Фінансовий контролінг як інструмент управління діяльністю суб'єкта господарювання

PURPOSE: Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. METHODS: A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. RESULTS: At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (−0.65, p = 0.014), hypoxic fraction (−0.60, p = 0.025) and TBR (−0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. CONCLUSION: The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00259-015-3169-4) contains supplementary material, which is available to authorized users

Neurocognition in adults with intracranial tumors:Does location really matter?

OBJECTIVE: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments. METHODS: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume). Potential effects of histological and molecular subtype and corresponding WHO grades on the risk of cognitive impairment were investigated using Chi square tests. P-values were adjusted for multiple comparisons (p < .001 and p < .05 for voxel- and cluster-level, resp.). RESULTS: A cohort of 179 intracranial tumor patients was included [aged 19-85 years, median age (SD) = 58.46 (14.62), 50% females]. In this cohort, test-specific impairment was detected in 20-30% of patients. Higher WHO grade was associated with lower processing speed, cognitive flexibility and delayed memory in gliomas, while no acute surgery-effects were found. No grading, nor surgery effects were found in meningiomas. The voxel-wise analyses showed that tumor locations in left temporal areas and right temporo-parietal areas were related to verbal memory and processing speed, respectively. INTERPRETATION: Patients with intracranial tumors affecting the left temporal areas and right temporo-parietal areas might specifically be vulnerable for lower verbal memory and processing speed. These specific patients at-risk might benefit from early-stage interventions. Furthermore, based on future validation studies, imaging-informed surgical and radiotherapy planning could further be improved

Imaging techniques for tumour delineation and heterogeneity quantification of lung cancer: overview of current possibilities

Imaging techniques for the characterization and delineation of primary lung tumours and lymph nodes are a prerequisite for adequate radiotherapy. Numerous imaging modalities have been proposed for this purpose, but only computed tomography (CT) and FDG-PET have been implemented in clinical routine. Hypoxia PET, dynamic contrast-enhanced CT (DCE-CT), dual energy CT (DECT) and (functional) magnetic resonance imaging (MRI) hold promise for the future. Besides information on the primary tumour, these techniques can be used for quantification of tissue heterogeneity and response. In the future, treatment strategies may be designed which are based on imaging techniques to optimize individual treatment

Long-lasting antitumor effects provided by radiotherapy combined with the immunocytokine L19-IL2

Recently, we have shown that radiotherapy (RT) combined with L19-IL2 can induce a long-lasting antitumor effect, dependent on ED-B expression and infiltration of cytotoxic T cells. These findings will be translated to a Phase I clinical study (NCT02086721) in patients with oligometastatic solid tumors. See this link for the animation: http://youtu.be/xHbwQuCTkRc

Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia - a simulation study

To investigate the effect of hypoxia tracer properties on positron emission tomography (PET) image quality for three tracers [18F]-fluoromisonidazole (FMISO), [18F]-fluoroazomycinarabinoside (FAZA) and [18F]-flortanidazole (HX4), using mathematical simulations based on microscopic tumor tissue sections.Oxygen distribution and tracer binding was mathematically simulated on immunohistochemically stained cross-sections of tumor xenografts. Tracer diffusion properties were determined based on available literature. Blood activity and clearance over a four-hour period post-injection (p.i.) were derived from clinical dynamic PET scans of patients suffering from head and neck or bronchial cancer. Simulations were performed both for average patient blood activities and for individual patients, and image contrast between normoxic and hypoxic tissue areas was determined over this four-hour period p.i.On average, HX4 showed a six-fold higher clearance than FMISO and an almost three-fold higher clearance than FAZA based on the clinical PET data. The absolute variation in clearance was significantly higher for HX4 than for FMISO (standard deviations of 5.75 *10-5 s-1 vs. 1.55 *10-5 s-1). The absolute tracer activity in these scans at four hours p.i. was highest for FMISO and lowest for HX4. Simulated contrast at four hours p.i. was highest for HX4 (2.39), while FMISO and FAZA were comparable (1.67 and 1.75, respectively). Variations in contrast of 7-11% were observed for each tracer depending on the vascularization patterns of the chosen tissue. Higher variations in clearance for HX4 resulted in an increased inter-patient variance in simulated contrast at four hours p.i.In line with recent experimental and clinical data, the results suggest that HX4 is a promising new tracer that provides high image contrast four hours p.i., though inter-patient variance can be very high. Nevertheless, the widely used tracer FMISO provides a robust and reproducible signal four hours p.i., but with a lower contrast. The simulations revealed tracer clearance to be the key factor in determining image contrast

