PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Pediatr Blood Cancer. Author manuscript; available in PMC 2013 December 15.
Published in final edited form as:
PMCID: PMC3468697
NIHMSID: NIHMS392988

Malnutrition and Obesity in Pediatric Oncology Patients: Causes, Consequences, and Interventions

Erica Co-Reyes, BA,1 Rhea Li, MPH, RD,2 Winston Huh, MD,3 and Joya Chandra, PhD2,*

Abstract

In children with cancer, suboptimal nutrition states are common consequences of the disease and its treatment. These nutrition states have been attributed to a number of etiologies dependent on the patient’s tumor type and treatment, and are associated with increased morbidity and mortality. Interventions vary from psychosocial to pharmacological and surgical management. Further research is necessary to understand the epidemiology and etiology of these nutrition states. Of great importance is the development and implementation of effective interventions to optimize nutritional status among children with cancer during and after therapy.

Keywords: nutrition, pediatric oncology, obesity, malnutrition, support care

MALNUTRITION AND CHEMOTHERAPY

Definition and Detection

Although malnutrition is a common complication of pediatric cancer and its treatment, firm criteria defining this state are not universally used. The Children’s Oncology Group (COG) Nutrition Committee has established categories of nutritional status and an algorithm for nutritional intervention based on body mass index (BMI), weight for length or height (WT/LT), or percentile ideal body weight for height or length (%IBW) [1]. In comparison to BMI, arm anthropometric measurement has been shown to be a more sensitive indicator of malnutrition among children with cancer, especially in those with tumor burden [2,3]. Despite the recommendation that triceps skinfolds be incorporated into the assessment of pediatric patients with cancer [4], a COG survey of nutritional practices found that only 5% (6/125) of institutions measured triceps skinfolds. Incorporation of arm anthropometric measurement in nutrition algorithms is urged. Femoral quadriceps muscle ultrasonography [5], bioelectrical impedance [6], total body potassium counting [7], and dual energy x-ray absorptiometry scanning [8] have all been used to analyze body composition, but larger studies in groups of children with cancer are lacking.

Laboratory indices such as serum albumin and prealbumin are common components of nutritional assessment [9], despite reports of their clinical limitations [10] and lack of correlation with other indices of nutritional status [11]. Still, arguments have been made for the utility of prealbumin measurements in patients with acute lymphoblastic leukemia (ALL) [12] or solid tumors [13]. In a prospective study of children in Latin America, the use of albumin adjunct to anthropometric measurements increased the sensitivity of malnutrition criteria [3]. Overall, the role of serial biochemical measurements in the continuing assessment of nutritional status in children with cancer remains unclear, and further studies in this area are warranted.

Subtle changes in micronutrients and metabolism may occur even in the absence of deviations from normal in height and weight. Low plasma 1,25-dihydroxy vitamin D levels have been demonstrated in children with ALL at diagnosis, consistent with the effect of leukemia on vitamin D metabolism and bone turnover [14]. Low levels of antioxidant nutrients, including vitamins A, C, E, as well as zinc and selenium, have also been observed in ALL patients at diagnosis and during treatment [15]. Additional study pertaining to the prevalence and consequences of micronutrient deficiencies in children with cancer is needed.

Prevalence and Risk Factors

It remains difficult to derive a clear understanding of the prevalence of malnutrition because most studies have focused on children with leukemia where generally small sample sizes have been used, and various methods have been employed to assess nutritional status. In a review of 11 observational studies, Brinkshma et al. [16] found that leukemia patients had the lowest prevalence of malnutrition, about 5%–10% at diagnosis and 0%–5% during treatment. Children with neuroblastoma demonstrated the highest rate at diagnosis, at 50%, whereas for children with other solid tumors, the estimated prevalence was 0%–30%. The etiologies of weight loss and malnutrition at diagnosis are variable; possible causes are energy deficiency and/or inflammation leading to loss of fat and fat free mass [16]. Table I lists factors associated with malnutrition risk in children with cancer based on tumor type, treatment modality, and patient demographics.

Table I
Factors Associated with High Nutritional Risk in Children with Cancer Undergoing Chemotherapy

Etiologies of Malnutrition

F actors leading to energy deficiency in children with cancer include insufficient intake, increased metabolic rate, altered physical activity, and inflammation [16]. Several studies have demonstrated lower energy intake at diagnosis among patients compared with healthy controls, but similar energy intake during patient treatment [1720]. Only one study, however, tested the relationship between altered energy intake and nutritional state [20], and further study in this area is warranted. Depression-related anorexia is another likely, but thus far unstudied, cause of low energy intake.

Among nine reviewed studies of metabolic rate in pediatric cancer patients, an increased metabolic rate could not be demonstrated in childhood cancer patients during treatment [16]. Conclusions about metabolic rate at diagnosis are conflicting, with reports of both normal [17,19] and elevated rates [21]. Also, no studies have tested the relationship between metabolic rate and changes in BMI.

Table II lists factors contributing to cancer cachexia, a phenomenon linked to inflammation resulting in decline in muscle mass and functional status, in pediatric oncology patients. Tumor and host released cytokines such as tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-γ (IFN-γ) are often used in the assessment of inflammation. The few available studies of inflammation in children with cancer have demonstrated increased TNF-α [59], IL-1 receptors [83], and protein turnover [103], though no relationship with fat or muscle mass [59] or nutritional status [83, 103] was found. Overall, only separate elements of energy balance have been studied, and few studies have tested the relationship between energy deficiency and nutritional status.

