4.1 Nutrition Screening and Assessment

• Recommendation

  • Complete nutrition assessment of all children with cancer should take precedence over routine nutritional screening. Nutritional screening is not mandatory but may be done to fulfil individual institutional requirements, if any.

  • Nutritional assessment is mandatory for all children at diagnosis and at regular intervals in children undergoing cancer treatment and in survivors after that.

  • The committee is of the opinion regarding the following routine reassessment

  • At risk of malnutrition or malnourished or receiving intensive treatment: at least once a week

  • Receiving less intense treatment- Monthly

  • In patients and ICU: Daily

  • Maintenance phase/ survivor- 6-12 months

• Rationale

Paediatric oncology patients are at high risk for developing short-term and long-term nutritional problems as a result of their disease and the side effects of multimodal treatments. Nutritional status can impact clinical outcomes, such as overall survival and event-free survival, treatment tolerance, risk of developing infections and quality of life 8.

ASPEN guidelines state that nutritional screening and assessment is an important first step in identifying malnutrition or risk of malnutrition in critically ill children 9. It is essential to assess nutritional status at diagnosis or as soon as possible because if the initial assessment is not carried out promptly at diagnosis, there is a risk of altered results due to the cancer therapy 8, 10.

If required, nutritional screening can be done to fulfil institutional requirements. However, it is essential to mention that complete nutritional assessment takes precedence over routine nutritional screening. The SCAN or the Strongkids tool can be used for nutritional screening. Nutrition screening tool for childhood cancer (SCAN) is a simple, quick and valid tool and can be used to identify children with cancer who are at risk of malnutrition 11. Fabiozzi et al., in their latest consensus statement, recommend the use of Screening Tool for Risk of Nutritional Status and Growth (Strong Kids), as it is more balanced and takes into account many aspects of the disease, the clinical status, and contributing factors, especially related to undernutrition 6.

Nutritional assessment should consider the patient's nutrition status, GI function, intensity of treatment and current or expected side effects of treatment 8. In the Western literature, it has been recommended that patients receiving periods of intensive treatment or at high risk of malnutrition require follow-up every 3–4 weeks. Children receiving less intensive treatment should be evaluated every three months and at 6 to 12 monthly intervals while in the maintenance phase of treatment, if applicable. Children admitted to intensive care units may need more frequent reassessment 6. However, in the context of Indian patients, due to the higher incidence of malnutrition compared to the Western population, experts recommend more frequent monitoring of nutritional status, especially in children who are malnourished or at risk of being malnourished.

4.2 Components of Nutritional Assessment

• Recommendation

Comprehensive nutritional assessment in a child with cancer should include the ABCD method of anthropometric measures, biochemical parameters, clinical parameters and dietary evaluation.

• Rationale

Regular and comprehensive assessment of a child's nutritional status is necessary at diagnosis and routinely after that 8, 12. The Nutrition Working Group (NWG) of the International Society of Pediatric Oncology (SIOP) recommends that a comprehensive nutritional assessment be performed for a better clinical representation and should consist of anthropometric measures, biochemistry exams, clinical evaluation and dietary intake 13.

4.3 Substrate requirements for a child under cancer treatment on oral feeds

• Recommendation

  • Nutritional requirements on oral feeds are similar to daily requirements (Recommended Dietary Allowance 2020, National Institute of Nutrition) of their respective age and gender unless the child with cancer is severely undernourished 38.

  • It is recommended that patients meet their requirements for micronutrients through food sources.

• Rationale

There has been a significant debate over the years regarding whether children diagnosed with cancer have a higher basal metabolic rate (BMR) compared to children who do not have cancer. Certain studies have indicated that BMR is higher at diagnosis in some solid tumours, which normalises as treatment progresses 8, 12. At the same time, it is known that cancer can alter the metabolism and predispose the patient to malnourishment 12. This has led to different opinions about requirements for children with cancer, and there is no single standardised formula that can help determine a patient's nutritional requirements 12. However, it has been reported recently that the nutritional requirements of patients with cancer generally correspond with those of healthy children of the same age and gender 6, 39.

It has also been proposed that a patient's nutritional status at diagnosis be used as a guideline to determine which requirements to use. If a patient is undernourished, then for an increase of 10 g/day in weight, a patient would need approximately 126 kcal/kg and 2.82 g/kg of protein per day 12, 40.

