Health benefits and harms of mammography screening in older women (75+ years)-a systematic review.

BACKGROUND: There is little evidence on the balance between potential benefits and harms of mammography screening in women 75 years and older. The aim of this systematic review was to synthesise the evidence on the outcomes of mammography screening in women aged 75 years and older. METHODS: A systematic review of mammography screening studies in women aged 75 years and over. RESULTS: Thirty-six studies were included in this review: 27 observational studies and 9 modelling studies. Many of the included studies used no or uninformative comparison groups resulting in a potential bias towards the benefits of screening. Despite this, there was mixed evidence about the benefits and harms of continuing mammography screening beyond the age of 75 years. Some studies showed a beneficial effect on breast cancer mortality, and other studies showed no effect on mortality. Some studies showed some harms (false positive tests and recalls) being comparable to those in younger age-groups, with other studies showing increase in false positive screens and biopsies in older age-group. Although reported in fewer studies, there was consistent evidence of increased overdiagnosis in older age-groups. CONCLUSION: There is limited evidence available to make a recommendation for/against continuing breast screening beyond the age of 75 years. Future studies should use more informative comparisons and should estimate overdiagnosis given potentially substantial harm in this age-group due to competing causes of death. This review was prospectively registered with PROSPERO (CRD42020203131).

Presence of crown-like structures in breast adipose tissue; differences between healthy controls, BRCA1/2 gene mutation carriers and breast cancer patients.

PURPOSE: Crown-like structures (CLS) in breast adipose tissue are associated with inflammation and a potential factor in breast cancer behaviour. Whether this effect varies between breast cancer subtypes and is influenced by BMI and BRCA mutation status is presently unknown. Therefore, we compared CLS presence between adipose tissue of healthy controls, BRCA1/2 gene mutation carriers and breast cancer patients, and assessed the relation of CLS with clinical outcome in breast cancer patients. METHODS: Immunohistochemical staining for CD68 was performed on breast adipose tissue sections of 48 healthy controls, 78 BRCA1/2 gene mutation carriers and 259 breast cancer patients. CLS presence and index (CLS/cm2) were correlated with BMI, BRCA status, tumour presence, intrinsic tumour subtype and tumour characteristics. Associations with clinical outcome were assessed. RESULTS: CLS were more often present in breast cancer patients compared to BRCA carriers and healthy controls. CLS presence was associated with the presence of breast cancer and high BMI. CLS were more often present in Luminal-B-like tumours compared to the other subtypes. No correlations between CLS and BRCA status or age was found. In TNBC, CLS were related to lymphovascular invasion. No association with survival was found. CONCLUSION: In conclusion, CLS were more frequently present in breast adipose tissue of breast cancer patients compared to BRCA1/2 gene mutation carriers and healthy controls. Furthermore, our study provides evidence of the association between obesity and presence of CLS. The prognostic significance and impact on clinical outcome of differences in CLS numbers should be further assessed in prospective studies.

Distribution of Solid Lung Nodules Presence and Size by Age and Sex in a Northern European Nonsmoking Population.

Background Most of the data regarding prevalence and size distribution of solid lung nodules originates from lung cancer screening studies that target high-risk populations or from Asian general cohorts. In recent years, the identification of lung nodules in non-high-risk populations, scanned for clinical indications, has increased. However, little is known about the presence of solid lung nodules in the Northern European nonsmoking population. Purpose To study the prevalence and size distribution of solid lung nodules by age and sex in a nonsmoking population. Materials and Methods Participants included nonsmokers (never or former smokers) from the population-based Imaging in Lifelines study conducted in the Northern Netherlands. Participants (age ≥ 45 years) with completed lung function tests underwent chest low-dose CT scans. Seven trained readers registered the presence and size of solid lung nodules measuring 30 mm3 or greater using semiautomated software. The prevalence and size of lung nodules (≥30 mm3), clinically relevant lung nodules (≥100 mm3), and actionable nodules (≥300 mm3) are presented by 5-year categories and by sex. Results A total of 10 431 participants (median age, 60.4 years [IQR, 53.8-70.8 years]; 56.6% [n = 5908] female participants; 46.1% [n = 4812] never smokers and 53.9% [n = 5619] former smokers) were included. Of these, 42.0% (n = 4377) had at least one lung nodule (male participants, 47.5% [2149 of 4523]; female participants, 37.7% [2228 of 5908]). The prevalence of lung nodules increased from age 45-49.9 years (male participants, 39.4% [219 of 556]; female participants, 27.7% [236 of 851]) to age 80 years or older (male participants, 60.7% [246 of 405]; female participants, 50.9% [163 of 320]). Clinically relevant lung nodules were present in 11.1% (1155 of 10 431) of participants, with prevalence increasing with age (male participants, 8.5%-24.4%; female participants, 3.7%-15.6%), whereas actionable nodules were present in 1.1%-6.4% of male participants and 0.6%-4.9% of female participants. Conclusion Lung nodules were present in a substantial proportion of all age groups in the Northern European nonsmoking population, with slightly higher prevalence for male participants than female participants. © RSNA, 2024 Supplemental material is available for this article.

Lung Nodule Management in Low-Dose CT Screening for Lung Cancer: Lessons from the NELSON Trial.

Screening with low-dose CT (LDCT) in a high-risk population, as defined by age and smoking behavior, reduces lung cancer-related mortality. However, LDCT screening presents a major challenge. Numerous, mostly benign, nodules are seen in the lungs during screening. The question is how to distinguish the malignant from the benign nodules. Various studies use different protocols for nodule management. The Dutch-Belgian NELSON (Nederlands-Leuvens Longkanker Screenings Onderzoek) trial, the largest European lung cancer screening trial, used distinctions based on nodule volumetric assessment and growth rate. This review discusses key findings from the NELSON study regarding the characteristics of screening-detected nodules, including nodule size and its volumetric assessment, growth rate, subtype, and their associated malignancy risk. These results are compared with findings from other screening studies and current recommendations for lung nodule management. By examining differences in nodule management strategies and providing a comprehensive overview of outcomes specific to lung cancer screening, this review aims to contribute to the broader discussion on optimizing lung nodule management in screening programs.

Low-Dose CT-derived Bronchial Parameters in Individuals with Healthy Lungs.

Background CT-derived bronchial parameters have been linked to chronic obstructive pulmonary disease and asthma severity, but little is known about these parameters in healthy individuals. Purpose To investigate the distribution of bronchial parameters at low-dose CT in individuals with healthy lungs from a Dutch general population. Materials and Methods In this prospective study, low-dose chest CT performed between May 2017 and October 2022 were obtained from participants who had completed the second-round assessment of the prospective, longitudinal Imaging in Lifelines study. Participants were aged at least 45 years, and those with abnormal spirometry, self-reported respiratory disease, or signs of lung disease at CT were excluded. Airway lumens and walls were segmented automatically. The square root of the bronchial wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10), luminal area (LA), wall thickness (WT), and wall area percentage were calculated. Associations between sex, age, height, weight, smoking status, and bronchial parameters were assessed using univariable and multivariable analyses. Results The study sample was composed of 8869 participants with healthy lungs (mean age, 60.9 years ± 10.4 [SD]; 4841 [54.6%] female participants), including 3672 (41.4%) never-smokers and 1197 (13.5%) individuals who currently smoke. Bronchial parameters for male participants were higher than those for female participants (Pi10, slope [ß] range = 3.49-3.66 mm; LA, ß range = 25.40-29.76 mm2; WT, ß range = 0.98-1.03 mm; all P < .001). Increasing age correlated with higher Pi10, LA, and WT (r2 range = 0.06-0.09, 0.02-0.01, and 0.02-0.07, respectively; all P < .001). Never-smoking individuals had the lowest Pi10 followed by formerly smoking and currently smoking individuals (3.62 mm ± 0.13, 3.68 mm ± 0.14, and 3.70 mm ± 0.14, respectively; all P < .001). In multivariable regression models, age, sex, height, weight, and smoking history explained up to 46% of the variation in bronchial parameters. Conclusion In healthy individuals, bronchial parameters differed by sex, height, weight, and smoking history; male sex and increasing age were associated with wider lumens and thicker walls. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Emrich and Varga-Szemes in this issue.

