Background: Cancer‐related fatigue is a debilitating late effect after treatment for childhood cancer. The prevalence of fatigue in childhood cancer survivors (CCSs) and associated factors for fatigue has varied widely in previous studies. Two important aspects of cancer‐related fatigue, its severity and chronicity, are often not assessed. This study investigated the prevalence of, and risk factors for, severe chronic fatigue (CF) in a national cohort of Dutch CCSs.Methods: In this study, 2810 CCSs (5‐year survivors of all childhood malignancies diagnosed between 1963 and 2001 with a current age of 12‐65 years) and 1040 sibling controls were included. CF was assessed with the Short Fatigue Questionnaire and was defined as a score ≥ 18 and persistence of fatigue for ≥6 months. Cancer‐ and treatment‐related characteristics, current health problems, and demographic and lifestyle variables were assessed as potential risk factors for CF via multivariable logistic regression analyses.Results: In adult CCSs and sibling controls (≥18 years old), the prevalence of CF was 26.1% and 14.1%, respectively (P < .001). In adolescent CCSs and sibling controls (2, 2.20; 95% CI, 1.50‐3.21), and a central nervous system diagnosis (OR, 1.74; 95% CI, 1.17‐2.60) were significantly associated with CF in adult CCSs.Conclusions: This study shows that CCSs, regardless of their cancer diagnosis, report CF more often than sibling controls. This study provides new evidence for the prevalence of fatigue in CCSs.

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m ^{− 2} : 1.24, 95% confidence interval (CI): 1.18–1.31), with more than twofold increased risk for survivors treated with ≥200 mg m ⁻² cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200–299 mg m ^{− 2} , HR: 2.33 for 300–399 mg m ^{− 2} and HR: 2.78 for ≥400 mg m ^{− 2} ). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59–6.63). For patients treated with or without chest irradiation, HRs per 100 mg m ^{− 2} of doxorubicin were 1.11 (95% CI: 1.02–1.21) and 1.26 (95% CI: 1.17–1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m ^{− 2} cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols.

Background: Childhood cancer survivors face late health problems; despite advances in research, details on risk remain unclear. We describe the methodological aspects of the Dutch Childhood Cancer Survivor Study (DCCSS) cross‐sectional clinical study (LATER 2 study).Procedure: From the multi‐center DCCSS LATER cohort of 6165 five‐year survivors diagnosed during 1963–2001, we invited 4735 eligible survivors in 2016, as well as siblings and parents of survivors. Gaps in evidence identified during development of surveillance guidelines were translated into clinical research questions for 16 outcome‐specific subprojects. The regular care visit to the LATER outpatient clinic forms the backbone of outcome assessment complemented with research‐defined measurements (physical examination, clinical tests, questionnaires). Furthermore, blood/saliva samples were taken for deoxyribonucleic acid (DNA) extraction.Results: In total, 2519 (53.2%) survivors participated in the LATER 2 study. When comparing participants with nonparticipants, we observed that males, CNS survivors, and those treated with surgery only were less likely to participate. Of the participating survivors, 49.3% were female. Median time since childhood cancer diagnosis was 26.9 years (range 14.8–54.7 years) and median attained age was 34.4 years (range 15.4–66.6 years).Conclusions: The high‐quality data generated in the LATER 2 study will provide valuable insights into risks of and risk factors for clinical and physical and psychosocial health outcomes and factors for early recognition of those health outcomes in long‐term childhood cancer survivors. This will contribute to fill in important gaps in knowledge and improve the quality of life and care for childhood cancer survivors.

In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

Background: Childhood cancer survivors are at risk for developing long‐term adverse health outcomes. To identify the risk of and risk factors for specific health outcomes, well‐established cohorts are needed with detailed information on childhood cancer diagnosis, treatment, and health outcomes. We describe the design, methodology, characteristics, and data availability of the Dutch Childhood Cancer Survivor Study LATER cohort (1963–2001) part 1; questionnaire and linkage studies.Methods: The LATER cohort includes 5‐year childhood cancer survivors, diagnosed in the period 1963–2001, and before the age of 18 in any of the seven former pediatric oncology centers in the Netherlands. Information on health outcomes from survivors and invited siblings of survivors was collected by questionnaires and linkages to medical registries.Results: In total, 6165 survivors were included in the LATER cohort. Extensive data on diagnosis and treatment have been collected. Information on a variety of health outcomes has been ascertained by the LATER questionnaire study and linkages with several registries for subsequent tumors, health care use, and hospitalizations.Conclusion: Research with data of the LATER cohort will provide new insights into risks of and risk factors for long‐term health outcomes. This can enhance risk stratification for childhood cancer survivors and inform surveillance guidelines and development of interventions to prevent (the impact of) long‐term adverse health outcomes. The data collected will be a solid baseline foundation for future follow‐up studies.

Objectives: The aim of this study was to identify the prevalence of and independent risk factors for long-term effects of childhood cancer treatment on the dentition and oral health in childhood cancer survivors (CCSs). Methods: This cross-sectional study is part of the Dutch Childhood Cancer Survivor Study (DCCSS) LATER 2. CCSs were diagnosed with cancer between 1963 and 2001. This study focuses on survey data of 154 CCSs on whom information about their oral health was received from their dentists (71.3%). Descriptive statistics and univariable and multivariable Poisson regression analyses were performed to determine the association between treatment characteristics and oral health data. Results: Of the study group, 36.3% had at least one DDD. The most prevalent DDDs were short-root anomaly (14.6%), agenesis (14.3%), and microdontia (13.6%). Risk factors for at least one DDD were younger age at diagnosis (<3 years) and dose-dependent alkylating agent therapy. Conclusions: This study provides more insight into risk factors for oral health problems in Dutch CCSs. This information is essential in order to improve early detection, prevention, dental care, and quality of life. Further studies are needed in order to better define dose-related radiotherapy exposure of the developing teeth in correlation with oral health problems.