Table II
Factors Contributing to Cancer Cachexia in Pediatric Oncology Patients

Consequences of Malnutrition During Treatment

Many studies, but not all [22,23], have found that malnutrition is a negative prognostic factor and reduces survival in direct proportion to its extent [2426]. Malnutrition and underweight have been associated with inferior survival in children with metastatic diseases [25,27], ALL [2830], and acute myeloid leukemia [AML] [31]. In a recent large prospective study of children with newly diagnosed cancer in Central America (n = 1787), children were stratified into three nutritional categories on the basis of arm anthropometric measurements and/or serum albumin levels. Event-free survival rates at 2 years differed significantly between adequately nourished and severely depleted children (65% vs. 48%) [P < 0.001] [3]. Malnutrition in children with cancer has also been associated with decreased treatment tolerance [27,32], unfavorable response to chemotherapy [4,3234], treatment delays [27], increased risk of infection [3537], and diminished quality of life [25,38]. Large prospective studies on the effect of nutritional status on morbidity and mortality among children are lacking.

Strategies for Intervention

The goals of nutritional intervention in children are to promote normal development, maintain body stores as close to ideal as possible, and maximize functional status as a child receives treatment. At present, there are no agreed-upon parameters regarding the criteria for, timing of, and duration of nutritional interventions in pediatric oncology patients [39]. Table III lists the indications, advantages, and disadvantages of oral, enteral tube, and parenteral interventions for children with cancer.

Table III
Indications, Advantages, and Disadvantages of Oral, Nasogastric, Gastrostomy, and Parenteral Nutritional Interventions for Children with Cancer

Behavioral and Educational Interventions

In clinical trials among adults with cancer, individualized nutritional intervention by a registered dietitian significantly improved nutritional status [40], weight maintenance, and quality of life [41]. Clinical studies are needed of how registered dietitian’s interventions in children with cancer affect nutritional status and clinical outcome. Unfortunately, institutions nationwide cited lack of a registered dietitian as the biggest barrier to providing optimal nutritional support [9].

Behavioral modification techniques have been used successfully among children with cystic fibrosis, for whom early and aggressive nutritional therapy is a cornerstone of treatment. In one study, a 9-week intervention that used self-monitoring and goal setting resulted in a significant increase in average energy intake and weight gain [42]. Although malnutrition in children with cystic fibrosis arises from distinct etiologies, such interventions could be adapted for pediatric oncology patients.

Education of the healthcare team is important, and a review of nutrition support methods in pediatric oncology is available in print for physicians and other healthcare providers [4]. For nurses, “Nutrition in Children and Young People with Cancer” (Royal College of Nursing 2010) is available online [43]. Useful resources for caregivers include “Nutrition for the Child with Cancer” (American Cancer Society, 2010) and “Helping Your Child to Eat” (Royal Marsden Hospital, 2004), both available online.

Oral Pharmacologic Interventions

Oral appetite-enhancing agents have been studied in small groups of pediatric cancer patients. In one study of children with cancer cachexia (n = 66), daily administration of the agents cyproheptadine hydrochloride and/or megestrol acetate resulted in significant weight gain at 4 weeks with response rates greater than 75% [44]. A randomized controlled trial of megestrol acetate in malnourished children with cancer is underway (ClinicalTrials.gov Identifier [CTID] NCT00439101), as is a randomized controlled trial evaluating cyproheptadine hydrochloride in children newly diagnosed with cancer (CTID: NCT01132547).

The benefits of these appetite-enhancing agents have not been universally demonstrated in oncology populations, however. In one trial, adults with advanced cancer (n = 295) treated with cyproheptadine hydrochloride showed reduced nausea but no weight gain [45]. In adult [46] and pediatric populations [47,48], studies involving megestrol acetate treatment have documented adrenal suppression, glucose intolerance, edema, thromboembolism, and the absence of gain in lean body mass. The prevalence of and risk factors for these adverse effects remain unknown and are barriers to the wider use of these measures.

Omega-3 fatty acid supplementation with eicosapentaenoic acid to promote weight gain has been studied in a small number of children with cancer (n = 52), with significant resultant weight gain [49]. A randomized controlled trial investigating the effects of enteral administration of omega-3 fatty acid supplementation on nutritional status in children with ALL is under way (CTID: NCT01051154).

In a prospective study that included children with ALL, suboptimal total antioxidant status during treatment was associated with significantly increased toxicity from chemotherapy and decreased quality of life [15]. Greater antioxidant intake in the same cohort resulted in fewer therapy delays, less toxicity, and lower incidence of infection [50]. Studies of antioxidant levels among children with other types of malignancies and larger prospective studies on the effect of increased antioxidant intake on clinical outcome are needed.

Enteral Tube and Parenteral Interventions

Recommendations have been made to consider proactive enteral tube feeding (EN) among children with cancer at high risk of malnourishment [1,32]. In retrospective studies, early EN intervention has been associated with less nutritional decline in children with medulloblastoma [32] or osteosarcoma [51]. Among the latter, children with percutaneous endoscopic gastrostomy (PEG) placed at diagnosis and EN lasting throughout chemotherapy [n = 29] also tended to have fewer surgical complications, relapses, and deaths. Further prospective studies are warranted to assess the effect of proactive EN on nutritional status and clinical outcome.

