Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas.

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight 'anomalous' cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first 'anomalous' non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Prognostic value of HPV-PCR, p16 and p53 immunohistochemical status on local recurrence rate and survival in patients with vulvar squamous cell carcinoma.

The primary aim of this study was to assess the association between human papilloma virus (HPV) and p53 expression and local recurrence (LR), disease specific survival (DSS), and overall survival (OS) in patients with vulvar squamous cell carcinoma (VSCC). Secondary, the accuracy of p16 immunohistochemistry for HPV status was assessed. The tumor tissue of 255 patients, surgically treated for primary unifocal VSCC between 2000 and 2010, was analyzed. HPV-PCR and P16 and p53 immunohistochemical stainings were performed. All histologic slides were independently reviewed by two expert gyneco-pathologists. Time to first LR, DSS, and OS for the variables p16, p53, and HPV-PCR were compared using univariable and multivariable Cox-regression analyses. In 211/255 (83.5%) patients, HPV-PCR was negative. The local recurrence rate was significantly lower in patients positive with HPV-PCR (10-year LR rate 24.6%) versus negative tumors (47.5%), p = 0.004. After multivariable analyses, this difference remained significant (HR 0.23 (95% CI 0.08-0.62) p = 0.004). There was no difference in LR rate correlated to the p53 expression. DSS and OS did not significantly differ after multivariable analyses for all different subgroups. Sensitivity and specificity of p16 staining for presence of HPV detected by HPV-PCR were 86.4% and 93.8%, respectively. In conclusion, patients with HPV-negative VSCCs have significantly more LR compared to patients with HPV-positive VSCCs, and p16 immunohistochemistry is a reliable surrogate marker for HPV status. No relevant subgroup for LR or survival based on HPV/p53 status could be identified. We advise to perform an HPV-PCR or p16 IHC staining in all patients with VSCC.

Validation of an AI-based algorithm for measurement of the thoracic aortic diameter in low-dose chest CT.

OBJECTIVES: To evaluate the performance of artificial intelligence (AI) software for automatic thoracic aortic diameter assessment in a heterogeneous cohort with low-dose, non-contrast chest computed tomography (CT). MATERIALS AND METHODS: Participants of the Imaging in Lifelines (ImaLife) study who underwent low-dose, non-contrast chest CT (August 2017-May 2022) were included using random samples of 80 participants <50y, ≥80y, and with thoracic aortic diameter ≥40 mm. AI-based aortic diameters at eight guideline compliant positions were compared with manual measurements. In 90 examinations (30 per group) diameters were reassessed for intra- and inter-reader variability, which was compared to discrepancy of the AI system using Bland-Altman analysis, paired samples t-testing and linear mixed models. RESULTS: We analyzed 240 participants (63 ± 16 years; 50 % men). AI evaluation failed in 11 cases due to incorrect segmentation (4.6 %), leaving 229 cases for analysis. No difference was found in aortic diameter between manual and automatic measurements (32.7 ± 6.4 mm vs 32.7 ± 6.0 mm, p = 0.70). Bland-Altman analysis yielded no systematic bias and a repeatability coefficient of 4.0 mm for AI. Mean discrepancy of AI (1.3 ± 1.6 mm) was comparable to inter-reader variability (1.4 ± 1.4 mm); only at the proximal aortic arch showed AI higher discrepancy (2.0 ± 1.8 mm vs 0.9 ± 0.9 mm, p < 0.001). No difference between AI discrepancy and inter-reader variability was found for any subgroup (all: p > 0.05). CONCLUSION: The AI software can accurately measure thoracic aortic diameters, with discrepancy to a human reader similar to inter-reader variability in a range from normal to dilated aortas.

A comparison of cardiovascular and pulmonary morbidities and risk factors in breast cancer survivors compared to an age-matched female control group in the Lifelines prospective population cohort.

