Genome-wide study identifies novel genes associated with bone toxicities in children with acute lymphoblastic leukaemia.

Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome-wide association study (GWAS) and a transcriptome-wide association study (TWAS) in 260 patients of European-descent from the DFCI 05-001 ALL trial, with validation in 101 patients of European-descent from the DFCI 11-001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05-001 trial (p = 1.7 × 10-8). In DFCI 11-001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, CD93 and THBD. In TWAS, genetically predicted ACAD9 expression was associated with an increased risk of bone toxicities, which was confirmed by meta-analysis of the two cohorts (meta-p = 2.4 × 10-6). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta-p = 2.3 × 10-3). Our findings highlight the genetic influence on treatment-related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment.

The Nutritional Burden of Cancer: Nutritional Status and Body Composition Differences Between Children with Acute Lymphoblastic Leukemia and their Siblings in Guatemala.

During treatment, children with acute lymphoblastic leukemia (ALL) gain fat mass and lose skeletal muscle mass. The great majority live in low- and middle-income countries with few studies of their body composition and none addressing the hypothesis that the disease itself contributes to nutritional morbidity. At diagnosis, children with ALL were compared to their siblings on socioeconomic status (SES). Nutritional status was assessed by mid-upper arm circumference (MUAC)-for-age Z scores and body composition by dual energy x-ray absorptiometry (DXA). Median SES scores for the patients (47.5) and their siblings (47.0) were very similar (P = 0.5). MUAC Z scores for patients aged >5 years were lower than for siblings (P < 0.001). On DXA siblings had a higher mean appendicular lean mass index Z score, a surrogate of skeletal muscle mass, than patients (P = 0.019). A logistic model to estimate the odds ratio (OR) of being severely/moderately under-nourished (classified by MUAC Z score) by SES revealed that, compared with siblings (n = 49), children with ALL (n = 60) had a higher probability of being under-nourished (OR 5.25, 95% CI 1.44-25.95, P = 0.02). The results support the hypothesis that children at diagnosis of ALL in Guatemala are more nutritionally depleted than their apparently healthy siblings.

Prevalence of Poverty and Hunger at Cancer Diagnosis and Its Association with Malnutrition and Overall Survival in South Africa.

Many South African children live in poverty and food insecurity; therefore, malnutrition within the context of childhood cancer should be examined. Parents/caregivers completed the Poverty-Assessment Tool (divided into poverty risk groups) and the Household Hunger Scale questionnaire in five pediatric oncology units. Height, weight, and mid-upper arm circumference assessments classified malnutrition. Regression analysis evaluated the association of poverty and food insecurity with nutritional status, abandonment of treatment, and one-year overall survival (OS). Nearly a third (27.8%) of 320 patients had a high poverty risk, associated significantly with stunting (p = 0.009), food insecurity (p < 0.001) and residential province (p < 0.001) (multinomial regression). Stunting was independently and significantly associated with one-year OS on univariate analysis. The hunger scale was significant predictor of OS, as patients living with hunger at home had an increased odds ratio for treatment abandonment (OR 4.5; 95% CI 1.0; 19.4; p = 0.045) and hazard for death (HR 3.2; 95% CI 1.02, 9.9; p = 0.046) compared to those with food security. Evaluating sociodemographic factors such as poverty and food insecurity at diagnosis is essential among South African children to identify at-risk children and implement adequate nutritional support during cancer treatment.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

A cross-sectional study evaluating the prevalence and predictors of malnutrition among children and adolescents visiting an urban academic hospital in Nepal.

