Nutritional Supportive Care
Sonia A. Ballal
Lori J. Bechard
Christopher Duggan
INTRODUCTION
The high prevalence of malnutrition in pediatric patients with cancer has been appreciated for decades.1 Although the prognostic significance of nutritional status among patients with cancer remains controversial,2 it is generally accepted that nutritional support is an important component of medical therapy (Table 41.1). An increasing prevalence of obesity in the healthy pediatric population, combined with additional risks associated with cancer treatment,3 has prompted care providers to appropriately confront the potential for obesity-related chronic diseases among childhood cancer survivors. Hence, tailored nutritional intervention is essential from diagnosis, through treatment, and beyond to longterm survival. Each newly diagnosed child with cancer warrants a systematic, comprehensive survey of his or her nutritional status, with periodic reassessments. Parents of children with cancer are often quite concerned about issues of appetite and other gastrointestinal symptoms, even when death is imminent.4 The frequent use of complementary and alternative dietary supplements among patients with cancer also underlines the importance that families attach to nutritional therapy.5 Here, we review the definitions, epidemiology, etiology, and practical therapy of nutritional problems of the pediatric cancer patient.
DEFINITION OF CANCER CACHEXIA
Cachexia has been defined as a severe state of malnutrition characterized by anorexia, weight loss, muscle wasting, and anemia. Roubenoff et al.6 have proposed that the terms wasting, cachexia, and sarcopenia be considered as three distinctly defined entities. Wasting is defined as involuntary weight loss, and is found in patients with anorexia nervosa, cancer, advanced HIV infection, and marasmus. Cachexia, in contrast, is defined as involuntary loss of fat-free mass in the setting of minimal or no overall weight loss. This type of malnutrition can be seen in some patients with cancer, as well as in those with critical illness and early HIV infection. In this scenario, patients of normal weight can still be malnourished due to reduced lean body mass. A decline in lean body mass has important functional and prognostic significance, even in the setting of stable or increasing weight. Sarcopenia refers to the involuntary loss of muscle mass that occurs with aging.
TABLE 41.1 Rationale for Nutrition Screening and Intervention in Pediatric Patients with Cancer | ||||||||||
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The pattern of weight loss and changes in body composition in patients with illness are important to be considered because differential loss of body fat versus fat-free mass implies a different etiology and prognosis of malnutrition. For example, prolonged fasting in the absence of metabolic perturbation (as can be seen in adolescents with anorexia nervosa) leads to a predictable decrement first in body fat, then in body protein stores. In these cases, energy repletion is usually successful with the provision of adequate energy, protein, and micronutrients.
In contrast, weight loss in the setting of cancer, infection, or other metabolic stress is composed of both fat and fat-free mass. Because the energy density of fat-free mass is lower than that of fat, the body’s use of lean body mass as an energy and amino acid source can lead to weight loss that can be quite profound and rapid. It is this loss of fat-free mass that is of significance, because loss of lean body mass is associated with important functional changes such as loss of strength, decreased immune function, decreased pulmonary function, increased disability, and death.
More importantly, the provision of nutritional support to these patients may not be adequate to reverse the catabolic effects of the underlying condition. In the early days of parenteral nutrition use, it was
hypothesized that aggressive parenteral nutrition could overcome the catabolism of cancer and other critical illnesses; however, this has not proven to be the case. Instead, a more realistic appreciation for the limitations of nutritional support has emerged. Methodologies and nutritional prescriptions for children with cancer are explored below.
hypothesized that aggressive parenteral nutrition could overcome the catabolism of cancer and other critical illnesses; however, this has not proven to be the case. Instead, a more realistic appreciation for the limitations of nutritional support has emerged. Methodologies and nutritional prescriptions for children with cancer are explored below.
