Dosimetric and radiation cancer risk evaluation of high resolution thorax CT during COVID-19 outbreak.

PURPOSE: The aim of this work was to evaluate the dosimetric impact of high-resolution thorax CT during COVID-19 outbreak in the University Hospital of Parma. In two months we have performed a huge number of thorax CT scans collecting effective and equivalent organ doses and evaluating also the lifetime attributable risk (LAR) of lung and other major cancers. MATERIALS AND METHOD: From February 24th to April 28th, 3224 high-resolution thorax CT were acquired. For all patients we have examined the volumetric computed tomography dose index (CTDIvol), the dose length product (DLP), the size-specific dose estimate (SSDE) and effective dose (E103) using a dose tracking software (Radimetrics Bayer HealthCare). From the equivalent dose to organs for each patient, LAR for lung and major cancers were estimated following the method proposed in BEIR VII which considers age and sex differences. RESULTS: Study population included 3224 patients, 1843 male and 1381 female, with an average age of 67 years. The average CTDIvol, SSDE and DLP, and E103 were 6.8 mGy, 8.7 mGy, 239 mGy·cm and 4.4 mSv respectively. The average LAR of all solid cancers was 2.1 cases per 10,000 patients, while the average LAR of leukemia was 0.2 cases per 10,000 patients. For both male and female the organ with a major cancer risk was lung. CONCLUSIONS: Despite the impressive increment in thoracic CT examinations due to COVID-19 outbreak, the high resolution low dose protocol used in our hospital guaranteed low doses and very low risk estimation in terms of LAR.

Radiation dose reduction and static image quality assessment using a channelized hotelling observer on an angiography system upgraded with clarity IQ.

The goal of this paper was the comparison of radiation dose and imaging quality before and after the Clarity IQ technology installation in a Philips AlluraXper FD20/20 angiography system using a Channelized Hotelling Observer model (CHO). The core characteristics of the Allura Clarity IQ technology are its real-time noise reduction algorithms (NRT) combined with state-of-the-art hardware; this technology allows to implement acquisition protocols able to significantly reduce patient entrance dose. To measure the system performances in terms of image quality we used a contrast detail phantom in a clinical scatter condition. A Leeds TO10 phantom has been imaged between two 10 cm thick homogeneous solid water slabs. Fluoroscopy images were acquired using a cerebral protocol at 3 dose levels (low, medium and high) with a field- of view (FOV) of 31 cm. Cineangiography images were acquired using a cerebral protocol at 2 fps. Thus, 4 acquisitions were obtained for the conventional technology and 4 acquisitions were taken after the Clarity IQ upgrade, for a total of 8 different image sets. A validated 40 Gabor channels CHO with an internal noise model compared the image sets. Human observers' studies were carried out to tune the internal noise parameter. We showed that the CHO did not detect any significant difference between any of the image sets acquired using the two technologies. Consequently, this x-ray imaging technology provides a non-inferior image quality with an average patient dose reduction of 57% and 28% respectively in cineangiography and fluoroscopy. The Clarity IQ installation has certainly allowed a considerable improvement in patient and staff safety, while maintaining the same image quality.

PHYSICAL CHARACTERISATION OF FOUR DIFFERENT COMMERCIAL DIGITAL BREAST TOMOSYNTHESIS SYSTEMS.

The aim of this article was to characterise the performance of four different digital breast tomosynthesis (DBT) systems in terms of dose and image quality parameters. One of them, GE Pristina, has never been tested before. Average glandular doses were measured both in DBT and 2D full field digital mammography mode. Several phantoms were employed to perform signal difference to noise ratio, slice sensitivity profile, slice to slice incrementation, chest wall offset, z-axis geometry, artefact spread function, low contrast detectability, contrast detail evaluations, image uniformity and in-plane MTF in chest wall-nipple and in tube-travel directions. There are many differences in DBT systems explored: the angular range, detector type, reconstruction algorithms, and the presence or not of the grid. Even if it is not simple to calculate a global figure of merit, the analysis of all the collected data can be useful in a contest of a quality assurance program to define a set of values that could be used as benchmarks.

Definition of Local Diagnostic Reference Levels in a Radiology Department Using a Dose Tracking Software.

