Effectiveness and safety of interventions to manage childhood overweight and obesity: An Overview of Cochrane systematic reviews

BackgroundChildhood overweight and obesity are associated with adverse physical, social, and psychological outcomes.ObjectivesWe conducted an overview of Cochrane systematic reviews on the effectiveness and risks of interventions to treat overweight and obesity in children and adolescents.MethodsIn June 2019, we searched the Cochrane Database of Systematic Reviews for eligible reviews. The primary outcomes were change in adiposity (body mass and body mass index [BMI] z-score) and adverse events. Two reviewers screened studies and one reviewer extracted and another verified data. Two reviewers assessed methodological quality and reached consensus. Data were synthesized narratively.ResultsWe included seven Cochrane reviews published between 2011 and 2017 containing evidence from 167 randomized controlled trials with 21,050 participants. Lifestyle and behavioural interventions more effectively reduced weight compared with no intervention, usual care, or another behavioural treatment (three reviews, low-to-moderate certainty). Parent–child lifestyle and behavioural interventions more effectively reduced BMI z-score compared with no intervention (one review, low certainty). Decision support tools for healthcare providers more effectively limited increases in BMI z-score compared with usual care (one review, moderate certainty). Pharmacologic treatments combined with behavioural modification more effectively reduced adiposity compared with placebo or usual care (one review, low certainty), but the risk of adverse events was greater than non-pharmacologic therapy. Surgical interventions (e.g., LAP-BAND) combined with behavioural modification more effectively reduced adiposity compared with behavioural modification alone (one review, low certainty). Those who underwent surgery reported a higher number of adverse events compared with those treated with lifestyle modification.ConclusionsThere is low-certainty evidence that lifestyle and behavioural interventions, pharmacologic interventions, and surgical interventions are effective in weight management for children with overweight and obesity. Safety data remain lacking across all intervention modalities. Future research should focus on implementation strategies. Further, a focus on overall well-being may be more beneficial than weight management specifically.     

An international strategy to determine the role of high dose therapy in recurrent Wilms’ tumour

PurposeTo review event-free (EFS) and overall survival (OS) from publications describing outcome for children with relapsed Wilms’ tumour. Comparisons are made between those receiving myeloablative high dose chemotherapy with autologous stem-cell rescue (HDT) and those not (NoHDT).Materials and methodsRelevant information was extracted from individual patient or summary data and 3-year EFS and OS rates established. These rates were combined in a weighted manner to derive hazard ratios (HRs).ResultsNineteen publications were identified (5 HDT, 6 NoHDT, 8 both). Pooling all studies suggested an advantage to HDT with a hazard ratio (HR) for EFS of 0.87 (95% confidence interval (CI) 0.67–1.12) and 0.94 (0.71–1.24) for OS. A stratified analysis confined to studies that provided individual patient data on both HDT and NoHDT gave HRs of 0.83 (0.56–1.24) and 0.92 (0.59–1.41). Further, analyses of risk groups, defined by treatment and/or histology prior to first relapse, suggested a HR for EFS of 0.90 (95% CI 0.62–1.31) for those of high and 0.50 (CI 0.31–0.82) for the very high risk patients.ConclusionThe evidence suggests, although there are many caveats since the information summarised here is not from randomised trials, a great deal of uncertainty concerning the role of HDT in patients following relapse after treatment for their Wilms’ tumour. For each risk group we propose a randomised trial comparing a standard with a more intensive therapy with specific choice of regimen tailored to the risk group (and co-operative groups) concerned. A synthesis of updated evidence from studies in this overview together with any emerging studies and future trial information will form the basis for future evidence-based clinical decision-making.     

Radiation dose and contralateral breast cancer risk associated with megavoltage cone-beam computed tomographic image verification in breast radiation therapy

PurposeTo measure and compare organ doses from a standard tangential breast radiation therapy treatment (50 Gy delivered in 25 fractions) and a megavoltage cone-beam computed tomography (MV-CBCT), taken for weekly image verification, and assess the risk of radiation-induced contralateral breast cancer.Methods and MaterialsOrgan doses were measured with thermoluminescent dosimeters placed strategically within a female anthropomorphic phantom. The risk of radiation-induced secondary cancer of the contralateral breast was estimated from these values using excess absolute risk and excess relative risk models.ResultsThe effective dose from a MV-CBCT (8-monitor units) was 35.9 ± 0.2 mSv. Weekly MV-CBCT imaging verification contributes 0.5% and 17% to the total ipsilateral and contralateral breast dose, respectively. For a woman irradiated at age 50 years, the 10-year postirradiation excess relative risk was estimated to be 0.8 and 0.9 for treatment alone and treatment plus weekly MV-CBCT imaging, respectively. The 10-year postirradiation excess absolute risk was estimated to be 4.7 and 5.6 per 10,000 women-years.ConclusionsThe increased dose and consequent radiation-induced second cancer risk as calculated by this study introduced by the imaging verification protocols utilizing MV-CBCT in breast radiation therapy must be weighed against the benefits of more accurate treatment. As additional image verification becomes more common, it is important that data be collected in regard to long-term malignancy risk.     

Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response

Background

Cytotoxic chemotherapy improves survival for some, but not all, cancer patients. Non-responders may experience unnecessary toxicity and cancer progression, thus creating an urgent need for biomarkers that can predict the response to chemotherapy. So far, the search for such biomarkers has primarily been focused on the cancer cells and less on their surrounding stroma. This stroma is known to act as a key regulator of tumour progression and, in addition, has been associated with drug delivery and drug efficacy. Fibroblasts represent the major cell type in cancer-associated stroma and they secrete extracellular matrix proteins as well as growth factors. This Medline-based literature review summarises the results from studies on epithelial cancers and aimed at investigating relationships between the quantity and quality of the intra-tumoral stroma, the cancer-associated fibroblasts, the proteins they produce and the concomitant response to chemotherapy. Biomarkers were selected for review that are known to affect cancer-related characteristics and patient prognosis.

Results

The current literature supports the hypothesis that biomarkers derived from the tumour stroma may be useful to predict response to chemotherapy. This notion appears to be related to the overall quantity and cellularity of the intra-tumoural stroma and the predominant constituents of the extracellular matrix.

Conclusion

Increasing evidence is emerging showing that tumour-stroma interactions may not only affect tumour progression and patient prognosis, but also the response to chemotherapy. The tumour stroma-derived biomarkers that appear to be most appropriate to determine the patient’s response to chemotherapy vary by tumour origin and the availability of pre-treatment tissue. For patients scheduled for adjuvant chemotherapy, the most promising biomarker appears to be the PLAU: SERPINE complex, whereas for patients scheduled for neo-adjuvant chemotherapy the tumour stroma quantity appears to be most relevant.