OBESITY AND THE PEDIATRIC PATIENT WITH CANCER
Over the last few decades, the prevalence of obesity in children has increased substantially, with approximately 15% of children and adolescents in the United States falling into that category.7 In certain populations, this number is even higher. Such numbers demand that pediatric oncologists feel comfortable in approaching the overweight/obese patient who is also diagnosed with cancer. One major concern is the effect of therapeutics and toxicities in the obese patient. One study of 621 acute lymphoblastic leukemia (ALL) patients that examined the influence of body mass index (BMI) on the pharmacokinetics, toxicity, and outcome of chemotherapy found that overall survival and toxicity did not vary across groups with different BMIs.8 Another study noted increased mortality because of treatment-related events, namely, infection, in both underweight and overweight patients with acute myelogenous leukemia, although the increased mortality seen in the overweight population did not appear to be secondary to higher doses of chemotherapy, or reduced clearance of toxic substances.9 In contrast, children with greater than 30% body fat were found to have decreased clearance of doxorubicinol, compared with children with less body fat, as measured by dual-energy x-ray absorptiometry (DXA).10
Obesity is an increasingly noted health problem among cancer survivors. Multiple theories exist regarding the alarming number of obese cancer survivors. A reduction in physical activity and thus a change in body composition of leukemia survivors may explain the subsequent onset of obesity. The frequent use of glucocorticoids in cancer treatment may also help explain a high prevalence of obesity. One study observed increased fat mass in children treated for ALL.11 Glucocorticoids may be associated not only with this rise in fat mass, but also with decreased adult height. As many as half of childhood leukemia survivors in one study became obese young adults. This incidence may be related to the impact of therapy on final adult height. A cohort of bone marrow transplant survivors, engrafted before or at the onset of puberty, had a significantly lower final height, compared to pretransplant height standard deviation scores. However, most of the patients achieved a height considered to be normal. In a study of 33 childhood leukemia survivors followed up for a median of 16.2 years, 36% of subjects were obese. All patients had reduced height standard deviation scores during treatment; however, only patients who received cranial radiation with chemotherapy (vs. chemotherapy alone) had reductions in final adult height. Cranial irradiation has also been linked with the development of metabolic syndrome and growth hormone deficiency, laying the foundation for the development of diabetes and heart disease in adulthood.12 In children, cranial irradiation may alter the leptin receptor in the hypothalamus, causing decreased sensitivity after treatment. An examination of a polymorphism of the leptin receptor could lead to targeted attempts to identify individuals more susceptible to obesity after radiation therapy.13 Some investigations suggest a gender divide, with a predilection for the development of obesity among female patients with cancer, while other studies find no difference between males and females.14
THE POPULATION AT RISK
The occurrence of undernutrition among patients with cancer is determined by host susceptibility, tumor type and location, and anticancer regimen. During infancy and adolescence there are increased energy needs for growth, and thus children in these age groups are at increased risk of malnutrition. Other patients at higher risk of malnutrition are those with advanced disease, metastatic solid tumors, and those needing protracted chemotherapy (Table 41.2). A striking example of malnutrition is the diencephalic syndrome in which a hypothalamic tumor presents with severe weight loss in the setting of a normal appetite and energy intake.15
TABLE 41.2 Risk Factors for Malnutrition in Pediatric Patients with Cancer | ||||||||||||||||||||||||||||||||||||||||||||||||
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In contrast, most patients with low-risk ALL, those with nonmetastatic solid tumors, and patients in remission are generally able to maintain a normal weight. Weight loss, however, may be the final step in a long process of nutritional perturbation in patients with cancer, and as such may not be a sufficiently sensitive marker for malnutrition. For example, one study of prepubertal children with low-risk ALL followed body weight and lean body mass over time (as measured by the sum of four skinfold measurements and bioelectrical impedance). Although body weight in the patients with cancer was no different from that in age- and sex-matched controls, lean body mass declined substantially with the use of chemotherapy. Another study of ALL survivors compared BMI values and whole-body percentage fat as measured by DXA with those of controls. ALL survivors had significantly higher percentage of body fat, while their BMI remained similar to that of controls. Thus, mere reliance on body weight or BMI to document normal nutritional status may lead to an underestimate of lean body mass depletion or fat accumulation.
ETIOLOGY AND PATHOPHYSIOLOGY
It is axiomatic that patients with weight loss exhibit reduced dietary intake, malabsorption or maldigestion of foods, or altered energy and nutrient needs. The challenge of nutritional care of pediatric patients with cancer is that all three mechanisms may be at play, and so the clinician’s diagnostic and therapeutic tools must be broadly considered.
Decreased Nutrient Intake
There are multiple reasons for decreased nutrient intake in the child receiving chemo- or radiotherapy. One is the well-known occurrence of circulating cytokines, including tumor necrosis factor alpha, that induce anorexia. Another important reason for decreased nutrient intake is the gastrointestinal symptoms of mucosal
injury related to chemo- and radiotherapy. Mucosal damage is generally dose related, with an increased risk of mucosal toxicity associated with high-dose induction therapy and combination chemotherapy treatments. High-dose chemotherapy and total-body irradiation as conditioning for hematopoietic cell transplantation (HCT) often produce painful oral mucositis that can reduce nutritional intake for days to weeks. Other gastrointestinal side effects of cancer treatment include esophagitis, enteritis with malabsorption, and diarrhea; these are more fully described in Chapter 10. Taste perception has also been shown to be altered in patients with cancer receiving chemotherapy, with an increasing sensitivity to bitter tastes; this phenomenon may lead to reduced food intake, and may make the use of oral supplements difficult.
injury related to chemo- and radiotherapy. Mucosal damage is generally dose related, with an increased risk of mucosal toxicity associated with high-dose induction therapy and combination chemotherapy treatments. High-dose chemotherapy and total-body irradiation as conditioning for hematopoietic cell transplantation (HCT) often produce painful oral mucositis that can reduce nutritional intake for days to weeks. Other gastrointestinal side effects of cancer treatment include esophagitis, enteritis with malabsorption, and diarrhea; these are more fully described in Chapter 10. Taste perception has also been shown to be altered in patients with cancer receiving chemotherapy, with an increasing sensitivity to bitter tastes; this phenomenon may lead to reduced food intake, and may make the use of oral supplements difficult.