The recommended macronutrient intake for children is based on acceptable macronutrient dietary ranges (AMDR), which are based on percent ranges of total calories.

For children:

• Between 1 and 3 years: Fat-30% to 40%, Carbohydrates -45%-65%, protein- 5%-20% of energy

• For ages 4 and 18 years: Fat -25 % to 35%, Carbohydrates -45 % to 65%. protein-10% to 35% 1, 13, 41.

It is advised that children suffering from Severe Acute Malnutrition (SAM) be managed using the IAP-WHO guidelines on integrated diagnosis and management of SAM 42, 43.

Macronutrient deficiencies may induce undernutrition; however, at the same time, overconsumption of certain macronutrients might lead to obesity. Micronutrient deficiencies can also present in the paediatric oncology patient. Deficiencies of iron, folate and B12 may cause anaemia 44. Deficiencies of zinc, vitamin C, and vitamin and D can cause impaired immunity and inadequate protein, iron, or iodine consumption can result in impaired cognitive development 45. The benefits and risks of supplementation with antioxidants during cancer therapy have been controversial. However, a recent study indicated that a well-balanced diet that includes an array of antioxidants from a wide variety of food sources alone may confer a benefit from infections and mucositis during treatment of childhood ALL (Acute lymphoblastic Leukemia) 46.

6.1 Indications for enteral nutrition

• Recommendation

Enteral Nutrition is indicated:

• • When the child is unable to take his or her nutritional needs orally (less than 50%) for more than five consecutive days;

  • For severely wasted or malnourished patients, as in low BMI for age (<5th percentile or z score less than –1) or mid-upper arm circumference ( <5th percentile or z score less than –1)

  • When the patients have over 5% weight loss since diagnosis, a decrease of >10% in MUAC since diagnosis, or a crossing of two growth percentiles over the course of treatment

  • Proactive EN may be indicated in high-risk children.

• Rationale

Enteral tube feeding is indicated in patients with a functional gut who are unable to meet daily nutrient requirements through oral means, children with malabsorption, intolerance to oral feeds, dysphagia and increased unmet nutritional requirements 48.

The main indications for EN include:

• When the child is unable to take his or her nutritional needs orally (less than 50%) for more than five consecutive days 51

• Severely wasted or malnourished patients, as in low BMI for age (<5^th percentile or z score less than –1) or the mid-upper arm circumference (MUAC; <5^th percentile or z score less than –1) 6.

• Patients with over 5% weight loss since diagnosis, a decrease of >10% in MUAC since diagnosis, or a crossing of two growth percentiles over the course of treatment41, 48, 52.

Meeting nutritional requirements may prove challenging in conditions where nasogastric (NG) insertion may be contraindicated e.g., persistent vomiting, gastrointestinal obstruction, severe gastroesophageal reflux, or any other clinical condition when the gut cannot be accessed. Care should also be taken during tube insertion when the child has moderate-to-severe mucositis or severe thrombocytopenia 47, 48, 51.

Proactive or prophylactic enteral nutrition can be considered in children identified to be at high risk of subsequently becoming nutritionally compromised 6, 51, 53. If patient/parental resistance is a barrier to implementing proactive enteral tube feeding, patients and their caregivers should be counselled extensively on the beneficial effects of enteral feeds 47, 51.

6.2 Types of Enteral Nutrition Access

• Recommendation

  • Nasogastric tubes should be the first preferred choice for delivering enteral nutrition.

  • When prolonged support is required (>4–6 weeks) or the nasopharynx needs to be bypassed, then a gastrostomy is preferred.

  • Jejunal enteral access is indicated when intragastric feeding is contraindicated.

• Rationale

Enteral nutrition can be administered by several routes: nasogastric, nasoduodenal, and nasojejunal. Nasogastric tube feeding should be the preferred choice in patients with persistent vomiting. Nasoduodenal and nasojejunal feeding tubes are recommended when patients are at high risk of pulmonary regurgitation or persistent and severe vomiting 6, 51. Gastrostomy feeding tubes (percutaneous endoscopic, radiologically inserted, or surgically inserted) can be used when prolonged enteral support is required (>4–6 weeks) or in conditions when the nasopharynx needs to be bypassed 6, 51.

