Quantification of Weight Changes Associated with New Diagnosis of Cancer in Pediatric Patients

JHOP - September 2013 VOL 3, NO 3 - Original Article
Download PDF

Dr Miller is Clinical Assistant Professor, Department of Pharmacy, Clinical and Administrative Sciences; Dr Lewis is Assistant Professor, Department of Pharmacy, Clinical and Administrative Sciences; Mr Webb is Research Biostatistician; Dr Fields is Assistant Professor, Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma College of Medicine; and Dr Hagemann is Professor, Department of Pharmacy, Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City.


Background: Children diagnosed with cancer undergo changes in body weight secondary to illness and treatment. With progression to malnutrition come a number of significant complications. A better understanding of these changes allows for earlier nutritional intervention, which could improve clinical outcomes and quality of life.

Objectives: The main purpose of this exploratory study was to track weight changes in children diagnosed with cancer. Secondary objectives were to identify factors that may influence body weight.

Methods: This study enrolled children aged 18 years or younger who were diagnosed with cancer for at least 6 months. Patients were divided into 4 age-groups to account for similar expected growth rates: 0 to <2 years, 2 to <6 years, 6 to <12 years, and 12 to 18 years. Linear mixed models were performed to predict changes in body mass index, height, weight, and percentiles of each of these elements over time. A manual reverse-stepwise model selection procedure was used with 2-sided alpha set at 0.05 for inclusion in the final model.

Results: A total of 42 children were diagnosed with cancer during the study between January 1, 2010, and June 30, 2010, resulting in 121 weight measurements. Patients diagnosed with solid tumors lost 13.2 weight percentiles over the study period whereas those with hematologic malignancies had an increase of 3.0 weight percentiles (P = .013). A significant (P = .041) gender difference was found, with female patients exhibiting a greater drop in weight percentiles (20.3) compared with males (0.51), and no other differences were observed.

Conclusion: A significant decrease in weight percentile was noted in patients diagnosed with solid tumors whereas patients with hematologic malignancies had an increase in weight. Female patients were more likely than male patients to have a decline in weight percentile. Providers should consider close monitoring and early nutritional intervention in children with cancer to prevent significant weight loss, which may improve long-term prognosis as well as quality of life.


Approximately 16 per 100,000 children are diagnosed with cancer each year in the United States.1 Patients diagnosed with cancer typically present with different symptoms depending on their type of cancer, most often including fatigue, infection, and weight loss. Changes in weight have not been described in children with cancer outside of anecdotal evidence, although the medical literature in adults indicates that as many as 50% of patients diagnosed with cancer lose up to 25% of their body weight.2

Weight loss and resulting malnutrition in patients with cancer are detrimental in several ways. Malnutrition in children has been associated with increased intolerance to chemotherapy, a decrease in immune status, leading to increased risk of infection, and increased mortality.3,4 Cachexia, a complex process including anorexia, wasting, and metabolic abnormalities also develops in up to 40% of children with advanced or progressing cancer.2,4 A change in weight status can also alter normal growth velocity, lead to detrimental psychological consequences, and decrease the quality of life for many patients with cancer and their family members.4

Weight loss may be of greater concern in children than in adults, because they have greater nutritional needs related to ongoing growth but fewer caloric stores than their adult counterparts.2,5 Although weight changes in children diagnosed with cancer are expected, these changes have not been described or quantified in the literature. Therefore, the purpose of this retrospective study was to identify weight changes seen in children diagnosed with cancer, examine possible contributing factors, and provide clinicians with an awareness for timing of supplemental nutrition initiation.

Methods

This study was an Institutional Review Board–approved retrospective chart review conducted at a pediatric academic hospital. All children aged 18 years and younger who were diagnosed with cancer and presented to the Children’s Hospital at the University of Oklahoma Medical Center (OUMC) between January 1, 2010, and June 30, 2010, were chosen for this study. The only exclusion criteria were incomplete records (eg, lack of recorded weight) and age greater than 18 years at diagnosis.