Psychological factors are also important to consider in evaluating the reasons behind inadequate dietary intake. Depression-related anorexia is probably underappreciated as a cause. Appetite and feeding behaviors are inherently complicated activities of all children, and this behavior can obviously be affected by the onset of illness, its treatment, as well as the psychosocial impact that cancer has on the child and family. The nature of cancer medical care is such that parents often feel that they are relinquishing much of their usual care-giving behavior to the medical and nursing staff. Some parents understandably cling to the provision of food and nutrients as a critical part of parenting; indeed, the terms nutrition, nursing, and nurture all share the same Latin root.
Changes in Energy Expenditure: Decreased Basal Metabolic Rate
Although decreased nutrient intake is common in cancer, anorexia alone cannot wholly explain the common development of malnutrition since some patients maintain an excellent intake but still suffer progressive weight loss. Much research has focused on the possible role of increased basal metabolic rate, or the resting energy expenditure (REE), of patients with cancer in trying to explain their cachexia; however, the issue has not been consistently resolved.
Some studies suggested that the energy needs of rapidly dividing cells of the tumor increased basal metabolic demands of the host from 20% to 90% over predicted needs, while other investigations have confirmed that hypermetabolism can occur, but not in all patients at all times. Knox et al.16 studied 200 adult patients with cancer by using the technique of indirect calorimetry, a noninvasive bedside measure of REE, the clinical estimate of basal metabolic rate. They found that one-third of patients were hypometabolic (REE was <90% of predicted levels), one-fourth were hypermetabolic (REE > 110% predicted), and the remaining 40% had normal REE (between 90% and 110% predicted).
In children, changes in REE have been observed in a variety of clinical scenarios. Stallings et al.17 measured REE in nine patients with ALL and found that patients with a higher tumor burden (elevated WBC count, organomegaly) had an increased REE. A study of 26 patients with ALL or solid tumors in remission showed no evidence of an increased REE, when compared with age- and sex-matched healthy controls. Changes in REE measured by indirect calorimetry have been demonstrated by several studies of children undergoing HCT. Ringwald-Smith et al.18 compared weekly measured REE in 34 children undergoing autologous or allogeneic HCT with standardized equations and found that REE was significantly less than predicted except at 14 days posttransplant. A prospective, multicenter trial of 26 children undergoing HCT revealed decreased REE in the initial weeks after transplant, leaving these patients especially vulnerable to overfeeding during this time.19 In this randomized trial, two levels of parenteral energy intake during HCT did not show a significant change in percentage body fat at 30 or 100 days after transplant, but both groups of patients showed substantial decrements (>10%) in lean body mass.20 Further explorations of REE changes in pediatric cancer are warranted.
Changes in Energy Expenditure: Decreased Energy of Activity
As noted earlier, total energy requirements include energy needed for physical activity. Reilly et al.21 studied 20 preadolescent children with ALL with doubly labeled water, a technique that reliably measures total energy expenditure (TEE) in free-living individuals.22 Compared with healthy controls matched for age, sex, and body composition, children with ALL had significantly lower TEE, mostly due to reduced physical activity. A similar study, using a combination of indirect calorimetry and ambulatory heart rate monitoring to measure REE and TEE, also concluded that ALL patients have lower levels of energy expenditure for activity. The implications of these findings for obesity prevention in ALL survivors, as well as children at large, may be significant.
CLINICAL ASSESSMENT OF NUTRITIONAL STATUS
The assessment of a child with cancer includes standard elements of a nutritional evaluation: history of past and present illness, review of dietary intake, physical examination, and anthropometric measurements. Attention should also be directed to the significance of body composition changes as well as a review of pertinent laboratory measures.
History
A detailed medical history is essential to the nutritional evaluation of a patient, including the type and stage of the tumor, the intensity of the planned antitumor therapy, and the presence or absence of remission. As noted earlier, there are important risk factors for the development of malnutrition in patients with cancer (Table 41.2). A comprehensive history of essential aspects can aid the practitioner in tailoring nutrition-based interventions (Table 41.3).
The ability of children to eat at their appropriate developmental level may affect the nutritional adequacy of their diet. Anorexia, mucositis, and other effects of cancer treatment may interrupt the normal progression of feeding skills in infants and young children. Once arrested, the development of these skills may be difficult to restore with poor swallowing and chewing abilities leading to inadequate consumption of many required nutrients. Children may
refuse to eat their preferred foods due to adverse associations or other impairments and thus may self-restrict their intake.
refuse to eat their preferred foods due to adverse associations or other impairments and thus may self-restrict their intake.
TABLE 41.3 Key Elements of a Nutritional History | ||||||||||||||||||||||||||
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