Educational achievement and employment outcomes are critical indicators of quality of life in survivors of childhood, adolescent, and young adult (CAYA) cancer. This review is aimed at providing an evidence‐based clinical practice guideline (CPG) with internationally harmonized recommendations for the surveillance of education and employment outcomes in survivors of CAYA cancer diagnosed before the age of 30 years. The CPG was developed by a multidisciplinary panel under the umbrella of the International Late Effects of Childhood Cancer Guideline Harmonization Group. After evaluating concordances and discordances of 4 existing CPGs, the authors performed a systematic literature search through February 2021. They screened articles for eligibility, assessed quality, and extracted and summarized the data from included articles. The authors formulated recommendations based on the evidence and clinical judgment. There were 3930 articles identified, and 83 of them, originating from 17 countries, were included. On a group level, survivors were more likely to have lower educational achievement and more likely to be unemployed than comparisons. Key risk factors for poor outcomes included receiving a primary diagnosis of a central nervous system tumor and experiencing late effects. The authors recommend that health care providers be aware of the risk of educational and employment problems, implement regular surveillance, and refer survivors to specialists if problems are identified. In conclusion, this review presents a harmonized CPG that aims to facilitate evidence‐based care, positively influence education and employment outcomes, and ultimately minimize the burden of disease and treatment‐related late adverse effects for survivors of CAYA cancers.Lay Summary: A multidisciplinary panel has developed guidelines for the surveillance of education and employment outcomes among survivors of childhood, adolescent, and young adult cancer. On the basis of evidence showing that survivors are at risk for lower educational achievement and unemployment, it is recommended that all survivors receive regular screening for educational and employment outcomes.

To uncover mechanisms underlying chemotherapy-induced cognitive impairment in breast cancer, we studied new biomarkers of neuroinflammation and neuronal survival. This cohort study included 74 women (47 ± 10 years) from 22 October 2017 until 20 August 2020. Nineteen chemotherapy-treated and 18 chemotherapy-naïve patients with breast cancer were assessed one month after the completion of surgery and/or chemotherapy, and 37 healthy controls were included. Assessments included neuropsychological testing, questionnaires, blood sampling for 17 inflammatory and two neuronal survival markers (neurofilament light-chain (NfL), and brain-derived neurotrophic factor (BDNF) and PET-MR neuroimaging. To investigate neuroinflammation, translocator protein (TSPO) [¹⁸F]DPA714-PET-MR was acquired for 15 participants per group, and evaluated by volume of distribution normalized to the cerebellum. Chemotherapy-treated patients showed higher TSPO expression, indicative for neuroinflammation, in the occipital and parietal lobe when compared to healthy controls or chemotherapy-naïve patients. After partial-volume correction, differences with healthy controls persisted (p_FWE < 0.05). Additionally, compared to healthy- or chemotherapy-naïve controls, cognitive impairment (17–22%) and altered levels in blood markers (F ≥ 3.7, p ≤ 0.031) were found in chemotherapy-treated patients. NfL, an axonal damage marker, was particularly sensitive in differentiating groups (F = 105, p = 4.2 × 10 ⁻²¹), with levels 20-fold higher in chemotherapy-treated patients. Lastly, in chemotherapy-treated patients alone, higher local TSPO expression was associated with worse cognitive performance, higher blood levels of BDNF/NfL, and decreased fiber cross-section in the corpus callosum (p_FWE < 0.05). These findings suggest that increased neuroinflammation is associated with chemotherapy-related cognitive impairment in breast cancer. Additionally, NfL could be a useful biomarker to assess neurotoxic effects of anticancer chemotherapies.

Background: Cognitive functioning is increasingly assessed as a secondary outcome in neuro-oncological trials. However, which cognitive domains or tests to assess, remains debatable. In this meta-analysis, we aimed to elucidate the longer-term test-specific cognitive outcomes in adult glioma patients. Methods: A systematic search yielded 7098 articles for screening. To investigate cognitive changes in glioma patients and differences between patients and controls 1-year follow-up, random-effects meta-analyses were conducted per cognitive test, separately for studies with a longitudinal and cross-sectional design. A meta-regression analysis with a moderator for interval testing (additional cognitive testing between baseline and 1-year posttreatment) was performed to investigate the impact of practice in longitudinal designs. Results: Eighty-three studies were reviewed, of which 37 were analyzed in the meta-analysis, involving 4078 patients. In longitudinal designs, semantic fluency was the most sensitive test to detect cognitive decline over time. Cognitive performance on mini-mental state exam (MMSE), digit span forward, phonemic and semantic fluency declined over time in patients who had no interval testing. In cross-sectional studies, patients performed worse than controls on the MMSE, digit span backward, semantic fluency, Stroop speed interference task, trail-making test B, and finger tapping. Conclusions: Cognitive performance of glioma patients 1 year after treatment is significantly lower compared to the norm, with specific tests potentially being more sensitive. Cognitive decline over time occurs as well, but can easily be overlooked in longitudinal designs due to practice effects (as a result of interval testing). It is warranted to sufficiently correct for practice effects in future longitudinal trials.