Biochemical control in intermediate- and high-risk prostate cancer after EBRT with and without brachytherapy boost.

PURPOSE: External beam radiotherapy (EBRT) with or without brachytherapy boost (BTB) has not been compared in prospective studies using guideline-recommended radiation dose and recommended androgen-deprivation therapy (ADT). In this multicenter retrospective analysis, we compared modern-day EBRT with BTB in terms of biochemical control (BC) for intermediate-risk (IR) and high-risk (HR) prostate cancer. METHODS: Patients were treated for primary IR or HR prostate cancer during 1999-2019 at three high-volume centers. Inclusion criteria were prescribed ≥ 76 Gy EQD2 (α/ß = 1.5 Gy) for IR and ≥ 78 Gy EQD2 (α/ß = 1.5 Gy) for HR as EBRT alone or with BTB. All HR patients received ADT and pelvic irradiation, which were optional in IR cases. BC between therapies was compared in survival analyses. RESULTS: Of 2769 initial patients, 1176 met inclusion criteria: 468 HR (260 EBRT, 208 BTB) and 708 IR (539 EBRT, 169 BTB). Median follow-up was 49 and 51 months for HR and IR, respectively. BTB patients with ≥ 113 Gy EQD2Gy experienced a stable, good BC outcome compared with BTB at lower doses. Patients treated with ≥ 113 Gy EQD2Gy also experienced significantly improved BC compared with EBRT (10-year BC failure rates after ≥ 113 Gy BTB and EBRT: respectively 20.4 and 41.8% for HR and 7.5 and 20.8% for IR). CONCLUSIONS: In patients with IR and HR prostate cancer, BTB with ≥ 113 Gy EQD2Gy offered a BC advantage compared with dose-escalated EBRT and lower BTB doses.

Determinants of the level of circulating-tumor HPV16 DNA in patients with HPV-associated oropharyngeal cancer at the time of diagnosis.

Circulating tumor HPV DNA (ctHPV16) assessed in liquid biopsy may be used as a marker of cancer in patients with HPV-associated oropharyngeal cancer (HPV + OPC). Factors influencing the initial ctHPV16 quantity are not well recognized. In this study we aimed to establish what factors are related to the level of ctHPV16 at the time of diagnosis. 51 patients (37 men and 14 women, median age of 57 years old) with HPV + OPC prior to definitive treatment were included. ctHPV16 was measured by qPCR. Tumor and nodal staging were assessed according to AJCC8. Blood derived factors included squamous cell carcinoma antigen (SCC-Ag), serum soluble fragment of cytokeratin 19 (CYFRA 21-1), C-reactive protein (CRP), albumin level (Alb), neutrophils (Neut), thrombocytes (Plt) and lymphocyte (Lym) count, Neut/Lym ratio were assessed. The volumes of the primary tumor (TV) and involved lymph nodes (NV) were calculated using MRI, CT or PET-CT scans. Data were analysed using parametric and nonparametric methods. Variables for multivariable linear regression analysis were chosen based on the results from univariable analysis (correlation, univariable regression and difference). There were 9 (18%), 10 (19%) and 32 (63%) patients who had TV and NV assessed in MRI, CT or PET respectively. Primary tumor neither as T-stage nor TV was related to ctHPV16 level. Significant differences in the ctHPV16 between patients with high vs low pain (P = 0.038), NV (P = 0.023), TV + NV (P = 0.018), CYFRA 21-1 (P = 0.002), CRP (P = 0.019), and N1 vs N3 (P = 0.044) were observed. ctHPV16 was significantly associated with CYFRA 21-1 (P = 0.017), N stage (P = 0.005), NV (P = 0.009), TV + NV (P = 0.002), CRP (P = 0.019), and pain (P = 0.038). In univariable linear regression analysis the same variables predicted ctHPV16 level. In multivariable analyses, CYFRA 21-1 and CRP (both as categorical variables) were predictors of ctHPV16 level even above NV. ctHPV16 at presentation is driven by tumor volume measured mostly by N. CYFRA 21-1 and CRP are additional factors related to ctHPV16 prior to the treatment.