After identification, patients were followed at baseline, 1 month, and 6 months after diagnosis. Patient information collected included age, gender, height, weight, and type of cancer. Based on this information, height percentile for age, weight percentile for age, body mass index (BMI) for age, and BMI percentile for age were calculated.

To assess the possibility of confounding measures, information on the patient’s nutritional status and interventions was also collected. The interventions reviewed included use of total parenteral nutrition (TPN), enteral tube feedings, and appetite stimulants. When available, albumin and prealbumin levels were also documented as markers of nutritional status. Cancer types were stratified into hematologic malignancies and solid tumors. Patients were also sorted into 4 groups based on their age, including 0 to <2 years, 2 to <6, 6 to <12, and 12 to 18. Groupings were based on similar predicted growth velocities.

Linear mixed effects models were used to test changes in height, weight percentile, BMI, or BMI percentile over time, using a manual reverse-stepwise selection procedure for each type of change. The independent variables of interest were cancer type (hematologic or solid tumor), time (in months), and the cancer type by time interaction. Other independent variables tested included age-group (in weight and BMI models) and gender.

To account for nonindependence among repeated measurements, patient-specific intercepts and slopes for time were used as random components of the models, and restricted maximum likelihood estimation was used. All analyses were performed using SAS v9.2. A 2-sided alpha level of 0.05 was considered significant for all analyses.

Results

A total of 42 children diagnosed with cancer were seen at the Children’s Hospital at OUMC in the 6 months of the study period, yielding 126 possible time points for data collection. One child moved shortly after diagnosis (and was not included in the study) and 2 children moved before their 6-month appointment but were included in the study. This resulted in a total of 121 weight measurements for study inclusion, representing 41 patients.

Baseline demographics are represented in Table 1. The most common age-groups at diagnosis were 2 to <6 years and 12 to 18 years. Overall, the mean age at diagnosis was 8.4 (± 0.9) years. Diagnosis with solid tumor was more common than hematologic cancer, occurring in 53.7% of patients. Within this group, brain tumors and sarcomas exceeded other forms of solid tumors while leukemias and lymphomas were nearly evenly split among the hematologic malignancies. Of note, acute lymphoblastic leukemia (ALL) was the most common form of leukemia, occurring in 8 of 10 cases (50% in females). Mean weight percentile at baseline for all ages was 60.6 (± 4.9); BMI percentile was similar at 60.8 (± 5.3).


Table 1

table2
Table 2

As seen in Figure 1, children diagnosed with solid tumors had a decrease in weight percentile, with a loss of 13.2 percentile points over the 6-month period, whereas children diagnosed with hematologic malignancies had an increase in weight of 3.0 percentile points (P = .013).


Figure 1

Change in BMI percentile over 6 months was compared among genders (Figure 2), also with significant results. Male patients demonstrated a decrease in BMI percentile of 0.51 and female patients had a loss of 20.3 in BMI percentile (P = .041). Because BMI is not a viable measurement until children reach age 2 years or older, 4 patients were excluded from this analysis, leaving 109 measurements. Differences in height and height percentile were not statistically significant among the genders or the type of cancer diagnosis.


Figure 2

Information on nutritional support was collected for each patient; however, the use of appetite stimulants, TPN, and enteral feedings occurred too infrequently to compare between the groups. Overall, 7 patients received appetite stimulants alone, 1 patient received TPN only, 1 patient received TPN and an appetite stimulant, and 3 patients received TPN, appetite stimulants, and enteral feeds. The most common appetite stimulants used were megestrol and cyproheptadine, each used in 5 patients; 2 patients received dronabinol.

Assessment of nutritional status was done through collection of albumin and prealbumin for each patient. A trend was found toward a more frequent decrease in albumin levels in children diagnosed with hematologic malignancies; however, this difference was not statistically significant. In addition, 3 of 4 prealbumin measurements were below normal; however, no baseline information was available to identify a trend over time.

