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Survivors of childhood cancer are at risk of anthracycline-induced cardiotoxicity, which might be prevented by dexrazoxane. However, concerns exist about the safety of dexrazoxane, and little guidance is available on its use in children. To facilitate global consensus, a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the existing literature and used evidence-based methodology to develop a guideline for dexrazoxane administration in children with cancer who are expected to receive anthracyclines. Recommendations were made in consideration of evidence supporting the balance of potential benefits and harms, and clinical judgement by the expert panel. Given the dose-dependent risk of anthracycline-induced cardiotoxicity, we concluded that the benefits of dexrazoxane probably outweigh the risk of subsequent neoplasms when the cumulative doxorubicin or equivalent dose is at least 250 mg/m 2 (moderate recommendation). No recommendation could be formulated for cumulative doxorubicin or equivalent doses of lower than 250 mg/m 2 , due to insufficient evidence to determine whether the risk of cardiotoxicity outweighs the possible risk of subsequent neoplasms. Further research is encouraged to determine the long-term efficacy and safety of dexrazoxane in children with cancer., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Coronary artery disease (CAD) is a concerning late outcome for cancer survivors. However, uniform surveillance guidelines are lacking., Aim: To harmonise international recommendations for CAD surveillance for survivors of childhood, adolescent and young adult (CAYA) cancers., Methods: A systematic literature review was performed and evidence graded using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Eligibility included English language studies, a minimum of 20 off-therapy cancer survivors assessed for CAD, and 75% diagnosed prior to age 35 years. All study designs were included, and a multidisciplinary guideline panel formulated and graded recommendations., Results: 32 of 522 identified articles met eligibility criteria. The prevalence of CAD ranged from 0 to 72% and was significantly increased compared to control populations. The risk of CAD was increased among survivors who received radiotherapy exposing the heart, especially at doses ≥15 Gy (moderate-quality evidence). The guideline panel agreed that healthcare providers and CAYA cancer survivors treated with radiotherapy exposing the heart should be counselled about the increased risk for premature CAD. While the evidence is insufficient to support primary screening, monitoring and early management of modifiable cardiovascular risk factors are recommended. Initiation and frequency of surveillance should be based on the intensity of treatment exposures, family history, and presence of co-morbidities but at least by age 40 years and at a minimum of every 5 years. All were strong recommendations., Conclusion: These systematically assessed and harmonised recommendations for CAD surveillance will inform care and guide research concerning this critical outcome for CAYA cancer survivors., Competing Interests: Conflict of interest statement None declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Children with cancer often undergo long treatment trajectories involving repeated needle procedures that potentially cause pain and distress. As part of a comprehensive effort to develop clinical practice guidelines (CPGs) to address pain prevention and management in children with cancer, we aimed to provide recommendations on the pharmacological and psychological management of procedure-related pain and distress., Methods: Of the international inter-disciplinary CPG development panel (44 individuals), two working groups including 13 healthcare professionals focused on procedural pain and distress. Grading of Recommendations Assessment, Development and Evaluation methodology was used, including the use of systematic literature reviews to inform recommendations and the use of evidence to decision frameworks. At an in-person meeting in February 2018, the guideline panel discussed these frameworks and formulated recommendations which were then discussed with a patient-parent panel consisting of 4 survivors and 5 parents., Results: The systematic reviews led to the inclusion of 48 randomised controlled trials (total number of participants = 2271). Quality of evidence supporting the recommendations ranged from very low to moderate. Strong recommendations were made for the use of topical anesthetics in all needle procedures, for offering deep sedation (DS)/general anesthesia (GA) to all children undergoing lumbar puncture, for the use of DS/ GA in major procedures in children of all ages, for the use of hypnosis in all needle procedures and for the use of active distraction in all needle procedures., Conclusion: In this CPG, an evidence-based approach to manage procedure-related pain and distress in children with cancer is