Radiomic signature accurately predicts the risk of metastatic dissemination in late-stage non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and the median overall survival (OS) is approximately 2-3 years among patients with stage III disease. Furthermore, it is one of the deadliest types of cancer globally due to non-specific symptoms and the lack of a biomarker for early detection. The most important decision that clinicians need to make after a lung cancer diagnosis is the selection of a treatment schedule. This decision is based on, among others factors, the risk of developing metastasis. Methods: A cohort of 115 NSCLC patients treated using chemotherapy and radiotherapy (RT) with curative intent was retrospectively collated and included patients for whom positron emission tomography/computed tomography (PET/CT) images, acquired before RT, were available. The PET/CT images were used to compute radiomic features extracted from a region of interest (ROI), the primary tumor. Radiomic and clinical features were then classified to stratify the patients into short and long time to metastasis, and regression analysis was used to predict the risk of metastasis. Results: Classification based on binarized metastasis-free survival (MFS) was applied with moderate success. Indeed, an accuracy of 0.73 was obtained for the selection of features based on the Wilcoxon test and logistic regression model. However, the Cox regression model for metastasis risk prediction performed very well, with a concordance index (C-index) score equal to 0.84. Conclusions: It is possible to accurately predict the risk of metastasis in NSCLC patients based on radiomic features. The results demonstrate the potential use of features extracted from cancer imaging in predicting the risk of metastasis.

Percutaneous tibial nerve stimulation in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients: a historically controlled study.

Background: Percutaneous tibial nerve stimulation (PTNS) is widely used in the treatment of neurogenic detrusor overactivity (NDO) in multiple sclerosis (MS); however, controlled studies are still lacking.Objective:: To assess effectiveness of PTNS in MS patients with NDO unresponsive to pharmacological and behavioural therapies. Methods: MS patients with NDO were enrolled. Inclusion criteria were NDO not responding to pharmacological and behavioural therapies. Exclusion criteria were the presence of relevant comorbidities and urinary tract infections. Patients were evaluated using 3-day bladder diaries and validated questionnaires at baseline, after 4 weeks of educational therapy and after 12 PTNS sessions. The primary outcome measure was the percentage of patients considered responders after the behavioural therapy and after the PTNS in a historical controlled fashion (definition of 'responder' was reduction ⩾50% of urgency episodes). Results: A total of 33 patients (26 women, 7 men) were enrolled. Two patients dropped out for reasons not related to the protocol. Two out of 31 patients (6.5%) and 21/29 (72.4%) were considered responders at visits 1 and 2, respectively. In PTNS responders, a statistically significant improvement in both bladder diary results and standardized questionnaire scores was recorded, compared with that obtained with behavioural therapy alone. No serious adverse events were reported. Conclusion: This historically controlled study suggests that PTNS may be effective in improving NDO in MS patients.

The Relationship between Histological Composition and Metabolic Profile in Breast Tumors and Peritumoral Tissue Determined with 1H HR-MAS NMR Spectroscopy.

Breast tumors constitute the complex entities composed of cancer cells and stromal components. The compositional heterogeneity should be taken into account in bulk tissue metabolomics studies. The aim of this work was to find the relation between the histological content and 1H HR-MAS (high-resolution magic angle spinning nuclear magnetic resonance) metabolic profiles of the tissue samples excised from the breast tumors and the peritumoral areas in 39 patients diagnosed with invasive breast carcinoma. The total number of the histologically verified specimens was 140. The classification accuracy of the OPLS-DA (Orthogonal Partial Least Squares Discriminant Analysis) model differentiating the cancerous from non-involved samples was 87% (sensitivity of 72.2%, specificity of 92.3%). The metabolic contents of the epithelial and stromal compartments were determined from a linear regression analysis of the levels of the evaluated compounds against the cancer cell fraction in 39 samples composed mainly of cancer cells and intratumoral fibrosis. The correlation coefficients between the levels of several metabolites and a tumor purity were found to be dependent on the tumor grade (I vs II/III). The comparison of the levels of the metabolites in the intratumoral fibrosis (obtained from the extrapolation of the regression lines to 0% cancer content) to those levels in the fibrous connective tissue beyond the tumors revealed a profound metabolic reprogramming in the former tissue. The joint analysis of the metabolic profiles of the stromal and epithelial compartments in the breast tumors contributes to the increased understanding of breast cancer biology.

Functional substitutions of amino acids that differ between GDF11 and GDF8 impact skeletal development and skeletal muscle.