PEG feeding is a well-tolerated method of EN in children with cancer [52]. In a retrospective study of pediatric oncology patients who received PEG (n = 74), 75% experienced weight gain or stabilization, with complication rates similar to those of a control neurological group (62% versus 76%, respectively) [51]. Elsewhere, the frequency of infection with PEG was reported as comparable to that of parenteral nutrition [53]. Larger prospective studies are needed to confirm these results.

Compared to parenteral nutrition, some clinical trials have found EN to be safer and more cost-effective, even in the setting of bone marrow transplantation [5456]. On the other hand, a Cochrane review of eight controlled trials of nutritional support in 159 children with cancer concluded there was limited evidence to suggest parenteral nutrition is more effective than enteral nutrition in well nourished children [57]. Larger clinical trials with well-defined outcome measures comparing enteral and parenteral methods of nutritional support in children undergoing chemotherapy are greatly needed.

OBESITY AND CHEMOTHERAPY

Obesity at Diagnosis

Definition, Prevalence, and Population at Risk

According to the American Academy of Pediatrics, children may be considered obese on the basis of a BMI standard deviation score (BMI-SDS) of greater than the 95th percentile [58]. Other definitions of obesity include WT/LT greater than the 90th percentile or %IBW greater than 120% [1]. Large retrospective studies have demonstrated a prevalence of obesity at diagnosis ranging from 8.6% of children with ALL [59] to 14.8% of children with AML [31]. Comparably less is known about the prevalence of obesity among children with solid and brain tumors. In adults, obesity is a risk factor for certain types of malignancies [60]; the effect of obesity on risk of childhood cancer has not been rigorously examined.

In children, obesity at diagnosis of cancer is associated with increased risk of obesity at treatment end and in survivorship [61]. All efforts should be taken to prevent obesity in survivorship because obese adults experience impaired glucose tolerance, diabetes mellitus, hypertension, cardiovascular disease, higher rates of some forms of cancer, and inferior survival when they develop cancer [60]. This is in addition to the finding that adult survivors of childhood cancer experience higher risks of cardiovascular disease and second malignancies than do their siblings [62,63]. The burden of obesity in childhood cancer survivors is not entirely known, and a request has been made for longitudinal prospective studies on body composition in patients from diagnosis through follow-up [64].

Consequences of Chemotherapy in Children Who Are Obese at Diagnosis

Obesity at diagnosis has been associated with inferior survival rates in children with cancer. In a retrospective analysis of 768 children with AML, Lange et al. [31] found that obese children had significantly inferior survival rates compared with middle-weight patients (BMI-SDS = 11th–94th percentiles) The authors attributed this to higher rates of treatment-related mortality in the obese group, although there was no evidence that these children had received excess chemotherapy. In a subsequent retrospective study of 4,260 children with ALL, Butturini et al. [59] found that overweight patients with a diagnosis of cancer after age 10 had a significantly lower mean 5-year event-free survival rate and a higher mean risk of relapse than did normal weight patients. Overweight was not associated with dose alterations, treatment delays, or increased toxicity, and the authors hypothesized that the higher risk of relapse might be due to differing pharmacokinetics of the drugs used in ALL maintenance. In contrast, Hijiya et al. [22] found in a retrospective study of 621 children treated for ALL that BMI had no influence on outcome or on the pharmacokinetics of several chemotherapeutic agents. Studies of chemotherapy pharmacokinetics with clinical correlations in obese children with cancer are limited to glucocorticoids, etoposide [22,65], methotrexate, teniposide, and doxorubicin [22]. Retrospective reviews of finished studies are needed to assess survival and toxicities associated with obesity and to determine the optimal methods of calculating chemotherapy dosages among obese children.

Mechanisms underlying the association between obesity and cancer are only starting to be understood. Obesity-related lymphokines can increase treatment toxicity by altering inflammation and can influence tumor biology by promoting angiogenesis and cell growth [66]. Glucose itself regulates the cell cycle [67], and high fasting levels of insulin have been associated with increased recurrences in adults with ALL [68]. Among obese children with ALL, a trend for higher initial white blood cell counts compared with normal-weight peers has been demonstrated and is consistent with an effect of obesity on cell growth [59].

Treatment-Related Obesity

Definition, Prevalence, and Population at Risk

Children with ALL or brain tumors have been the subjects of most studies of obesity risk during and after treatment because of the high risk of hypothalamic-pituitary axis damage secondary to cancer therapies or to primary tumor location. In one retrospective study of children treated for ALL (n = 102), the proportion of overweight patients increased steadily from 15% at diagnosis to 40% by treatment end [69]. Similarly, in a study of 46 children who underwent successful treatment for suprasellar brain tumors, the prevalence of overweight increased more than seven-fold from 6% at diagnosis to 43% at follow-up [70]. Table I lists factors associated with high risk of adiposity. Longitudinal studies of changes in body composition during treatment are needed to identify risk factors and optimal timing for interventions.