6.3 Enhancing tolerance to Enteral feeds

• Recommendation

  • Enteral nutrition can be delivered by continuous feeding, or bolus feeds if the patient shows good tolerance without experiencing symptoms such as vomiting or abdominal distension.

Bolus feeding, continuous feeding, or a combination of the two are the methods by which enteral feeds can be delivered 6. Bolus feeds can be administered through a feeding pump, a syringe or gravity bags 48, 54. Bolus feeds are more physiological than continuous feeds as they stimulate a normal enzymatic response; however, continuous feeding may be safer and better tolerated by the patients in certain conditions 33, 51.

In the absence of feeding pumps, bolus feeds can also be administered using a syringe with a maximum feed rate of 20 ml/min administered over a period of 15 mins. In case of intolerance of feeds or to feed even at a slower rate, feeding is recommended by a gravity feed bag hung at least 60 cm above the patient's head 48, 54. Fabozzi et al. suggest starting with continuous feeding and switching to bolus feeding if well tolerated (i.e., no vomiting or abdominal distension) 6.

6.4 Types of Enteral Nutrition formulas

• Recommendation

  • Commercial feeds are recommended when nutrient demands are high and/or in scenarios of impaired gastrointestinal tolerance.

  • Standard polymeric formulas are ideal for patients with a normally functioning gut.

  • Concentrated formulas can be used in patients with reduced gastric capacity, fluid restriction, or limitations in the duration of time for tube feeds.

  • Predigested or partially hydrolysed or semi-elemental feeds are indicated in patients with significant impairment of gastrointestinal digestive and absorptive functions

  • Nutrient-dense blenderised feeds can be used if cost is a concern. However, this committee would like to highlight the importance of maintaining hygiene and cleanliness throughout the preparation and handling of blenderised feeds, especially in those who are immunocompromised.

• Rationale

The EN formula should be chosen considering the patient's age and gastrointestinal functional status. Standard polymeric formulas are suitable for a functioning gastrointestinal tract, as they contain intact proteins and long-chain triglycerides 6, 33, 51. Semi-elemental predigested or partially hydrolysed formulas containing amino acids and medium-chain triglycerides may be indicated in malabsorption conditions 6, 33, 51. Concentrated formulas can be used in case of fluid restriction or reduced gastric capacity; however, gastrointestinal side effects should be monitored due to the high osmolarity of these feeds 6, 33, 51.

It is essential to thoroughly strain all feeds to prevent clogging of the enteral tube. Educating the patient and caregivers on food safety and hygiene and maintaining the calorie and nutrient density of the preparation is essential 48, 51.

7.1 Indications for Parenteral Nutrition (PN)

• Recommendation

  • PN is indicated when EN is expected to be inadequate to meet nutritional requirements for at least 5-7 days or in clinical conditions where EN or oral feeds are contraindicated.

  • Small amounts of oral feeds should be introduced as soon as possible when clinical conditions improve and it is medically feasible.

• Rationale

Feeding through PN should always be the last resort and is indicated if EN is expected to be inadequate to meet nutritional requirements for at least 5–7 days or in conditions where EN or oral feeds are contraindicated 6, 26. PN is also indicated in conditions of neutropenic enterocolitis, severe malabsorption, persistent vomiting, paralytic ileus, intestinal obstruction, intestinal perforation, short bowel syndrome, diffuse peritonitis, intestinal perforation, active gastrointestinal bleed, gastrointestinal ischemia, graft vs host disease and state of severe shock 6, 26. Additional indications for PN include severe pancreatitis, peritoneal carcinomatosis or the occurrence of chylous ascites after surgery for abdominal tumour 26. Minimal or small amounts of enteral feeding should be introduced as soon as medically feasible as it helps restore a healthy microbiome, which is essential for intestinal function and overall health 26, 55.

7.2 Nutritional requirements and delivery of PN

• Recommendation

  • The committee recommends adopting the nutritional recommendations provided by the ESPGHAN/ESPEN/ESPR/CSPEN parenteral nutrition guidelines when planning PN feeds.

  • Covering the PN bag and administration set to protect it from photo-degradation is recommended.

• Expert Opinion

  • Based on practical field experience, supplementation with intravenous amino acids may be helpful in patients whose oral intake is expected to be reduced during high-dose chemotherapy.