PURPOSE: To provide more insight into late treatment-related toxicities among breast cancer (BC) survivors by comparing morbidities and risk factors between BC survivors and age-matched controls. MATERIALS AND METHODS: All female participants diagnosed with BC before inclusion in Lifelines, a population-based cohort in the Netherlands, were selected and matched 1:4 to female controls without any oncological history on birth year. Baseline was defined as the age at BC diagnosis. Outcomes were obtained from questionnaires and functional analyses performed at entry to Lifelines (follow-up 1; FU1) and several years later (FU2). Cardiovascular and pulmonary events were defined as morbidities that were absent at baseline but present at FU1 or FU2. RESULTS: The study consisted of 1,325 BC survivors and 5,300 controls. The median period from baseline (i.e., BC treatment) to FU1 and FU2 was 7 and 10 years, respectively. Among BC survivors more events of heart failure (OR: 1.72 [1.10-2.68]) and less events of hypertension (OR: 0.79 [0.66-0.94]) were observed. At FU2, more electrocardiographic abnormalities were found among BC survivors compared to controls (4.1% vs. 2.7%, respectively; p = 0.027) and Framingham scores for the 10-year risk of coronary heart disease were lower (difference: 0.37%; 95% CI [-0.70 to -0.03%]). At FU2, BC survivors had more frequently a forced vital capacity below the lower limit of normal than controls (5.4% vs. 2.9%, respectively; p = 0.040). CONCLUSION: BC survivors are at risk of late treatment-related toxicities despite a more favourable cardiovascular risk profile compared to age-matched female controls.

Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme.

BACKGROUND: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology. METHODS: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel. RESULTS: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified. CONCLUSION: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.

Influenza season influence on outcome of new nodules in the NELSON study.

We evaluated the impact of the influenza season on outcome of new lung nodules in a LDCT lung cancer screening trial population. NELSON-trial participants with ≥ 1 new nodule detected in screening rounds two and three were included. Outcome (resolution or persistence) of new nodules detected per season was calculated and compared. Winter (influenza season) was defined as 1st October to 31st March, and compared to the summer (hay-fever season), 1st April to 30th September. Overall, 820 new nodules were reported in 529 participants. Of the total new nodules, 482 (59%) were reported during winter. When considering the outcome of all new nodules, there was no statistically significant association between summer and resolving nodules (OR 1.07 [CI 1.00-1.15], p = 0.066), also when looking at the largest nodule per participant (OR 1.37 [CI 0.95-1.98], p = 0.094). Similarly, there was no statistically significant association between season and screen detected cancers (OR 0.47 [CI 0.18-1.23], p = 0.123). To conclude, in this lung cancer screening population, there was no statistically significant association between influenza season and outcome of new lung nodules. Hence, we recommend new nodule management strategy is not influenced by the season in which the nodule is detected.

Quality of life after treatment with immune checkpoint inhibitors for lung cancer; the impact of age.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment. However, it remains unclear as to whether changes in Health-Related Quality-of-Life (HRQoL) are associated with the age of lung cancer patients treated using ICIs. This study aimed to evaluate this possible association and to compare ICI-treated patients' HRQoL scores with normative data of an age-matched non-cancer general population. METHODS: Lung cancer patients from the OncoLifeS data-biobank were included if they were treated with ICIs, irrespective of other treatments, at the University Medical Center Groningen between 2015 and 2021 and had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30), both at the start of ICI treatment and after six months. Association of age as a continuous variable (per 10 years) and changes in HRQoL scores between baseline and 6 months was assessed using multivariable regression analyses. Clinical relevance of differences in HRQoL scores between OncoLifeS and the general population was classified into trivial, small, medium, and large, for three age groups (<60, 60-69 and ≥ 70 years). RESULTS: 151 patients were included with a mean age of 65.8 years. An increase in age per 10 years was associated with a larger decrease in the summary HRQoL score(ß = -3.28,CI95%-6.42;-0.14), physical(ß = -4.8, CI95% -8.71;-0.88), cognitive(ß = -4.51,CI95%-8.24;-0.78), role functioning(ß = -5.41,CI95%-10.78;-0.05), symptom burden(ß = -3.66,CI95%-6.6;-0.73), and smaller negative changes in financial difficulties(ß = 6.5 95 % CI 3.16; 9.85). OncoLifeS HRQoL scores were lower than those of the general population and differences were most often classified as large and medium. CONCLUSION: Older lung cancer patients experience larger deteriorations in most HRQoL domains after 6 months of ICI treatment. Also, these patients showed significantly lower HRQoL scores compared to the general population.

Mammographic breast density and the risk of breast cancer: A systematic review and meta-analysis.