Etiologies of Treatment-Related Obesity

In children with ALL, excessive weight gain has been attributed to growth hormone [GH] deficiency/hypothalamic-pituitary axis damage due to cranial RT [71], leptin deregulation [72], exposure to corticosteroids [73], reduced physical activity [74,75], and poor dietary habits during survivorship [76]. Female survivors of ALL or brain tumors, especially if treated with cranial RT, demonstrate increased prevalence of obesity compared with the general population [64,77]. Cranial RT has been strongly associated with GH deficiency, which leads to raised leptin and fasting insulin concentrations, altered body fat distribution (abdominal obesity), and dyslipidemia (particularly in women) [78].

Excessive weight gain during ALL treatment is often attributed to the adverse effects of glucocorticoids [GC], which are known to promote adiposity in central fat and directly blunt adipocyte insulin sensitivity [79]. In small cross-sectional studies, childhood ALL-survivors demonstrated increased fat mass during the first years after corticosteroid treatment [64], but it is not clear whether this change was temporary or persistent. ALL patients have also had higher levels of energy intake and less physical activity during treatment with GC than they did on nontreatment days and compared with healthy controls [80]. The influences of glucocorticoids on body composition are still uncertain, and longitudinal prospective research to elucidate the long-term effect of corticosteroids on body habitus is warranted.

Children treated for ALL, compared with controls and with children treated for other malignancies, demonstrate significantly reduced total daily energy expenditure [81,82]. There has been no strong evidence of abnormalities in basal metabolic rate in long-term survivors of childhood ALL [82], and in general, researchers have concluded that decreased levels of physical activity account for the alterations in total daily energy expenditure. The mechanisms responsible for the patterns of reduced activity remain unknown; exercise intolerance, lower self-esteem, and habitual inactivity have all been postulated [81]. The effect of physical activity intervention on outcome has yet to be assessed.

Brain tumor survivors with hypothalamic insult present with an often intractable form of weight gain termed “hypothalamic obesity.” The cause of weight gain is not completely understood but is thought to arise from damage to the ventromedial hypothalamus, the center responsible for interpreting afferent vagal and hormonal signals from the liver, gut, pancreas, and adipose tissue. This leads to dysregulation of pancreatic beta-cell vagally mediated insulin release and insulin hypersecretion with enhanced weight gain. Significantly reduced physical activity has been observed in craniopharyngioma patients [83] and has been associated with overall reduction in sympathetic tone [84].

Strategies for Intervention

Studies have called for clinical guidelines to prevent and manage obesity in children with cancer, especially ALL or brain tumors [70,85]. Figure 1 illustrates the major causes and consequences of obesity in pediatric cancer patients and/or survivors with recommended interventions.

Fig. 1
Major causes and consequences of obesity in childhood cancer patients and/or survivors with recommended interventions

In one study, children with brain tumors and high risk of hypothalamic obesity (n = 39) attended a comprehensive care clinic that provided family-centered treatment with assessment by a dietician, behavior psychologist, neuropsychologist, exercise consultant, and an endocrinologist. During the time that children attended this clinic, their median % weight gain, % IBW, and rate of increase in % BMI were significantly lower than were the values obtained during standard care [86]. There is great need for similar models to be applied to diverse pediatric oncology populations.

Novel interventions involving interactive electronic media are being implemented increasingly as a youth-friendly means of promoting behavioral change [87]. A video game intervention has successfully increased medication adherence in children with cancer [88], and in another instance, an ongoing clinical trial is investigating the ways in which weight-related tailored text messages as part of a weight management program affect BMI among obese adolescents [CTID: NCT01448551].

Interventions directed towards hypothalamic obesity are challenging, since no standard pharmacological or surgical intervention has consistently had positive outcomes [89]. Lustig et al. [90] used octreotide, which prevents insulin hypersecretion, in a randomized controlled study in children with hypothalamic obesity after successful treatment for brain tumors and showed significant reductions in weight gain. However, this was followed by a larger multinational study that demonstrated no efficacy in the primary end-point of change in BMI [89]. Recently, a pilot trial of daily diazoxide and metformin among 9 pediatric patients with craniopharyngioma and hypothalamic obesity found significantly less weight gain in the treatment group (+1.2 ± 5.9 kg versus +9.5 ± 2.7 kg; P = .004) [91]. Surgery is usually considered the last resort, and varying efficacy with malabsorptive procedures such as gastric bypass [92] has been reported. In general, randomized controlled trials of, and experience with, interventions are rare, and treatment algorithms remain to be clarified.

CONCLUSION

Nutritional intervention for children with cancer is challenging and is compounded by an incomplete understanding of the etiologies of suboptimal nutritional states in this population and a paucity of evidence regarding the clinical efficacy of interventions. Despite a number of publicized guidelines suggesting effective approaches to nutritional support [9396], pediatric care centers nationwide vary widely with respect to nutritional practice and management, which are frequently based on opinion instead of evidence [9]. Ladas et al. [97] described the establishment of The International Committee on Nutrition & Health for Children with Cancer, a multinational group of allied health professionals that will strive to develop modifiable nutritional guidelines and education tools, will facilitate research collaboration, and will establish administrative support. These efforts are direly needed.