Growth differentiation factor 11 (GDF11) and GDF8 (MSTN) are closely related TGF-ß family proteins that interact with nearly identical signaling receptors and antagonists. However, GDF11 appears to activate SMAD2/3 more potently than GDF8 in vitro and in vivo. The ligands possess divergent structural properties, whereby substituting unique GDF11 amino acids into GDF8 enhanced the activity of the resulting chimeric GDF8. We investigated potentially distinct endogenous activities of GDF11 and GDF8 in vivo by genetically modifying their mature signaling domains. Full recoding of GDF8 to that of GDF11 yielded mice lacking GDF8, with GDF11 levels ∼50-fold higher than normal, and exhibiting modestly decreased muscle mass, with no apparent negative impacts on health or survival. Substitution of two specific amino acids in the fingertip region of GDF11 with the corresponding GDF8 residues resulted in prenatal axial skeletal transformations, consistent with Gdf11-deficient mice, without apparent perturbation of skeletal or cardiac muscle development or homeostasis. These experiments uncover distinctive features between the GDF11 and GDF8 mature domains in vivo and identify a specific requirement for GDF11 in early-stage skeletal development.

Manual Physiotherapy Combined with Pelvic Floor Training in Women Suffering from Stress Urinary Incontinence and Chronic Nonspecific Low Back Pain: A Preliminary Study.

Stress urinary incontinence (SUI) represents one of the most common subtypes of urinary incontinence (UI) reported by women. Studies have shown an association of SUI with nonspecific low back pain (NSLBP). The primary aim of the present study was to explore the long-term effects of a combined treatment of manual techniques and pelvic floor muscle (PFM) training in women suffering from SUI associated with NSLBP. The secondary aim was to evaluate which manual approach combined with PFM rehabilitation is more effective in improving symptoms related to SUI and in reducing pain perception related to NSLBP. Twenty-six patients suffering from SUI associated with chronic NSLBP were randomly assigned to one of two groups: the postural rehabilitation group (PRg) or the spinal mobilization group (SMg). Both groups performed a manual approach combined with PFM rehabilitation. All patients were evaluated before the treatment (T0), after 10 sessions (T1) and after 30 days from the end of the treatment (T2). The results showed an improvement in both groups in all of the investigated outcomes. Combining manual therapy and PFM training within the same therapy session may be useful for improving both SUI and NSLBP and increasing the quality of life of women suffering from SUI associated with NSLBP.

Efficiency of 124I radioisotope production from natural and enriched tellurium dioxide using 124Te(p,xn)124I reaction.

BACKGROUND: 124I Iodine (T[Formula: see text] = 4.18 d) is the only long-life positron emitter radioisotope of iodine that may be used for both imaging and therapy as well as for 131I dosimetry. Its physical characteristics permits taking advantages of the higher Positron Emission Tomography (PET) image quality, whereas the availability of new molecules to be targeted with 124I makes it a novel innovative radiotracer probe for a specific molecular targeting. RESULTS: In this study Monte Carlo and SRIM/TRIM modelling was applied to predict the nuclear parameters of the 124I production process in a small medical cyclotron IBA 18/9 Cyclone. The simulation production yields for 124I and the polluting radioisotopes were  calculated for the natural and enriched 124TeO2  +  Al2O3  solid targets irradiated with 14.8 MeV protons. The proton beam was degraded energetically from 18 MeV with 0.2 mm Havar foil. The 124Te(p,xn)124I reactions were taken into account in the simulations. The optimal thickness of the target material was calculated using the SRIM/TRIM and Geant4 codes. The results of the simulations were compared with the experimental data obtained for the natural TeO2 +Al2O3 target. The dry distillation technique of the 124-iodine was applied. CONCLUSIONS: The experimental efficiency for the natural Te target was better than 41% with an average thick target (>0.8 mm) yield of 1.32 MBq/µAh. Joining the Monte Carlo and experimental approaches makes it possible to optimize the methodology for the 124I production from the expensive Te enriched targets.

The application of 18F-FDG-PET/CT in gastric cancerstaging and factors affecting its sensitivity.

