc therapy (VMAT), no significant differences were observed between DVH metrics derived from the TPS and those obtained from re-evaluated dose distributions. In contrast, significant differences were found in the low-dose region (<10 Gy) for non-VMAT techniques, with the largest discrepancies for three-dimensional conformal RT (3DCRT). CONCLUSIONS:For studies of normal-tissue responses below 10 Gy, limitations of TPS dose calculations beyond the field edge must be considered.

Table S3 displays all the keywords used to search articles in the WOS database.

This retrospective cohort study estimated the healthcare expenditure of infertility treatment in women who survived childhood cancer and analyzed associated factors using data from the French Childhood Cancer Survivor Study (FCCSS) cohort. From 2578 women in the FCCSS cohort, 118 exposed who received infertility treatment, aged 18–42, were identified based on first recorded drug therapy and/or in vitro fertilization/intracytoplasmic sperm injection and/or medically assisted procreation between 2011 and 2018. Six hundred eight unexposed who had not undergone infertility treatment were selected using propensity score matching. Expenditure related to infertility treatment was estimated as the difference between cases’ expenditures and average expenditures of their controls yearly, over a maximum follow-up period of 4 years unexposed. Average annual expenditure related to infertility treatment per patient over 4 years was 3043 euros (95

Table S2 displays all the keywords used to search articles in the Scopus database.

BACKGROUND AND AIMS:Cardiotoxic treatments like anthracyclines and heart-directed radiotherapy increase the risk of cardiac diseases (CDs) in childhood cancer survivors (CCSs), but individual differences in CD incidence are not fully understood. This study aims to identify transcriptomic biomarkers associated with CD occurrence after childhood cancer treatment. METHODS:A matched case-control study was conducted on a sample of 330 CCS: 165 cases with CD and 165 CD-free controls. The expression of 8557 genes was investigated to select those associated with CD and heart failure (HF), using three stabilization approaches derived for the conditional logistic regression with Lasso (Percentile lasso, Bolasso, and Sublasso). The intersection of the three selected gene sets formed the final selection. The interactions between cancer treatment doses and selected genes were investigated. RESULTS:One promising gene, NFE2L2, constituted the final selection, and its expression was lower in cases than in controls [CD: odds ratio (OR) .16, 95% confidence interval (CI) .09-.29; HF: OR .11, 95% CI .03-.37]. No interaction between treatment doses and NFE2L2 expression levels was found in our study. Incorporating NFE2L2 gene expression into prognostic models improved discrimination between cases and controls compared with models based solely on clinical and treatment variables [CD: area under the curve (AUC) .85 vs .66; HF: AUC .87 vs .77]. CONCLUSIONS:Using high-dimensional data selection methods has enabled the identification of the gene NFE2L2, associated with CD and HF in CCS. Further research is needed to validate this finding and achieve a better understanding of the biological mechanisms leading to cardiac toxicities and so to develop risk-adapted treatment and surveillance strategies.

Background: Differentiated thyroid cancer (DTC) is a prevalent malignancy with increasing global incidence, yet its genetic susceptibility remains poorly understood. Although previous genome-wide association studies (GWAS) have identified several susceptibility loci, the genetic, transcriptomic, and proteomic factors influencing DTC risk remain unclear. Methods: We conducted a large-scale GWAS of 7,681 cases and 963,550 controls of European ancestry. Transcriptome-wide association studies (TWAS) used the joint tissue imputation across thyroid, pituitary, blood, and hypothalamus tissues. Proteome-wide association studies (PWAS) integrated brain and plasma proteomic data to identify proteins influencing DTC risk. Mendelian randomization (MR) and Bayesian colocalization were conducted to infer causality. Findings: GWAS identified 18 novel loci associated with DTC risk, four of which were previously suggested and are now confirmed. TWAS identified 29 significant genes, including five genes (LRRC34, NRG1, HEMGN, PTCSC3, and SMAD3) located within known loci and three novel genes (SAMD4A, RAD51-AS1, and MPHOSPH6) validated as causal through MR and Bayesian colocalization. PWAS identified seven significant proteins, with three (MTHFR, KDELC2, and SAMD4A) confirmed as causal, further highlighting 15q15.1 as a novel risk locus consistently emerging across all omics layers. Interpretation: This integrated multi-omics approach reveals novel genetic and molecular mechanisms underlying DTC, linking genomic variation to gene expression and protein abundance. The consistent implication of the 15q15.1 locus highlights a potential key regulatory pathway contributing to DTC susceptibility.