OBJECTIVE: To examine the prevalence of malnutrition among children and adolescents visiting Kanti Children's Hospital (KCH) and identify predictors associated with malnutrition. Results will guide the development of a newly established nutrition programme at KCH. DESIGN: This cross-sectional pilot study recruited children and adolescents over a 1-month period. Nutritional anthropometrics (height, weight and mid-upper arm circumference (MUAC)) and socio-demographic questionnaires were administered. Clinical data were abstracted from the medical chart. SETTING: KCH in Kathmandu, Nepal. PARTICIPANTS: 370 children and adolescents. RESULTS: Most participants were male (65·1 %); mean age was 3·9 years (±3·4 years). The prevalence of stunting was 25·9 %, wasting was 17·3 % and 24·0 % when classified by BMI-for-age Z-score or MUAC, respectively. Two percent of participants were overweight. Notably, 32·1 % of children ≥5 years were classified with wasting based on MUAC-for-age Z-score, which is higher than that observed in children <5 (20·2 %). Food insecurity was reported among 58·2 % of children with stunting and 34·0 % with wasting. Chronic medical conditions predicted stunting and wasting. The lowest level of wealth predicted stunting, while ethnicity predicted wasting. Ethnicity and education level predicted food insecurity. CONCLUSIONS: We found that the prevalence of stunting and wasting at KCH are higher than previously published studies in Nepal. Malnutrition persists beyond 5 years, and we identified several predictors of malnutrition. Increased provision of and access to clinical nutrition programmes is an essential need for KCH. Twinning programs that provide local clinicians with increased opportunities for education and mentorship of local staff remains a pressing need in Nepal.

Prevalence of vitamin and iron deficiencies at cancer diagnosis at two pediatric oncology units in South Africa.

This study investigates the prevalence of vitamin and iron deficiencies at cancer diagnosis. Newly diagnosed children between October 2018 and December 2020 at two South African pediatric oncology units (POUs) were assessed for nutritional and micronutrient status (Vit A, Vit B12, Vit D, folate, and iron). A structured interview with caregivers provided information regarding hunger and poverty risks. There were 261 patients enrolled with a median age of 5.5 years and a male-to-female ratio of 1:0.8. Nearly half had iron deficiency (47.6%), while a third had either Vit A (30.6%), Vit D (32.6%), or folate (29.7%) deficiencies. Significant associations existed between moderate acute malnutrition (MAM) and low levels of Vit A (48.4%; p = .005), Vit B12 (29.6%; p < .001), and folate (47.3%; p = .003), while Vit D deficiency was associated with wasting (63.6%) (p < .001). Males had significantly lower Vit D levels (respectively, 40.9%; p = .004). Folate deficiency was significantly associated with patients born at full term (33.5%; p = .017), age older than five years (39.8%; p = .002), residing in provinces Mpumalanga (40.9%) and Gauteng (31.5%) (P = .032); as well as having food insecurity (46.3%; p < .001), or hematological malignancies (41.3%; p = .004). This study documents the high prevalence of Vit A, Vit D, Vit B12, folate, and iron deficiency in South African pediatric cancer patients, demonstrating the need to include micronutrient assessment at diagnosis to ensure optimal nutritional support for macro-and micronutrients.

Current status of African pediatric oncology education efforts aligned with the Global Initiative for Childhood Cancer.

Education of the pediatric oncology workforce is an important pillar of the World Health Organization CureAll technical package. This is not only limited to healthcare workers, but all stakeholders in the childhood cancer management process. It includes governmental structures, academic institutions, parents and communities. This review evaluated the current educational and advocacy training resources available to the childhood cancer community, the contribution of SIOP Africa in the continental educational needs and evaluated future needs to improve the management of pediatric malignancies in reaching the Global Initiative for Childhood Cancer goals. Childhood cancer, unlike adult cancers, has not been prioritized in African cancer control plans nor the teaching and advocacy surrounding pediatric oncology. The availability of formal training programs for pediatric oncologists, pediatric surgeons and radiotherapy specialists are limited to particular countries. In pharmacy and nutritional services, the exposure to pediatric oncology is limited while training in advocacy doesn't exist. Many nonacademic stakeholders are creating the opportunities in Africa to gain experience and train in these various fields, but formal training programs should still be advocated for. LEARNING POINTSThe African continent has various resources to increase the capacity of childhood cancer care stakeholders to increase their knowledge.African pediatric oncology teams rely on a multitude of international sources for training while developing their own.There is a greater need for formal, standardized cancer training especially for pediatric surgeons, radio-oncologists and nurses.Greater inclusion of pathologists, pediatric oncology pharmacists and dieticians into multidisciplinary care and childhood cancer training should be facilitated and resourced.Successful advocacy programs and tool kits exist in parts of Africa, but the training in advocacy is still underdeveloped.

Addition of arm anthropometry to body mass index for age, but not serum albumin, improves the accuracy of the nutritional assessment in severely and moderately malnourished children with cancer.