OBJECTIVES: Mammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of breast cancer. However, it is questioned whether this increased risk estimate is applicable to current breast density classification methods. Therefore, the aim of this study was to further investigate and clarify the association between mammographic density and breast cancer risk based on current literature. METHODS: Medline, Embase and Web of Science were systematically searched for articles published since 2013, that used BI-RADS lexicon 5th edition and incorporated data on digital mammography. Crude and maximally confounder-adjusted data were pooled in odds ratios (ORs) using random-effects models. Heterogeneity regarding breast cancer risks were investigated using I2 statistic, stratified and sensitivity analyses. RESULTS: Nine observational studies were included. Having extremely dense breast tissue (BI-RADS density D) resulted in a 2.11-fold (95% CI 1.84-2.42) increased breast cancer risk compared to having scattered dense breast tissue (BI-RADS density B). Sensitivity analysis showed that when only using data that had adjusted for age and BMI, the breast cancer risk was 1.83-fold (95% CI 1.52-2.21) increased. Both results were statistically significant and homogenous. CONCLUSIONS: Mammographic breast density BI-RADS D is associated with an approximately two-fold increased risk of breast cancer compared to having BI-RADS density B in general population women. This is a novel and lower risk estimate compared to previously reported and might be explained due to the use of digital mammography and BI-RADS lexicon 5th edition.

Irregular screening participation increases advanced stage breast cancer at diagnosis: A population-based study.

OBJECTIVE: To evaluate the effect of irregular screening behaviour on the risk of advanced stage breast cancer at diagnosis in Flanders. METHODS: All women aged 50-69 who were invited to the organized breast cancer screening and diagnosed with breast cancer before age 72 from 2001 to 2018 were included. All prevalent screen and interval cancers within 2 years of a prevalent screen were excluded. Screening behaviour was categorized based on the number of invitations and performed screenings. Four groups were defined: regular, irregular, only-once, and never attenders. Advanced stage cancer was defined as a stage III + breast cancer. The association between screening regularity and breast cancer stage at diagnosis was evaluated in multivariable logistic regression models, taking age of diagnosis and socio-economic status into account. RESULTS: In total 13.5% of the 38,005 breast cancer cases were diagnosed at the advanced stage. Compared to the regular attenders, the risk of advanced stage breast cancer for the irregular attenders, women who participated only-once, and never attenders was significantly higher with ORadjusted:1.17 (95%CI:1.06-1.29) and ORadjusted:2.18 (95%CI:1.94-2.45), and ORadjusted:5.95 (95%CI:5.33-6.65), respectively. CONCLUSIONS: In our study, never attenders were nearly six times more likely to be diagnosed with advanced stage breast cancer than regular attenders, which was much higher than the estimates published thus far. An explanation for this is that the ever screened women is a heterogeneous group regarding the participation profiles which also includes irregular and only-once attenders. The benefit of regular screening should be informed to all women invited for screening.

The effect of sarcopenic obesity and muscle quality on complications after DIEP-flap breast reconstruction.

Introduction: The aim of this study was to evaluate whether sarcopenic obesity and muscle quality as expressed by skeletal muscle radiodensity (SMD) are associated to postoperative complications in women undergoing DIEP-flap breast reconstruction (BR). Methods: All patients who underwent DIEP-flap BR at our tertiary center between 2010 and 2018 were asked to sign informed consent for the use of their electronic medical records and images. By outlining anatomical skeletal muscle contours on the preoperative abdominal CT-scan at lumbar level L3, SMD and skeletal muscle indices (SMI) were measured by two observers independently. Using logistic regression analyses, the association between sarcopenic obesity (BMI >25 & SMI <39), low SMD (<40HU), and Clavien-Dindo (CD) grade ≥ II complications was evaluated. In this way odds ratios (OR) and adjusted odds ratios (ORadjusted) were provided. Results: Out of the 103 patients included in this study, 36% had CD grade ≥ II complications within 30 days of surgery. Twenty patients (19%) suffered from sarcopenic obesity of whom eleven patients (55%) had CD grade ≥ II complications (OR = 2.7, p = 0.05). In a multivariate analysis, sarcopenic obesity was not significantly related to a higher complication rate (ORadjusted = 2.2, p = 0.14) but women with SMD below average and those with prior radiotherapy had a higher risk for grade ≥ II complications (ORadjusted = 2.9, p = 0.02 and ORadjusted = 2.7, p = 0.02 respectively). Conclusion: Below average SMD (<40HU) was found to be associated with the development of postoperative CD grade ≥ II complications in women undergoing DIEP-flap BR. Future research should evaluate whether improving SMD reduces the complication incidence in this patient group.