OBJECTIVE: To evaluate the accuracy offluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), to correctly determine initial tumor stage in treatment-naive gastric cancer patients and to analyze the factors influencing the risk of false negative results. SUBJECTS AND METHODS: The baseline 18F-FDG PET/CT scans of 111 previously untreated gastric cancer patients were retrospectively assessed. Sensitivity, specificity, positive (PPV) and negative prediction value (NPV) were evaluated. An array of clinical, pathological and metabolic variables was analyzed to identify factors contributing to the risk of a false positive (FP) and false negative (FN) PET/CT result in detecting primary and metastatic tumor sites. RESULTS: The sensitivity, specificity, PPV and NPV of PET/CT to visualize distant metastases were 76.4%; 86.7%; 83% and 81.2%, respectively. In 13 (11.7%) patients the PET/CT exam was able to identify metastatic sites not recognized in radiographic staging, significantly altering the initially planned management. Of 64 PET/CT studies negative for distant metastases, 12 (18.75%) were clinically confirmed to be false negative. The risk of acquiring a FN result for primary tumor was 10.8% (12/111) and the overall risk of any FN readout for either primary and metastatic sites was 18.9% (21/111). The factors that contributed to increased probability of a FN result for primary tumor detection were early primary tumor stage T1-T2 (+16.2%; χ2=5.0, P=0.025), female sex (+10.1%; χ2=5.71, P=0.017) and neutrophil count below 4.2k/µL (9.7%; χ2=6.1, P=0.014). Patients with non-intestinal Lauren histologic type (+18.7%; χ2=8.9, P=0.003) or signet-ring/mucinous carcinoma (+9.6%; χ2=7.7, P=0.005) had increased probability of PET/CT being unable to identify their distant metastases. Women and patients with low neutrophil count featured borderline insignificantly increased percentage of non-intestinal tumor histology (P=0.07 and P=0.057, respectively). CONCLUSION: Fluorine-18-FDG PET/CT is a valuable diagnostic method in gastric cancer patients which significantly contributes to determining the TNM stage and thus helps choose correct patient management. Histology and primary tumor stage as well as patient cohorts in which these factors may vary should be considered when evaluating results to decrease a chance of a false negative readout.

Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma.

The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m2 for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided "boosts" represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.

Radiomics and artificial Intelligence for PET imaging analysis.

In recent years, processing of the imaging signal derived from CT, MR or positron emission has proven to be able to predict outcome parameters in cancer patients. The processing techniques of the signal constitute the discipline of radiomics. The quantitative analysis of medical images outperform the information that can be obtained through traditional visual analysis. The recognition of neoplasm molecular and genetic characteristics in a non-invasive way, based on routine radiological examinations, potentially allow complete tumor profiling and subsequent treatment customization at practically zero costs. This process is further boosted with the availability of increased computing power and development of artificial intelligence approaches.

Circulating HPV16 DNA may complement imaging assessment of early treatment efficacy in patients with HPV-positive oropharyngeal cancer.

BACKGROUND: Early detection of treatment failure may improve clinical outcome and overall survival in patients with head and neck cancer after first-line treatment. Circulating cell-free HPV16 DNA (cfHPV16 DNA) was evaluated as a possible complementary marker to radiological assessment of early response in patients with HPV-related oropharyngeal cancer (OPC) after radiotherapy alone or combined with chemotherapy. METHODS: The study included 66 patients with HPV-related OPC receiving radical radiotherapy alone or in combination with chemotherapy. cfHPV16 DNA was assessed in the blood of all patients before treatment using TaqMan-based qPCR. Subsequent analysis of cfHPV16 DNA was performed 12 weeks after treatment completion, along with radiological assessment of early treatment results. RESULTS: Complete (CRR) and incomplete radiological response (IRR) was found in 43 (65%) and 23 (35%) patients respectively. cfHPV16 DNA was present in 5 (28%) patients with IRR, while only in 1 (4%) with CRR. Three of five patients with IRR that were positive for cfHPV16 DNA exhibited histopathologically confirmed local or regional treatment failure, and other two developed distant metastases. None of the patients with negative cfHPV16 DNA presented disease failure. CONCLUSION: The post-treatment assessment of cfHPV16 DNA in patients with HPV-related OPC may be used as a complementary biomarker to conventional imaging-based examinations for early identification of treatment failure.

The Prognostic Value of Pretreatment Gallium-68 DOTATATE Positron Emission Tomography/Computed Tomography in Irradiated Non-benign Meningioma.