presented. As children with cancer often undergo repeated needle procedures during treatment, prevention and alleviation of procedure-related pain and distress is of the utmost importance to increase quality of life in these children and their families., Competing Interests: Conflict of interest statement The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors, the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies, it is important to know the risk of, and associated risk factors for, hepatic late adverse effects. This review is an update of a previously published Cochrane review., Objectives: To evaluate all the existing evidence on the association between antineoplastic treatment (that is, chemotherapy, radiotherapy involving the liver, surgery involving the liver and BMT) for childhood cancer and hepatic late adverse effects., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2018, Issue 1), MEDLINE (1966 to January 2018) and Embase (1980 to January 2018). In addition, we searched reference lists of relevant articles and scanned the conference proceedings of the International Society of Paediatric Oncology (SIOP) (from 2005 to 2017) and American Society of Pediatric Hematology/Oncology (ASPHO) (from 2013 to 2018) electronically., Selection Criteria: All studies, except case reports, case series, and studies including fewer than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment)., Data Collection and Analysis: Two review authors independently performed the study selection and 'risk of bias' assessment. The 'risk of bias' assessment was based on earlier checklists for observational studies. For the original version of the review, two review authors independently performed data extraction. For the update of the review, the data extraction was performed by one reviewer and checked by another reviewer., Main Results: Thirteen new studies were identified for the update of this review. In total, we included 33 cohort studies including 7876 participants investigating hepatic late adverse effects after antineoplastic treatment (especially chemotherapy and radiotherapy) for different types of childhood cancer, both haematological and solid malignancies. All studies had methodological limitations. The prevalence of hepatic late adverse effects, all defined in a biochemical way, varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well-defined as alanine aminotransferase (ALT) above the upper limit of normal, indicating cellular liver injury, resulted in eight studies. In this subgroup, the prevalence of hepatic late adverse effects ranged from 5.8% to 52.8%, with median follow-up durations varying from three to 23 years since cancer diagnosis in studies that reported the median follow-up duration. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal, resulted in five studies, with a prevalence ranging from 0.9% to 44.8%. One study investigated biliary tract injury, defined as gamma-glutamyltransferase (γGT) above the upper limit of normal and above twice the upper limit of normal and reported a prevalence of 5.3% and 0.9%, respectively. Three studies investigated disturbance in biliary function, defined as bilirubin above the upper limit of normal and reported prevalences ranging from 0% to 8.7%. Two studies showed that treatment with radiotherapy involving the liver (especially after a high percentage of the liver irradiated), higher BMI, and longer follow-up time or older age at evaluation increased the risk of cellular liver injury in multivariable analyses. In addition, there was some suggestion that busulfan, thioguanine, hepatic surgery, chronic viral hepatitis C, metabolic syndrome, use of statins, non-Hispanic white ethnicity, and higher alcohol intake (> 14 units per week) increase the risk of cellular liver injury in multivariable analyses. Chronic viral hepatitis was shown to increase the risk of cellular liver injury in six univariable analyses as well. Moreover, one study showed that treatment with radiotherapy involving the liver, higher BMI, higher alcohol intake (> 14 units per week), longer follow-up time, and older age at cancer diagnosis increased the risk of biliary tract injury in a multivariable analysis., Authors' Conclusions: The prevalence of hepatic late adverse effects among studies with an adequate outcome definition varied considerably from 1% to 53%. Evidence suggests that radiotherapy involving the liver, higher BMI, chronic viral hepatitis and longer follow-up time or older age at follow-up increase the risk of hepatic late adverse effects. In addition, there may be a suggestion that busulfan, thioguanine, hepatic surgery, higher alcohol intake (>14 units per week), metabolic syndrome, use of statins, non-Hispanic white ethnicity, and older age at cancer diagnosis increase the risk of hepatic late adverse effects. High-quality studies are needed to evaluate the effects of different therapy doses, time trends, and associated risk factors after antineoplastic treatment for childhood cancer.

Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems-such as speech and language, social-emotional development, and learning difficulties-for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infection, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent infection and (infection-related) mortality in cancer patients receiving chemotherapy that causes episodes of neutropenia, but much remains unclear. This review is an update of a previously published Cochrane review., Objectives: The primary objective of this review was to determine the efficacy of an LBD versus a control diet in preventing infection and in decreasing (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy that causes episodes of neutropenia. Secondary objectives were to assess time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life., Search Methods: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 4), the Database of Abstracts of Reviews of Effects (DARE) (2015, Issue 4), PubMed (from 1946 to 4 May 2015), EMBASE (from 1980 to 4 May 2015) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1981 to 4 May 2015).In addition, we searched the reference lists of relevant articles and conference proceedings of American Society of Hematology (ASH; from 2000 to 2015), European Bone Marrow Transplantation (EBMT; from 2000 to 2015), Oncology Nurses Society (ONS; from 2000 to 2015), International Society for Paediatric Oncology (SIOP; from 2000 to 2014), Multinational Association of Supportive Care in Cancer (MASCC; from 2000 to 2015), American Society of Clinical Oncology (ASCO; from 2000 to 2015), Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC; from 2000 to 2015), European Society for Clinical Nutrition and Metabolism (ESPEN; from 2000 to 2015), American Society for Parenteral and Enteral Nutrition (ASPEN; from 2000 to 2015) and European Hematology Association (EHA; from 2000 to 2015). In May 2015, we scanned the National Institutes of Health Register via clinicaltrials.gov and the International Standard Randomised Controlled Trial Number (ISRCTN) Register (www.controlled-trials.com)., Selection Criteria: Randomised controlled trials (RCTs) comparing use of an LBD versus a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia., Data Collection and Analysis: Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: In the original version of this review, we identified three RCTs that assessed different intervention and control diets in 192 participants (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. For the update, we identified no eligible new studies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices, colony-stimulating factors) and outcome definitions also differed between studies. In all included studies, it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the participants diagnosed with an infection. Two studies included adults and one study included children. In all studies, only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies, no statistically significant differences in infection rate were identified between intervention and control diets; another study showed no significant differences between treatment groups in the number of chemotherapy cycles with an infection. None of the studies mentioned infection-related mortality, but in one study, no significant difference in overall survival was observed between treatment groups. Time from onset of neutropenia to fever, duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes, no statistically significant differences between treatment arms were identified., Authors' Conclusions: At the moment, no evidence from individual RCTs in children and adults with different malignancies underscores use of an LBD for prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions and intervention and control diets. As pooling of results was not possible, and as all studies had serious methodological limitations, we could reach no definitive conclusions. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. On the basis of currently available evidence, we are not able to provide recommendations for clinical practice. Additional high-quality research is needed.

Background: Current treatment strategies in pediatric oncology are intensive and lead to high survival rates but also to treatment-related complications. Therefore, supportive care plays an increasingly important role. This study was designed to evaluate variations in supportive care practice in children with cancer in the Netherlands and adherence to selected existing international guidelines through an in-depth review of local guidelines and protocols at all 6 Dutch pediatric cancer centers., Methods: Based on shared expert opinion, a questionnaire regarding current supportive care practice was compiled. For each center, the required information was extracted from local supportive care guidelines, and the list was sent to a pediatric oncologist of that center to verify its correspondence with local daily practice. Subsequently, it was determined whether clinical practice was concordant (same in ≥ 5 of 6 centers), partly concordant (highly overlapping in ≥ 5 of 6 centers), or discordant (same in < 5 of 6 centers). Local practices were compared with strong recommendations from high-quality, evidence-based guidelines., Results: The questionnaire comprised 67 questions regarding supportive care practice. Concordance was observed for 11 of 67 practice items (16%), partial concordance was observed for 6 of 67 practice items (9%), and discordance was observed for 50 of 67 practice items (75%). Adherence to strong recommendations of 4 high-quality, evidence-based guidelines varied but was generally low., Conclusions: Large variations exist in pediatric oncology supportive care practice, and this could negatively influence care. Adherence to existing evidence-based guidelines and the development and implementation of new clinical practice guidelines have the potential of standardizing supportive care practice and thereby improving outcomes for children with cancer., (© 2015 American Cancer Society.)