Further investigation of the epidemiology and etiologies of malnutrition and obesity, in conjunction with the initiation of well-designed clinical trials to investigate efficacy of nutritional interventions, will enable the development and validation of uniform nutrition protocols. These are necessary to optimize nutritional status in children with cancer during and after treatment and to leverage this modifiable factor to improve quality of life and survival for pediatric cancer patients and survivors.

Acknowledgments

Research support from the Gerber Foundation and from the Santa’s Elves Fundraiser organized by the University of Texas MD Anderson’s Advance Team is gratefully acknowledged. Dr. Joya Chandra receives research support through RO1 CA115811 from the National Institutes of Health. Thank you to editors at MD Anderson’s Scientific Publications Department, who reviewed a draft of this review. The ON (Optimizing Nutrition) to Life Program is supported in part by a grant from the Farrah Fawcett Foundation, a grant from the Children’s Art Project, and the National Institutes of Health through MD Anderson’s Cancer Center Support Grant CA016672.

Footnotes

CONFLICTS OF INTEREST STATEMENT

All authors declare no conflicts of interest.

References

1. Rogers PC, Melnick SJ, Ladas EJ, et al. Children’s Oncology Group (COG) Nutrition Committee. Pediatr Blood Cancer. 2008;50:447–450. [PubMed]
2. Oguz A, Karadeniz C, Pelit M, et al. Arm anthropometry in evaluation of malnutrition in children with cancer. Pediatr Hematol Oncol. 1999;16:35–41. [PubMed]
3. Sala A, Rossi E, Antillon F, et al. Nutritional status at diagnosis is related to clinical outcomes in children and adolescents with cancer: A perspective from Central America. EJC. 1990;48(2):243–252. [PubMed]
4. Ballal A, Bechard L, Jaksic T, Duggan C. Nutrtional supportive care. In: Pizzo PAPD, editor. Principles and practice of pediatric oncology. Philadelphia: Williams & Wilkins; 2010. pp. 1243–1255.
5. Taskinen MS. Evaluation of muscle protein mass in children with solid tumors by muscle thickness measurement with ultrasonography, as compared with anthropometric methods and visceral protein concentrations. Eur J Clin Nutr. 1998;52:402–406. [PubMed]
6. Yanovski S, Hubbard V. Biolectrical impedance analysis in body composition measurement. Am J Clin Nutr. 1994;64:387S–532S.
7. Murphy AJ, White M, Davies PSW. Body composition of children with cancer. Am Jr Clin Nutr. 2010;92(1):55–60. [PubMed]
8. Zemel B, Riley E, Stallings V. Evaluation of methodology for nutritional assessment in children: anthropometry, body composition, and energy expenditure. Annu Rev Nutr. 1997;12:443–448. [PubMed]
9. Ladas EJ, Sacks N, Brophy P, et al. Standards of nutritional care in pediatric oncology: results from a nationwide survey on the standards of practice in pediatric oncology: A Children’s Oncology Group study. Pediatr Blood Cancer. 2006;46:339–44. [PubMed]
10. Motil KJ. Sensitive measures of nutritional status in children in hospital and in the field. Int J Cancer. 1998;11:2–9. [PubMed]
11. Merrit R, Kalsch M, Roux L, Ashley-Mills J. Significance of hypoalbuminemia in pediatric oncology patients; malnutrition or infection? J Parent Enteral Nutr. 1985;9:303–306. [PubMed]
12. Yu L, Kuvibidila S, Ducos R, Warrier R. Nutritional status of children with leukemia. Med Pediatr Oncol. 1994;22:73–77. [PubMed]
13. Elhasid R, Laor A, Lischinski S, Postovosky S. Nutritional status of children with solid tumors. Cancer. 1999;86:119–125. [PubMed]
14. Atkinson S, Halton J, Bradley C. Bone and mineral abnormalities in childhood acute lymphoblastic leukemia: influence of disease, drugs and nutrition. Int J Cancer. 1998;11:35–49. [PubMed]
15. Kennedy DD, Ladas EJ, Rheingold SR, et al. Antioxidant status decreases in children with acute lymphoblastic leukemia during the first six months of chemotherapy treatment. Pediatr Blood Cancer. 2005;44:378–385. [PubMed]
16. Brinksma A, Huizinga G, Sulkers E, et al. Malnutrition in childhood cancer patients: A review on its prevalence and possible causes. Crit Rev Oncol Hematol. 2012 [Epub ahead of print] [PubMed]
17. Delbecque-Boussard L, Gottrand F, Ategbo S, Smith C. Nutritional status of children with acute lymphoblastic leukemia: a longitudinal study. Am J Clin Nutr. 1997;01(65):95–100. [PubMed]
18. Smith DE, Stevens MC. Malnutrition at diagnosis of malignancy in childhood: common but mostly missed. Eur J Pediatr. 1991;150:318–322. [PubMed]
19. Bond S, Han A, Wootton S, Kohler J. Energy intake and basal metabolic rate during maintenance chemotherapy. Arch Dis Child. 1992;02(67):229–232. [PMC free article] [PubMed]
20. Carter P, Carr D, Van E, Ramirez I, et al. Energy and nutrient intake of children with cancer. J Am Diet Assoc. 1983;6(82):610–615. [PubMed]