Who is at risk of lung nodules on low-dose CT in a Western country? A population-based approach.

BACKGROUND: This population-based study aimed to identify the risk factors for lung nodules in a Western European general population. METHODS: We quantified the presence or absence of lung nodules among 12 055 participants of the Dutch population-based ImaLife (Imaging in Lifelines) study (age ≥45 years) who underwent low-dose chest computed tomography. Outcomes included the presence of 1) at least one solid lung nodule (volume ≥30 mm3) and 2) a clinically relevant lung nodule (volume ≥100 mm3). Fully adjusted multivariable logistic regression models were applied overall and stratified by smoking status to identify independent risk factors for the presence of nodules. RESULTS: Among the 12 055 participants (44.1% male; median age 60 years; 39.9% never-smokers; 98.7% White), we found lung nodules in 41.8% (5045 out of 12 055) and clinically relevant nodules in 11.4% (1377 out of 12 055); the corresponding figures among never-smokers were 38.8% and 9.5%, respectively. Factors independently associated with increased odds of having any lung nodule included male sex, older age, low educational level, former smoking, asbestos exposure and COPD. Among never-smokers, a family history of lung cancer increased the odds of both lung nodules and clinically relevant nodules. Among former and current smokers, low educational level was positively associated with lung nodules, whereas being overweight was negatively associated. Among current smokers, asbestos exposure and low physical activity were associated with clinically relevant nodules. CONCLUSIONS: The study provides a large-scale evaluation of lung nodules and associated risk factors in a Western European general population: lung nodules and clinically relevant nodules were prevalent, and never-smokers with a family history of lung cancer were a non-negligible group.

Methylation Analysis to Detect CIN3+ in High-Risk Human Papillomavirus-Positive Self-Samples From the Population-Based Cervical Cancer Screening Program.

Since 2017, a self-sampling device has been introduced to the Dutch population-based screening program to enable higher participation rates. However, routine triage cytology cannot be performed on self-sampling material. Methylation is an alternative triage method that can be performed directly on DNA extracted from self-samples. Recently, we tested a set of 15 published cervical intraepithelial neoplasia grade 3 or worse (CIN3+)-specific methylation markers and found a panel of 3 markers with a sensitivity of 82% and a specificity of 74%. In this study, we determined the sensitivity and specificity of 2 commercial assays using quantitative methylation-specific PCR. DNA from the same cohort of high-risk human papillomavirus-positive self-sampled material obtained through the population-based screening program in the North of the Netherlands from women with CIN2 or less (

The Association Between Intraoperative Compromised Intestinal Integrity and Postoperative Complications in Cancer Patients.

BACKGROUND: Because of perioperative splanchnic hypoperfusion, the gut wall becomes more permeable for intraluminal microbes to enter the splanchnic circulation, possibly contributing to development of complications. Hypoperfusion-related injured enterocytes release intestinal fatty acid binding protein (I-FABP) into plasma, which is used as proxy of intestinal integrity. This study investigates the occurrence of intestinal integrity loss during oncologic surgery, measured by I-FABP change. Secondary the relationship between compromised intestinal integrity, and related variables and complications were studied. METHODS: Patients undergoing oncologic surgery from prospective cohort studies were included. Urine I-FABP samples were collected preoperatively (T0) and at wound closure (T1), and in a subgroup on Day 1 (D1) and Day 2 (D2) postoperatively. I-FABP dynamics were investigated and logistic regression analyses were performed to study the association between I-FABP levels and patient-related, surgical variables and complications. RESULTS: A total of 297 patients were included with median age of 70 years. Median I-FABP value increased from 80.0 pg/mL at T0 (interquartile range [IQR] 38.0-142.0) to 115 pg/mL at T1 (IQR 48.0-198.0) (p < 0.05). Age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02-1.08) and anesthesia time (OR 1.13, 95% CI 1.02-1.25) were related to stronger I-FABP increase. When comparing I-FABP change in patients experiencing any complications versus no complications, relative I-FABP change at T1 was 145% of T0 (IQR 86-260) versus 113% (IQR 44-184) respectively (p < 0.05). CONCLUSIONS: A significant change in I-FABP levels was seen perioperatively indicating compromised intestinal integrity. Age and anesthesia time were related to higher I-FABP increase. In patients experiencing postoperative complications, a higher I-FABP increase was found.