Automatic Cardiac Structure Contouring for Small Datasets with Cascaded Deep Learning Models.

Cardiac structure contouring is a time consuming and tedious manual activity used for radiotherapeutic dose toxicity planning. We developed an automatic cardiac structure segmentation pipeline for use in low-dose non-contrast planning CT based on deep learning algorithms for small datasets. Fifty CT scans were retrospectively selected and the whole heart, ventricles and atria were contoured. A two stage deep learning pipeline was trained on 41 non contrast planning CTs, tuned with 3 CT scans and validated on 6 CT scans. In the first stage, An InceptionResNetV2 network was used to identify the slices that contained cardiac structures. The second stage consisted of three deep learning models trained on the images containing cardiac structures to segment the structures. The three deep learning models predicted the segmentations/contours on axial, coronal and sagittal images and are combined to create the final prediction. The final accuracy of the pipeline was quantified on 6 volumes by calculating the Dice similarity coefficient (DC), 95% Hausdorff distance (95% HD) and volume ratios between predicted and ground truth volumes. Median DC and 95% HD of 0.96, 0.88, 0.92, 0.80 and 0.82, and 1.86, 2.98, 2.02, 6.16 and 6.46 were achieved for the whole heart, right and left ventricle, and right and left atria respectively. The median differences in volume were -4, -1, + 5, -16 and -20% for the whole heart, right and left ventricle, and right and left atria respectively. The automatic contouring pipeline achieves good results for whole heart and ventricles. Robust automatic contouring with deep learning methods seems viable for local centers with small datasets.

Oxidative Stress Predicts Post-Surgery Complications in Gastrointestinal Cancer Patients.

INTRODUCTION: An excessive perioperative inflammatory reaction can lead to more postoperative complications in patients treated for gastrointestinal cancers. It has been suggested that this inflammatory reaction leads to oxidative stress. The most important nonenzymatic antioxidants are serum free thiols. The purpose of this study was to evaluate whether high preoperative serum free thiol levels are associated with short-term clinical outcomes. METHODS: Blood samples were drawn before, at the end of, and 1 and 2 days after surgery of a consecutive series of patients with gastrointestinal cancer. Serum free thiols were detected using a colorimetric detection method using Ellman's reagent. Short-term clinical outcomes were defined as 30-day complications (Clavien-Dindo ≥2) and length of hospital stay. Logistic regression was applied to examine the association between serum free thiol levels and short-term patient outcomes. RESULTS: Eighty-one patients surgically treated for gastrointestinal cancer were included in the study. Median age was 68 (range 26-87) years, and 28% were female. Patients in the lowest tertile of preoperative serum free thiols had a threefold higher risk to develop postoperative complications (odds ratio [OR]: 3.4; 95% confidence interval [CI]:1.1-10.7) and a fourfold higher risk to have an increased length of stay in the hospital (OR 4.0; 95% CI 1.3-12.9) compared with patients in the highest tertile. CONCLUSIONS: Patients with lower preoperative serum free thiol levels, indicating a decrease in extracellular antioxidant capacity and therefore an increase in systemic oxidative stress, are more likely to develop postoperative complications and show a longer in hospital stay than patients with higher serum free thiol levels.

Qualitative Evaluation of Common Quantitative Metrics for Clinical Acceptance of Automatic Segmentation: a Case Study on Heart Contouring from CT Images by Deep Learning Algorithms.

Organs-at-risk contouring is time consuming and labour intensive. Automation by deep learning algorithms would decrease the workload of radiotherapists and technicians considerably. However, the variety of metrics used for the evaluation of deep learning algorithms make the results of many papers difficult to interpret and compare. In this paper, a qualitative evaluation is done on five established metrics to assess whether their values correlate with clinical usability. A total of 377 CT volumes with heart delineations were randomly selected for training and evaluation. A deep learning algorithm was used to predict the contours of the heart. A total of 101 CT slices from the validation set with the predicted contours were shown to three experienced radiologists. They examined each slice independently whether they would accept or adjust the prediction and if there were (small) mistakes. For each slice, the scores of this qualitative evaluation were then compared with the Sørensen-Dice coefficient (DC), the Hausdorff distance (HD), pixel-wise accuracy, sensitivity and precision. The statistical analysis of the qualitative evaluation and metrics showed a significant correlation. Of the slices with a DC over 0.96 (N = 20) or a 95% HD under 5 voxels (N = 25), no slices were rejected by the readers. Contours with lower DC or higher HD were seen in both rejected and accepted contours. Qualitative evaluation shows that it is difficult to use common quantification metrics as indicator for use in clinic. We might need to change the reporting of quantitative metrics to better reflect clinical acceptance.

Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely.

Ultra-low-dose CT combined with noise reduction techniques for quantification of emphysema in COPD patients: An intra-individual comparison study with standard-dose CT.

PURPOSE: Phantom studies in CT emphysema quantification show that iterative reconstruction and deep learning-based noise reduction (DLNR) allow lower radiation dose. We compared emphysema quantification on ultra-low-dose CT (ULDCT) with and without noise reduction, to standard-dose CT (SDCT) in chronic obstructive pulmonary disease (COPD). METHOD: Forty-nine COPD patients underwent ULDCT (third generation dual-source CT; 70ref-mAs, Sn-filter 100kVp; median CTDIvol 0.38 mGy) and SDCT (64-multidetector CT; 40mAs, 120kVp; CTDIvol 3.04 mGy). Scans were reconstructed with filtered backprojection (FBP) and soft kernel. For ULDCT, we also applied advanced modelled iterative reconstruction (ADMIRE), levels 1/3/5, and DLNR, levels 1/3/5/9. Emphysema was quantified as Low Attenuation Value percentage (LAV%, ≤-950HU). ULDCT measures were compared to SDCT as reference standard. RESULTS: For ULDCT, the median radiation dose was 84 % lower than for SDCT. Median extent of emphysema was 18.6 % for ULD-FBP and 15.4 % for SDCT (inter-quartile range: 11.8-28.4 % and 9.2 %-28.7 %, p = 0.002). Compared to SDCT, the range in limits of agreement of emphysema quantification as measure of variability was 14.4 for ULD-FBP, 11.0-13.1 for ULD-ADMIRE levels and 10.1-13.9 for ULD-DLNR levels. Optimal settings were ADMIRE 3 and DLNR 3, reducing variability of emphysema quantification by 24 % and 27 %, at slight underestimation of emphysema extent (-1.5 % and -2.9 %, respectively). CONCLUSIONS: Ultra-low-dose CT in COPD patients allows dose reduction by 84 %. State-of-the-art noise reduction methods in ULDCT resulted in slight underestimation of emphysema compared to SDCT. Noise reduction methods (especially ADMIRE 3 and DLNR 3) reduced variability of emphysema quantification in ULDCT by up to 27 % compared to FBP.

Diffusion weighted imaging of the breast: Performance of standardized breast tumor tissue selection methods in clinical decision making.

OBJECTIVES: In breast diffusion weighted imaging (DWI) protocol standardization, it is recently shown that no breast tumor tissue selection (BTTS) method outperformed the others. The purpose of this study is to analyze the feasibility of three fixed-size breast tumor tissue selection (BTTS) methods based on the reproducibility, accuracy and time-measurement in comparison to the largest oval and manual delineation in breast diffusion weighted imaging data. METHODS: This study is performed with a consecutive dataset of 116 breast lesions (98 malignant) of at least 1.0 cm, scanned in accordance with the EUSOBI breast DWI working group recommendations. Reproducibility of the maximum size manual (BTTS1) and of the maximal size round/oval (BTTS2) methods were compared with three smaller fixed-size circular BTTS methods in the middle of each lesion (BTTS3, 0.12 cm3 volume) and at lowest apparent diffusion coefficient (ADC) (BTTS4, 0.12 cm3; BTTS5, 0.24 cm3). Mean ADC values, intraclass-correlation-coefficients (ICCs), area under the curve (AUC) and measurement times (sec) of the 5 BTTS methods were assessed by two observers. RESULTS: Excellent inter- and intra-observer agreement was found for any BTTS (with ICC 0.88-0.92 and 0.92-0.94, respectively). Significant difference in ADCmean between any pair of BTTS methods was shown (p = <0.001-0.009), except for BTTS2 vs. BTTS3 for observer 1 (p = 0.10). AUCs were comparable between BTTS methods, with highest AUC for BTTS2 (0.89-0.91) and lowest for BTTS4 (0.76-0.85). However, as an indicator of clinical feasibility, BTTS2-3 showed shortest measurement times (10-15 sec) compared to BTTS1, 4-5 (19-39 sec). CONCLUSION: The performance of fixed-size BTTS methods, as a potential tool for clinical decision making, shows equal AUC but shorter ADC measurement time compared to manual or oval whole lesion measurements. The advantage of a fixed size BTTS method is the excellent reproducibility. A central fixed breast tumor tissue volume of 0.12 cm3 is the most feasible method for use in clinical practice.