21. Schmid I, Schmitt M, Streiter M, Meilbeck R. Effects of soluble TNF receptor II (sTNF-RII), IL-1 receptor antagonist (IL-1ra), tumor load and hypermetabolism on malnutrition in children with acute leukemia. Eur J Med Res. 2005;11/16(10):457–461. [PubMed]
22. Hijiya N, Panetta JC, Zhou Y, et al. Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia. Blood. 2006;108:3997–4002. [PubMed]
23. Weir J, Reilly JJ, McColl JH, et al. No evidence for an effect of nutritional status at diagnosis on prognosis in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 1998;20:534–538. [PubMed]
24. Gomez-Almaguer D, Ruiz-Argüelles GJ, Poncede-Leon S. Nutritional status and socioeconomic conditions as prognostic factors in the outcome of therapy in childhood acute lymphoblastic leukemia. Int J Cancer. 1998;2:52–55. [PubMed]
25. Donaldson SS, Wesley MN, DeWys WD, et al. A study of the nutritional status of pediatric cancer patients. Am J Dis Child. 1981;135:1107–1112. [PubMed]
26. Lobato-Mendizabal E, Ruiz-Argüelles GJ. Leukemia and malnutrition, III: effect of chemotherapeutic treatment on the nutritional state and its repercussion on the therapeutic response of patients with acute lymphoblastic leukemia with standard risk. Sangre (Barc) 1990;35:189–195. [PubMed]
27. Rickard KA, Detamore CM, Coates TD, et al. Effect of nutrition staging on treatment delays and outcome in Stage IV neuroblastoma. Cancer. 1983;52:587–598. [PubMed]
28. Lobato-Mendizabal E, Ruiz-Argüelles GJ, Marín-López A. Leukaemia and nutrition, I: malnutrition is an adverse prognostic factor in the outcome of treatment of patients with standard-risk acute lymphoblastic leukaemia. Leuk Res. 1989;13:899–906. [PubMed]
29. Viana MB, Murao M, Ramos G, et al. Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis. Arch Dis Child. 1994;71:304–10. [PMC free article] [PubMed]
30. Lobato-Mendizábal E, López-Martínez B, Ruiz-Argüelles GJ. A critical review of the prognostic value of the nutritional status at diagnosis in the outcome of therapy of children with acute lymphoblastic leukemia. Rev Invest Clin. 2003;55:31–35. [PubMed]
31. Lange BJ, Gerbing RB, Feusner J, et al. Mortality in Overweight and Underweight Children With Acute Myeloid Leukemia. JAMA. 2005;293:203–211. [PubMed]
32. Ward E, Hopkins M, Arbuckle L, et al. Nutritional problems in children treated for medulloblastoma: implications for enteral nutrition support. Pediatr Blood Cancer. 2009;53:570–575. [PubMed]
33. Schein PS, Macdonald JS, Waters C, et al. Nutritional complications of cancer and its treatment. Semin Oncol. 1975;2:337–347. [PubMed]
34. Flegal KM, Graubard BI, Williamson DF, et al. Excess deaths associated with underweight, overweight, and obesity. JAMA. 2005;293:1861–1867. [PubMed]
35. Taj MM, Pearson AD, Mumford DB, et al. Effect of nutritional status on the incidence of infection in childhood cancer. Pediatr Hematol Oncol. 1993;10:281–287. [PubMed]
36. Halton JM. Impact of nutritional status on morbidity and dose intensity of chemotherapy during consolidation therapy in children with acute lymphoblastic leukemia (ALL) J Pediatr Hematol Oncol. 1999;21:317.
37. Hingorani P, Seidel K, Krailo M, et al. Body mass index (BMI) at diagnosis is associated with surgical wound complications in patients with localized osteosarcoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2011;57(6):939–942. [PMC free article] [PubMed]
38. Andrassy RJ, Chwals WJ. Nutritional support of the pediatric oncology patient. Nutrition. 1998;14:124–129. [PubMed]
39. Bauer J, Jürgens H, Frühwald MC. Important Aspects of Nutrition in Children with Cancer. Nutrition. 2011;2:67–77. [PMC free article] [PubMed]
40. Ireton-Jones CS, Garritson B, Kitchens L. Nutrition intervention in cancer patients: Does a registered dietitian make a difference? Top Clin Nutr. 1995;10:42–48.
41. Isenring EA, Capra S, Bauer J. Nutrition intervention is beneficial in oncology outpatients receiving radiotherapy to the gastrointestinal or head and neck area. Br J Cancer. 2004;91:447–452. [PMC free article] [PubMed]
42. Stark L. Can nutrition counseling be more behavioural? Lessons learned from dietary management of cystic fibrosis. Proc Nutr Soc. 2003;62:793–799. [PubMed]
43. Shipway L. Providing nutritional support for patients during cancer treatment. Paediatr Nurs. 2010;22(4):20–25. [PubMed]
44. Couluris M, Mayer JLR, Freyer DR, et al. The effect of cyproheptadine hydrochloride (periactin) and megestrol acetate (megace) on weight in children with cancer/treatment-related cachexia. J Pediatr Hematol Oncol. 2008;30:791–797. [PMC free article] [PubMed]
45. Kardinal CG, Loprinzi CL, Schaid DJ, et al. A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer. 1990;65(12):2657–2662. [PubMed]