• Rationale

PN formulations should be prescribed, considering age requirements and nutritional status, as well as the fluid requirement and type of venous access available 6. When PN is needed for less than ten days, PN administration through peripheral lines is acceptable. However, when concentrations greater than 12.5% glucose or a prolonged period of PN are anticipated, the central line is preferred 26. In the absence of India-specific studies, the nutritional composition of PN feeds (macronutrient and micronutrient) can be planned as per the guidelines laid out by the ESPGHAN/ESPEN/ESPR/CSPEN working group on paediatric parenteral nutrition (2018) 56, 57, 58, 59, 60, 61, 62, 63, 64 . The guidelines can be accessed online at https://espghan.info/published-guidelines/

Fluid requirements are based on the Holliday Segar formula for calculating maintenance fluid. The formula recommends parenteral fluid and electrolyte intake for children and infants beyond the neonatal period, which is age and weight-dependent 65.

Light protection is recommended for both PN bags and administration sets. The use of PUFAs in PN increases the risk of peroxidation. Vitamins are prone to stability issues due to photo-degradation, oxidation and interactions with PN bags and administration sets. Lipid opacity is insufficient to prevent photo-degradation; therefore, the bags and administration sets must be light-protected 66.

Based on practical field experience, partial parenteral nutrition may be helpful in patients whose oral intake is expected to be reduced during high-dose chemotherapy. Supplementation with intravenous amino acids along with an oral diet can help meet nutrient requirements in such scenarios.

7.3 Monitoring patients on PN

• Recommendation

  • Monitoring for complications may be based on the patient's clinical condition (from once daily to 2 to 3 times weekly).

  • A nutritional assessment should be done at baseline before starting PN, and daily weight should be monitored after initiation until the child is stable on TPN.

• Rationale

Some of the possible complications related to the use of PN include mechanical or equipment-related complications, such as CVC thrombosis, occlusion, or dislodgement; infective complications; and metabolic complications, such as deficiency or excess of PN components (hypertriglyceridemia and hyperglycemia), acid-base or electrolyte imbalance, drug interaction or compatibility problems, intestinal failure associated liver disease, refeeding syndrome and gut dysbiosis on exclusive PN 6, 67.

Therefore, monitoring for complications is essential 48. It is recommended that a baseline nutritional assessment comprising anthropometric parameters like weight, height, head circumference (if applicable), biochemical parameters and urine analysis be done 6, 67.

The frequency of laboratory assessment may be based on the patient's clinical condition (from once daily to 2-3 times per week) 68. Daily weight monitoring is ideal until the patient is stable on TPN, followed by weight monitoring twice weekly 66.

7.4 Weaning off from PN

• Recommendation

Weaning off PN should be attempted when clinical conditions are stabilised, there is improvement in nutritional status, and when small amounts of oral or enteral feeds can be tolerated.

• Rationale

Complete enteral starvation may be avoided during PN administration. Children on PN without intestinal obstruction or other EN contraindications should continue to have a minimum amount of enteral feed to maintain pancreaticobiliary secretion and promote gut mucosal integrity whenever possible. The volume should be increased as soon as a small amount of feed is tolerated 68. A reduction in the amount of PN may be attempted as soon as the child is stabilised, i.e. intestinal losses from vomiting and diarrhoea have been minimised, and an optimal nutrition state is reached 68.

10.1 Nutritional requirements in HSCT

• Recommendation

  • Patients need to be monitored for malnutrition prior to and during the transplant.

  • Appropriate nutritional support must be provided depending on oral intake, feed tolerance, and nutritional status.

• Rationale

Patients undergoing HSCT, particularly allogeneic -HSCT, are at an increased risk for malnutrition 87. Malnutrition is associated with poor clinical outcomes, decreased overall survival, higher risk of infectious and immunologic complications, delayed neutrophil engraftment and prolonged hospital stay 88, 89.

