Whole-body tumour burden on [18F]DCFPyL PET/CT in biochemical recurrence of prostate cancer: association with tumour biology and PSA kinetics.

PURPOSE: The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). MATERIAL AND METHODS: We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 12), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. RESULTS: Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. CONCLUSION: Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform.

Clinical impact and immunological alterations in asthmatic patients allergic to grass pollen subjected to high urban pollution in Madrid.

BACKGROUND: The prevalence of asthma has increased in recent decades. Among the reasons for this increase is environmental pollution. Pollutants cause bronchial inflammation and introduce modifications in the pollen, making it more allergenic. OBJECTIVE: Assess symptoms and medication requirements of asthmatic patients with grass allergies in Madrid (high urban pollution) and Ciudad Real (low pollution), and simultaneously evaluate the in vitro effects that pollen collected in both areas has on the immune cells of patients. METHODS: During two pollen seasons, patients from both cities were included. The patients recorded their symptoms and the asthma medication they took daily. In both cities, pollen data, pollutants and meteorological variables were evaluated. The response to different cell populations from patients in both areas were analysed after "in vitro" stimulation with pollen from both cities. RESULTS: The symptoms and medication use of the patients in Madrid was 29.94% higher. The NO2 concentration in Madrid was triple that of Ciudad Real (33.4 vs. 9.1 µg/m3 of air). All other pollutants had very similar concentrations during the study period. Pollen from the high pollution area caused a significant enhancement of T-CD8+ and NK cells proliferation compared with pollen of low pollution area, independently of the patient's origin. CONCLUSION: Asthmatic patients from Madrid have a worse clinical evolution than those from Ciudad Real because of higher levels of urban pollution, and this could be driven by the higher capacity of pollen of Madrid to activate T-CD8+ and NK cells.

SUVmax to tumor perimeter distance: a robust radiomics prognostic biomarker in resectable non-small cell lung cancer patients.

OBJECTIVE: The purpose of this study was to evaluate the prognostic value of novel geometric variables obtained from pre-treatment [18F]FDG PET/CT with respect to classical ones in patients with non-small cell lung cancer (NSCLC). METHODS: Retrospective study including stage I-III NSCLC patients with baseline [18F]FDG PET/CT. Clinical, histopathologic, and metabolic parameters were obtained. After tumor segmentation, SUV and volume-based variables, global texture, sphericity, and two novel parameters, normalized SUVpeak to centroid distance (nSCD) and normalized SUVmax to perimeter distance (nSPD), were obtained. Early recurrence (ER) and short-term mortality (STM) were used as end points. Univariate logistic regression and multivariate logistic regression with respect to ER and STM were performed. RESULTS: A cohort of 173 patients was selected. ER was detected in 49/104 of patients with recurrent disease. Additionally, 100 patients died and 53 had STM. Age, pathologic lymphovascular invasion, lymph nodal infiltration, TNM stage, nSCD, and nSPD were associated with ER, although only age (aOR = 1.06, p = 0.002), pathologic lymphovascular invasion (aOR = 3.40, p = 0.022), and nSPD (aOR = 0.02, p = 0.018) were significant independent predictors of ER in multivariate analysis. Age, lymph nodal infiltration, TNM stage, nSCD, and nSPD were predictors of STM. Age (aOR = 1.05, p = 0.006), lymph nodal infiltration (aOR = 2.72, p = 0.005), and nSPD (aOR = 0.03, p = 0.022) were significantly associated with STM in multivariate analysis. Coefficient of variation (COV) and SUVmean/SUVmax ratio did not show significant predictive value with respect to ER or STM. CONCLUSION: The geometric variables, nSCD and nSPD, are robust biomarkers of the poorest outcome prediction of patients with NSCLC with respect to classical PET variables. KEY POINTS: • In NSCLC patients, it is crucial to find prognostic parameters since TNM system alone cannot explain the variation in lung cancer survival. • Age, lymphovascular invasion, lymph nodal infiltration, and metabolic geometrical parameters were useful as prognostic parameters. • The displacement grade of the highest point of metabolic activity towards the periphery assessed by geometric variables obtained from [18F]FDG PET/CT was a robust biomarker of the poorest outcome prediction of patients with NSCLC.

Morphological MRI-based features provide pretreatment survival prediction in glioblastoma.

