Assessment of Plasma Antioxidants, Oxidative Stress and Polyunsaturated Fatty Acids in Paediatric Cancer Patients: A Prospective Cohort Pilot Study

Background: Paediatric cancer patients may have a limited dietary intake, particularly nutrients high in antioxidants, docosahexanoic acid (DHA) and eicosapentanoic acid (EPA). Objective: To investigate the antioxidant status (TAS), antioxidant capacity (TAC), oxidative stress, DHA and EPA of paediatric cancer patients during treatment. Methods: A prospective cohort study of Scottish children aged <18 years, diagnosed with and treated for cancer between April-2013 to Jan-2014 was performed. Clinical data and blood samples were collected at baseline and 6 months. Data were stratified by treatment risk (low, medium and high) and nutritional support. We used Oxygen Radical Absorbance Capacity (ORAC) Antioxidant Assay to measure TAC, thiobarbituric acid reactive substances (TBARS) for lipid peroxidation and high performance liquid chromatography and Inductively Coupled Plasma Mass Spectrometry for TAS. The analyses of DHA and EPA were performed by analysing fatty acidmethyl esters (FAME) using gas-liquid chromatography. The reference ranges used were: Yagi 1998 (1.86-3.94) _mol for lipid peroxidation and Damsgaard.,et al. 2014 for EPA (0.45-0.77) % and DHA (2.22-3.76) %. Results: 20 patients (median (IQR) age 4.2 (1.5-8.5) years; 50% males) were recruited. There were no significant changes in plasma TAS, TAC and EPA, but lipid peroxidation significantly decreased from 7.4 (6.2-9.0) at baseline to 5.3 (4.5-6.4) _mol/MDA at 6 months(p = 0.003). The median (IQR) blood percentage of DHA significantly increased from 1.3 (0.9-1.9) to 1.8 (1.3-2.1) (p = 0.001). Lipid peroxidation was high in 95% (19/20) of patients at baseline and 94% (15/16) at 6 months; whilst DHA and EPA were low in 95%(19/20) and 70% (14/20) at baseline and 87.5% (14/16) and 60% (12/16) at 6 months. Children on high-treatment risk exhibited the highest oxidative stress levels. No statitically significant differences were found between non-supplemented and supplemented children in any of the following parameters (TAS, TAC, oxidative stress, EPA and DHA). Conclusion: There was a high prevalence of oxidative stress, especially in children treated with high-risk protocols and during the initial phases of treatment. Nutritional support does not appear to provide enough TAS, EPA and DHA in this cohort; however, larger high-quality population based studies are warranted to confirm these findings. Keywords: Paediatric cancer; Antioxidants; Oxidative stress; Docosahexanoic acid; Eicosapentanoic acidsch_dieThe Determinants of Nutritional Risk in Paediatric Cancer2pub4313pub

Low Plasma Vitamin D (25-Hydroxycholecalciferol) in Children and Adolescents Diagnosed with Cancer: A Case-Control Study

Introduction: Children and young people with cancer are less likely to spend time outdoors and they may also have a limited dietary intake. In addition, some cancer treatments can increase vitamin D catabolism. Objectives: This study aimed to investigate if there was an increased risk of poor vitamin D status in newly diagnosed childhood cancer patients compared to healthy controls in Scotland. Methods: Plasma 25 (OH) D was measured in children and adolescents during initial cancer treatment and compared to 33 healthy controls. Vitamin D deficiency was classified as plasma 25 (OH) D <25 nmol/l, with a plasma 25 (OH) D of 25-49 nmol/l classified as insufficient. Results: Forty-one patients (median age 3.8 years, IQR 1.9-8.0) were diagnosed with cancer, 63% were male. Twenty-three (56 %) had solid tumours, 18 (44%) had haematological cancers. Median (IQR) plasma 25 (OH) D at recruitment was 37.0 nmol/l (23.7-58.2). Ten patients (24%) had vitamin D deficiency and 17 (41%) patients were classified as insufficient. The median (IQR) plasma 25 (OH) D in the control group (n = 33) was 37.5 nmol/l (29.0-58.0). Six controls (18%) had vitamin D deficiency and 14 (42%) were classified as having insufficient results. Plasma 25 (OH) D did not differ (p > 0.05) between the patients and the controls. Conclusions: Almost three in four Scottish children treated for cancer had vitamin D deficiency or insufficiency; there was no increased risk of poor vitamin D status compared to healthy controls. Assessment of vitamin D status at diagnosis and in response to the course of treatment appears necessary to optimise nutritional management.sch_dieThe determinants of nutritional risk in children and young people with cancer3pub4423pub

Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: A report of the Malignant Germ Cell International Consortium.