PURPOSE OF THE STUDY: The purpose of this study was to evaluate the potential value of gallium-68 (Ga-68)-DOTATATE positron emission tomography/computed tomography (PET/CT) in predicting the risk of progression in nonbenign meningioma after definite irradiation. We retrospectively reviewed our patients with meningiomas who had the highest risk of progression: WHO histological Grade II and III tumors and with macroscopic disease as identified in Ga-68-DOTATATE PET/CT. MATERIALS AND METHODS: Thirteen patients were included in this study. For each tumor, the following quantifiers were measured: maximum and mean standardized uptake volume (SUV), standard deviation, metabolic tumor volume (MTV), total lesion activity, and coefficient of variation. Each of the quantifiers except for maximum SUV was obtained with three different SUV thresholds: muscle based (ms), liver based (liv), and gradient based (gb). The quantifiers were analyzed in univariate Cox model for their prognostic value for progression-free survival (PFS) and overall survival (OS). RESULTS: Mean follow-up of the patients was 28.2 months. The 2-year PFS and OS was 28.1% and 76.9%, respectively. The MTVgb was a significant predictor for PFS (risk of progression of disease above vs. below the 34 cm3 threshold: 100% vs. 28.3%, P = 0.0003). Clinically, the male sex also influenced PFS (Hazard ratio =13.06; 95% confidence interval: 1.56-109.25; P = 0.018). The mean SUVms(P = 0.041) and SUVgb(P = 0.048) had a prognostic value for predicting the risk of death. CONCLUSION: Ga-68-DOTATATE PET/CT has potential to predict disease progression in nonbenign meningioma patients. Further prospective studies for validating and standardizing these findings are indicated.

Optimisation of [11C]-choline synthesis.

The importance of [11C]-choline as a PET/CT marker has been extensively described, although its production presents considerable technical difficulties. The main ones are short half-lives and the occurrence of dimethylformamide (DMF) as a residual solvent. While the losses resulting from the radionuclide decay can be minimised by shortening the duration of the process, the best solution for reducing the content of DMF is its elimination from the reaction environment. In the current work two methods are compared for [11C]-choline synthesis - a green chemistry approach (with ethanol as a green solvent) and a dry synthesis. The results were compared with each other and with those of the method based on DMF. The solid phase synthesis proved to be the most effective in total elimination of DMF, its final release was the highest, and the synthesis time was the shortest. The optimised synthesis led to the formation of the desired radiotracer with a high radiochemical yield (65% ±3%) in a short production time (12 min) and the residual precursor in the final product at the level of 1 µg/ml. 27% increase of the saturation yield was possible, which resulted in 9 GBq higher activity from 40 minutes of beaming. Each test batch passed all standard quality control requirements, and the levels of residual DMEA were below the limits that have been published in the last Pharmacopoeia monograph.

18-Fluorodeoxy-Glucose Positron Emission Tomography- Computed Tomography (18-FDG-PET/CT) for Gross Tumor Volume (GTV) Delineation in Gastric Cancer Radiotherapy

Purpose: Evaluation of the 18-fluorodeoxy-glucose positron emission tomography-computed tomography (18-FDGPET/ CT) for gross tumor volume (GTV) delineation in gastric cancer patients undergoing radiotherapy. Methods: In this study, 29 gastric cancer patients (17 unresectable and 7 inoperable) were initially enrolled for radical chemoradiotherapy (45Gy/25 fractions + chemotherapy based on 5 fluorouracil) or radiotherapy alone (45Gy/25 fractions) with planning based on the 18-FDG-PET/CT images. Five patients were excluded due to excess blood glucose levels (1), false-negative positron emission tomography (1) and distant metastases revealed by 18-FDG-PET/CT (3). The analysis involved measurement of metabolic tumor volumes (MTVs) performed on PET/CT workstations. Different threshold levels of the standardized uptake value (SUV) and liver uptake were set to obtain MTVs. Secondly, GTVPET values were derived manually using the positron emission tomography (PET) dataset blinded to the computed tomography (CT) data. Subsequently, GTVCT values were delineated using a radiotherapy planning system based on the CT scans blinded to the PET data. The referenced GTVCT values were correlated with the GTVPET and were compared with a conformality index (CI). Results: The mean CI was 0.52 (range, 0.12-0.85). In 13/24 patients (54%), the GTVPET was larger than GTVCT, and in the remainder, GTVPET was smaller. Moreover, the cranio-caudal diameter of GTVPET in 16 cases (64%) was larger than that of GTVCT, smaller in 7 cases (29%), and unchanged in one case. Manual PET delineation (GTVPET) achieved the best correlation with GTVCT (Pearson correlation = 0.76, p <0.0001). Among the analyzed MTVs, a statistically significant correlation with GTVCT was revealed for MTV10%SUVmax (r = 0.63; p = 0.0014), MTVliv (r = 0.60; p = 0.0021), MTVSUV2.5 (r = 0.54; p = 0.0063); MTV20%SUVmax (r = 0.44; p = 0.0344); MTV30%SUVmax (r = 0.44; p = 0.0373). Conclusion: 18-FDG-PET/CT in gastric cancer radiotherapy planning may affect the GTV delineation.