Background: Great improvements in diagnostics and treatment for malignant disease in childhood have led to a major increase in survival. However, childhood cancer survivors (CCS) are at great risk for developing adverse effects caused by multimodal treatment for their malignancy. Nephrotoxicity is one of these known (acute) side effects of several treatments, including cisplatin, carboplatin, ifosfamide, radiotherapy and nephrectomy, and can cause glomerular filtration rate impairment, proteinuria, tubulopathy and hypertension. However, evidence about the long-term effects of these treatments on renal function remains inconclusive. To reduce the number of (long-term) nephrotoxic events in CCS, it is important to know the risk of, and risk factors for, early and late renal adverse effects, so that ultimately treatment and screening protocols can be adjusted., Objectives: To evaluate existing evidence on the effects of potentially nephrotoxic treatment modalities on the prevalence of and associated risk factors for renal dysfunction in survivors treated for childhood cancer with a median or mean survival of at least one year after cessation of treatment, where possible in comparison with healthy controls or CCS treated without potentially nephrotoxic treatment., Search Methods: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2011), MEDLINE/PubMed (from 1945 to December 2011) and EMBASE/Ovid (from 1980 to December 2011)., Selection Criteria: With the exception of case reports, case series and studies including fewer than 20 participants, we included studies with all study designs that reported on renal function (one year or longer after cessation of treatment) in children and adults who were treated for a paediatric malignancy (aged 18 years or younger at diagnosis) with cisplatin, carboplatin, ifosfamide, radiation including the kidney region and/or a nephrectomy., Data Collection and Analysis: Two review authors independently performed study selection, risk of bias assessment and data extraction using standardised data collection forms. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: The search strategy identified 5504 studies, of which 5138 were excluded on the basis of title and/or abstract. The full-text screening of the remaining 366 articles resulted in the inclusion of 57 studies investigating the prevalence of and sometimes also risk factors for early and late renal adverse effects of treatment for childhood cancer. The 57 studies included at least 13,338 participants of interest for this study, of whom at least 6516 underwent renal function testing. The prevalence of renal adverse effects ranged from 0% to 84%. This variation may be due to diversity in included malignancies, prescribed treatments, reported outcome measurements and the methodological quality of available evidence.Chronic kidney disease/renal insufficiency (as defined by the authors of the original studies) was reported in 10 of 57 studies. The prevalence of chronic kidney disease ranged between 0.5% and 70.4% in the 10 studies and between 0.5% and 18.8% in the six studies that specifically investigated Wilms' tumour survivors treated with a unilateral nephrectomy.A decreased (estimated) glomerular filtration rate was present in 0% to 50% of all assessed survivors (32/57 studies). Total body irradiation; concomitant treatment with aminoglycosides, vancomycin, amphotericin B or cyclosporin A; older age at treatment and longer interval from therapy to follow-up were significant risk factors reported in multivariate analyses. Proteinuria was present in 0% to 84% of all survivors (17/57 studies). No study performed multivariate analysis to assess risk factors for proteinuria.Hypophosphataemia was assessed in seven studies. Reported prevalences ranged between 0% and 47.6%, but four of seven studies found a prevalence of 0%. No studies assessed risk factors for hypophosphataemia using multivariate analysis. The prevalence of impairment of tubular phosphate reabsorption was mostly higher (range 0% to 62.5%; 11/57 studies). Higher cumulative ifosfamide dose, concomitant cisplatin treatment, nephrectomy and longer follow-up duration were significant risk factors for impaired tubular phosphate reabsorption in multivariate analyses.Treatment with cisplatin and carboplatin was associated with a significantly lower serum magnesium level in multivariate analysis, and the prevalence of hypomagnesaemia ranged between 0% and 37.5% in the eight studies investigating serum magnesium.Hypertension was investigated in 24 of the 57 studies. Reported prevalences ranged from 0% to 18.2%. A higher body mass index was the only significant risk factor noted in more than one multivariate analysis. Other reported factors that significantly increased the risk of hypertension were use of total body irradiation, abdominal irradiation, acute kidney injury, unrelated or autologous stem cell donor type, growth hormone therapy and older age at screening. Previous infection with hepatitis C significantly decreased the risk of hypertension.Because of the profound heterogeneity of the studies, it was not possible to perform any meta-analysis., Authors' Conclusions: The prevalence of renal adverse events after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region and/or nephrectomy ranged from 0% to 84%. With currently available evidence, it was not possible to draw any conclusions with regard to prevalence of and risk factors for renal adverse effects. Future studies should focus on adequate study design and reporting and should deploy multivariate risk factor analysis to correct for possible confounding. Until more evidence becomes available, CCS should be enrolled into long-term follow-up programmes to monitor their renal function and blood pressure.

