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Background: In recent decades, new first and subsequent lines of anticancer treatment and supportive care have improved survival for children with cancer. We investigated recent temporal changes in the incidence of relapse and survival after relapse among children with cancer in Denmark., Procedure: This register-based study included 2890 children diagnosed before age 15 years with haematological cancers and solid tumours (2001-2021) and central nervous system (CNS) tumours (2010-2021). We used the Aalen-Johansen and Kaplan-Meier estimators to assess cumulative incidence of relapse-defined as cancer recurrence or progression-and survival probability after relapse., Results: Comparing the periods 2001-2010 and 2011-2021, the 5-year cumulative incidence of relapse decreased from 14% to 11% among children with haematological cancers (p = .07), and from 21% to 18% among children with solid tumours (p = .26). Concurrently, the 5-year survival after relapse increased among children with haematological cancers (from 44% to 61%, p = .03) and solid tumours (from 38% to 46%, p = .25). Among children with malignant CNS tumours, the 5-year cumulative incidence of relapse and the 5-year survival after relapse remained stable (49% and 51%, p = .82; and 20% and 18%, p = .90) comparing 2010-2015 and 2016-2021., Conclusions: In recent decades in Denmark, improvements were observed in reducing relapse incidence and increasing survival after relapse in children with haematological cancers and solid tumours. However, the persistent survival gap between children who relapse and those who do not across all childhood cancers underlines the need for intensified and highly targeted treatments for children at high risk of relapse., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

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: Severely delayed elimination of methotrexate (MTX) is difficult to predict in patients treated with high-dose MTX (HD-MTX), but it may cause life-threatening toxicity. It has not been defined how an increase in plasma creatinine can be best used as a predictor for severely delayed MTX elimination, thus providing a guide for therapeutic interventions to minimize renal toxicity., Methods: Pharmacokinetic data were retrospectively collected on 218 Danish children with acute lymphoblastic leukemia treated with HD-MTX 5 or 8 g/m 2 on the NOPHO2000 protocol. Moderately delayed MTX elimination was defined as 42-hour plasma MTX ≥ 4.0-9.9 μM, and severely delayed elimination was defined as 42-hour plasma MTX ≥ 10 μM., Results: Median 42-hour plasma MTX was 0.61 μM (interquartile range, 0.4-1.06 μM). Of 1295 MTX infusions with 5 g/m 2 (n = 140 patients) or 8 g/m 2 (n = 78 patients), 5.1% were severely (1.5%) or moderately (3.6%) delayed. The risk of having delayed elimination was highest in the first of eight infusions with MTX 5 g/m² (7.4% vs 0.0 to 4.1% for subsequent MTX infusions) (P < 0.02). A 25 μM increase or a 1.5-fold increase in plasma creatinine within 36 hours from start of the MTX infusion had a sensitivity of 92% (95% CI, 82%-97%) and a specificity of 85% (95% CI, 83%-87%) for predicting 42-hour MTX ≥4.0 μM., Conclusions: A 25 μM increase or a 1.5-fold in plasma creatinine within 36 hours after start of an HD-MTX infusion can predict delayed MTX elimination, thus allowing intensification of hydration and alkalization to avoid further renal toxicity and promote the elimination of MTX., (© 2019 Wiley Periodicals, Inc.)