The investigators plan to enroll a minimum of 45 subjects between the ages of 2-18 years old, over the course of one year, including males and females of all ethnicities. The subject will be a newly diagnosed pediatric patient with cancer who will actively receive chemotherapy at UK Healthcare's Kentucky Children's Hospital (KCH).

All those who enroll will have a baseline ultrasound and biomarkers taken at enrollment. Participants will also receive 'standard of care' medical nutrition therapy (MNT) counseling at diagnosis for following a high protein/high-calorie diet. If any of the enrolled participants lose \>10% of the diagnosis weight, the participants will then be randomized to receive (1) oral nutrition supplements, (2) age-appropriate appetite stimulants, or (3) enteral nutrition via a feeding tube. At the point of randomization, participants will receive another ultrasound and biomarkers. Those randomized will then receive additional ultrasounds and biomarkers at 1 month and 3 months after randomization. The remaining patients that have either weight maintenance or weight gain, will be utilized as a comparator group and will receive an ultrasound at 3 months and 6 months from enrollment/diagnosis. Each group will have a goal of at least 10 patients per group.

Those receiving ONS will be prescribed a standard ONS (1.0 kcal per mL) that will meet a minimum of 50% of estimated energy needs to promote weight gain but allow for continued regular dietary intakes. The ONS will be prescribed as 8oz (240mL) per dose at least once a day, but up to six times per day depending on estimated nutrient needs. Those receiving age-appropriate appetite stimulants will be provided either cyproheptadine or olanzapine. Subjects will be given cyproheptadine if the participants fall between the ages of 2-12 years of age and olanzapine if the participants are \>12 years of age or older. Table 1 summarizes the medication dosage forms, initial and dose titration options, and precautions/contraindications of each appetite stimulant. Medication adjustments will be made within 2-4 weeks of initiation due to the variable peak effect times, and chemotherapy treatment plans dictating clinic follow-up. Those randomized to EN will have a feeding tube placed and started on tube feeds via a designated pump for overnight feeds, meeting at least 50% of estimated energy needs to allow for continued regular dietary intakes during the day. After placement of a feeding tube, an abdominal x-ray will be obtained per hospital policy to confirm the appropriate placement of the feeding tube prior to use to ensure the safety of using said feeding tube.

Baseline demographics will be collected, including gender, age, diagnosis, QMLT ultrasound measurement, subjective global assessment (SGA) malnutrition risk, pediatric z-scores, and activity levels. Investigators will assess the subjects' nutritional intake, body composition via QMLT ultrasound, mid-upper arm circumference, pediatric z-scores (weight, length, and body mass index), biomarkers (leptin, IL-6, Lipid profiles, Cystatin-C, Vitamin D, and C-reactive protein), compliance and tolerance to nutrition intervention, physical activity, and clinical outcomes (rates of infection, number of hospital days for non-chemotherapy administration, number of clinic visits for non-chemotherapy administration, chemotherapy toxicity CTCAE grade, rate or relapse, and 1-year survival rates) at multiple time points throughout the study. Nutritional assessment will involve a 24-hour food recall which will be performed at diagnosis, randomization, and then every 1-2 weeks once randomized to an intervention. Weight loss and pediatric z-scores (weight-for-age, length-for-age, and BMI-for-age) will be assessed every 1-2 weeks throughout the study enrollment. Ultrasound assessment will be of the QMLT by measuring at the midpoint between the ASIS and the upper pole of the patella. The measurements will be taken bilaterally, three times, and averaged together for the final measurement. Ultrasound assessment will occur at enrollment when weight loss criteria are met for randomization, and then at 1 month and 3 months after randomization (or when the weight lost is regained).

Pediatric physical activity will be assessed every 1-2 weeks in combination with ultrasound measurements. Adherence and adverse effects to medications, tube feeds, or oral nutrition supplements will be assessed at each clinic visit. Biomarkers will be analyzed at randomization, 1 month, and 3 months after randomization.

Standard of care for patients are to receive MNT education at diagnosis. For those that lose weight, standard of care is to receive the nutrition interventions listed above (oral nutrition supplements, appetite stimulants, or enteral nutrition via feeding tube). The standard of care is to generally go from a least invasive to a more invasive approach. The research components of this study include being randomized to a nutrition intervention rather than a non-validated step-wise approach, the ultrasound measurements, and the biomarkers. These components are not considered standard of care and are research procedures. Baseline demographics will be collected, including gender, age, diagnosis, QMLT ultrasound measurement, subjective global assessment (SGA) malnutrition risk, pediatric z-scores, and activity levels. The team will assess the subjects' nutritional intake, body composition via QMLT ultrasound, mid-upper arm circumference, pediatric z-scores (weight, length, and body mass index), biomarkers (leptin, IL-6, Lipid profiles, Cystatin-C, Vitamin D, and C-reactive protein), compliance and tolerance to nutrition intervention, physical activity, and clinical outcomes (rates of infection, number of hospital days for non-chemotherapy administration, number of clinic visits for non-chemotherapy administration, chemotherapy toxicity CTCAE grade, rate or relapse, and 1-year survival rates) at multiple timepoints throughout the study. Nutritional assessment will involve a 24-hour food recall which will be performed at diagnosis, randomization, and then every 1-2 weeks once randomized to an intervention. Weight loss and pediatric z-scores (weight-for-age, length-for-age, and BMI-for-age) will be assessed every 1-2 weeks throughout the study enrollment. Ultrasound assessment will be of the QMLT by measuring at the midpoint between the ASIS and the upper pole of the patella, a total of 4 ultrasounds will be conducted during the study. The measurements will be taken bilaterally, three times, and averaged together for the final measurement. Ultrasound assessment will occur at enrollment when weight loss criteria are met for randomization, and then every 1-2 weeks for up to 8 weeks after randomization. Pediatric physical activity will be assessed every 1-2 weeks in combination with ultrasound measurements. Adherence and adverse effects to medications, tube feeds, or oral nutrition supplements will be assessed at each clinic visit.

Biomarkers will be analyzed at randomization, and weeks 4 and 8 after randomization. Additionally, measurements of resource utilization will be measured such as the number of hospital days for non-chemotherapy-related problems, the number of sick visits to the clinic, dietitian visits, infections, and rates of relapse or overall survival. Biomarkers will be drawn when the children are in the clinic for chemotherapy or lab work. The participants will already have their central venous line accessed by a qualified clinic RN and labs will be drawn at that time to ensure no extra harm to the patient. Additionally, all patients will have EMLA cream used to numb the area prior to having a clinic RN who is trained in accessing ports and has accessed the ports during previous clinic visits and will continue to do so throughout therapy.