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ORIGINAL ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 2  |  Page : 163-168

Clinical Implications of Undernutrition in Childhood Cancer: A Single Centre Experience from a Developing Country


1 Department of Pediatrics, Sri Ramachandra Institute of higher Education and Research, Chennai, India
2 Division of Pediatric Hemato Oncology, Sri Ramachandra Institute of higher Education and Research, Chennai, India

Date of Submission06-Dec-2020
Date of Decision21-Jan-2021
Date of Acceptance31-Jan-2021
Date of Web Publication22-Apr-2021

Correspondence Address:
Latha M Sneha
Division of Pediatric Hemato oncology Sri Ramachandra Institute of Higher Education and Research, No.1, Ramachandra Nagar, Porur, Chennai 600116, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijnpnd.ijnpnd_112_20

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   Abstract 


Introduction: Coexisting malnutrition is one of the known influencing factor of the survival rates in childhood cancer. Malnutrition contributes to poor immune function, altered drug metabolism—thereby causing drug toxicities and adverse clinical outcome. This study was done to assess the impact of undernutrition during treatment for childhood cancer, among the children diagnosed at our center. Methods: All children ≤18 years diagnosed with cancer between June 2011 and June 2019 treated at our institution were included in this study. Nutrition was assessed using body mass index (BMI) Z-score and a Z-score < −2SD was classified as undernourished. Weight loss of more than 10% or a decrease in BMI Z-score by ≥1SD below the previous Z-score was considered significant. All adverse effects and outcomes were compared between malnourished and adequately nourished children. Results: Three hundred six patients were included in this study, 114 (37.2%) were undernourished at diagnosis. One hundred two (33.3%) of 306 had significant weight loss. Malnutrition at diagnosis and significant weight loss was associated with an increased risk of febrile neutropenia, anemia, dosage modifications, and mucositis. Patients undernourished and those with significant weight loss showed a worse outcome (death or relapse) (P < 0.001). Conclusion: Nutritional status represents a modifiable risk factor long suggested to affect survival and treatment-related toxicity in pediatric malignancies and hence early nutritional intervention should be an essential part of the multi-disciplinary treatment protocol.

Keywords: Cancer, children, malnutrition, outcome, prognosis


How to cite this article:
Sakthikumar L, Sneha LM, Chandran S, Scott J, Soundarapandiyan L, Kumar Y. Clinical Implications of Undernutrition in Childhood Cancer: A Single Centre Experience from a Developing Country. Int J Nutr Pharmacol Neurol Dis 2021;11:163-8

How to cite this URL:
Sakthikumar L, Sneha LM, Chandran S, Scott J, Soundarapandiyan L, Kumar Y. Clinical Implications of Undernutrition in Childhood Cancer: A Single Centre Experience from a Developing Country. Int J Nutr Pharmacol Neurol Dis [serial online] 2021 [cited 2021 Jun 12];11:163-8. Available from: https://www.ijnpnd.com/text.asp?2021/11/2/163/314382




   Introduction Top


The past few decades have witnessed a substantial increase in the survival rates of the pediatric malignancies as whole. The contributing factors such as early diagnosis, multimodality treatment, development of risk stratification, intensification of treatment when needed, and enhanced supportive care have helped to attain cure rates of >85% in developed countries. These advances in survival rates unfortunately are not translated completely into the developing countries. About 80% of the children and adolescents with malignancies live in low- or middle-income countries that have limited access to curative treatment.

In developing countries, in addition to the confounding factors like limited health care facilities, high rates of treatment abandonment, treatment-related morbidity and mortality, malnutrition among the cancer children and adolescents at diagnosis, and significant weight loss during treatment greatly influences the course of the disease and the outcome of the treatment. Malnutrition among pediatric oncology patients has been a well-recognized negative prognostic factor that is associated with increased morbidity and or decreased survival.[1] Depending upon the nature of the disease, location and stage of the disease, nature of study population, and methods of evaluation, the incidence of malnutrition has been reported to vary from 6% to 50%.[2] In addition to its impact on survival, malnutrition is also associated with treatment delays, poor response to treatment, inferior tolerance of chemotherapy, increased risk of infection, and poor quality of life.[3]

Hence, we aimed to study the relationship between malnutrition and treatment-related morbidity and survival rates among children and adolescents with malignancies.


