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Background: Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001–2021. Method: Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen–Johansen estimators and assessed associated risk factors using Cox regression. Results: Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001–2010 and 2.5% during 2011–2021 (p = 0.20). During 2011–2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. Interpretation: Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities., BACKGROUND: Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001-2021. METHOD: Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen-Johansen estimators and assessed associated risk factors using Cox regression. RESULTS: Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001-2010 and 2.5% during 2011-2021 (p = 0.20). During 2011-2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. INTERPRETATION: Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities.

Importance Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone. Objective To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers. Design, Setting, and Participants This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023. Exposure Duration of exclusive breastfeeding in infancy. Main Outcomes and Measures Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models. Results A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to, IMPORTANCE: Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone.OBJECTIVE: To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers.DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023.EXPOSURE: Duration of exclusive breastfeeding in infancy.MAIN OUTCOMES AND MEASURES: Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models.RESULTS: A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to decrea

Objectives Asparaginase-associated pancreatitis (AAP) occurs in up to 18% of patients treated for acute lymphoblastic leukemia (ALL); however, long-term sequelae are largely unexplored. We aimed to explore pancreatic sequelae among ALL survivors with and without AAP. Methods We investigated pancreatic sequelae in a national cohort of ALL survivors, aged 1–45 years at ALL diagnosis treated according to the NOPHO-ALL2008 protocol and included sex- and age-matched community controls. Results We included 368 survivors (median follow-up 6.9 years), including 47 survivors with AAP and 369 controls. The p-lipase and p-pancreas-type amylase levels were lower in AAP survivors compared with both non-AAP survivors (Medians: 23 U/L [IQR 14–32] and 18 U/L [IQR 10–25] versus 29 [IQR 24–35] and 22 [17–28], p < .001 and p = .002) and community controls (28 U/L [IQR 22–33] and 21 U/L [IQR 17–26], both p < .006). Fecal-elastase was more frequently reduced in AAP survivors compared with non-AAP survivors (7/31 vs. 4/144, p = .001). Persisting pancreatic sequelae were found in 15/47 of AAP survivors and 20/323 of non-AAP survivors (p < .001), including diabetes mellitus in 2/39 of AAP survivors and 2/273 of non-AAP survivors. Conclusions ALL survivors with AAP are at increased risk of persisting pancreatic dysfunction and require special attention during follow-up., Objectives: Asparaginase-associated pancreatitis (AAP) occurs in up to 18% of patients treated for acute lymphoblastic leukemia (ALL); however, long-term sequelae are largely unexplored. We aimed to explore pancreatic sequelae among ALL survivors with and without AAP. Methods: We investigated pancreatic sequelae in a national cohort of ALL survivors, aged 1–45 years at ALL diagnosis treated according to the NOPHO-ALL2008 protocol and included sex- and age-matched community controls. Results: We included 368 survivors (median follow-up 6.9 years), including 47 survivors with AAP and 369 controls. The p-lipase and p-pancreas-type amylase levels were lower in AAP survivors compared with both non-AAP survivors (Medians: 23 U/L [IQR 14–32] and 18 U/L [IQR 10–25] versus 29 [IQR 24–35] and 22 [17–28], p <.001 and p =.002) and community controls (28 U/L [IQR 22–33] and 21 U/L [IQR 17–26], both p <.006). Fecal-elastase was more frequently reduced in AAP survivors compared with non-AAP survivors (7/31 vs. 4/144, p =.001). Persisting pancreatic sequelae were found in 15/47 of AAP survivors and 20/323 of non-AAP survivors (p <.001), including diabetes mellitus in 2/39 of AAP survivors and 2/273 of non-AAP survivors. Conclusions: ALL survivors with AAP are at increased risk of persisting pancreatic dysfunction and require special attention during follow-up.

BACKGROUND: The cerebrospinal fluid (CSF) proteome could offer important insights into central nervous system (CNS) malignancies. To advance proteomic research in pediatric CNS cancer, the current study aims to (1) evaluate past mass spectrometry-based workflows and (2) synthesize previous CSF proteomic data, focusing on both qualitative summaries and quantitative re-analysis. MAIN: In our analysis of 11 studies investigating the CSF proteome in pediatric patients with acute lymphoblastic leukemia (ALL) or primary brain tumors, we observed significant methodological variability. This variability negatively affects comparative analysis of the included studies, as per GRADE criteria for quality of evidence. The qualitative summaries covered 161 patients and 134 non-tumor controls, while the application of validation cohort varied among the studies. The quantitative re-analysis comprised 15 B-ALL vs 6 "healthy" controls and 15 medulloblastoma patients vs 22 non-tumor controls. Certain CSF proteins were identified as potential indicators of specific malignancies or stages of neurotoxicity during chemotherapy, yet definitive conclusions were impeded by inconsistent data. There were no proteins with statistically significant differences when comparing cases versus controls that were corroborated across studies where quantitative reanalysis was feasible. From a gene ontology enrichment, we observed that age disparities between unmatched case and controls may mislead to protein correlations more indicative of age-related CNS developmental stages rather than neuro-oncological disease. Despite efforts to batch correct (HarmonizR) and impute missing values, merging of dataset proved unfeasible and thereby limited meaningful data integration across different studies.CONCLUSION: Infrequent publications on rare pediatric cancer entities, which often involve small sample sizes, are inherently prone to result in heterogeneous studies-particularly when conducted within a r