Arm anthropometry is a more sensitive measure of nutritional status than body mass index for age (BMI) in children with cancer, but the added utility of serum albumin remains uncertain. Concordance was determined among four forms of classifying nutritional status in a cohort of undernourished children with cancer: method 1: BMI-for-age Z score; method 2: method 1 + mid-upper arm circumference (MUAC) percentile; method 3: method 2 + triceps skinfold thickness (TSFT) percentile; and method 4: method 3 + serum albumin. Concordance was highest between methods 2 and 3, followed closely by 3 and 4, indicating that addition of arm anthropometry, but not serum albumin, to BMI increased the sensitivity of baseline nutritional assessment.

Survey of the use of traditional and complementary medicine among children with cancer at three hospitals in Cameroon.

INTRODUCTION: There is lack of diagnostic and treatment resources with variable access to childhood cancer treatment in low- and middle-income countries (LMIC), which may lead to subsequent poor survival. The primary aim of this study was to determine the prevalence and types of traditional and complementary medicine (T&CM) used in Cameroon. Secondarily, we explored determinants of T&CM use, associated costs, perceived benefits and harm, and disclosure of T&CM use to medical team. METHODS: A prospective, cross-sectional survey among parents and carers of children younger than 15 years of age who had a cancer diagnosis and received cancer treatment at three Baptist Mission hospitals between November 2017 and February 2019. RESULTS: Eighty participants completed the survey. Median patient age was 8.1 years (IQR4.1-11.1). There was significant availability (90%) and use (67.5%) of T&CM, whereas 24% thought T&CM would be good for cancer treatment. Common T&CM remedies included herbs and other plant remedies or teas taken by mouth, prayer for healing purposes and skin cutting. Living more than five hours away from the treatment center (P = 0.030), anticipated costs (0.028), and a habit of consulting a traditional healer when sick (P = 0.006) were associated with the use of T&CM. T&CM was mostly paid for in cash (53.7%) or provided free of charge (29.6%). Of importance was the fact that nearly half (44%) did not want to disclose the use of TM to their doctor. CONCLUSION: Pediatric oncology patients used T&CM before and during treatment but were unlikely to disclose its use to the child's health care team.

Malnutrition at diagnosis and throughout therapy in pediatric patients with solid tumors: A single-institution study in a developing country.

BACKGROUND: Changesin nutritional status can constitute a risk factor for reduced tolerance and effectiveness of antineoplastic treatment. Knowledge of the nutritional status of pediatric patients is important for implementing interventions to improve outcomes. We aimed to evaluate nutritional status at diagnosis and throughout therapy in pediatric patients with solid tumors. OBJECTIVES: To study the prevalence of malnutrition at diagnosis, compare different assessment tools, and examine longitudinal changes in nutritional status during the treatment of pediatric patients with solid tumors in a Brazilian institution. METHODS: This prospective single-center study enrolled patients with solid tumors (age <19 years) from June 2017 to May 2018. Nutritional evaluations were performed at diagnosis and after 3 and 6 months of treatment. z-Scores for height for age (H/A) and body mass index for age (BMI/A) were calculated using the Anthro/AnthroPlus software and mid-upper arm circumference (MUAC) percentile was used for nutritional classification. RESULTS: The prevalence of nutritional status at diagnosis was 29.3% malnourished, 49.5% adequate, and 21.2% overweight/obese. Nutritional status improved during the first 3 months of treatment, with a reduction in the proportion of malnourished patients and an increased number of patients with adequate nutritional status. CONCLUSIONS: The two combined indices, BMI/A and MUAC, facilitated the diagnosis of a greater number of patients with solid tumors who had nutritional alterations. A high prevalence of malnutrition was present at diagnosis. Nutritional status improved in the first 3 months of treatment and could be related to the multidisciplinary institutional approach following the diagnosis.