Advancing Ki67 hotspot detection in breast cancer: a comparative analysis of automated digital image analysis algorithms.

AIM: Manual detection and scoring of Ki67 hotspots is difficult and prone to variability, limiting its clinical utility. Automated hotspot detection and scoring by digital image analysis (DIA) could improve the assessment of the Ki67 hotspot proliferation index (PI). This study compared the clinical performance of Ki67 hotspot detection and scoring DIA algorithms based on virtual dual staining (VDS) and deep learning (DL) with manual Ki67 hotspot PI assessment. METHODS: Tissue sections of 135 consecutive invasive breast carcinomas were immunohistochemically stained for Ki67. Two DIA algorithms, based on VDS and DL, automatically determined the Ki67 hotspot PI. For manual assessment; two independent observers detected hotspots and calculated scores using a validated scoring protocol. RESULTS: Automated hotspot detection and assessment by VDS and DL could be performed in 73% and 100% of the cases, respectively. Automated hotspot detection by VDS and DL led to higher Ki67 hotspot PIs (mean 39.6% and 38.3%, respectively) compared to manual consensus Ki67 PIs (mean 28.8%). Comparing manual consensus Ki67 PIs with VDS Ki67 PIs revealed substantial correlation (r = 0.90), while manual consensus versus DL Ki67 PIs demonstrated high correlation (r = 0.95). CONCLUSION: Automated Ki67 hotspot detection and analysis correlated strongly with manual Ki67 assessment and provided higher PIs compared to manual assessment. The DL-based algorithm outperformed the VDS-based algorithm in clinical applicability, because it did not depend on virtual alignment of slides and correlated stronger with manual scores. Use of a DL-based algorithm may allow clearer Ki67 PI cutoff values, thereby improving the clinical usability of Ki67.

Long-term outcome of high-grade serous carcinoma established in risk-reducing salpingo-oophorectomy specimens in asymptomatic BRCA1/2 germline pathogenic variant carriers.

OBJECTIVE: The aim of this study was to describe the long-term outcome of asymptomatic BRCA1/2 germline pathogenic variant (GPV) carriers with high-grade serous carcinoma (HGSC) in their risk-reducing salpingo-oophorectomy (RRSO) specimen. METHODS: In a previously described cohort of asymptomatic BRCA1/2 GPV carriers derived from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study, women with HGSC at RRSO were identified. Main outcome was ten-year disease-free survival (DFS). Secondary outcomes were time to recurrence, ten-year disease-specific survival (DSS), ten-year overall survival (OS). Patient, disease and treatment characteristics associated with recurrence were described. RESULTS: The 28 included women with HGSC at RRSO were diagnosed at a median age of 55.3 years (range: 33.5-74.3). After staging, eighteen women had (FIGO) stage I, three stage II and five had stage III disease. Two women did not undergo surgical staging and were classified as unknown stage. After a median follow-up of 13.5 years (range: 9.1-24.7), six women with stage I (33%), one woman with stage II (33%), two women with stage III (40%) and none of the women with unknown stage developed a recurrence. Median time to recurrence was 6.9 years (range: 0.8-9.2 years). Ten-year DFS was 68%, ten-year DSS was 88% and ten-year OS was 82%. CONCLUSION: Most asymptomatic BRCA1/2 GPV carriers with HGSC at RRSO were diagnosed at an early stage. Nevertheless, after a median follow-up of 13.5 years, nine of the 28 women with HGSC at RRSO developed a recurrence after a median of 6.9 years.

