1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Growth differentiation factor 15 (GDF15) elevation in children with newly diagnosed cancer

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Growth differentiation factor 15 (GDF15), an inflammatory marker and mediator of adult cancer cachexia, remains largely unexplored in children. GDF15 increases nausea, vomiting, and anorexia in cancer and contributes to malnutrition, with the potential to be a cachexia therapeutic target. No studies have examined GDF15 in children with newly diagnosed cancer. Our pilot study compares GDF15 in children with newly diagnosed cancer to age- and sex-matched controls and correlates levels with anthropometric measurements and quality of life (QOL).

          Methods

          Children with newly diagnosed cancer aged 2-21 years were enrolled with serum GDF15 ELISA, anthropometric measures [height, weight, and mid-upper arm circumference (MUAC)], and QOL assessments (using PedsQL™ Core and Gastrointestinal Modules), which were collected at baseline and repeated 3 months later. Serum GDF15 levels were obtained from age- and sex-matched controls for comparison.

          Results

          A total of 57 participants enrolled (N=30, cancer group; N=27, control group) with a median age of 8.8 years (IQR 5.6-15.9 years). The participants were primarily male (54.4%), white (82.5%), and non-Hispanic (82.5%). Cancer diagnoses included acute lymphoblastic leukemia (N=8), lymphoma (N=8), neuroblastoma (N=5), soft tissue tumors (N=4), acute myeloid leukemia (N=2), and single participants with brain, kidney, and bone tumors. Baseline GDF15 was higher in the cancer cohort compared to the control cohort (median=614.6pg/mL and 320.5pg/mL, respectively; p<0.001). When examining participants with evaluable baseline and 3-month follow-up GDF15 levels (N=18), GDF15 was not statistically different (median=657.1pg/mL and 675.3pg/mL, respectively; p=0.702). A total of 13 of the 30 participants and 21 caregivers completed the PedsQL™ Core and Gastrointestinal symptom modules. QOL scores did not differ significantly at 3-month follow-up compared to baseline, but diarrhea worsened (p=0.017). Median participant response for diarrhea at baseline was 92.9 (IQR=92.9-96.4; N=13), which was significantly better than the follow-up (median=78.6; IQR= 71.4-92.9; p=0.017). There were no correlations between change in height, weight, or MUAC and change in GDF15 levels (p=0.351, 0.920, and 0.269 respectively).

          Conclusion

          GDF15 was elevated in children with cancer at diagnosis compared to controls but did not correlate with anthropometric measurements or QOL. This pilot study will inform future prospective studies to better describe the natural history of GDF15 and its role in cachexia and as a potential therapeutic target.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.

          Emerging evidence suggests muscle depletion predicts survival of patients with cancer. At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001). CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Childhood and adolescent cancer statistics, 2014.

            In this article, the American Cancer Society provides estimates of the number of new cancer cases and deaths for children and adolescents in the United States and summarizes the most recent and comprehensive data on cancer incidence, mortality, and survival from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries (which are reported in detail for the first time here and include high-quality data from 45 states and the District of Columbia, covering 90% of the US population). In 2014, an estimated 15,780 new cases of cancer will be diagnosed and 1960 deaths from cancer will occur among children and adolescents aged birth to 19 years. The annual incidence rate of cancer in children and adolescents is 186.6 per 1 million children aged birth to 19 years. Approximately 1 in 285 children will be diagnosed with cancer before age 20 years, and approximately 1 in 530 young adults between the ages of 20 and 39 years is a childhood cancer survivor. It is therefore likely that most pediatric and primary care practices will be involved in the diagnosis, treatment, and follow-up of young patients and survivors. In addition to cancer statistics, this article will provide an overview of risk factors, symptoms, treatment, and long-term and late effects for common pediatric cancers. © 2014 American Cancer Society, Inc.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Nutrition and brain development in early life.

              Presented here is an overview of the pathway from early nutrient deficiency to long-term brain function, cognition, and productivity, focusing on research from low- and middle-income countries. Animal models have demonstrated the importance of adequate nutrition for the neurodevelopmental processes that occur rapidly during pregnancy and infancy, such as neuron proliferation and myelination. However, several factors influence whether nutrient deficiencies during this period cause permanent cognitive deficits in human populations, including the child's interaction with the environment, the timing and degree of nutrient deficiency, and the possibility of recovery. These factors should be taken into account in the design and interpretation of future research. Certain types of nutritional deficiency clearly impair brain development, including severe acute malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency. While strategies such as salt iodization and micronutrient powders have been shown to improve these conditions, direct evidence of their impact on brain development is scarce. Other strategies also require further research, including supplementation with iron and other micronutrients, essential fatty acids, and fortified food supplements during pregnancy and infancy. © 2014 International Life Sciences Institute.
                Bookmark

                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2506523Role: Role: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role:
                Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2583040Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role: Role: Role: Role:
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                11 December 2023
                2023
                : 13
                : 1295228
                Affiliations
                [1] 1 Department of Pediatrics, Riley Hospital for Children at Indiana University Health , Indianapolis, IN, United States
                [2] 2 Division of Pediatric Hematology/Oncology, Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN, United States
                [3] 3 Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine , Indianapolis, IN, United States
                [4] 4 Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN, United States
                [5] 5 Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN, United States
                [6] 6 Department of Biostatistics and Health Data Science, Indiana University School of Medicine , Indianapolis, IN, United States
                [7] 7 Department of Surgery, Indiana University School of Medicine , Indianapolis, IN, United States
                [8] 8 Indiana Center for Musculoskeletal Health, Indiana University School of Medicine , Indianapolis, IN, United States
                [9] 9 Department of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University , Portland, OR, United States
                Author notes

                Edited by: Edoardo Muratore, University of Bologna, Italy

                Reviewed by: Parthasarathy Seshacharyulu, University of Nebraska Medical Center, United States

                Fabio Penna, University of Turin, Italy

                Egidio Candela, University of Bologna, Italy

                *Correspondence: Daniel V. Runco, drunco@ 123456iupui.edu
                Article
                10.3389/fonc.2023.1295228
                10749306
                38146512
                586a59e6-a176-4185-ae82-cd50153231c0
                Copyright © 2023 Runco, DiMeglio, Vanderpool, Han, Daggy, Kelley, Mikesell and Zimmers

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 September 2023
                : 20 November 2023
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 42, Pages: 12, Words: 5366
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the IU Simon Comprehensive Cancer Center Cancer Biomarker Pilot Grant and Translational Research Core (DR) funded by IU Simon Cancer Center P30 Support Grant (P30CA082709). This research was also supported in part by grants from the National Institutes of Health R01CA122596 (TZ) and R01CA194593 (TZ).
                Categories
                Oncology
                Original Research
                Custom metadata
                Pediatric Oncology

                Oncology & Radiotherapy
                childhood cancer,pediatric,cachexia,gdf15,anthropometrics measurements,body composition,malnutrition

                Comments

                Comment on this article