Discussion

This is the first study to quantify and assess associated factors of weight loss in children with different types of malignancies. Weight changes in children diagnosed with cancer are expected at the initial stage, considering the many factors affecting their metabolism, intake, and treatments. Tumors induce a hypermetabolic state associated with the release of inflammatory cytokines, including tumor necrosis factor alpha and interleukins 1 and 6.6 In addition to causing an increase in energy expenditure, these mediators also lead to glycogenolysis, lipolysis, proteolysis, and gluconeogenesis.6

Malnutrition can quickly develop in patients with cancer, particularly if their premorbid weight is below or within the normal range. In this study, children’s baseline measurements were at a normal weight and BMI percentile and exhibited significant weight changes. Females and patients diagnosed with solid tumors were at greater risk for the most significant decreases; these findings indicate that these populations should be followed more closely and possibly receive earlier interventions than their counterparts.

Children diagnosed with hematologic malignancies were more likely to have a positive change in weight than any other population studied. As noted, 80% of these children were diagnosed with ALL, for which chemotherapy typically includes a corticosteroid for induction and maintenance therapy. Because corticosteroids can cause appetite stimulation and weight gain, the results of this study are not entirely unexpected. However, the alterations in metabolism secondary to corticosteroid therapy lead to an increase in lipolysis, protein catabolism, hyperglycemia, and often obesity.7-9 Quantitatively, these changes are positive, but qualitatively they are not; these children should still be closely monitored and encouraged to maintain adequate nutrition.

Reduced intake is also a component of weight loss in children with cancer. Gastrointestinal adverse events, including nausea, vomiting, diarrhea, and constipation associated with chemotherapy, radiation, and the cancer itself, are well-described in the literature.6,10 Other aspects affecting patients’ intake include early satiety, food aversions, and taste changes.10 Mucositis, which can last for several days, can also negatively impact a child’s willingness to eat or drink. Only 9% of children in this study received forms of nutritional support, including appetite stimulants, TPN, nasogastric feeding, and orogastric feeding.

Healthcare professionals have a limited number of available therapeutic options to attempt to mitigate the weight loss associated with cancer diagnosis and treatment. Patients may receive nutrition via enteral or parenteral administration. These alternative measures are often initiated once the patient has already lost a significant amount of body mass, potentially limiting their full benefits. Providing clinicians with a greater guidance in populations with increased likelihood of having significant weight loss should improve the appropriate use of this type of support and reduce the development of negative consequences such as cachexia, delayed treatment, and infection.

Limitations

This study had limitations. First, the size of the patient population is relatively small. Including patients diagnosed over a longer time period or across several centers could allow for greater scrutiny on each cancer type rather than a generalization of solid and hematologic malignancies.

In addition, information on chemotherapy regimens was not collected in this study. Although many chemotherapeutic agents cause some degree of nausea and vomiting, certain agents have a greater emetogenicity than others. Furthermore, corticosteroids can lead to an increase in weight, potentially preventing the provider from noticing the loss of lean body weight. Neither BMI nor weight loss accurately indicates the changes in lean body weight or the presence of malnutrition.

Finally, weight measurements were taken without consideration of timing of chemotherapy, hydration status, or nutrition, each of which can impact potential changes. Despite these limitations, we believe that this exploratory study provides preliminary data to help clinicians identify at-risk populations, as well as providing background information for further research in appropriate nutritional support.

Conclusion

This exploratory study quantified the changes in weight percentile in pediatric patients diagnosed with cancer, demonstrating a significant decrease in patients with solid tumors and an increase in weight in patients with hematologic malignancies. Female patients endured a greater decrease in weight percentile than their male counterparts. This information provides a background for clinicians to better identify patients at risk for malnutrition and the development of cachexia. It can also be an impetus for further research in nutritional status and supplementation in pediatric patients diagnosed with cancer.