Imaging of tumour hypoxia and metabolism in patients with head and neck squamous cell carcinoma

Background. Tumour hypoxia and a high tumour metabolism increase radioresistance in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the correlation between hypoxia ([F-18]HX4 PET) and glucose metabolism ([F-18]FDG PET) molecular imaging.Material and methods. [F-18]HX4 and [F-18]FDG PET/CT images of 20 HNSCC patients were acquired prior to (chemo)radiotherapy, in an immobilisation mask, with a median time interval of seven days (NCT01347281). Gross tumour volumes of the primary lesions (GTV(prim)) and pathological lymph nodes (GTV(ln)) were included in the analysis. [F-18]FDG PET/CT images were rigidly registered to the [F-18]HX4 PET/CT images. The maximum and mean standardised uptake values (SUVmax, SUVmean) within both GTVs were determined. In addition, the overlap was compared between the [F-18]HX4 high volume ([F-18]HX4 HV) with a tumour-to-muscle ratio &gt; 1.4 and the [F-18]FDG high volume ([F-18]FDG HV) with an SUV &gt; 50% of the SUVmax. We report the mean standard deviation.Results. PET/CT scans including 20 GTV(prim) and 12 GTV(ln)were analysed. There was a significant correlation between several [F-18]FDG and [F-18]HX4 parameters, the most pronounced being the correlation between [F-18]FDG HV and [F-18]HX4 HV (R = 0.93, p &lt;0.001). The fraction of the GTV(prim) with a high HX4 uptake (9 +/- 10%) was on average smaller than the FDG high fraction (51 +/- 26%; p &lt;0.001). In 65% (13/20) of the patients, the GTV(prim) was hypoxic. In four of these patients the [F-18]HX4 HV was located within the [F-18]FDG HV, whereas for the remaining nine GTV(prim) a partial mismatch was observed. In these nine tumours 25 +/- 21% (range 5-64%) of the HX4 HV was located outside the FDG HV.Conclusions. There is a correlation between [F-18]HX4 and [F-18]FDG uptake parameters on a global tumour level. In the majority of lesions a partial mismatch between the [F-18]HX4 and [F-18]FDG high uptake volumes was observed, therefore [F-18]FDG PET imaging cannot be used as a surrogate for hypoxia. [F-18]HX4 PET provides complementary information to [F-18]FDG PET imaging

Prediction Models for Radiation-Induced Neurocognitive Decline in Adult Patients With Primary or Secondary Brain Tumors: A Systematic Review.

Although an increasing body of literature suggests a relationship between brain irradiation and deterioration of neurocognitive function, it remains as the standard therapeutic and prophylactic modality in patients with brain tumors. This review was aimed to abstract and evaluate the prediction models for radiation-induced neurocognitive decline in patients with primary or secondary brain tumors. MEDLINE was searched on October 31, 2021 for publications containing relevant truncation and MeSH terms related to "radiotherapy," "brain," "prediction model," and "neurocognitive impairments." Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool. Of 3,580 studies reviewed, 23 prediction models were identified. Age, tumor location, education level, baseline neurocognitive score, and radiation dose to the hippocampus were the most common predictors in the models. The Hopkins verbal learning ( = 7) and the trail making tests ( = 4) were the most frequent outcome assessment tools. All studies used regression ( = 14 linear, = 8 logistic, and = 4 Cox) as machine learning method. All models were judged to have a high risk of bias mainly due to issues in the analysis. Existing models have limited quality and are at high risk of bias. Following recommendations are outlined in this review to improve future models: developing cognitive assessment instruments taking into account the peculiar traits of the different brain tumors and radiation modalities; adherence to model development and validation guidelines; careful choice of candidate predictors according to the literature and domain expert consensus; and considering radiation dose to brain substructures as they can provide important information on specific neurocognitive impairments