   Methodology Top


This is a retrospective cohort study, conducted at the Pediatric Oncology Unit of Sri Ramachandra Institute of Higher Education and Research, Chennai, India. Institutional Ethics Committee approval was obtained. All children ≤18 years diagnosed with cancer between June 2011 and June 2019 and treated at our center were included in our study. Patients above 18 years, presenting with a relapse, pretreated at another hospital, and transferred for further management were excluded.

The patients’ medical records were accessed for details such as demographic data, date of diagnosis, modalities of treatment, drugs used, stage/risk stratification of disease, presence of any established infections, and chronic diseases at diagnosis. The patient’s height in centimeters and weight in kilograms at the time of diagnosis and 1, 3, and 6 months later were noted. Laboratory records were accessed to get the hemoglobin, serum albumin, and serum electrolytes levels at diagnosis. Adverse events during treatment such as febrile neutropenia, drug interruption or dose modification, mucositis, bone marrow suppression, blood products transfusion, and other documented infections were identified.

Patient’s socioeconomic status was determined using the Revised Kuppuswamy’s Socioeconomic Status Scale. It defines five socioeconomic classes, namely Upper (I), Upper Middle (II), Lower Middle (III), Upper Lower (IV), and Lower (V).[4]

Anemia was diagnosed according to the WHO criteria.[5] A serum albumin level <2.5 g/dL for children aged <7 months and <3.5 g/dL for children aged >7 months was diagnosed as hypoalbuminemia.[6] Serum potassium <3.5 meq/L was diagnosed as hypokalemia.[7]

The Anthro Software of the world Health Organization (version 3.0.1; Department of nutrition, WHO) was used to calculate the body mass index (BMI) and BMI-for-Age Z-score of patients up to the age of 5 completed years (60 months). The WHO Anthro-plus software (version 1.0.2) was used to calculate the BMI and BMI-for-Age Z-score for children above 5 years of age (completed 60 months). Nutritional status was classified according to the WHO criteria.[8],[9]

The study cohort was categorized into the following three groups:
  1. Undernourished: Patients with Z-score more than 2 standard deviations below mean BMI for age (< −2 SD). (Group I)
  2. Adequately Nourished: Patients with a Z-score between 2 standard deviations below (up till −2 SD and 1 standard deviation (up to +1 SD) above the mean BMI for age; (Group II)
  3. Overnourished: Patients with a Z-score above 1 Standard Deviation (>+1 S.D.) above mean BMI for age. (group III)


Weight loss >10% or a decrease in BMI Z-score by ≥1 SD below the previous Z-scores was considered significant.

The three possible outcomes were (i) completed treatment and well, (ii) on active treatment and well, and (iii) relapse and death.

Febrile neutropenia, mucositis, infections requiring intravenous antibiotics for more than 7 days, drug dosage modifications, and interruptions in chemotherapy for more than 2 weeks were all considered significant events.

Statistical Analysis was done using SPSS version 17.0 (Statistical Package for Social Sciences version 17.0). Demographics and clinical variables were analyzed using frequencies and percentages for categorical variables. Chi-square test was used to determine the association between various parameters including nutritional status at diagnosis and outcome. The Kaplan–Meier method was used to depict survival curves.[10] Crude Odds ratio (OR) and 95% confidence interval were calculated with the reference category as Completed Treatment & Well. The statistical significance level was set at 5%.