Author Disclosure Statement

Dr Lewis has received research funding from Cubist Pharmaceutical. Dr Hagemann is a Consultant to Lexicomp. Dr Miller, Mr Webb, and Dr Fields reported no conflicts of interest.

References
1. National Cancer Institute. SEER Cancer Statistics Review, 1975-2010. Updated June 14, 2013. http://seer.cancer.gov/csr/1975_2008/. Accessed August 9, 2013.
2. Lai JS, Cella D, Peterman A, et al. Anorexia/cachexia-related quality of life for children with cancer. Cancer. 2005;104:1531-1539.
3. Mosby TT, Barr RD, Pencharz PB. Nutritional assessment of children with cancer.
J Pediatr Oncol Nurs. 2009;26:186-197.
4. Couluris M, Mayer JL, 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.
5. 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 J Parenter Enteral Nutr. 2002;26(1suppl):1SA–138SA. Erratum in: JPEN J Parenter Enteral Nutr. 2002;26:144.
6. Andrassy RJ, Chwals WJ. Nutritional support of the pediatric oncology patient. Nutrition. 1998;14:124-129.
7. Lexi-Comp Online. Pediatric and Neonatal Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc; August 5, 2011.
8. Mok CC, To CH, Ma KM. Changes in body composition after glucocorticoid therapy in patients with systemic lupus erythematosus. Lupus. 2008;17:1018-1022.
9. Reilly JJ, 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.
10. Yavuzsen T, Walsh D, Davis MP, et al. Components of the anorexia-cachexia syndrome: gastrointestinal symptom correlates of cancer anorexia. Support Care Cancer. 2009;17:1531-1541.

Related Items
Evaluation of a Pharmacist-Driven High-Dose MTX Monitoring Protocol
JHOP - February 2024 Vol 14, No 1 published on February 23, 2024 in Original Article
Duration of PARP Inhibitor Maintenance Therapy in Patients With Ovarian Cancer With Germline or Somatic BRCA Mutations
JHOP - February 2024 Vol 14, No 1 published on February 22, 2024 in Original Article
Real-World Analysis of Oral Chemotherapy Dose Modifications During Maintenance Therapy for Young Adults With ALL
JHOP - February 2024 Vol 14, No 1 published on February 22, 2024 in Original Article
Clinical Pharmacist–Initiated TKI Discontinuation in Patients with CML
JHOP - December 2023 Vol 13, No 6 published on December 20, 2023 in Original Article
Real-World Efficacy and Safety of Tixagevimab Plus Cilgavimab in Patients with Cancer
JHOP - December 2023 Vol 13, No 6 published on December 20, 2023 in Original Article
COVID-19 as a Primer for Drug-Induced Pneumonitis in Patients With Cancer
JHOP - December 2023 Vol 13, No 6 published on December 18, 2023 in Original Article
Tolerance of Oral Targeted Agents in Patients With Advanced or Metastatic RCC With and Without Renal Impairment
JHOP - October 2023 Vol 13, No 5 published on October 17, 2023 in Original Article
Clinical, Laboratory, and Genetic Profiles and Outcomes of Patients With aHUS and Restrictive Use of Eculizumab: A Single-Center Experience
JHOP - October 2023 Vol 13, No 5 published on October 17, 2023 in Original Article
Evaluation of Same-Day Versus Next-Day Administration of Pegfilgrastim in Patients With Breast Cancer
JHOP - October 2023 Vol 13, No 5 published on October 5, 2023 in Original Article
Effects of Vascular Endothelial Growth Factor Inhibitor–Induced Proteinuria on Treatment Course and Outcomes: Retrospective Analysis and Review of the Literature
JHOP - August 2023 Vol 13, No 4 published on August 17, 2023 in Original Article
© Amplity Health. All rights reserved.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: