ABSTRACT
The objective of this study is to investigate possible biological effects of radiofrequency electromagnetic fields (RF-EMF) as used in modern wireless telecommunication in a well-controlled experimental environment using chicken embryo development as animal model. Chicken eggs were incubated under continuous experimental exposure to GSM (1.8 GHz), DECT (1.88 GHz), UMTS (2.1 GHz), and WLAN (5.6 GHz) radiation, with the appropriate modulation protocol, using a homogeneous field distribution at a field strength of approximately 3 V/m, representing the maximum field level in a normal living environment. Radiation-shielded exposure units/egg incubators were operating in parallel for exposed and control eggs in a climatized homogeneous environment, using 450 eggs per treatment in three successive rounds per treatment. Dosimetry of the exposure (field characteristics and specific absorption rate) were studied. Biological parameters studied included embryo death during incubation, hatching percentage, and various morphological and histological parameters of embryos and chicks and their organs, and gene expression profiles of embryos on day 7 and day 18 of incubation by microarray and qPCR. No conclusive evidence was found for induced embryonic mortality or malformations by exposure to the used EMFs, or for effects on the other measured parameters. Estimated differences between treatment groups were always small and the effect of treatment was not significant. In a statistical model that ignored possible interaction between rounds and exposure units, some of the many pairwise comparisons of exposed versus control had P-values lower than 0.05, but were not significant after correction for multiple testing. Bioelectromagnetics. 38:186-203, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
Electromagnetic Fields/adverse effects , Wireless Technology , Animals , Body Weight , Chick Embryo , Chickens , Female , Gene Expression Regulation, Developmental , Organ Size , Polymerase Chain Reaction/methods , Radiation Exposure/adverse effects , Radiation Exposure/analysis , Radio Waves , Reproducibility of Results , Toxicity Tests/instrumentation , Toxicity Tests/methodsABSTRACT
PURPOSE: Tumour response assessment to therapy is crucial in oncology. We analysed the morphology of liver metastases (LM) in gastrointestinal stromal tumour (GIST) patients to determine whether uni-dimensional measurement of lesions by Response Evaluation Criteria in Solid Tumours (RECIST), accurately reflects lesion volume. MATERIALS AND METHODS: The volumes of LM (n=139) from a GIST patient cohort were measured using computed tomography (CT) at baseline, 3, 6 and 12 months after commencement of imatinib therapy. Baseline measurements were obtained by two independent investigators and inter-observer agreement assessed using Bland-Altman plots. Actual lesion volumes (V(ACTUAL)) were measured and compared with volumes based on the RECIST measure (V(RECIST)), and with volumes based on three orthogonal measures (V(ELLIPSOID)) at several time-points. RESULTS: At baseline, the inter-observer bias for V(ACTUAL) was just 1.8%. V(RECIST) and V(ELLIPSOID) overestimated V(ACTUAL) by a mean of 35% and only 9% respectively (P<0.0001 for both). At baseline, 44% (61/139) of LM were classified as spheroidal and 56% (78/139) as ellipsoidal. During treatment, only 42% of LM retained their original morphology. The remainder demonstrated significant changes in morphology (from spheroidal to ellipsoidal and vice versa) over time, while the RECIST measure did not reflect such changes. CONCLUSIONS: The morphology of LM in GIST is rarely spherical (an underlying assumption for RECIST) and can change considerably during imatinib therapy. In this setting, measurements using RECIST do not reflect changes in size and morphology. Additionally, whilst V(ELLIPSOID) is a more suitable surrogate for volume estimation, it is still somewhat limited by the morphology and orientation of such lesions. Studies are warranted to further explore the clinical impact of these findings.
Subject(s)
Benzamides/therapeutic use , Gastrointestinal Stromal Tumors/drug therapy , Liver Neoplasms/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Cohort Studies , Gastrointestinal Stromal Tumors/pathology , Humans , Imatinib Mesylate , Liver/drug effects , Liver/pathology , Liver Neoplasms/secondary , Observer Variation , Outcome Assessment, Health Care/methods , Time Factors , Tomography, X-Ray Computed , Tumor Burden/drug effectsABSTRACT
BACKGROUND: Assessment of tumor size changes is crucial in clinical trials and patient care. We compared imatinib-induced volume changes of liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST and Choi criteria and their association with overall survival (OS). METHODS: LM from 84 GIST patients (training and validation set) were evaluated using manual and semi-automated Computed Tomography measurements at baseline, after 3, 6 and 12 months of imatinib. The ability of uni-dimensional (1D) and three-dimensional (3D) measurements to detect size changes (increase/decrease) ≥20% was evaluated. Volumetric response cut-offs were derived from minimally relevant changes (+20/-30%) by RECIST, considering lesions as spherical or ellipsoidal. RESULTS: 3D measurements detected size changes ≥20% more frequently than 1D at every time-point (P≤0.008). 3D and Choi criteria registered more responses than RECIST at 3 and 6 months for 3D-spheres (P≤0.03) and at all time-points for 3D-ellipsoids and Choi criteria (P<0.001). Progressive disease by 3D criteria seems to better correlate to OS at late time-points than other criteria. CONCLUSION: Volume criteria (especially ellipsoids) classify a higher number of patients as imatinib-responders than RECIST. Volume discriminates size changes better than diameter in GIST and constitutes a feasible and robust method to evaluate response and predict patient benefit.