Background: Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infections, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent the occurrence of infections and (infection-related) mortality in cancer patients receiving chemotherapy causing episodes of neutropenia, but much remains unclear., Objectives: The primary objective was to determine the efficacy of an LBD versus a control diet in preventing the occurrence of infection and to decrease (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. Secondary objectives were to assess the time to first febrile episode, the need for empirical antibiotic therapy, diet acceptability and quality of life., Search Methods: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 3 2011), Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library, issue 3 2011), PubMed (from 1946 to 20 October 2011), EMBASE (from 1980 to 20 October 2011) and CINAHL (from 1981 to 20 October 2011). In addition, we searched several conference proceedings (from 2000 to either 2010 or 2011) and reference lists of relevant articles. To identify ongoing trials we contacted researchers working on this topic and we scanned the National Institute of Health Register and the ISRCTN Register (www.controlled-trials.com; searched May 2012)., Selection Criteria: Randomised controlled trials (RCTs) comparing the use of an LBD with a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability, and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia., Data Collection and Analysis: Two review authors independently performed the study selection, 'Risk of bias' assessment and data extraction. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: We identified three RCTs assessing different intervention and control diets in 192 patients (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices and colony-stimulating factors) and outcome definitions also differed between studies. In all included studies it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the patients diagnosed with an infection. Two studies included adults and one study included children. In all studies only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies no statistically significant difference in infection rate between the intervention and control diet was identified; another study showed no significant difference in the number of chemotherapy cycles with an infection between the treatment groups. None of the studies mentioned infection-related mortality, but in one study no significant difference in overall survival between the treatment groups was observed. Time from onset of neutropenia to fever, the duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes no statistically significant differences between the treatment arms was observed., Authors' Conclusions: At the moment there is no evidence from individual RCTs in children and adults with different malignancies that underscores the use of an LBD for the prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions, and intervention and control diets. Since pooling of results was not possible and all studies had serious methodological limitations, no definitive conclusions can be made. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. Based on the currently available evidence, we are not able to give recommendations for clinical practice. More high-quality research is needed.

Background: Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies it is important to know the risk of, and associated risk factors for, hepatic late adverse effects., Objectives: To evaluate the existing evidence on the association between antineoplastic treatment for childhood cancer and hepatic late adverse effects., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009) and EMBASE (1980 to June 2009). In addition, we searched reference lists of relevant articles and conference proceedings., Selection Criteria: All studies except case reports, case series and studies including less than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment)., Data Collection and Analysis: Two review authors independently performed the study selection, risk of bias assessment and data extraction., Main Results: We identified 20 cohort studies investigating hepatic late adverse effects after antineoplastic treatment for childhood cancer. All studies had methodological limitations. The prevalence of hepatic late adverse effects varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well defined as alanine aminotransferase (ALT) above the upper limit of normal resulted in five studies. In this subgroup the prevalence of hepatic late adverse effects ranged from 8.0% to 52.8%, with follow-up durations varying from one to 27 years after the end of treatment. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal resulted in three studies, with a prevalence ranging from 7.9% to 44.8%. Chronic viral hepatitis was identified as a risk factor for hepatic late adverse effects in univariate analyses. It is unclear which specific antineoplastic treatments increase the risk of hepatic late adverse effects, Authors' Conclusions: The prevalence of hepatic late adverse effects ranged from 7.9% to 52.8% when selecting studies with an adequate outcome definition. It has not been established which childhood cancer treatments result in hepatic late adverse effects. There is a suggestion that chronic viral hepatitis increases the risk of hepatic late adverse effects. More well-designed studies are needed to reliably evaluate the prevalence of, and risk factors for, hepatic late adverse effects after antineoplastic treatment for childhood cancer.