It is recommended that screening for malnutrition be done at admission for transplantation using the NRS-2002 screening tool. General nutritional management of patients includes:

• • Early involvement of dietitians

  • Considering the placement of the nasogastric tube on day +1

  • Standardised monitoring of nutritional intake, especially calories and protein

  • Daily review of oral food tolerance

  • Nutritional reassessment every three days 90

Indications for nutritional intervention include: 90

• Oral intake <60% for three days consecutively

• Pre-existing malnutrition and/or BMI < 18

Nutritional intervention through oral means can be increased or intensified by adding snacks rich in proteins and energy, protein or calorie enrichment of main courses and additional protein and energy drinks. However, EN is recommended if oral support alone cannot reach nutritional goals. If nutritional goals cannot be achieved in patients with gastrointestinal failure and/or intolerance for NGT, then PN is recommended 90.

10.2 Nutritional Management of side-effects of HSCT

• Recommendation

  • Side effects such as mucositis, vomiting, nausea and diarrhoea are common post-HSCT. Prompt and appropriate intervention, depending on individual requirements, should be provided. A nutritionist who can provide appropriate dietetic advice should ideally be part of each HSCT unit.

• Rationale

The National Guidelines for Hematopoietic Cell Transplantation from the Indian Council of Medical Research(ICMR) notes that high-dose chemotherapy with or without total body irradiation leads to grade III or IV mucositis in over half of the patients undergoing transplantation. In the event of these side effects, the guideline recommends that supportive care in the form of EN or PN should be considered. It also recommends that a nutritionist who can provide appropriate dietetic advice in each HSCT unit be available 91.

The parental guide for post-HSCT patients from the Indian Academy of Pediatrics recommends small, bland oral feeds that are easily digestible in the event of nausea and vomiting. If the child suffers from diarrhoea, it is recommended to keep the child well hydrated and avoid milk products and fruit juices that may further worsen loose stool due to lactose and fructose intolerance 92.

10.3 Nutrition in Acute Graft Versus Host Disease (GvHD)

• Recommendation

  • Patients with acute GVHD can be managed orally or through enteral feeds. Feeds should be low in fibre and fat.

  • In the absence of severe renal impairment protein requirements can range between 1.5-2 g/day.

  • In severe cases, complete bowel rest and total PN are indicated.

• Rationale

GvHD is a side-effect that occurs after HSCT. Patients with GvHD of the digestive tract are at a higher risk of malnutrition and compilations due to excessive diarrhoea, abdominal pain, nausea, vomiting, gastrointestinal bleeding, dysphagia and malabsorption 93.

Calorie demands are mainly driven by energy loss through diarrhoea. Enteral solutions low in fat and lactose-free are advised. It has been seen that maintaining a minimal amount of oral or enteral nutrition facilitates early dietary recovery 94, 95. Complete bowel rest and total PN are indicated in severe GVHD grade IV and when stool volume >1500ml in 24 hours 94, 96.

Protein requirements are elevated, and recommendations range from 1.2 to 2.5 g/kg/day. The EBMT handbook recommends protein in the range of 1.5-2 g/kg/day in the absence of severe renal impairment96, 97, 98. Vitamin and trace elements may need to be supplemented if levels indicate deficiency 90, 98, 99, 100.

11.1 Nutritional Assessment

• Recommendation

Nutritional assessment should be conducted during the first year of follow-up. The following schedule is recommended:

• • Ideally, monthly for undernourished patients

  • Quarterly for obese children and well-nourished patients with nutritional risk factors;

  • Once in six months for children without risk factors

  • Beyond the first year, well-nourished patients with nutritional risk factors or inadequate eating habits should be assessed yearly, focusing on dietary habits, exercise and height/weight gain.

• Rationale

Childhood cancer survivors are at a higher risk of developing chronic health conditions, including cardiovascular disease, metabolic syndrome, hormonal abnormalities, and osteoporosis as adults compared to their peers. The prevalence of these late effects increases as time elapses from cancer diagnosis 101.

It is therefore strongly advised to conduct regular nutritional assessments for cancer survivors 6, 13. For survivors who are undernourished, monthly assessments are highly recommended. However, this may not be achievable in some situations as patients may visit the hospital once a quarter for follow-up. For obese patients, assessments should be conducted every quarter. Those without specific risk factors can undergo evaluations every six months during the initial year of follow-up and subsequently every year. Western recommendations advise that well-nourished patients with nutritional risk factors such as dyslipidemia, hyperglycemia, or inadequate eating habits should be assessed quarterly in the first year, every six months until the fifth year, and then annually thereafter 6, 13. However, in the Indian scenario and keeping in mind the number and schedule of hospital follow-ups beyond the first year, well-nourished patients with nutritional risk factors or inadequate eating habits should be assessed yearly with a focus on dietary habits, exercise and height/weight gain.