Effects of obesity on IL-33/ST2 system in heart, adipose tissue and liver: study in the experimental model of Zucker rats.

Suppression of tumorigenicity 2 (ST2) mediates the effect of Interleukin-33 (IL-33). Few data are reported on the relationship between IL-33/ST2 and obesity. We aimed to investigate effects of obesity on IL-33/ST2 system in heart, adipose tissue and liver in a rodent model of obesity. The relationship of cardiac expression of IL-33/ST2 system with natriuretic peptides (NPs) system and inflammatory mediators was also studied. mRNA expression of IL-33/ST2 system was evaluated in cardiac, adipose and hepatic biopsies from obese Zucker rats (O) and controls (CO). Expression levels of sST2 was significantly lower in O rats compared with CO (p<0.05) in all tissues. Besides, the mRNA levels of IL-33 decreased significant in fat of O respect to CO, while, expression levels of ST2L was significantly higher in liver of CO than in O. A strong relationship of IL-33/ST2 with NPs and classical inflammatory mediators was observed in cardiac tissue. Expression of sST2 in cardiac, adipose and liver tissue decreased in O compared with controls, suggesting an involvement for IL-33/ST2 system in molecular mechanisms of obesity. The strong relationships with NP systems and inflammatory mediators could suggest an involvement for IL-33/ST2 in molecular pathways leading to cardiac dysfunction and inflammation associated with obesity.

Prognostic value and clinical correlations of 18-fluorodeoxyglucose metabolism quantifiers in gastric cancer.

AIM: To investigate the correlations of pre-treatment positron emission tomography-computer tomography (PET-CT) metabolic quantifiers with clinical data of unstratified gastric cancer (GC) patients. METHODS: Forty PET-CT scans utilising 18-fluorodeoxyglucose in patients who received no prior treatment were analysed. Analysis involved measurements of maximum and mean standardised uptake volumes (SUV), coefficient of variation (COV), metabolic tumour volumes and total lesion glycolysis of different thresholds above which the tumor volumes were identified. The threshold values were: SUV absolute value of 2.5, 30% of SUVmax, 40% of SUVmax, and liver uptake-based (marked 2.5, 30, 40 and liv, respectively). Clinical variables such as age, sex, clinical stage, performance index, weight loss, tumor histological type and grade, and CEA and CA19.9 levels were included in survival analysis. Patients received various treatment modalities appropriate to their disease stage and the outcome was defined by time to metastasis (TTM) and overall survival (OS). Clinical and metabolic parameters were evaluated by analysis of variance, receiver operating characteristics, univariate Kaplan-Meier, and multivariate Cox models. P < 0.05 was considered statistically significant. RESULTS: Significant differences were observed between initially disseminated and non-disseminated patients in mean SUV (6.05 vs 4.13, P = 0.008), TLG2.5 (802 cm(3) vs 226 cm(3); P = 0.031), and TLG30 (436 cm(3) vs 247 cm(3), P = 0.018). Higher COV was associated with poor tumour differentiation (0.47 for G3 vs 0.28 for G1 and G2; P = 0.03). MTV2.5 was positively correlated to patient weight loss (< 5%, 5%-10% and > 10%: 40.4 cm(3) vs 123.6 cm(3) vs 181.8 cm(3), respectively, P = 0.003). In multivariate Cox analysis, TLG30 was prognostic for OS (HR = 1.001, 95%CI: 1.0009-1.0017; P = 0.047) for the whole group of patients. In the same model yet only including patients without initial disease dissemination TLG30 (HR = 1.009, 95%CI: 1.003-1.014; P = 0.004) and MTV2.5 (HR = 1.02, 95%CI: 1.002-1.036; P = 0.025) were prognostic for OS; for TTM TLG30 was the only significant prognostic variable (HR = 1.006, 95%CI: 1.001-1.012; P = 0.02). CONCLUSION: PET-CT in GC may represent a valuable diagnostic and prognostic tool that requires further evaluation in highly standardised environments such as randomised clinical trials.