OBJECTIVES: We wished to determine whether tumor morphology descriptors obtained from pretreatment magnetic resonance images and clinical variables could predict survival for glioblastoma patients. METHODS: A cohort of 404 glioblastoma patients (311 discoveries and 93 validations) was used in the study. Pretreatment volumetric postcontrast T1-weighted magnetic resonance images were segmented to obtain the relevant morphological measures. Kaplan-Meier, Cox proportional hazards, correlations, and Harrell's concordance indexes (c-indexes) were used for the statistical analysis. RESULTS: A linear prognostic model based on the outstanding variables (age, contrast-enhanced (CE) rim width, and surface regularity) identified a group of patients with significantly better survival (p < 0.001, HR = 2.57) with high accuracy (discovery c-index = 0.74; validation c-index = 0.77). A similar model applied to totally resected patients was also able to predict survival (p < 0.001, HR = 3.43) with high predictive value (discovery c-index = 0.81; validation c-index = 0.92). Biopsied patients with better survival were well identified (p < 0.001, HR = 7.25) by a model including age and CE volume (c-index = 0.87). CONCLUSIONS: Simple linear models based on small sets of meaningful MRI-based pretreatment morphological features and age predicted survival of glioblastoma patients to a high degree of accuracy. The partition of the population using the extent of resection improved the prognostic value of those measures. KEY POINTS: • A combination of two MRI-based morphological features (CE rim width and surface regularity) and patients' age outperformed previous prognosis scores for glioblastoma. • Prognosis models for homogeneous surgical procedure groups led to even more accurate survival prediction based on Kaplan-Meier analysis and concordance indexes.

Correction to: Morphological MRI-based features provide pretreatment survival prediction in glioblastoma.

The original version of this article, published on 15 October 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The name of Mariano Amo-Salas and the affiliation of Ismael Herruzo were presented incorrectly.

18F-fluorodeoxyglucose positron emission tomography in the diagnosis of malignancy in patients with paraneoplastic neurological syndrome: a systematic review and meta-analysis.

PURPOSE: The detection of occult cancer in patients suspected of having a paraneoplastic neurological syndrome (PNS) poses a diagnostic challenge. The aim of our study was to perform a systematic review and meta-analysis to assess the diagnostic performance of FDG PET for the detection of occult malignant disease responsible for PNS. METHODS: A systematic review of the literature (MEDLINE, EMBASE, Cochrane, and DARE) was undertaken to identify studies published in any language. The search strategy was structured after addressing clinical questions regarding the validity or usefulness of the test, following the PICO framework. Inclusion criteria were studies involving patients with PNS in whom FDG PET was performed to detect malignancy, and which reported sufficient primary data to allow calculation of diagnostic accuracy parameters. When possible, a meta-analysis was performed to calculate the joint sensitivity, specificity, and detection rate for malignancy (with 95% confidence intervals [CIs]), as well as a subgroup analysis based on patient characteristics (antibodies, syndrome). RESULTS: The comprehensive literature search revealed 700 references. Sixteen studies met the inclusion criteria and were ultimately selected. Most of the studies were retrospective (12/16). For the quality assessment, the QUADAS-2 tool was applied to assess the risk of bias. Across 16 studies (793 patients), the joint sensitivity, specificity, and detection rate for malignancy with FDG PET were 0.87 (95% CI: 0.80-0.93), 0.86 (95% CI: 0.83-0.89), and 14.9% (95% CI: 11.5-18.7), respectively. The area under the curve (AUC) of the summary ROC curve was 0.917. Homogeneity of results was observed for sensitivity but not for specificity. Some of the individual studies showed large 95% CIs as a result of small sample size. CONCLUSIONS: The results of our meta-analysis reveal high diagnostic performance of FDG PET in the detection of malignancy responsible for PNS, not affected by the presence of onconeural antibodies or clinical characteristics.

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

BACKGROUND: The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. METHODS: A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. RESULTS: Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). CONCLUSION: Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. KEY POINTS: • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

The utility of hyperthermic intra-abdominal chemotherapy with gemcitabine for the inhibition of tumor progression in an experimental model of pancreatic peritoneal carcinomatosis, in relation to their behavior with pancreatic cancer stem cells CD133+ CXCR4.