BACKGROUND:Survivors of childhood cancer are at risk of subsequent primary melanoma, but the magnitude of the risk after different childhood cancer types and beyond age 50 years remains inadequately characterized. We quantified risks in the largest cohort of childhood cancer survivors worldwide. METHODS:The PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies cohort includes 68 002 five-year childhood cancer survivors across Europe (diagnosed 1940-2008). Subsequent primary melanoma risks were quantified using standardized incidence ratios (SIRs), absolute excess risks (AERs), cumulative incidence, and relative risks (RRs). RESULTS:Over 1 239 675 person-years, 197 subsequent primary melanoma were ascertained, whereas 84.9 were expected (SIR = 2.3, 95% confidence interval [CI] = 2.0 to 2.7). Although the standardized incidence ratio decreased with attained age (P for trend < .001), it remained increased at 2.1-fold (95% CI = 1.5 to 3.1) at age 50 years and older. By age 65 years, cumulative incidence was 1.2% (0.8% expected). Of all cancer types, heritable retinoblastoma survivors had the greatest risk (SIR = 16.5, 95% CI = 10.8 to 25.3; AER = 94.4, 95% CI = 59.9 to 148.9), with cumulative incidence of 3.3% at age 50 years and 5.5% at age 60 years. Survivors treated with radiotherapy had a 70% greater risk than those treated without (RR = 1.7, 95% CI = 1.1 to 2.7), increasing to 4.0-fold by age 50 years and older (RR = 3.9, 95% CI = 1.1 to 13.9). For chemotherapy, no statistically significant association was found (RR = 0.9, 95% CI = 0.5 to 1.6). CONCLUSIONS:Childhood cancer survivors, particularly those with heritable retinoblastoma and those treated with radiotherapy, remain at increased risk of melanoma beyond age 50 years. Current survivorship guidelines focus principally on treatment history; however, our findings suggest that long-term follow-up guidelines should additionally include childhood cancer type and attained age as risk-stratifying factors, particularly where individual treatment records are unavailable.

Table S5 summarizes the reasons behind the exclusion of 15 articles following the review of their full texts.

Supplementary Table 3 shows the estimated adjusted relative risks of renal hospitalisation by exposure to ifosfamide (stratified by cumulative dose) according to nephrectomy status.

Importance:Substantial improvements in childhood cancer survival have created a critical need to address serious long-term health complications, such as valvular heart disease (VHD). Objective:To identify treatment-related risk factors for VHD in a large European cohort of long-term childhood cancer survivors. Design, Setting, and Participants:This nested case-control study used data from the PanCareSurFup (PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies) and ProCardio cohorts, including detailed radiation dose reconstruction and chemotherapy exposure, for childhood cancer survivors from 7 European countries, diagnosed between 1940 and 2009, who survived at least 5 years after cancer diagnosis. Case patients, defined as having symptomatic VHD, were matched with controls 1:2 by subcohort, sex, age at cancer diagnosis, and calendar year of initial diagnosis. Data were analyzed from October 2023 to June 2025. Exposures:Doses were calculated by performing a whole-body dosimetric reconstruction using a voxel-based anthropomorphic phantom with more than 200 delineated anatomic structures or substructures. Cumulative dose to cytotoxic agents was also assessed. Main Outcome and Measure:Development of symptomatic VHD (grade ≥3 per the Common Terminology and Criteria for Adverse Events, version 4.03). Results:Of the 225 cases, 136 participants (60.4%) were male, and 195 (86.7%) were diagnosed with VHD beyond 20 years from childhood cancer. Survivors receiving a mean heart radiation therapy (RT) dose of 5 to less than 15 Gy had an increased risk of VHD (odds ratio [OR], 4.7; 95% CI, 2.1-10.7) compared to those without heart RT, with higher risk when more than half of the heart was exposed. The heart RT dose response appeared exponential, with the OR being 104.1 (95% CI, 27.8-389.6) for mean heart dose of 30 Gy or more, increasing considerably with follow-up from 6.0 (95% CI, 1.4-26.5) after 5 to 19 years to 71.4 (95% CI, 20.4-250.0) after 30 or more years. Cumulative anthracycline doses of 400 mg/m2 or higher were also associated with increased VHD risk (OR, 3.8; 95% CI, 1.4-10.3), showing an exponential dose-response pattern. Cumulative exposure to platinum agents was associated with VHD risk in a linear manner. No statistically significant associations were found for other chemotherapy agents or radiation to the spleen. Conclusion and Relevance:In this case-control study, heart RT, anthracyclines, and platinum agents were associated with increased VHD risk in childhood cancer survivors. Risks from both RT and anthracyclines were amplified with age and follow-up, underscoring the need for long-term cardiac surveillance.

Supplementary Table 2 shows the estimated relative risks from multivariable analyses, with and without cardiac pathologies adjustment.