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Background and Purpose: MRI, applying dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) sequences, and 18F-fluorodeoxyglucose (18F-FDG) PET/CT provide information about tumor aggressiveness that is unexploited in treatment of locally advanced cervical cancer (LACC). We investigated the potential of a multimodal combination of imaging parameters for classifying patients according to their risk of recurrence., Materials and Methods: Eighty-two LACC patients with diagnostic MRI and FDG-PET/CT, treated with chemoradiotherapy, were collected. Thirty-eight patients with MRI only were included for validation of MRI results. Endpoints were survival (disease-free, cancer-specific, overall) and tumor control (local, locoregional, distant). K trans , reflecting vascular function, apparent diffusion coefficient (ADC), reflecting cellularity, and standardized uptake value (SUV), reflecting glucose uptake, were extracted from DCE-MR, DW-MR and FDG-PET images, respectively. By applying an oxygen consumption and supply-based method, ADC and K trans parametric maps were voxel-wise combined into hypoxia images that were used to determine hypoxic fraction (HF)., Results: HF showed a stronger association with outcome than the single modality parameters. This association was confirmed in the validation cohort. Low HF identified low-risk patients with 95% precision. Based on the 50th SUV-percentile (SUV 50 ), patients with high HF were divided into an intermediate- and high-risk group with high and low SUV 50 , respectively. This defined a multimodality biomarker, HF/SUV 50 . HF/SUV 50 increased the precision of detecting high-risk patients from 41% (HF alone) to 57% and showed prognostic significance in multivariable analysis for all endpoints., Conclusion: Multimodal combination of MR- and FDG-PET/CT-images improves classification of LACC patients compared to single modality images and clinical factors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: Several investigators have indicated that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to provide biomarkers for personalized treatment of cervical carcinoma. However, some clinical studies have suggested that treatment failure is associated with low tumor signal enhancement, whereas others have reported associations between high signal enhancement and poor outcome. The purpose of this investigation was to clear up these conflicting reports and to provide a method for identifying biomarkers that easily can be implemented in routine DCE-MRI diagnostics., Methods: The study involved 85 patients (FIGO stage IB through IVA) treated with concurrent chemoradiotherapy. Low-enhancing tumor volume (LETV) and low-enhancing tumor fraction (LETF), defined as the volume and fractional volume of low-enhancing voxels, respectively, were calculated from signal intensities recorded within 1 min after contrast administration by using two methods reported to give conflicting conclusions., Results: Multivariate analysis involving tumor volume, lymph node status, FIGO stage, and LETV or LETF revealed that LETV and LETF provided independent prognostic information on treatment outcome, independent of the method of calculation., Conclusion: Low signal enhancement is associated with poor prognosis in cervical carcinoma, and biomarkers predicting poor outcome can be provided by short-term DCE-MRI without advanced image analysis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: High tumor interstitial fluid pressure (IFP) is associated with poor outcome in locally advanced carcinoma of the uterine cervix. We have recently developed a noninvasive assay of the IFP of tumors, and in this assay, the outward interstitial fluid flow velocity at the tumor surface (v0) is measured by Gd-DTPA-based DCE-MRI and used as a parameter for IFP. Here, we investigated the independent prognostic significance of v0 in cervical cancer patients given cisplatin-based concurrent chemoradiotherapy with curative intent., Patients: The study involved 62 evaluable patients from a cohort of 74 consecutive patients (Stage IB through IIIB) with a median follow-up of 5.5 years., Results: The actuarial disease-free survival (DFS) and overall survival (OS) at 5 years were 67% and 76%, respectively. Significant associations were found between v0 dichotomized about the median value and DFS and OS, both in the total patient cohort and a subcohort of 40 Stage IIB patients. Multivariate analysis involving stage, tumor volume, lymph node status, and v0 revealed that only v0 provided independent prognostic information about DFS and OS., Conclusion: This investigation demonstrates a strong, independent prognostic impact of the pretreatment peritumoral fluid flow velocity in cervical