OBJECTIVE: The origin of pancreatic cancer has been identified as a population of malignant pancreatic stem cells CD133+ CXCR4+ immunophenotype. These cells have high capacity for early locoregional invasion, being responsible for early recurrence and high mortality rates of pancreatic cancer. We propose a study for decreasing tumor progression of pancreatic cancer by reducing the volume and neoplastic subpopulation of pancreatic cancer stem cells CD133+ CXCR4+. Therefore, we develop a new therapeutic model, characterized by the application of HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with gemcitabine. DESIGN: Pancreatic tumor cell line: human cell line BxPC-3. The animal model involved 18 immunosuppressed rats 5 weeks weighing 150-200 gr. The implantation of 13 × 10(6) cells/mL was performed with homogeneous distribution in the 13 abdominopelvic quadrants according to the peritoneal carcinomatosis index (PCI) and were randomized into three treatment groups. Group I (4 rats) received intravenous saline. Group II (6 rats) received intravenous gemcitabine. Group III (8 rats) received HIPEC at 41 °C for 30 min with gemcitabine + gemcitabine IV. A histological study confirmed pancreatic cancer and immunohistochemical quantification of pancreatic cancer stem cells CD133+ CXCR4+ tumor cells. RESULTS: There was a population decline of pancreatic cancer stem cells CD133+ CXCR4+ in the HIPEC group with respect to the other two groups (p < 0.001). There was a decrease in PCI between treatment groups (p < 0.05). CONCLUSION: The initial results are encouraging since there is a declining population of cancer stem cells CD133+ CXCR4+ in the HIPEC group and decreased tumor volume compared to the other two treatment groups. All the conclusions are only valid for BxPC3 cell line, and the effects HIPEC on Kras-driven pancreatic tumors remain to be determined.

Intraperitoneal chemotherapy hyperthermia (HIPEC) for peritoneal carcinomatosis of ovarian cancer origin by fluid and CO2 recirculation using the closed abdomen technique (PRS-1.0 Combat): A clinical pilot study.

Background This paper reports a study of 21 patients with peritoneal carcinomatosis from ovarian cancer who underwent cytoreductive surgery and HIPEC by means of PRS-1.0 Combat®, a new model for closed abdomen HIPEC aimed at improving fluid distribution with assistance from a CO2 recirculation system. This new technology has been previously shown to be successful in an experimental study (pig model) performed by our group, and has been approved for use in our hospital. Methods Twenty-one patients with peritoneal carcinomatosis of ovarian cancer origin were included in the study. Cytoreductive surgery and HIPEC were performed by a closed abdomen fluid and CO2 recirculation technique using the PRS-1.0 Combat(®) model. We analysed the intraoperative safety tolerance and post-operative morbidity and mortality during the first 30 days. Results Between November 2011 and March 2014 21 patients with epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stage II-IV, were included in the study. During the procedure there were no significant haemodynamic or analytical disturbances. Complication rates were 38.1% and 57.14% for grade III/IV and minor (grade I/II) complications, respectively. Post-operative mortality was 4.76% (one patient). Complete cytoreductive surgery and intraperitoneal chemotherapy improved overall survival and disease-free survival in women with advanced ovarian cancer. The association of intra-abdominal hyperthermia with chemotherapy (HIPEC) increased the therapeutic benefit. Conclusions This study has shown that closed abdomen intraperitoneal chemohyperthermia by a fluid and CO2 recirculation system (PRS-1.0 Combat(®)) can be a safe and feasible model for the treatment of peritoneal carcinomatosis of ovarian cancer origin.

Basal ¹8F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer.

AIM: To explore the relationship between basal (18) F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). METHODS: This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent (18) F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. RESULTS: The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. CONCLUSION: PET imaging with (18) F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively.

Design of experiments for zeroth and first-order reaction rates.

This work presents optimum designs for reaction rates experiments. In these experiments, time at which observations are to be made and temperatures at which reactions are to be run need to be designed. Observations are performed along time under isothermal conditions. Each experiment needs a fixed temperature and so the reaction can be measured at the designed times. For these observations under isothermal conditions over the same reaction a correlation structure has been considered. D-optimum designs are the aim of our work for zeroth and first-order reaction rates. Temperatures for the isothermal experiments and observation times, to obtain the most accurate estimates of the unknown parameters, are provided in these designs. D-optimum designs for a single observation in each isothermal experiment or for several correlated observations have been obtained. Robustness of the optimum designs for ranges of the correlation parameter and comparisons of the information gathered by different designs are also shown.

