Zhou C, et al. - This is the first systematic review and meta-analysis investigating both chemotherapy- and/or radiotherapy-induced changes in the brain and cognitive function and their connection, in childhood acute lymphoblastic leukaemia (ALL) survivors. A total of 1,712 articles were found in the initial search. Nine hundred eighty-five articles remained after eliminating duplicates. Ultimately, the study comprised 20 studies of 853 childhood ALL survivors and 600 healthy control. The authors provide evidence of ALL treatment neurotoxicity in cortical and several subcortical brain regions, which can lead to neurocognitive impairment in childhood ALL survivors. In addition, replacement of cranial radiotherapy by systemic/intrathecal chemotherapy could lead to a decline, yet not complete resolution, of late neurocognitive sequelae, which could possibly be moderated by several other factors. Continued work with advanced MRI techniques would hopefully allow early CNS changes to be identified as biomarkers to help guide early diagnosis and intervention in patients with childhood ALL for neurocognitive deficiencies.