46. Reuben DB, Hirsch SH, Zhou K, et al. The effects of megestrol acetate suspension for elderly patients with reduced appetite after hospitalization: a phase II randomized clinical trial. J Am Geriatr Soc. 2005;53(6):970–975. [PubMed]
47. Marchand V, Baker SS, Stark TJ, et al. Randomized, double-blind, placebo-controlled pilot trial of megestrol acetate in malnourished children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2000;31(3):264–269. [PubMed]
48. Orme LM, Bond JD, Humphrey MS, et al. Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression. Cancer. 2003;98(2):397–405. [PubMed]
49. Bayram I, Celik N, Nelson JL. The use of a protein and energy dense eicosapentaenoic acid containing supplement for malignancy-related weight loss in children. Pediatr Blood Cancer. 2009;52(5):571–574. [PubMed]
50. Kennedy DD, Tucker KL, Ladas ED, et al. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. Am J Clin Nutr. 2004;79:1029–1036. [PubMed]
51. Schmitt F, Caldari D, Corradini N, Gicquel P. Tolerance and efficacy of preventative gastrostomy feeding in pediatric oncology. Pediatr Blood Cancer. 2012 Apr 10; [PubMed]
52. Avitsland TL, Kristensen C, Emblem R, et al. Percutaneous endoscopic gastrostomy in children: a safe technique with major symptom relief and high parental satisfaction. J Pediatr Gastroenterol Nutr. 2006;43(5):624–628. [PubMed]
53. Parbhoo DM, Tiedemann K, Catto-Smith AG. Clinical outcome after percutaneous endoscopic gastrostomy in children with malignancies. Pediatr Blood Cancer. 2011;56(7):1146–1148. [PubMed]
54. Aquino VM, Harvey AR, Garvin JH, et al. A double-blind, randomized, placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: A pediatric blood and marrow transplant consortium study. Bone Marrow Transplant. 2005;36:611–616. [PubMed]
55. Deswarte-Wallace J, Firouzbakhsh S, Finklestein JZ. Using research to change practice: Enteral feedings for pediatric oncology patients. J Pediatr Oncol Nurs. 2001;18:217–223. [PubMed]
56. Mehta NM, Compher CA. S.P.E.N. Board of Directors. A.S.P.E.N. Clinical Guidelines: nutrition support of the critically ill child. JPEN. 2009;33(3):260–276. [PubMed]
57. Jones L, Watling RM, Wilkins S, Pizer B. Nutritional support in children and young people with cancer undergoing chemotherapy. Cochrane Database Syst Rev. 2010;7(7):CD003298. [PubMed]
58. Ogden C, Carroll MD, Flegal KM. High body mass index for age among US children and adolescents, 2003–2006. JAMA. 2008;299:2401–2405. [PubMed]
59. Butturini AM, Dorey FJ, Lange BJ, et al. Obesity and outcome in pediatric acute lymphoblastic leukemia. J Clin Oncol. 2007;25:2063–2069. [PubMed]
60. Rogers PC, Meacham LR, Oeffinger KC, et al. Obesity in pediatric oncology. Pediatric blood & cancer. 2005;45:881–891. [PubMed]
61. Withycombe JS, Post-White JE, Meza JL, et al. Weight patterns in children with higher risk ALL: A report from the Children’s Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer. 2009;53:1249–1254. [PMC free article] [PubMed]
62. Janiszewski PM, Oeffinger KC, Church TS, et al. Abdominal obesity, liver fat, and muscle composition in survivors of childhood acute lymphoblastic leukemia. J Clin Endocrinol Metab. 2007;92(10):3816–3821. [PubMed]
63. Diller L, Chow EJ, Gurney JG, et al. Chronic disease in the Childhood Cancer Survivor Study cohort: a review of published findings. J Clin Oncol. 2009;27(14):2339–2355. [PMC free article] [PubMed]
64. Brouwer CJ, Gietema J, Kamps W, et al. Changes in body composition after childhood cancer treatment: impact on future health status--a review. Crit Rev Oncol Hematol. 2007;63(1):32–46. [PubMed]
65. Palle J, Britt-Marie F, Gustafsson G, et al. Etoposide pharmacokinetics in children treated for acute myeloid leukemia. Anticancer Drugs. 2006;17(9):1087–1094. [PubMed]
66. Brakenhielm E, Veitonmaki N, Cao R, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA. 2004;101:2476–2481. [PubMed]
67. Wilson WA, Roach PJ. Nutrient-regulated protein kinases in budding yeast. Cell. 2002;111:155–158. [PubMed]
68. Weiser MA, Cabanillas ME, Konopleva M, et al. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004;100:1179–1185. [PubMed]
69. Collins L, Zarzabal LA, Nayiager T, et al. Growth in children with acute lymphoblastic leukemia during treatment. J Pediatr Hematol Oncol. 2010;32:304–307. [PubMed]
70. Lek N, Prentice P, Williams RM, et al. Risk factors for obesity in childhood survivors of suprasellar brain tumours: a retrospective study. Acta Paediatrica. 2010;99:1522–1526. [PubMed]
71. Sklar C, Mertens A, Walter A, et al. Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: Role of cranial irradtiation. Med Pediatr Oncol. 2000;35:91–95. [PubMed]
72. Wallace A, Tucker P, Williams D, et al. Short-term effects of prednisolone and dexamethsaone on circulating concentration of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia. Clin Endocrinol. 2003;58:770–776. [PubMed]
