Hepatic late adverse effects after antineoplastic treatment for childhood cancer.
Study Goal
The researchers aimed to evaluate the association between antineoplastic treatment for childhood cancer and hepatic late adverse effects, including cellular liver injury indicated by elevated alanine aminotransferase (ALT).
Results Summary
The prevalence of hepatic late adverse effects, particularly elevated ALT, varied widely (5.8% to 52.8%). Risk factors included radiotherapy involving the liver, higher BMI, chronic viral hepatitis, and longer follow-up time.
Population
Long-term childhood cancer survivors (aged 18 years or less at diagnosis).
Effective Dosage
Not specified
Duration
Follow-up durations varied from 3 to 23 years post-cancer diagnosis.
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
antineoplastic treatment for childhood cancer | increase | hepatic late adverse effects | long-term childhood cancer survivors | - | increased the risk of | #1 |
radiotherapy involving the liver | increase | cellular liver injury | long-term childhood cancer survivors | - | increased the risk of | #2 |
higher BMI | increase | cellular liver injury | long-term childhood cancer survivors | - | increased the risk of | #3 |
longer follow-up time | increase | cellular liver injury | long-term childhood cancer survivors | - | increased the risk of | #4 |
older age at evaluation | increase | cellular liver injury | long-term childhood cancer survivors | - | increased the risk of | #5 |
busulfan | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #6 |
thioguanine | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #7 |
hepatic surgery | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #8 |
chronic viral hepatitis C | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #9 |
metabolic syndrome | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #10 |
use of statins | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #11 |
non-Hispanic white ethnicity | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #12 |
higher alcohol intake (> 14 units per week) | increase | cellular liver injury | long-term childhood cancer survivors | - | increase the risk of | #13 |
chronic viral hepatitis | increase | cellular liver injury | long-term childhood cancer survivors | - | increased the risk of | #14 |
radiotherapy involving the liver | increase | biliary tract injury | long-term childhood cancer survivors | - | increased the risk of | #15 |
higher BMI | increase | biliary tract injury | long-term childhood cancer survivors | - | increased the risk of | #16 |
higher alcohol intake (> 14 units per week) | increase | biliary tract injury | long-term childhood cancer survivors | - | increased the risk of | #17 |
longer follow-up time | increase | biliary tract injury | long-term childhood cancer survivors | - | increased the risk of | #18 |
older age at cancer diagnosis | increase | biliary tract injury | long-term childhood cancer survivors | - | increased the risk of | #19 |
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.