Coverage determinants of breast cancer screening in Flanders: an evaluation of the past decade.

BACKGROUND: Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown. OBJECTIVE: To assess the determinants of BC screening coverage in Flanders. METHODS: Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008-2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type. RESULTS: Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50-54.40%) and 14.10% (IQR: 9.80-19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199-4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455-2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624-0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967-0.972). CONCLUSION: Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP.

Symptoms in long-term breast cancer survivors: A cross-sectional study in primary care.

PURPOSE: Various long-term symptoms can manifest after breast cancer treatment, but we wanted to clarify whether these are more frequent among long-term breast cancer survivors than matched controls and if they are associated with certain diagnoses. METHODS: This was a cross-sectional, population-based study of 350 breast cancer survivors treated with chemo- and/or radiotherapy ≥5 years (median 10) after diagnosis and 350 women without cancer matched by age and primary care physician. All women completed a questionnaire enquiring about symptoms, underwent echocardiography to assess the left ventricle ejection fraction, and completed the Hospital Anxiety and Depression Scale. Cardiovascular diseases were diagnosed from primary care records. In a multivariable logistic regression analysis, symptoms were adjusted for the long-term effects and compared between cohorts and within the survivor group. RESULTS: Concentration difficulties, forgetfulness, dizziness, and nocturia were more frequent among breast cancer survivors compared with controls, but differences could not be explained by cardiac dysfunction, cardiovascular diseases, depression, or anxiety. Intermittent claudication and appetite loss were more frequent among breast cancer survivors than controls and associated with cardiac dysfunction, depression, and anxiety. Breast cancer survivors treated with chemotherapy with/without radiotherapy were at significantly higher odds of forgetfulness and nocturia, but significantly lower odds of dizziness, compared with breast cancer survivors treated with radiotherapy alone. CONCLUSIONS: Intermittent claudication and appetite loss are common among breast cancer survivors and are associated with cardiac dysfunction and mood disorders. Other symptoms varied by whether the patient underwent chemotherapy with/without radiotherapy (forgetfulness and nocturia) radiotherapy alone (dizziness).

Satisfaction with cosmetic outcomes of breast reconstruction: Investigations into the correlation between the patients' Breast-Q outcome and the judgment of panels.

OBJECTIVES: We aimed to determine the relation between breast reconstruction method, patient satisfaction, and surgeon reported cosmetic outcome among women who underwent breast reconstruction after mastectomy. STUDY DESIGN: A cross-sectional study of patients treated between 2006 and 2010. MAIN OUTCOME: Women's satisfaction with cosmetic outcomes after breast reconstruction. MEASURES: Cosmetic outcomes were evaluated by (1) women using the Breast-Q to rate satisfaction with breasts outcomes, and (2) an independent panel using the Strasser score. The relationships between the Breast-Q rating, Strasser scores, and breast reconstruction methods, including laterality and timing, were evaluated by Mann-Whitney U tests, Spearman's rank correlations, and Wilcoxon signed-rank tests. RESULTS: Ninety-four women were included. Patients were more satisfied with their breasts if they had undergone autologous, unilateral, or secondary breast reconstruction compared with those who underwent alloplastic, bilateral, or primary breast reconstruction (p-values 0.008, 0.011, and 0.001, respectively). The Strasser system did not reveal significant cosmetic differences, with all breast reconstructions graded as mediocre or poor. CONCLUSIONS: Patient satisfaction with breast outcomes, as measured by the Breast-Q, was described as mediocre or poorly reflected by the Strasser score. If doctors are to support patients to make informed decisions on the optimal method of breast reconstruction, we need a more sensitive, comprehensive tool reflecting patients' cosmetic outcomes.