73. Reilly J, Brougham M, Montgomery C, et al. Effect of glucocorticoid therapy on energy intake in children treated for acute lymphoblastic leukemia. J Clin Endocrinol Metab. 2001;86:3742–3745. [PubMed]
74. Didi M, Didcock E, Davies H, et al. High incidence of obesity in young adults after treatment of acute lymphoblastic leukemia in childhood. J Pediatr. 1995;127:63–67. [PubMed]
75. Warner J, Bell W, Webb D, et al. Daily energy expenditure and physical activity in survivors of childhood malignancy. Pediatr Res. 1998;43:607–613. [PubMed]
76. Cohen J, Nutr M, Wakefield CE, et al. Dietary intake after treatment in child cancer survivors. Pediatr Blood Cancer. 2012;58(5):752–757. [PubMed]
77. Garmey EG, Liu Q, Sklar CA, et al. Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2008;26:4639–4645. [PMC free article] [PubMed]
78. Gurney JG, Ness KK, Sibley SD, et al. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer. 2006;107(6):1303–1312. [PubMed]
79. Siviero-Miachon AA, Spinola-Castro AM, Guerra-Junior G. Adiposity in childhood cancer surivors: insights into obeseity physiopathology. Arg Bras Endocrinol Metabol. 2009;53(2):190–200. [PubMed]
80. Jansen H, Postma A, Stolk RP, Kamps WA. Acute lymphoblastic leukemia and obesity: increased energy intake or decreased physical activity? Support Care Center. 2009;17(1):103–106. [PubMed]
81. Warner JT. Body composition, exercise and energy expenditure in survivors of acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2008;50(2 Suppl):456–461. [PubMed]
82. Reilly J, Ventham J, Ralston J, et al. Reduced energy expenditure in preobese children treated for acute lymphoblastic leukemia. Pediatr Res. 1998;44:557–562. [PubMed]
83. Harz K, Müller H, Waldeck E, Pudel V. Obesity in patients with craniopharyngioma: assessment of food intake and movement counts indicating physical activity. J Clin Endocrinol Metab. 2003;88:5527–5231. [PubMed]
84. Roth C, Hunnerman D, Gebhardt U, Smith C. Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. Pediatr Res. 2007;61:496–501. [PubMed]
85. Reilly JJ, Ventham JC, Newell J, et al. Risk factors for excess weight gain in children treated for acute lymphoblastic leukaemia. Int J Obes Relat Metab Disord. 2000;24:1537–1541. [PubMed]
86. Rakhshani N, Jeffery AS, Schulte F, et al. Evaluation of a comprehensive care clinic model for children with brain tumor and risk for hypothalamic obesity. Obesity. 2010;18(9):1768–1774. [PubMed]
87. Nguyen B, Kornman KP, Baur La. A review of electronic interventions for prevention and treatment of overweight and obesity in young people. Obes Rev. 2011;12:298–314. [PubMed]
88. Kato PM, Cole SW, Bradlyn AS, et al. A video game improves behavioral outcomes in adolescents and young adults with cancer: a randomized trial. Pediatrics. 2008;122:305–317. [PubMed]
89. Bereket A, Kiess W, Lustig RH, et al. Hypothalamic obesity in children. Obes Rev. 2012;10:1–19.
90. Lustig RH, Hinds PS, Ringwald-Smith K, et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2003;88(6):2586–2592. [PubMed]
91. Hamilton JK, Conwell LS, Syme C, et al. Hypothalamic obesity following craniopharyngiomasurgery: results of a pilot trial of combined diazoxide and metformin therapy. Int J Pediatr Endocrinol. 2011 [PMC free article] [PubMed]
92. Schultes B, Ernst B, Schmid F, Thurnheer M. Distal gastric bypass surgery for the treatment of hypothalamic obesity after childhood craniopharyngioma. Eur J Endocrinol. 2009;161(1):201–206. [PubMed]
93. ASPEN Board of Directors and the Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN. 2002;26:1SA–138SA. [PubMed]
94. Ladas EJ, Sacks N, Meacham LR, et al. A review of the nutritional practices for the pediatric oncology population: Assessment, intervention, nursing, pharmacology, quality of life, and survivorship. Nutr Clin Pract. 2005;20:377–393. [PubMed]
95. Kleinman RE, editor. Pediatric nutrition handbook. Elk Grove Village: American Academy of Pediatrics; 2004. p. 1000.
96. Altman AJ, editor. Supportive care of children with cancer. Baltimore: The Johns Hopkins University Press; 2004. p. 440.
97. Ladas EJ, Sacks N, Brophy P, et al. Standards of nutritional care in pediatric oncology: results from a nationwide survey on the standards of practice in pediatric oncology: A Children’s Oncology Group study. Pediatr Blood Cancer. 2006;46:339–44. [PubMed]
98. Argilés JM, Busquets S, Toledo M, et al. The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care. 2009;3:263–268. [PubMed]
99. Plata-Salaman CR. Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. Nutrition. 2000;16:1009–1012. [PubMed]
100. Nolan S, Gerber J, Zaoutis T, et al. Outbreak of vancomycin-resistant enterococcus colonization among pediatric oncology patients. Infect Control Hosp Epidemiol. 2009;30(4):338–345. [PMC free article] [PubMed]