   Results Top


Three hundred six children were included in this study. At the time of analysis, 109 (35.6%) children were still on treatment and completed minimal 6 months from diagnosis. Out of the remaining 208, 156 (50.9%) children have completed the treatment and are well; 41 (13.3%) died during the study period. Out of the 41 deaths, the common cause of death was relapse or refractory disease and its complications in 33 cases (80.4%) and 8 (19.5%) children in remission died due to sepsis. Forty-three (14%) of the study population had relapse. Out of the 43 relapses, 33 (76.7%) of them had progressive/refractory disease and died. The remaining 10 (23.2%) of the 43 relapsed cases are on treatment and well. One hundred two children (33.3%) had significant weight loss during the study period.

The demographic, clinical, and laboratory data at the time of diagnosis are shown in [Table 1]. The most common diagnosis was acute lymphoblastic leukemia (43.8% of all malignancies). The most common solid tumor was Wilms tumor (8.5% of all malignancies). At the time of diagnosis, 154 (50.3%) of the children were adequately nourished, 114 (37.3%) were undernourished and 38 (12.4%) were overnourished. Among 306 children, 166 (54.2%) children had anemia at diagnosis. Out of these, 166 children with anemia, 43.3% of these children were undernourished at diagnosis (P < 0.001, CI = 95%). Although 47.05% of the children with hypoalbuminemia and 63.63% of children with hypokalemia at diagnosis were undernourished, there was no statistical significance. A total of 102 (33.3%) children had significant weight loss. Among these 102 children with significant weight loss, 46 (45%) were adequately nourished at diagnosis. The mean Z-score at diagnosis was −1.0483 (standard deviation: ±2.31695).
Table 1 Patient demographics and medical characteristics at diagnosis

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[Table 2] details about the socioeconomic class versus nutritional status at diagnosis and significant weight loss during the treatment. Among 114 undernourished children, 38 (33.3%) were from the Lower (V) socioeconomic class. There were no overnourished children from the Lower (V) socioeconomic class. Undernutrition was found to be more common among children from a lower socioeconomic class (V) (P < 0.001, CI = 95%). Significant weight loss was higher among children from a lower middle class (III) (P = 0.004, CI = 95%).
Table 2 Socioeconomic class according to Revised Kuppuswamy’s Socioeconomic Status Scale versus Nutritional Status at Diagnosis and significant weight loss during treatment

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[Table 3] indicates the adverse events among the children during the treatment. One hundred ninety-eight episodes of febrile neutropenia were noted and Group I (undernourished) accounted for 55.1% and group II (adequately nourished) accounted for 38.3% and Group III (overnourished) for 6.5%, respectively. The chance of having febrile neutropenia was higher among undernourished children (P = 0.005, CI = 95%) and also in children with significant weight loss (P < 0.001).
Table 3 Adverse events during treatment

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One hundred twenty-one episodes of mucositis and 32 episodes of pneumonia were noted among our study population; 57% of group I (undernourished) and 33.8% of group II (adequately nourished), and 9% of group III had mucositis; 56.2% of group I (undernourished) and 34.3% of group II (adequately nourished) and 9.3% of group III (overnourished) had pneumonia. Among 98 episodes of drug modifications or interruptions noted, 67 episodes (68.3%) of them were noted in solid tumors.

Statistical significance was seen between the nutritional status at diagnosis and the chance of having dosage modification and drug interruption (P < 0.001, CI = 95%), mucositis (P < 0.001, CI = 95%). The odds of having dosage modification and drug interruptions (P < 0.001, CI = 95%), febrile neutropenia (P < 0.001, CI = 95%), pneumonia (P = 0.002, CI = 95%), and mucositis (P < 0.001, CI = 95%) were much higher among children with significant weight loss.