Analytical performance validation of aPROMISE platform for prostate tumor burden, index and dominant tumor assessment with 18F-DCFPyL PET/CT. A pilot study.

To validate the performance of automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) in quantifying total prostate disease burden with 18F-DCFPyL PET/CT and to evaluate the interobserver and histopathologic concordance in the establishment of dominant and index tumor. Patients with a recent diagnosis of intermediate/high-risk prostate cancer underwent 18F-DCFPyL-PET/CT for staging purpose. In positive-18F-DCFPyL-PET/CT scans, automated prostate tumor segmentation was performed using aPROMISE software and compared to an in-house semiautomatic-manual guided segmentation procedure. SUV and volume related variables were obtained with two softwares. A blinded evaluation of dominant tumor (DT) and index tumor (IT) location was assessed by both groups of observers. In histopathological analysis, Gleason, International Society of Urological Pathology (ISUP) group, DT and IT location were obtained. We compared all the obtained variables by both software packages using intraclass correlation coefficient (ICC) and Cohen's kappa coefficient (k) for the concordance analysis. Fifty-four patients with a positive 18F-DCFPyL PET/CT were evaluated. The ICC for the SUVmax, SUVpeak, SUVmean, tumor volume (TV) and total lesion activity (TLA) was: 1, 0.833, 0.615, 0.494 and 0.950, respectively (p < 0.001 in all cases). For DT and IT detection, a high agreement was observed between both softwares (k = 0.733; p < 0.001 and k = 0.812; p < 0.001, respectively) although the concordances with histopathology were moderate (p < 0001). The analytical validation of aPROMISE showed a good performance for the SUVmax, TLA, DT and IT definition in comparison to our in-house method, although the concordance was moderate with histopathology for DT and IT.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA).

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Dual-Time-Point 18F-FDG PET/CT in Infective Endocarditis: Impact of Delayed Imaging in the Definitive Diagnosis of Endocarditis.

Infective endocarditis (IE) is a major public health condition due to the associated high morbidity and mortality. Our objective was to evaluate the utility of dual-time 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) imaging in the diagnosis of active IE in patients with suspected native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). For this purpose, a retrospective study was carried out, including patients suspicious of NVE or PVE who underwent a dual-time-point 18F-FDG PET/CT. A final diagnosis was established by the Endocarditis Team after patient follow-up using all the available findings. Sixty-nine patients were assessed. A final diagnosis of NVE was established in 3 patients of the 34 by 18F-FDG PET/CT and in the case of PVE was established in 20 patients of the 35. A statistically significant association was found when evaluating the association between PET diagnosis at early acquisition and final diagnosis of IE (χ2 = 30.198, p < 0.001) and PET diagnosis at delayed acquisition for final diagnosis of IE (χ2 = 9.412, p = 0.002). Delayed PET/CT imaging determined the IE diagnosis in 16/58 of the studies. In conclusion, delayed 18F-FDG PET/CT imaging seems to be useful in improving the definitive diagnosis of IE.

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects.

INTRODUCTION: Patients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies. Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. MATERIAL AND METHODS: Patients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy. Patients were reclassified in the following 6-18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels. The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. RESULTS: Sixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses. A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). CONCLUSIONS: In selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

Head-to-Head Comparison of [18F]F-choline and Imaging of Prostate-Specific Membrane Antigen, Using [18F]DCFPyL PET/CT, in Patients with Biochemical Recurrence of Prostate Cancer.