Dose optimization in radiological examinations is a mandatory issue: in this study local Diagnostic Reference Levels (lDRLs) for Clinical Mammography (MG), Computed Tomography (CT) and Interventional Cardiac Procedures (ICP) performed in our Radiology Department were established. Using a dose tracking software, we have collected Average Glandular Dose (AGD) for two clinical mammographic units; CTDIvol, Size-Specific Dose Estimate (SSDE), Dose Length Product (DLP) and total DLP (DLPtot) for five CT scanners; Fluoro Time, Fluoro Dose Area Product (DAP) and total DAP (DAPtot) for two angiographic systems. Data have been compared with Italian Regulation and with the recent literature. The 75th percentiles of the different dosimetric indices have been calculated. Automated methods of radiation dose data collection allow a fast and detailed analysis of a great amount of data and an easy determination of lDRLs for different radiological procedures.

Porphyrin conjugated SiC/SiOx nanowires for X-ray-excited photodynamic therapy.

The development of innovative nanosystems opens new perspectives for multidisciplinary applications at the frontier between materials science and nanomedicine. Here we present a novel hybrid nanosystem based on cytocompatible inorganic SiC/SiOx core/shell nanowires conjugated via click-chemistry procedures with an organic photosensitizer, a tetracarboxyphenyl porphyrin derivative. We show that this nanosystem is an efficient source of singlet oxygen for cell oxidative stress when irradiated with 6 MV X-Rays at low doses (0.4-2 Gy). The in-vitro clonogenic survival assay on lung adenocarcinoma cells shows that 12 days after irradiation at a dose of 2 Gy, the cell population is reduced by about 75% with respect to control cells. These results demonstrate that our approach is very efficient to enhance radiation therapy effects for cancer treatments.

Surgical preparation: are patients "ready" for stress urinary incontinence surgery?

INTRODUCTION AND HYPOTHESIS: Patient preparedness for stress urinary incontinence (SUI) surgery is associated with improvements in post-operative satisfaction, symptoms and quality of life (QoL). This planned secondary analysis examined the association of patient preparedness with surgical outcomes, treatment satisfaction and quality of life. METHODS: The ValUE trial compared the effect of pre-operative urodynamic studies with a standardized office evaluation of outcomes of SUI surgery at 1 year. In addition to primary and secondary outcome measures, patient satisfaction with treatment was measured using a five-point Likert scale (very dissatisfied to very satisfied) that queried subjects to rate the treatment's effect on overall incontinence, urge incontinence, SUI, and frequency. Preparedness for surgery was assessed using an 11-question Patient Preparedness Questionnaire (PPQ). RESULTS: Based on PPQ question 11, 4 out of 5 (81 %) of women reported they "agreed" or "strongly agreed" that they were prepared for surgery. Selected demographic and clinical characteristics were similar in unprepared and prepared women. Among SUI severity baseline measures, total UDI score was significantly but weakly associated with preparedness (question 11 of the PPQ; Spearman's r = 0.13, p = 0.001). Although preparedness for surgery was not associated with successful outcomes, it was associated with satisfaction (r s = 0.11, p = 0.02) and larger PGI-S improvement (increase; p = 0.008). CONCLUSIONS: Approximately half (48 %) of women "strongly agreed" that they felt prepared for SUI. Women with higher pre-operative preparedness scores were more satisfied, although surgical outcomes did not differ.

SU-E-T-466: TCP and NTCP: Is That All?

PURPOSE: Concerns about the secondary cancer risks associated to the peripheral neutron and photon contamination in photon modern radiotherapy (RT) techniques (e.g., Intensity Modulated RT -IMRT- or Intensity Modulated Arc Therapy -IMAT) have been widely raised. Benefits in terms of better tumor coverage have to be balanced against the drawbacks of poorer organ at risk sparing and secondary cancer risk in order to make the decision on the optimum treatment technique. The aim of this study was to develop a tool which estimates treatment success taking into consideration the neutron secondary cancer probability. METHODS: A methodology and benchmark dataset for radiotherapy real time assessment of patient neutron dose and application to a novel digital detector (DD) has been carried out (submitted to PMB, 2011). Our DD provides real time neutron equivalent dose distribution in relevant organs along the patient. This information, together with TCP and NTCP estimated from the DVH of target and organs at risks, respectively, have been built into a general biological model which allows us to evaluate the success of the treatments (Sánchez-Nieto et al., ESTRO meeting 2012). This model has been applied to make estimation of treatment success in a variety of treatment techniques (3DCRT, forward and inverse IMRT, RapidArc, Volumetric Modulated Arc Therapy and Helical Tomotherapy) to low and high energy. RESULTS: MU-demanding techniques at high energies were able to deliver treatment plans with the highest complicated-free tumour control. Nevertheless, neutron peripheral dose must be taken into consideration as the associated risk could be of the same order of magnitude than the usually considered NTCPs. CONCLUSIONS: The methodology developed to provide an online organ neutron peripheral dose can be successfully combined with biological models to make predictions on treatment success taking into consideration secondary cancer risks.

Quality of life after surgery for stress incontinence.

This study investigated changes in condition-specific quality of life (QOL) after surgery for stress urinary incontinence. Data from 655 women in a clinical trial comparing the Burch and fascial sling were examined. Improvement in QOL, measured with the Incontinence Impact Questionnaire (mean decrease 133.1; SD 109.8), was observed 6 months after surgery and persisted at 24 months. Women for whom surgery was successful (regardless of surgery type) had greater improvement in QOL (mean decrease 160.0; SD 103.9) than did women for whom surgery was not successful (mean decrease 113.6; SD 110.9; p < 0.0001), although not statistically significant after adjusting for covariates. Multivariable analysis showed that QOL improvement was related to decreased urinary incontinence (UI) symptom bother, greater improvement in UI severity, younger age, Hispanic ethnicity, and receiving Burch surgery. Among sexually active women, worsening sexual function had a negative impact on QOL. Improved QOL was explained most by UI symptom improvement.

Prolapse severity, symptoms and impact on quality of life among women planning sacrocolpopexy.

OBJECTIVES: To explore the relationship between severity of pelvic organ prolapse (POP), symptoms of pelvic dysfunction and quality of life using validated measures. METHOD: Baseline data from 314 participants in the Colpopexy And Urinary Reduction Efforts (CARE) trial were analyzed. Pelvic symptoms and impact were assessed using the Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire (PFIQ). PFDI and PFIQ scores were compared by prolapse stage and history of incontinence or POP surgery. Regression analyses were performed to identify other predictors of symptoms and impact. RESULTS: Women were predominantly (90%) Caucasian and had mean age of 61 years. Women with stage II POP, especially those with prior surgery, reported more symptoms and impact than women with more advanced POP. There were no other significant predictors of symptoms or life impact. CONCLUSIONS: Women planning sacrocolpopexy with stage II prolapse and prior pelvic surgery reported more symptoms and quality of life impact than those with more advanced prolapse.

Human antibodies against the polymorphic epithelial mucin in ovarian cancer patients recognise a novel sequence in the tandem repeat region.

The humoral immune response to the polymorphic epithelial mucin (PEM) was studied by characterising the reactivity of human antibodies generated by EBV-immortalised B-cells from tumour-draining lymph nodes of ovarian cancer patients. All the human antibodies, selected in ELISA for their reactivity to the protein tandem core repeat sequence, reacted with PEM-expressing tumour cells. Aberrant glycosylation of the peptide core of the PEM molecule in cancer cells leads to the exposure of peptide epitopes that can be considered tumour specific. The epitope mapping of six human antibodies revealed that only one of them contained the PDTR sequence, shown to be the immunodominant epitope in the mouse. Four of the six human antibodies recognised a novel common immunogenic sequence (APPAH) in the tandem repeats. The binding of these human antibodies did not appear to be modulated by the length of the carbohydrate side chains, as shown by O-glycosylation inhibition studies. These results indicate that distinct sequences within the tandem repeat of PEM are target for a humoral immune response in humans. The presence of antibodies directed against different epitopes within the same antigenic region may modulate the antigen presentation process and the ongoing immune response. This data may help in clarifying the mechanisms of the immune response to PEM in cancer patients for the development of PEM-based immunotherapy.

Human B cell immune response to selected epitopes of the polymorphic epithelial mucin (PEM) in cancer patients.

Human antibodies were generated by Epstein-Barr Virus (EBV) immortalization of B cells derived from tumor draining lymph nodes of cancer patients. Antibodies were screened for reactivity in ELISA against a synthetic peptide corresponding to the protein core of the Polymorphic Epithelial Mucin (PEM). Epitopes within this region are in fact considered to be tumor specific since they are selectively exposed on tumor cells due to aberrant glycosylation. Human antibodies thus selected react in ELISA and immunohistochemistry with PEM-expressing tumor cells. This is the first demonstration of the existence of B cell immune response against selected epitopes of PEM and, in association with the cytotoxic T cell (CTL) response already demonstrated, represents the basis for the use of synthetic peptides as vaccines in cancer patients.