11.2 Nutritional management during survivorship

• Recommendation

Implementing targeted nutritional interventions beyond cancer treatment is recommended to help reduce the risk of chronic diseases.

• Rationale

Specific nutritional interventions and lifestyle changes beyond cancer treatment and survival may help prevent or reduce the incidence of chronic diseases as these children grow into adulthood 102, 103.

Nutritional interventions recommended** include:

• Including a variety of foods from each food group.

• Avoiding fad diets with no scientific evidence.

• Consuming five or more servings of fruits (including citrus fruits) and vegetables (including green and yellow vegetables) daily.

• Limiting 100% fruit juices and juices sweetened with sugar.

• Consuming plenty of high-fibre foods such as whole-grain cereals.

• Restricting refined carbohydrates, including soft drinks and foods containing sugar.

• Restricting fried foods.

• Switching to low-fat dairy products.

• Adopting healthy cooking methods like steaming, baking and boiling.

• Opting for leaner portions of meat - fish or poultry, instead of red meat.

• Avoiding salt-cured and pickled products.

** Adapted from the Children's Oncology Group, Diet and Physical Activity | Version 5.0 | October 2018 104

Dietary supplements are only required if the child needs to increase protein and energy requirements and if it is not achievable through the daily diet 104.

11.3 Physical activity

• Recommendation

  • It is recommended that children undergoing active treatment and survivors make graded physical activity as per their tolerance a part of their everyday routine.

  • Aerobic activities, resistance exercises and exercises that improve flexibility and coordination can be incorporated into the exercise regimen, which a physical or occupational therapist should ideally create.

• Rationale

Although specific guidelines tailored to children and adolescents are currently unavailable, engaging in exercise and sports offers all patients a chance for interventions to combat their lack of physical activity. It is essential to address this with parents and caregivers as they may fail to motivate their child or need help understanding the importance of physical activity during active treatment 105.

Spreafico et al. outline the fundamental principles that can serve as the foundation for integrating exercise into the everyday routines of childhood cancer patients 106. These include the creation of an exercise regimen that takes into consideration patient capabilities and preferences; the FITT principles (i.e., frequency [sessions per week], intensity [how hard per session], type [exercise modality], and time [session duration]); goals of intervention and safety among others 106.

Aerobic activities, which encompass continuous exercises that enhance cardiovascular and respiratory function while also improving the body's utilisation of oxygen, can be initiated right at the onset of cancer treatment. An expert exercise professional should provide resistance exercises that use the patient's body weight or resistance bands, which help strengthen or build muscles. Exercises that improve flexibility, like yoga, and those that improve coordination, such as balancing balls and martial arts, can also be incorporated into the exercise regimen. These activities can be incorporated 2 to 3 times a week for an average of 15 to 20 minutes or as tolerated 106.

Survivors with special needs should seek the help of a physical or occupational therapist who can help tailor an appropriate exercise regime 106.

Disclaimer

In the absence of good clinical trials, the recommendations are based primarily on expert opinion with available evidence. Nutrition practitioners should consider the limitations expressed by the authors in adopting into their practice. There is a paucity of Indian clinical studies. The recommendations are primarily based on Western studies and experts' opinions. This calls for Indian clinical research papers on the topics discussed and many more that are not included here. More clinical research is needed to formulate evidence-based practical guidelines in this area of interest. Our recommendations are an overview of the role of nutrition in paediatric cancer treatment. The committee states that the recommendations must be put to practice only after considering the intent and type of treatment, social and economic barriers, cultural practices, and available resources at the treating centres, especially when a reasonably invasive intervention is proposed.

Author Contributions

Lekha Sreedharan and Sripriya Venkiteswaran organised and conducted the weekly meetings. Lekha Sreedharan, Sripriya Venkiteswaran and Shivshankar Timmanpyati were involved in data curation, reviewing content from other authors and manuscript writing. Maya Prasad provided valuable insights and facilitated deeper conversations after reviewing the preliminary draft of the manuscript. All authors critically reviewed and revised the manuscript for important intellectual content, and all authors provided final approval of the version to be submitted. All authors have read and agreed to the published version of the manuscript.