PURPOSE: To analyse diagnostic and therapeutic impact of molecular imaging TNM (miTNM) stage obtained with [18F]DCFPyL versus [18F]F-choline in head-to-head comparison in biochemical recurrence (BCR) of prostate cancer (PCa). MATERIAL AND METHODS: Patients with BCR of PCa after radical treatment with previous [18F]F-choline-PET/CT (negative or oligometastatic disease) were recruited to [18F]DCFPyL-PET/CT. Patients were classified according to: grade group, European Association of Urology classification, PSA, PSA doubling time (PSAdt) and PSA velocity (PSAvel). The overall detection rate (DR) and miTNM stage according to PROMISE criteria were assessed for both radiotracers and also correlated (Kappa). The influence of PSA and kinetics on both PET/CT (DR and miTNM) and predictive value of unfavourable kinetics on miTNM were determined. Cut-off PSA, PSAdt and PSAvel values able to predict PET/CT results were determined. Change in miTNM and treatment derived from [18F]DCFPyL information compared with [18F]F-choline were also evaluated. RESULTS: We studied 138 patients. [18F]DCFPyL showed a higher DR than [18F]F-choline (64.5% versus 33.3%) with a fair agreement. [18F]DCFPyL and [18F]F-choline detected T in 33.3% versus 19.6%, N in 27.5% versus 13.8%, and M in 30.4% versus 8.7%. Both tracers' DR showed significant associations with PSA and PSAvel. Significant association was only found between miTNM and PSA on [18F]F-choline-PET/CT (p = 0.033). For [18F]F-choline and [18F]DCFPyL-PET/CT, a PSAdt cut-off of 4.09 and 5.59 months, respectively, were able to predict M stage. [18F]DCFPyL changed therapeutic management in 40/138 patients. CONCLUSIONS: [18F]DCFPyL provides a higher DR and superior miTNM staging than [18F]F-choline in restaging BCR, especially with high PSA and unfavourable PSA kinetics, showing a fair agreement to [18F]F-choline.

Diagnostic and therapeutic impact of PET/CT with 18F-DCFPyL versus 18F-Fluorocholine in initial staging of intermediate-/high-risk prostate cancer: a pilot study.

AIM: To assess the diagnostic and therapeutic impact of PET/CT with 18F-DCFPyL with respect to 18F-Fluorocholine in initial staging of intermediate-/high-risk prostate cancer (PCa). MATERIAL AND METHODS: Patients with recent diagnosis of intermediate-/high-risk PCa without androgen deprivation therapy and previous 18F-Fluorocholine-PET/CT (negative for extraprostatic disease or with oligometastatic disease) were referred to 18F-DCFPyL-PET/CT. Patients' disease characteristic as grade group, D'Amico risk category (intermediate/high), prostate-specific antigen (PSA) closest to PET/CTs and its kinetics were obtained. The overall detection rate (DR) and molecular imaging TNM (miTNM) stage according to the prostate cancer molecular imaging standardized evaluation (PROMISE) criteria were assessed for both radiotracers, and their concordance (Kappa coefficient) was analyzed. The diagnostic and therapeutic impact of 18F-DCFPyL with respect to 18F-Fluorocholine was evaluated. RESULTS: Fifty-eight patients were analyzed (84.5% high-risk). 18F-Fluorocholine showed a higher DR than 18F-DCFPyL of prostate gland involvement (100% versus 93.1%) and pelvic node disease (37.9% versus 31%; k = 0.436, p = 0.001). On the other hand, 18F-DCFPyL-PET/CT showed a higher DR of metastatic disease than 18F-Fluorocholine-PET/CT, 9/58 patients (15.5%): 3 M1a, 5 M1b and 1 M1c) versus 5/58 (8.6%) patients: 1 M1a and 4 M1b), k = 0.426; p = 0.001. No significant association was found between clinical characteristics (grade group, risk category, PSA level and kinetic) and 18F-Fluorocholine or 18F-DCFPyL results. The results of 18F-DCFPyL-PET/CT modified the previously planned treatment compared to 18F-Fluorocholine-PET/CT in 13 patients (22.4%). CONCLUSIONS: 18F-Fluorocholine and 18F-DCFPyL PET/CT showed a similar DR of prostate gland and lymph node involvement, although with moderate concordance for the latter. 18F-DCFPyL was superior to 18F-Fluorocholine in detecting regional and distant metastasis with a therapeutic impact in one of every five patients.

Formaldehyde, acrolein and other carbonyls in dwellings of university students. Levels and source characterization.