[Table 4] and [Table 5] detail the outcome of treatment based on nutritional status and socioeconomic class. At the time of analysis, 41 children had died, 33 of them due to disease progression or relapse, and eight of them due to sepsis. All the children who had died had significant weight loss. Overall 51.2% of the deaths were among children from socioeconomic classes 4 and 5. Children who had a poor nutritional status at the time of diagnosis had an increased chance of a poor outcome (death or relapse; P < 0.001, CI = 95%). The odds of a poor outcome (death or relapse) was also much higher among children who had a deterioration (significant weight loss) in their nutritional status through the course of the illness (P < 0.001, CI = 95%).
Table 4 Outcome of treatment based on nutritional status

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Table 5 Outcome of treatment based on socioeconomic class

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   Discussion Top


Children are at a greater risk of nutritional depletion because of their more rapid metabolic rate and greater caloric needs for growth and development. For a long time, undernutrition among childhood cancer patients was considered a part of the symptom complex of cancer, until it was identified as an important factor in treatment response and chemotherapy tolerance.

Among 306 children of our study population, 37% were undernourished at diagnosis. In our study group, 21.6% of acute leukemias and 28.4% of solid tumors were found to be malnourished at diagnosis. Priscilla Dos Santos Maia Lemos et al.[11] observed that the incidence of malnutrition was more among children with solid tumors (12.2%) than hematological tumors (9.52%). In our study group, children with solid tumors were found to be malnourished than children with hematological malignancies could be attributed to the fact that 41.8% of the solid tumors belonged to lower socioeconomic class (V), as well as that solid tumors, had diagnostic delays and late referrals and advanced stage at presentation and were more in numbers than acute leukemias.

Yazbeck et al.[12] has reported a prevalence of 25.2% of malnutrition at diagnosis among children with Acute lymphoblastic leukemia and odds of having poor final outcomes such as death and relapse was higher among malnourished children and more so among stunted.[12] Two Indian studies, Kumar et al.[13] and Jain et al.,[14] on therapy for ALL, studied factors of prognostic significance with respect to tolerance to chemotherapy in ALL and established definite poor treatment tolerances and increased complications in undernourished patients. Viana et al.[15] had compared malnutrition with the risk of relapse in ALL.[15] In our study, among the 33 children with Acute leukemias, who relapsed, 13 (39.3%) were malnourished at diagnosis, and among the 11 children with solid tumor, who had a refractory/progressive disease, five (45.4%) had significant weight loss.

Abnormal BMI was significantly associated with poor histologic response (tumor necrosis < 90%) and worse outcomes in children with Ewing sarcoma in a study by Goldstein et al.[16] Triarico et al.[17] has reported that malnutrition at diagnosis is an independent risk factor that increases the rate of hospitalization for febrile neutropenia.[17] Among our study group, 55.1% of group I (undernourished), 38.3% of group II (adequately nourished), and 6.5% of group III (overnourished) developed febrile neutropenia. The duration of neutropenia and severity of neutropenia was less among the group III population. Loeffen et al.[18] also reported a strong association between a rapid loss of weight in the first 3 months of diagnosis with an increased rate of febrile neutropenia episodes.

The nadir values of absolute neutrophil counts and hemoglobin were found to be lower in group I (undernourished) than in group II (adequately nourished). The treatment tolerance was also poor in groups I and II with an increased requirement of PRBCs and platelets in these groups (P < 0.001). Tandon et al.[19] has shown an association of hypoalbuminemia, folate, and vitamin B12 deficiency with increased toxicity leading to an increased number of induction deaths in ALL.

We noted that the risk of malnutrition is greater in children with a high-risk disease across all cancer types as this category requires more intensive therapy and therefore a higher risk of treatment-related morbidity. Malnutrition was also associated with clinically increased severity of infection. Among the 121 episodes of mucositis and 32 episodes of pneumonia in our study population, 57% of group I (undernourished) and 33.8% of group II (adequately nourished) had mucositis, 56.2% of group I and 34.3% of group II had pneumonia. The incidence of pneumonia among malnourished and those with significant weight loss had no statistical significance, whereas prevalence of mucositis was statistically significant in these two groups.