A bilingual dietary intervention early in treatment is feasible and prevents weight gain in childhood acute lymphoblastic leukemia.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. The onset of obesity during childhood ALL has been well established and is associated with inferior survival rates and increased treatment-related toxicities. This pilot study sought to determine if a dietary intervention is feasible and minimizes weight gain during the initial phases of treatment for ALL. METHODS: Participants were recruited from four institutions, fluent in English or Spanish, between 5 and 21 years old, and enrolled within 3 days of starting induction therapy. Participants were counseled for 6 months to follow a low glycemic diet. Dietary and anthropometric data were collected at diagnosis, end of induction, and end of month 6 (NCT03157323). RESULTS: Twenty-three of 28 participants (82.1%) were evaluable and included in the analysis. Dietary changes targeted by the nutrition intervention were successful; sugar intake declined (P = .003), whereas vegetable intake increased (P = .033). The majority of participants were able to adhere to the dietary principles prescribed: ≥70.0% reduced glycemic load and ≥60.0% increased fiber intake and decreased sugar intake. Importantly, we did not observe an increase in body mass index z-score during induction or over the 6-month intervention period. Most families found the nutrition intervention easy to follow (60%) and affordable (95%) despite simultaneous initiation of treatment for ALL. CONCLUSIONS: A 6-month nutrition intervention initiated during the initial phase of treatment for childhood ALL is feasible and may prevent weight gain. Our preliminary findings need to be confirmed in a larger clinical trial.

Efficacy of ready-to-use therapeutic food in malnourished children with cancer: Results of a randomized, open-label phase 3 trial.

BACKGROUND: The adverse influence of undernutrition in children with cancer may be remediated by early nutritional intervention. This study assessed the efficacy of ready-to-use therapeutic food (RUTF) in improving nutritional status and reducing treatment-related toxicities (TRTs) in such children. METHODS: In a randomized controlled phase-3 open-label trial, severely and moderately undernourished children with cancer were randomized 1:1 to receive standard nutritional therapy (SNT) or SNT+RUTF for 6 weeks. The primary outcome (weight gain >10%) and secondary outcomes (improved/maintained nutritional status, improved body composition) were assessed after 6 weeks. TRTs were assessed over 6 months. RESULTS: Between July 2015 and March 2018, 260 subjects were enrolled, 126 were analyzable in both arms at 6 weeks. More children on RUTF had weight gain (98 [77.8%] vs. 81 [64.2%], p = .025) with a greater increase in fat mass as a percentage of body mass (median 2% [IQR -0.12 to 4.9] vs. 0.5% [IQR -1.45 to 2.27, p = .005]) but a greater loss of lean mass (median -1.86% [IQR -4.4 to 0.50] vs. -0.4% [IQR -2.4 to 1.4, p = .007]) compared to the SNT arm. Fewer subjects on the RUTF arm had episodes of severe infection (10.6% vs. 31%, p < .0001), treatment delays (17.7% vs. 39%, p < .0001), and severe mucositis (11% vs. 23.8%, p = .006) compared to the SNT arm. The odds of developing TRTs on the RUTF arm were lower even after adjusting for improvement in nutritional status. CONCLUSIONS: RUTF is efficacious in improving weight gain and nutritional status in undernourished children with cancer and decreases TRTs. Incorporating RUTF into a healthy, balanced diet should be considered in undernourished children with cancer.

The importance of enteral nutrition to prevent or treat undernutrition in children undergoing treatment for cancer.

Nutrition therapy is a therapeutic approach to treating medical conditions and symptoms via diet, which can be done by oral, enteral or parenteral routes. It is desirable to include nutritional interventions as a standard of care in pediatric cancer units (PCUs) at all levels of care. The interventions are dependent on available resources and personnel across all clinical settings. Enteral nutrition is easy, inexpensive, uses the gastrointestinal tract, maintains gut mucosal integrity, and allows for individualized nutritional strategies. This narrative review describes enteral nutritional interventions for children undergoing cancer treatment and is aimed at PCUs of all levels of care located in a low- and middle-income country.

Nutritional traditional and complementary medicine strategies in pediatric cancer: A narrative review.

Traditional and complementary medicine (T&CM) strategies are commonly used by pediatric cancer patients. Nutritional approaches to T&CM include bioactive compounds, supplements, and herbs as well as dietary approaches. Pediatric cancer patients and their families commonly request and use nutritional T&CM strategies. We review the potential risks and benefits of nutritional T&CM use in pediatric cancer care and provide an overview of some commonly used and requested supplements, including probiotics, antioxidants, cannabinoids, vitamins, turmeric, mistletoe, Carica papaya, and others. We also discuss the role of specific diets such as the ketogenic diet, caloric restriction diets, whole-food diets, and immune modulating diets. There is a growing body of evidence to support the use of some T&CM agents for the supportive care of children with cancer. However, further study is needed into these agents and approaches. Open communication with families about T&CM use is critical.