cancer., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: Determine prevalence of diabetes, and describe use of blood glucose lowering (BGL) drugs and glycemic control in Norwegian nursing homes., Methods: In this cross-sectional study we collected details of BGL drugs, capillary blood glucose measurements (CBGM) in the last four weeks and HbA1c measurements in the last 12 months from the medical records of patients with diabetes, within a population of 742 long-term care patients from 19 randomly selected nursing homes in Western Norway. Descriptive statistics were applied, and Pearson's chi-squared (P≤0.05) or non-overlapping 95% confidence intervals were interpreted as significant effects., Results: 116 patients (16%) had diabetes, 100 of these gave informed consent and medical data were available. BGL treatment was as follows: (1) insulin only (32%), (2) insulin and oral antidiabetics (OADs) (15%), (3) OADs only (27%) and (4) no drugs (26%). Patients with cognitive impairment were less likely to receive medical treatment (P=0.04). CBGM and HbA1c measurements were performed for 73% and 77% of patients, respectively. Mean HbA1c was 7.3% (57 mmol/mol), 46% of patients had an HbA1c <7.0% (53 mmol/mol), and CBGM consistent with risk of hypoglycemia was found for 60% of these patients., Conclusions: Prevalence of diabetes and BGL treatment in Norwegian nursing homes is comparable to other European countries. Although special care seems to be taken when choosing treatment for patients with cognitive impairment, there are signs of overtreatment in the population as a whole. The strict glycemic control unveiled may negatively affect these frail patients' quality of life and increase the risk of early death., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Purpose: To assess the prognostic value of pharmacokinetic parameters derived from pre-chemoradiotherapy dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of cervical cancer patients., Materials and Methods: Seventy-eight patients with locally advanced cervical cancer underwent DCE-MRI with Gd-DTPA before chemoradiotherapy. The pharmacokinetic Brix and Tofts models were fitted to contrast enhancement curves in all tumor voxels, providing histograms of several pharmacokinetic parameters (Brix: A(Brix), k(ep), k(el), Tofts: K(trans), ν(e)). A percentile screening approach including log-rank survival tests was undertaken to identify the clinically most relevant part of the intratumoral parameter distribution. Clinical endpoints were progression-free survival (PFS) and locoregional control (LRC). Multivariate analysis including FIGO stage and tumor volume was used to assess the prognostic significance of the imaging parameters., Results: A(Brix), k(el), and K(trans) were significantly (P<0.05) positively associated with both clinical LRC and PFS, while ν(e) was significantly positively correlated with PFS only. k(ep) showed no association with any endpoint. A(Brix) was positively correlated with K(trans) and ν(e), and showed the strongest association with endpoint in the log-rank testing. k(el) and K(trans) were independent prognostic factors in multivariate analysis with LRC as endpoint., Conclusions: Parameters estimated by pharmacokinetic analysis of DCE-MR images obtained prior to chemoradiotherapy may be used for identifying patients at risk of treatment failure., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We have applied the sensitive and specific in situ proximity ligation assay (PLA) to characterize Tyr1068 phosphorylation of the epidermal growth factor receptor (EGFR) in cervical cancer in relation to the protein level and gene dosage., Materials and Methods: Pretreatment tumor biopsies from 178 patients were analyzed. EGFR protein level was determined by immunohistochemistry, and Tyr1068 phosphorylation was detected with PLA in 97 EGFR positive tumors. EGFR gene dosage was derived from array comparative genomic hybridization of 86 cases., Results: EGFR was expressed in most tumors, whereas phosphorylation was seen in about half of the EGFR positive ones. A correlation was found between the expression of EGFR and phosphorylated EGFR (p=0.016, membrane; p=0.012, cytoplasm). However, tumor regions with high protein level without phosphorylation were occasionally seen and the percentage of EGFR positive cells was higher than the phosphorylated percentage (p<0.001). Moreover, an increase in the phosphorylation in both the membrane (p=0.014) and cytoplasm (p=0.002) was seen in 11 tumors with gain of EGFR. The protein level was not correlated with gene dosage., Conclusion: In contrast to gain of the EGFR chromosomal region, high EGFR protein level may not necessarily indicate Tyr1068 phosphorylation and thereby receptor activation in cervical cancer., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)