Performance of Lung-RADS in different target populations: a systematic review and meta-analysis.

OBJECTIVES: Multiple lung cancer screening studies reported the performance of Lung CT Screening Reporting and Data System (Lung-RADS), but none systematically evaluated its performance across different populations. This systematic review and meta-analysis aimed to evaluate the performance of Lung-RADS (versions 1.0 and 1.1) for detecting lung cancer in different populations. METHODS: We performed literature searches in PubMed, Web of Science, Cochrane Library, and Embase databases on October 21, 2022, for studies that evaluated the accuracy of Lung-RADS in lung cancer screening. A bivariate random-effects model was used to estimate pooled sensitivity and specificity, and heterogeneity was explored in stratified and meta-regression analyses. RESULTS: A total of 31 studies with 104,224 participants were included. For version 1.0 (27 studies, 95,413 individuals), pooled sensitivity was 0.96 (95% confidence interval [CI]: 0.90-0.99) and pooled specificity was 0.90 (95% CI: 0.87-0.92). Studies in high-risk populations showed higher sensitivity (0.98 [95% CI: 0.92-0.99] vs. 0.84 [95% CI: 0.50-0.96]) and lower specificity (0.87 [95% CI: 0.85-0.88] vs. 0.95 (95% CI: 0.92-0.97]) than studies in general populations. Non-Asian studies tended toward higher sensitivity (0.97 [95% CI: 0.91-0.99] vs. 0.91 [95% CI: 0.67-0.98]) and lower specificity (0.88 [95% CI: 0.85-0.90] vs. 0.93 [95% CI: 0.88-0.96]) than Asian studies. For version 1.1 (4 studies, 8811 individuals), pooled sensitivity was 0.91 (95% CI: 0.83-0.96) and specificity was 0.81 (95% CI: 0.67-0.90). CONCLUSION: Among studies using Lung-RADS version 1.0, considerable heterogeneity in sensitivity and specificity was noted, explained by population type (high risk vs. general), population area (Asia vs. non-Asia), and cancer prevalence. CLINICAL RELEVANCE STATEMENT: Meta-regression of lung cancer screening studies using Lung-RADS version 1.0 showed considerable heterogeneity in sensitivity and specificity, explained by the different target populations, including high-risk versus general populations, Asian versus non-Asian populations, and populations with different lung cancer prevalence. KEY POINTS: • High-risk population studies showed higher sensitivity and lower specificity compared with studies performed in general populations by using Lung-RADS version 1.0. • In non-Asian studies, the diagnostic performance of Lung-RADS version 1.0 tended to be better than in Asian studies. • There are limited studies on the performance of Lung-RADS version 1.1, and evidence is lacking for Asian populations.

Serous Tubal Intraepithelial Carcinoma After Neoadjuvant Chemotherapy: A Report of 2 Cases.

Serous tubal intraepithelial carcinoma (STIC) is regarded as the origin of most high-grade serous carcinomas (HGSC). After a diagnosis of isolated STIC, risk of developing HGSC is substantial. Since surveillance cannot detect HGSC in time to cure the disease, there is no consensus on the optimal treatment after a diagnosis of isolated STIC, but chemotherapy is considered one of the possible strategies. In this case report, we describe 2 women with advanced-stage HGSC treated with 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery. In both women, histopathological examination showed a complete histopathological tumor response, but a vital STIC was found in both cases. The 2 cases presented here indicate that STICs may not respond to chemotherapy. Further research focused on the underlying biology and chemosensitivity of STIC, as well as the effectiveness of treatment to prevent HGSC in case of isolated STIC, is needed.