Validation of an algorithmic nutritional approach in children undergoing chemotherapy for cancer.

BACKGROUND: Undernutrition impacts clinical outcome adversely in children with cancer. This study aimed to validate a nutritional algorithm with specific application to the low- and middle-income country (LMIC) setting. PROCEDURE: Fifty children with a new diagnosis of cancer were enrolled in this randomized interventional study. Weight, height/length, and mid-upper-arm circumference (MUAC) were measured at baseline. The study arm was administered nutritional care as per the algorithm and the control arm received the institutional standard of care. Weight was monitored regularly and MUAC was repeated after 3 months. Children were classified based on weight for height if <2 years of age or body mass index if ≥2 years, as normal, wasted, and severely wasted. The algorithmic approach comprised administration of oral supplements, nasogastric feeds, and/or parenteral nutrition based on objective assessment of the nutritional status. RESULTS: Fifty patients were analyzed (study: 25, control: 25). Four in the study arm (16%) and six in the control arm (24%) had wasting at baseline. MUAC was <5th percentile in 15 (60%) and 13 (52%) patients in the study and control arms, respectively. At the end of 3 months, the median increment in weight was 0.8 kg (interquartile range [IQR]: -0.02; 2.00) and 0.0 kg (IQR: -0.70; 1.25) in the study and control arms, respectively (P = .153). The median increment in MUAC was 1.20 cm (IQR: 0.10; 2.30) and 0.00 cm (IQR: -0.50; 1.10) in the study and control arms, respectively (P = .020). CONCLUSIONS: The application of an algorithm designed for use in LMICs resulted in significant improvement in nutritional status, as measured by MUAC.

Nutritional status at diagnosis of cancer in children and adolescents in Guatemala and its relationship to socioeconomic disadvantage: A retrospective cohort study.

BACKGROUND: At least 80% of children with cancer live in low- and middle-income countries where the prevalence of malnutrition and socioeconomic disadvantage is high. We examined the relationship between nutritional status (NS), assessed by arm anthropometry, and socioeconomic status (SES) in children diagnosed with cancer at Unidad Nacional de Oncologia Pediatrica (UNOP) in Guatemala over a three-year period. METHOD: Patients aged 0 to 18 years of age diagnosed between January 2015 and December 2017 were included. NS was evaluated by mid-upper arm circumference, triceps skin fold thickness, and serum albumin level, and subjects were classified as adequately nourished, moderately depleted, and severely depleted nutritionally. SES was measured by a 15-item instrument developed at UNOP. RESULTS: Of 1365 patients diagnosed in the study period, 1060 (78%) fulfilled the eligibility criteria. Only 6% of patients were classified as medium to high, the remainder as medium-low to extremely low SES. Almost 47% were severely depleted at diagnosis, 19% moderately depleted, and 34% adequately nourished. SES was shown to be a determinant of NS; with progressively lower SES, the probability of a decline in NS increased by a factor of 1.04 points (P < 0.0001). Leukemia and lymphoma were also important predictors of nutritional depletion with odds ratios of 6.08 (95% CI, 1.74-28.28; P = 0.008) for leukemias and 4.83 (95% CI, 1.33-23.03; P = 0.03) for lymphomas. CONCLUSION: Both low SES and a diagnosis of leukemia or lymphoma are strong predictors of poor NS at diagnosis in children with cancer in Guatemala.

Unmet Needs in Nutritional Care in African Paediatric Oncology Units.