The role of positron emission tomography in mediastinal staging of patients with non-small cell lung cancer.

OBJECTIVE: To examine the diagnostic accuracy of positron emission tomography/computed tomography in evaluating the mediastinum of patients with non-small cell lung cancer compared to histopathology results. METHODS: The prospective study was conducted at the Department of Thoracic Surgery of the Pulmonary Hospital in Zakopane, Poland, from September 2008 to August 2012 and comprised patients with radiologically-suspected lung cancer. All patients underwent histological verification by either mediastinoscopy alone or thoracotomy with mediastinal lymphanedectomy. Computed tomography and positron emission tomography/computed tomography data sets were compared with the results of the histopathology examinations. RESULTS: There were 80 patients in the study. In the diagnosis of mediastinal lymph nodes, computed tomography was able to detect 9(11.25%) true-positive, 17(21.25%) false-positive, 40(50%) true-negative and 14(17.5%) false-negative cases. The sensitivity, specificity and accuracy of the method were found to be 39%, 70% and 61% respectively, while the positive and negative predictive values were 35% and 74%. Positron emission tomography/computed tomography yielded 15(18.75%) true-positive, 12(15%) false-positive, 46(57.5%) true-negative and 7(8.75%) false-negative cases. Sensitivity was 68% while specificity was 79%. The accuracy was 96%, and the positive and negative predictive values were 55% and 87% respectively. CONCLUSION: Positron emission tomography/computed tomography had higher diagnostic accuracy than computed tomography in assessing mediastinal lymph nodes of patients with non-small cell lung cancer. However, a positive test requires histopathology confirmation.

The Use of 68Ga-DOTA-(Tyr3)-Octreotate PET/CT for Improved Target Definition in Radiotherapy Treatment Planning of Meningiomas - A Case Report.

Due to somatostatin receptor expression in meningiomas, PET with somatostatin analogs appears to be useful in radiotherapy treatment planning. We report the case of a 63-year-old man diagnosed with meningioma of the left frontal lobe in 2011. He underwent total tumor excision (pathology was atypical meningioma WHO 2) and radiotherapy, but one year after the completion of treatment, he complained about diplopia and left upper eyelid ptosis. The MRI showed a new parasagittal lesion and the patient received stereotactic radiotherapy. Few weeks later, two new lesions were found - one in the sella turcica region and the other adjacent to the greater wing of the right sphenoid bone. The patient underwent transsphenoidal biopsy, but was not qualified for neurosurgery due to high risk of bleeding. In the radiotherapy treatment planning, we used a fusion of MRI and 68Ga-DOTA-(Tyr3)-octreotate PET/CT images. The patient received stereotactic radiotherapy, first to the parasellar lesion and then to the progressing tumor adjoining the sphenoid bone. In both cases, PET/CT scans helped to define the target, its volume being bigger on PET/CT than on MRI images. In patients with meningiomas, 68-Ga-DOTA-(Tyr3)-octreotate PET/CT can be considered as a useful imaging modality in radiotherapy treatment planning, which helps to visualize the tumor extension and to define the target.

Adenosine receptor transcriptomic profile in cardiac tissue of a Zucker rat model.

To evaluate the possible variations of adenosine receptor (AR) profile together with TNF-α and IL-6 mRNA in cardiac tissue of obese Zucker rats (OZR) during fasting conditions (fc) and during the induction of acute hyperglycemia (AH). OZR (O, n=21) and age-matched lean control rats (CO, n=18) were studied during fc (COfc, n=8; Ofc, n=13) and during the induction of AH (COAH, n=10; OAH, n=8). The histopathologic analysis performed on O and CO heart samples did not show abnormalities of myocardial structure. The AR transcriptomic profile was analyzed in O and CO by real-time polymerase chain reaction (PCR) and a significantly lower mRNA expression was observed for A2AR in O with respect to CO (p=0.047), while a significant upregulation was observed for A3R in O with respect to CO (p=0.002). No significant differences between O and CO were observed for TNF-α or IL-6. Correlations were found between glycemia and A1R (p=0.03) and A2BR (p=0.002); total cholesterol and A2BR (p=0.02) and A3R (p=0.0002), as well as between IL-6 and A1R (p=0.05) and TNF-α and A2AR (p<0.0001). The modulation of ARs in these settings could represent a promising approach to pharmacological treatment, which must be supported by diet restrictions and physical exercise.