PURPOSE: To compare the outcomes of paediatric and adolescent extracranial malignant germ cell tumour (GCT) patients treated with either carboplatin or cisplatin on clinical trials conducted by the Children's Oncology Group (COG) and the Children's Cancer and Leukaemia Group (CCLG). METHODS: The Malignant Germ Cell International Consortium (MaGIC) has created a database of the GCT clinical trials conducted since 1983 by COG (United States, Canada and Australia), which used cisplatin-based regimens, and by CCLG (United Kingdom), which used carboplatin-based regimens. Using the parametric cure model, this study compared the overall 4-year event-free survival (EFS), stratified by age, stage, site and the a-priori defined MaGIC 'risk' groups: standard risk ((SR) 1 (EFS >80%; age 80%, age ≥ 11y) and poor risk (PR) (EFS ≤ 70%, age ≥ 11y). RESULTS: Cisplatin-based therapy was used in 620 patients; carboplatin was used in 163 patients. In the overall multivariate cure model, the two regimens did not differ significantly (cisplatin: 4-year EFS 86%; 95% confidence interval (CI) 83-89% versus carboplatin 4-year EFS 86%; 95% CI 79-90%; p = 0.87). No significant differences were noted in stratified analyses by site, stage, age and MaGIC risk groups: SR1 (p = 0.20), SR2 (p = 0.55) or PR (p = 0.72) patients. CONCLUSIONS: In these trials conducted contemporaneously, there is no significant difference in outcome observed overall, or any subset of patients, who were treated with regimens containing cisplatin versus carboplatin These results suggested sufficient equipoise to justify a randomised trial to evaluate the effectiveness of carboplatin versus cisplatin in the treatment of children, adolescents and young adults with standard risk GCT, which is currently underway

Adjuvant chemotherapy does not improve outcome in children with ovarian immature teratoma: A comparative analysis of clinical trial data from the Malignant Germ Cell International Consortium.

BACKGROUND/OBJECTIVES: Surgery is the mainstay of therapy for children with ovarian immature teratoma (IT), whereas adults receive adjuvant chemotherapy, except those with stage-I, grade-1 disease. In Brazil, children with metastatic ovarian IT received postoperative chemotherapy. This practice variation allowed evaluation of the value of chemotherapy, by comparison of Brazilian patients with those in the United States and United Kingdom. DESIGN/METHODS: From the Malignant Germ Cell International Consortium data commons, data on ovarian IT patients from two recently added Brazilian trials (TCG-99/TCG-2008) were compared with data from US/UK (INT-0106/GC-2) trials. Primary outcome measure was event-free (EFS) and overall survival (OS). RESULTS: Forty-two Brazilian patients were included (stage I: 27, stage II: 4, stage III: 8, stage IV: 3). Twenty-nine patients had surgery alone, whereas 13 patients received postoperative chemotherapy. The EFS and OS for entire cohort was 0.80 (95% CI: 0.64-0.89) and 0.97 (0.84-0.99). There was no difference in relapse risk based on stage, grade, or receipt of chemotherapy. Comparing the Brazilian cohort with 98 patients in US/UK cohort (stage I: 59, stage II: 12, stage III: 27), there was no difference in EFS and OS across all stages, despite 87% of stage II-IV Brazilian patients receiving postoperative chemotherapy compared with only 13% of US/UK patients. The EFS and OS for Brazilian compared with US/UK cohort was stage I: 88% versus 98% (p = .05), stage II-IV EFS: 67% versus 79% (p = .32), stage II-IV OS: 93% versus 97% (p = .44); amongst grade-3 patients, there was no difference in EFS or OS. CONCLUSION: Addition of postoperative chemotherapy did not improve outcome in children with ovarian IT, even at higher grade or stage, compared with surgery alone.The St Baldricks Foundation Consortium Grant; reference number 358099