Head and neck cancer patients with geriatric deficits are more often non-responders and lost from follow-up in quality of life studies.

OBJECTIVES: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models. RESULTS: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04-9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27-8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85-8.45)], cognitive decline [OR 4.85 (2.28-10.35)] and assisted living (OR 5.54 (2.63-11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51-4.59) and 2.52 (1.44-4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death. CONCLUSION: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data.

Postoperative muscle loss, protein intake, physical activity and outcome associations.

BACKGROUND: Skeletal muscle loss is often observed in intensive care patients. However, little is known about postoperative muscle loss, its associated risk factors, and its long-term consequences. The aim of this prospective observational study is to identify the incidence of and risk factors for surgery-related muscle loss (SRML) after major abdominal surgery, and to study the impact of SRML on fatigue and survival. METHODS: Patients undergoing major abdominal cancer surgery were included in the MUSCLE POWER STUDY. Muscle thickness was measured by ultrasound in three muscles bilaterally (biceps brachii, rectus femoris, and vastus intermedius). SRML was defined as a decline of 10 per cent or more in diameter in at least one arm and leg muscle within 1 week postoperatively. Postoperative physical activity and nutritional intake were assessed using motility devices and nutritional diaries. Fatigue was measured with questionnaires and 1-year survival was assessed with Cox regression analysis. RESULTS: A total of 173 patients (55 per cent male; mean (s.d.) age 64.3 (11.9) years) were included, 68 of whom patients (39 per cent) showed SRML. Preoperative weight loss and postoperative nutritional intake were statistically significantly associated with SRML in multivariable logistic regression analysis (P < 0.050). The combination of insufficient postoperative physical activity and nutritional intake had an odds ratio of 4.00 (95 per cent c.i. 1.03 to 15.47) of developing SRML (P = 0.045). No association with fatigue was observed. SRML was associated with decreased 1-year survival (hazard ratio 4.54, 95 per cent c.i. 1.42 to 14.58; P = 0.011). CONCLUSION: SRML occurred in 39 per cent of patients after major abdominal cancer surgery, and was associated with a decreased 1-year survival.

The validation of low-dose CT scans from the [18F]-FDG PET-CT scan to assess skeletal muscle mass in comparison with diagnostic neck CT scans.

PURPOSE: Radiologically defined sarcopenia, or a low skeletal muscle index (SMI), is an emerging biomarker for adverse clinical outcomes in head and neck cancer (HNC) patients. Recently, SMI measurements have been validated at the level of the third cervical vertebra (C3) on diagnostic neck CT scans but are not yet validated on low-dose (LD) neck CT scans from the [18F]-FDG PET-CT. This hampers SMI analysis in HNC patients without a diagnostic neck CT but with a [18F]-FDG PET-CT scan. Therefore, the aim was to study whether (low) SMI based on LD CT scan from [18F]-FDG PET-CT is comparable to those derived from diagnostic neck CT scans. METHODS: HNC patients with both diagnostic CT and [18F]-FDG PET-CT of the neck were prospectively included into the OncoLifeS data-biobank. Skeletal muscle was retrospectively delineated at the level of the third cervical vertebra (C3), and (low) SMI (cm2/m2) was calculated for diagnostic and LD neck CTs. (Low) SMI from the diagnostic neck CT was considered the reference standard. Intra-class correlation coefficient (ICC), Bland-Altman plots, and Cohen's Kappa analysis were performed. RESULTS: The cohort (n = 233) mean age was 66.2 ± 12.8 years, and 74.2% of patients were male. Inter-rater reliability was excellent (ICC > 0.990, 95% confidence interval 0.975-0.996, p < 0.001). The agreement of SMI between both modalities was high according to the Bland-Altman plot (mean ΔSMI = - 0.19 cm2/m2), and there was no substantial bias. Cohen's Kappa analysis showed an almost perfect agreement of low SMI between the two modalities (κ = 0.911, p < 0.001). The position of arms didn't affect the high agreement of (low) SMI. CONCLUSION: Skeletal muscle mass, as measured with (low) SMI, remains constant irrespective of CT acquisition parameters (diagnostic neck CT scans versus LD neck scans of the [18F]-FDG PET-CT scan), positioning of arms, and observers. These findings contribute to the construction of a clinically useful radiological biomarker for SMI and therefore identify patients at risk for adverse clinical outcomes.