Human B-cell immune response to the polymorphic epithelial mucin.

Human antibodies generated by Epstein-Barr virus immortalized B-cells from tumor-draining lymph nodes of an ovarian cancer patient were screened for reactivity in enzyme-linked immunosorbent assay with a synthetic peptide corresponding to the protein core of the polymorphic epithelial mucin. Epitopes within this region are in fact considered tumor specific since they are selectively exposed in tumor cells due to aberrant glycosylation. Human antibody BB5, thus selected, reacts in enzyme-linked immunosorbent assay and immunohistochemistry with polymorphic epithelial mucin-expressing tumor cells. This is the first demonstration of the existence of a B-cell immune response to selected epitopes of polymorphic epithelial mucin and, together with the cytotoxic T-cell response already demonstrated, constitutes the basis for the use of synthetic peptides as a vaccine in cancer patients.

MHC antigens expressed on 3LL metastatic variants: correlation with the expression of a TSP-180 protein.

In attempts to correlate metastatic potential with specific properties of tumor cells, homogeneous subpopulations, which are endowed with low or high metastatic potential, have been selected from Lewis lung carcinoma (3LL). In particular, since cell surface constituents are possibly involved in the metastatic process, changes in antigen expression have been correlated with the metastatic potential of 3LL variants. In this view, we quantitated the expression of MHC (Db,Kb) antigens and of a tumor specific protein (TSP) identified by the monoclonal antibody (MoAb) 135-13C on some "in vitro" and "in vivo" variants of 3LL. The MoAb 135-13C was found to recognize a TSP-180 protein that appears on the cell surface of several murine carcinomas, but is not detected on normal cells in culture. Studies of the MHC expression on these variants, by the use of the indirect immunofluorescent staining or the direct binding of the MoAb to H-2Db (28-14-8) and the MoAb to H-2Kb (28-13-3), demonstrate that "in vivo" and "in vitro" 3LL variants which, are endowed with a higher metastatic potential, express on the cell surface a higher amount of the Db antigen. By contrast, all the 3LL lines have few cells recognized by the MoAb to H-2Kb and express low amounts of this antigen on the cell surface. The direct binding to different tumor lines and the analysis of the immunoprecipitates from the cell lysates by the use of the MoAb 135-13C demonstrate that the TSP-180 protein is highly expressed on 3LL cells which possess high capacity to metastasize to the lung. The variations induced in 3LL metastatic phenotype by the injection of the variant lines in allogeneic mice (Balb/c, C3HeB:H-2d,H-2k, respectively) or after treatment with the specific MoAb 135-13C have, also, been studied. An attempt was made to correlate the changes in 3LL metastatic phenotype with the expression of the TSP-180 protein and of the MHC antigens. We conclude that a high expression on the cell surface of the Db antigen and of the TSP-180 protein, is associated with a high malignant phenotype of 3LL tumor cells.

Metastatic dissemination of 3LL variants after treatment with monoclonal antibody to a tumor-associated antigen.

Two tumor lines derived from 3LL (Lewis lung carcinoma) endowed with different metastatic potential and stable for their metastatic phenotype during serial in vivo passages, have been analysed for growth and dissemination following treatment with a monoclonal antibody. We have used a recently developed MoAb 135-13C to a tumor-associated antigen of murine lung carcinoma having an apparent molecular weight of 180,000 (TSP-180). The metastatic dissemination of the 3LL variants before and after treatment with the MoAb has been correlated with the expression on the cell surface of the MHC antigens (Db, Kb) and of the TSP-180 protein. The results of this study indicate that cell with high TSP-180 protein expression and MHC antigen expression have the greatest metastatic potential. Administration of MoAb 135-13C to tumor-bearing mice or i.v. injection of cells preincubated with the MoAb 135-13C increase the dissemination capacity of the variant endowed with lower metastatic potential while inducing a reverse effect on the high metastatic one. Studies on the MHC expression demonstrate that MoAb 135-13C treatment induces changes in the Db and Kb expression at level of secondary neoplasms. The results are discussed in view of the importance of the use of the metastatic variants to study therapeutic effect of specific targeting agent.