Fifteen carbonyl compounds were investigated in the living rooms and bedrooms of 25 university student flats in the urban area of Ciudad Real (Central Southern Spain) in wintertime. Carbonyls were sampled using Radiello ® passive samplers refilled in the laboratory according to the method described in ISO 16000-3 Standard. The most abundant carbonyls in the living rooms and bedrooms were formaldehyde, acetone, acetaldehyde, hexaldehyde and butyraldehyde. The median concentration levels in the living rooms and bedrooms were: 28.6 and 34.2 µg m-3 for formaldehyde, 18.3 and 23.1 µg m-3 for acetone, 14.3 and 15.8 µg m-3 for acetaldehyde, 11.4 and 14.1 µg m-3 for hexaldehyde and 10.8 and 12.4 µg m-3 for butyraldehyde. The median concentration of formaldehyde, benzaldehyde, valeraldehyde and hexaldehyde was significantly higher in the bedrooms than in the living rooms. Indoor concentrations were significantly higher than outdoor concentrations for all carbonyl measured, indicating that sources in the indoor environment are prevailing in all flats. Principal component analysis, multiple linear regressions and Spearman correlation coefficients were used to investigate the origin, the indoor pollutants determinants and to establish common sources between carbonyls. Eight components were extracted from the application of PCA to the indoor and outdoor measurements accounting for 97.7% of the total variance. Formaldehyde, acetone, acetaldehyde and acrolein presented different indoor sources. In the multiple linear regression analysis, higher formaldehyde concentrations were found in those living rooms with wood floor and smoking was positively associated to acetone, propionaldehyde, benzaldehyde and isovaleraldehyde. Formaldehyde, acetaldehyde, acrolein, acetone, propionaldehyde and benzaldehyde concentrations were compared with relevant international guidelines, being their concentrations below recommended values except acrolein, where all measured flats exceeded the reference levels; it would be important to focus on the characterization of emission sources of acrolein in indoor air in order to minimise the exposure and health risk.

Early Recurrence Detection of Glioma Using 18 F-Fluorocholine PET/CT : GliReDe Pilot Study.

OBJECTIVE: The aim of this study was to analyze the usefulness of 18 F-fluorocholine PET/CT in the early diagnosis of tumor recurrence, increasing the diagnosis confidence of MRI. METHODS: Patients with a previous gross total resection of glioma and the first suspicious or doubtful for recurrence MRI were prospectively included and subjected to 18 F-fluorocholine PET/CT. An independent and combined assessment of 18 F-fluorocholine PET/CT and multimodal MRI was performed classifying the studies as positive or negative for tumor recurrence. Final diagnosis (recurrence or not) was obtained by histological confirmation or clinical and imaging follow-up. The relation of SUV max and tumor-to-background ratio with progression, the diagnostic performance of imaging techniques, and their concordance (κ Cohen) were analyzed. RESULTS: Twenty-four studies on 21 patients were assessed. Recurrence was diagnosed in 20 cases. PET/CT was positive in 23 cases (3 false positive), whereas MRI was positive in 15 cases (1 false positive). MRI was false negative in 6 cases. There was no false negative on 18 F-fluorocholine PET/CT. Accuracy of PET/CT versus MRI was 87.5% and 70.8%, respectively. The combined evaluation of both techniques did not show any advantage with respect to PET/CT results alone. The concordance between both imaging techniques was low (κ = 0.135; P = 0.375). SUV max and tumor-to-background ratio were related to recurrence (areas under the curve of 0.844 [ P = 0.033] and 0.869 [ P = 0.022], respectively). CONCLUSIONS: 18 F-fluorocholine PET/CT was helpful for increasing the diagnostic confidence in the cases of MRI doubtful for recurrence in order to avoid a delayed diagnosis.

Increasing the confidence of 18F-Florbetaben PET interpretations: Machine learning quantitative approximation.

AIM: To assess the added value of semiquantitative parameters on the visual assessment and to study the patterns of 18F-Florbetaben brain deposition. MATERIALS AND METHODS: Retrospective analysis of multicenter study performed in patients with mild cognitive impairment or dementia of uncertain origin. 18F-Florbetaben PET scans were visually interpreted by two experienced observers, analyzing target regions in order to calculate the interobserver agreement. Semiquantification of all cortical regions with respect to three reference regions was performed to obtain standardized uptake value ratios (SUVRs). The ability of SUVRs to predict the visual evaluation, the possibility of preferential radiotracer deposition in some target regions and interhemisphere differences were analyzed. RESULTS: 135 patients were evaluated. In the visual assessment, 72 were classified as positive. Interobserver agreement was excellent. All SUVRs were significantly higher in positive PET scans than in negative ones. Prefrontal area and posterior cingulate were the cortical regions with the best correlations with the visual evaluation, followed by the composite region. Using ROC analysis, the SUVRs obtained in same target locations showed the best diagnostic performance. CONCLUSIONS: The derived information from target regions seems to help the visual classification, based on a preferential amyloid ß deposit, allowing machine learning. The amyloid ß deposit, although diffuse in all cortical regions, seems not to be uniform and symmetric.