BACKGROUND: Up to 50% of children diagnosed with cancer in low- and middle-income countries are malnourished, which likely affects survival. SUBJECTS AND METHODS: An online survey to paediatric oncology units (POUs) in Africa was done regarding nutritional assessment and care. RESULTS: Sixty-six surveys were received from POUs in 31 countries. Only 44.4% had a dedicated dietician for nutritional assessment and support; 29.6% undertook routine nutritional assessment during treatment. None reported defined criteria for nutritional intervention. Total parenteral nutrition was not available for 42.6% of POUs, while 51.8% did not have access to commercial enteral nutrition for inpatients, and 25.9% of the hospitals could not supply any home-based nutritional supplements. CONCLUSION: Nutritional assessment in POUs in Africa is neither routinely undertaken nor are there defined criteria to initiate nutritional interventions. Standardized guidelines for nutritional assessment and interventions are needed for African POUs to enable improved outcome.

Psychosocial determinants of physical activity and dietary behaviors in adolescents and young adults with cancer and survivors.

BACKGROUND: Survivors of childhood cancer are at increased risk of lifestyle influenced health issues. We sought to understand the association between stages of change (SOC) and psychosocial variables related to modifiable health behaviors: physical activity (PA), dietary fat intake, and intake of fruits and vegetables among adolescents and young adults at different phases of cancer therapy. METHODS: We conducted an exploratory cross-sectional survey of adolescents and young adults currently being treated for cancer or who are survivors of childhood cancer. We evaluated SOC and several psychosocial variables using the previously validated Patient-Centered Assessment and Counseling for Exercise (PACE+): Physical Activity and Diet Surveys for Adolescents tool. Current dietary behaviors were evaluated with 24 hr diet recall. RESULTS: One hundred and eighteen patients participated in the survey. SOC did not vary by phase of treatment. Ethnicity and body mass index were strongly associated with SOC for PA, but not for dietary behaviors. There was a significant association between SOC and self-efficacy, knowledge of strategies, and family or friend support for PA, dietary fat, and fruits and vegetables. Higher self-efficacy and family support were significant variables impacting SOC and participants' reported intake of fruits and vegetables servings. CONCLUSION: We demonstrate that SOC for the investigated behaviors did not change based on phase of treatment, supporting the initiation of lifestyle interventions early on in treatment. We identify several psychosocial variables that may act as important targets for future lifestyle interventions aimed to improve dietary and exercise behaviors in adolescents and young adults with cancer and survivors.

A systematic review of integrative clinical trials for supportive care in pediatric oncology: a report from the International Society of Pediatric Oncology, T&CM collaborative.

PURPOSE: Traditional and complementary medicine (T&CM) use in children with cancer is well established among high-income, upper middle-income, low-middle-income, and low-income countries (HIC, UMIC, LMIC, LIC, respectively). In HIC, a developing body of evidence exists for several T&CM therapies; however, evidence in other income settings is less well described despite a significantly higher use when compared to reports from HIC. The aim of this systematic review was to evaluate the evidence for T&CM for a variety of supportive care indications among children with cancer. METHODS: We performed a systematic review following the PRISMA guidelines of randomized, controlled clinical trials from inception through September 2016. Our eligibility criteria were limited to T&CM studies performed in children and adolescents undergoing treatment for a pediatric malignancy. RESULTS: Of 6342 studies identified, 44 met inclusion criteria. Two clinical trials reported on acupuncture, 1 reported on aromatherapy, 9 evaluated massage therapy, and 32 reported on dietary supplements. Twenty-two studies were performed in HIC, 15 in UMIC, and 7 in LMIC. T&CM therapies were most commonly investigated for the prevention or management of mucositis, weight loss, and febrile neutropenia. Encouraging results were reported for select interventions; however, the majority of studies were classified as poor to fair quality. CONCLUSION: Our search revealed numerous clinical studies investigating the use of T&CM for supportive care purposes in pediatric oncology in HIC, UMIC, and LMIC. Although limited, these results could inform supportive care resource allocation and indicate where T&CM may serve to fill gaps where access to care may be limited.

Traditional and complementary medicine used with curative intent in childhood cancer: A systematic review.

Traditional and complementary medicine (T&CM) strategies are widely utilized in pediatric oncology, with many families reporting T&CM use with the intention to cure cancer. Study of T&CM agents presents many challenges, as a heterogeneous group of agents and techniques are used for a variety of different purpose in many different oncologic conditions. We present a systematic review of the literature examining published reports in which T&CM agents are used with an intention of cure. Twenty-two reports were identified, with most reports being of poor quality. Novel paradigms are likely needed to further investigate T&CM agents.