One hundred two children of our study population had significant weight loss. Forty-nine percent of them occurred in group II (adequately nourished), 43.1% in group I (undernourished), and 6.8% in group III (overnourished). The significant weight loss was noted within the first 60 days of diagnosis. In another study, Federico Antillon et al.[20] reported that among a group of 241 newly diagnosed cancer children, 100 were severely depleted at diagnosis and those who were severely depleted after 6 months of treatment had a 2.4-fold higher risk of death when compared to children who were adequately nourished and moderately depleted.

A total of 98 episodes of drug modifications or interruptions were noted during the study period, 67 episodes (68.3%) of them were noted in solid tumors. The drug modifications or interruptions were due to severe grade of mucositis or prolonged neutropenia. Fifty-three percent of group I and 38.7% of group II had drug modifications/interruptions. In our study also, malnourished children and children with significant weight loss were found to have more dosage interruptions and dosage modifications as they had severe mucositis and prolonged neutropenia as reported by Halton et al. [21]


   Conclusion Top


Maintaining adequate nutritional status throughout the cancer treatment is crucial for good treatment response and good quality of life, and to minimize the cost of care. Hence, simple and cost-effective nutritional interventions such as education, assessment, and intervention should be devised and made an integral part of the treatment protocol and we strongly recommend incorporating a dedicated nutrition specialist in the pediatric oncology team so that the prospect of survival of these children can be enhanced.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: growth velocity based on weight, length and head circumference: methods and development. Geneva, Switzerland: WHO; 2009.  Back to cited text no. 8
    
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Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.  Back to cited text no. 10
    
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Lemos PdMS, de Oliveira FLC, Caran EMM. Nutritional status of children and adoloscents at diagnosis of hematologic and solid malignancies. Rev Bras Hematol Hemoter 2014;36:420-23.  Back to cited text no. 11
    
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Yazbeck N, Samia L, Saab R, Abboud MR, Solh H, Muwakkit S. Effect of malnutrition at diagnosis on clinical outcomes of children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2016;38:107-10.  Back to cited text no. 12
    
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Kumar R, Marwaha RK, Bhalla AK, Gulati M. Protein energy malnutrition and skeletal muscle wasting in childhood acute lymphoblastic leukemia. Indian Pediatr 2000;37:720-6.  Back to cited text no. 13
    
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Jain V, Dubey AP, Gupta SK. Nutritional parameters in children with malignancy. Indian Pediatr 2003;40:976-84.  Back to cited text no. 14
    
15.
Viana MB, Fernandes RA, de Carvalho RI, Murao M. Low socioeconomic status is a strong independent predictor of relapse in childhood acute lymphoblastic leukemia. Int J Cancer Suppl 1998;11:56-61.  Back to cited text no. 15
    
16.
Goldstein G, Shemesh E, Frenkel T, Jacobson JM, Toren A. Abnormal body mass index at diagnois in patients with Ewing Sarcoma is associated with inferior tumor necrosis. Pediatr Blood Cancer 2015;62:1982-6.  Back to cited text no. 16
    
17.
Triarico S, Rinninella E, Cintoni M et al. Impact of malnutrition on survival and infections among pediatric patients with cancer: a retrospective study. Eur Rev Med Pharmacol Sci 2019;23:1165-75.  Back to cited text no. 17
    
18.
Loeffen EA, Brinksm A, Miedema KGE, de Bock GH, Tissing WJ. Clinical implications of malnutrition in childhood cancer patients-infections and mortality. Support Care Cancer 2015;23:143-50.  Back to cited text no. 18
    
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Tandon S, Moulik NR, Kumar A, Mahdi AA, Kumar A. Effect of pre-treatment nutritional status, folate and vitamin B12 levels on induction chemotherapy in children with acute lymphoblastic leukemia. Indian Pediatr 2015;52:385-9.  Back to cited text no. 19
    
20.
Antillon F, Rossi E, Molina AL et al. Nutritional Status of children during the treatment for Acute Lymphoblastic Leukemia in Guatemala. Pediatr Blood Cancer 2013;60:911-5.  Back to cited text no. 20
    
21.
Halton JM, Scissons-Fisher CC. 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.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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