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Background Children with high-grade CNS cancers frequently experience malnutrition during treatment. We assessed the effects of proactive enteral tube (ET) placement/enteral tube feedings (ETF) on weight in infants/children with high-grade CNS tumors treated with aggressive chemotherapy. Methods We conducted a retrospective study of patients age 0 to 19 years treated for new high-grade CNS tumors between 2002 and 2017 at a tertiary pediatric hospital system. Patients underwent placement of proactive ET (≤ 31 days postdiagnosis; n = 45), rescue ET (> 31 days, due to weight loss; n = 9), or no ET (n = 18). Most received surgically placed ET (98%), with percutaneous endoscopic gastrojejunostomy or gastrojejunostomy tubes favored to allow jejunal feeding. The majority of patients with ET used ETF (91%). Using mixed-effects regression models, we examined differences in mean weights between ET/ETF groups across the first year of treatment. We also evaluated observed weight changes. Results All infants (n = 22, median age, 1.5 years) had proactive ET placed and 21 of 22 used proactive ETF. Infants showed an initial increase in mean percentage weight change that eventually leveled off, for an estimated increase of 10.4% over the year. For the pediatric cohort (n = 50, median, 8.1 years), those receiving proactive ETF experienced weight increases (+9.9%), those with rescue ETF experienced an initial decline and eventually rebounded for no net change (0.0%), and those with no ETF demonstrated an initial decline that persisted (–11.9%; P interaction <.001). Analysis of observed weights revealed nearly identical patterns. Conclusions Proactive ETF was effective at maintaining weight and/or facilitating weight gain over the first year of treatment and was acceptable to patients/families. [ABSTRACT FROM AUTHOR]