No abstract

Purpose-Hypoxia is one of the main causes of the failure to achieve local control using radiotherapy. This is due to the increased radioresistance of hypoxic cells. 18 F-fluoromisonidazole ( 18 F-FMISO) positron emission tomography (PET) is a noninvasive imaging technique that can assist in the identification of intratumor regions of hypoxia. The aim of this study was to evaluate the reproducibility of 18 F-FMISO intratumor distribution using two pretreatment PET scans.Methods and Materials-We enrolled 20 head and neck cancer patients in this study. Of these, 6 were excluded from the analysis for technical reasons. All patients underwent an 18 Ffluorodeoxyglucose study, followed by two 18 F-FMISO studies 3 days apart. The hypoxic volumes were delineated according to a tumor/blood ratio ≥1.2. The 18 F-FMISO tracer distributions from the two 18 F-FMISO studies were co-registered on a voxel-by-voxel basis using the computed tomography images from the PET/computed tomography examinations. A correlation between the 18 F-FMISO intensities of the corresponding spatial voxels was derived.Results-A voxel-by-voxel analysis of the 18 F-FMISO distributions in the entire tumor volume showed a strong correlation in 71% of the patients. Restraining the correlation to putatively hypoxic zones reduced the number of patients exhibiting a strong correlation to 46%.Conclusion-Variability in spatial uptake can occur between repeat 18 F-FMISO PET scans in patients with head and neck cancer. Blood data for one patient was not available. Of 13 patients, 6 had well-correlated intratumor distributions of 18 F-FMISO-suggestive of chronic hypoxia. More work is required to identify the underlying causes of changes in intratumor distribution before singletime-point 18 F-FMISO PET images can be used as the basis of hypoxia-targeting intensity-modulated radiotherapy.

Objectives: To assess the overall effect of vitamin D supplementation on risk of acute respiratory infection (ARI), and to identify factors modifying this effect. Design: We conducted a systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard RCT Number (ISRCTN) registry from inception to May 2020. Eligibility Criteria for Selecting Studies: Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Results: We identified 40 eligible RCTs (total 30,956 participants, aged 0 to 95 years). Data were obtained for 29,841 (96.5%) of 30,909 participants in 39 studies. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.89, 95% CI 0.81 to 0.98; P for heterogeneity 0.009). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.94). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.94, 95% CI 0.81 to 1.08). Risk of bias within individual studies was assessed as being low for all but two trials. A funnel plot showed asymmetry, suggesting that small trials showing non-protective effects of vitamin D may have been omitted from the meta-analysis. Conclusions: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. The overall effect size may have been over-estimated due to publication bias. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation.

Observational studies and randomised controlled studies suggest that vitamin D plays a role in the prevention of acute respiratory tract infection (ARTI); however, findings are inconsistent and the optimal serum 25-hydroxyvitamin D (25(OH)D) concentration remains unclear. To review the link between 25(OH)D concentration and ARTI, we searched PubMed and EMBASE databases to identify observational studies reporting the association between 25(OH)D concentration and risk or severity of ARTI. We used random-effects meta-analysis to pool findings across studies. Twenty-four studies were included in the review, 14 were included in the meta-analysis of ARTI risk and five in the meta-analysis of severity. Serum 25(OH)D concentration was inversely associated with risk and severity of ARTI; pooled odds ratios (95% confidence interval) were 1.83 (1.42–2.37) and 2.46 (1.65–3.66), respectively, comparing the lowest with the highest 25(OH)D category. For each 10 nmol/L decrease in 25(OH)D concentration, the odds of ARTI increased by 1.02 (0.97–1.07). This was a non-linear trend, with the sharpest increase in risk of ARTI occurring at 25(OH)D concentration < 37.5 nmol/L. In conclusion, there is an inverse non-linear association between 25(OH)D concentration and ARTI.