Urinary albumin excretion and cancer risk: the PREVEND cohort study.

BACKGROUND: Chronic kidney disease (CKD) is believed to be associated with an increased risk for cancer, especially urinary tract cancer. However, previous studies predominantly focused on the association of decreased estimated glomerular filtration rate (eGFR) with cancer. In this study, we investigated the association of albuminuria with cancer incidence, adjusted for eGFR. METHODS: We included 8490 subjects in the Prevention of Renal and Vascular End-stage Disease (PREVEND) observational study. Urinary albumin excretion (UAE) was measured in two 24-hour urine specimens at baseline. Primary outcomes were the incidence of overall and urinary tract cancer. Secondary outcomes were the incidence of other site-specific cancers, and mortality due to overall, urinary tract, and other site-specific cancers. RESULTS: Median baseline UAE was 9.4 (IQR, 6.3-17.8) mg/24 h. During a median follow-up of 17.7 years, 1341 subjects developed cancer (of which 177 were urinary tract cancers). After multivariable adjustment including eGFR, every doubling of UAE was associated with a 6% (hazard ratios (HR), 1.06, 95% confidence intervals (CI), 1.02-1.10), and 14% (HR, 1.14, 95% CI, 1.04-1.24) higher risk of overall and urinary tract cancer incidence, respectively. Except for lung and hematological cancer, no associations were found between UAE and the incidence of other site-specific cancer. Doubling of UAE was also associated with a higher risk of mortality due to overall and lung cancer. CONCLUSIONS: Higher albuminuria is associated with a higher incidence of overall, urinary tract, lung, and hematological cancer, and with a higher risk of mortality due to overall and lung cancers, independent of baseline eGFR.

Image quality of DWI at breast MRI depends on the amount of fibroglandular tissue: implications for unenhanced screening.

OBJECTIVES: To compare image quality of diffusion-weighted imaging (DWI) and contrast-enhanced breast MRI (DCE-T1) stratified by the amount of fibroglandular tissue (FGT) as a measure of breast density. METHODS: Retrospective, multi-reader, bicentric visual grading analysis study on breast density (A-D) and overall image and fat suppression quality of DWI and DCE-T1, scored on a standard 5-point Likert scale. Cross tabulations and visual grading characteristic (VGC) curves were calculated for fatty breasts (A/B) versus dense breasts (C/D). RESULTS: Image quality of DWI was higher in the case of increased breast density, with good scores (score 3-5) in 85.9% (D) and 88.4% (C), compared to 61.6% (B) and 53.5% (A). Overall image quality of DWI was in favor of dense breasts (C/D), with an area under the VGC curve of 0.659 (p < 0.001). Quality of DWI and DCE-T1 fat suppression increased with higher breast density, with good scores (score 3-5) for 86.9% and 45.7% of density D, and 90.2% and 42.9% of density C cases, compared to 76.0% and 33.6% for density B and 54.7% and 29.6% for density A (DWI and DCE-T1 respectively). CONCLUSIONS: Dense breasts show excellent fat suppression and substantially higher image quality in DWI images compared with non-dense breasts. These results support the setup of studies exploring DWI-based MR imaging without IV contrast for additional screening of women with dense breasts. CLINICAL RELEVANCE STATEMENT: Our findings demonstrate that image quality of DWI is robust in women with an increased amount of fibroglandular tissue, technically supporting the feasibility of exploring applications such as screening of women with mammographically dense breasts. KEY POINTS: • Image and fat suppression quality of diffusion-weighted imaging are dependent on the amount of fibroglandular tissue (FGT) which is closely connected to breast density. • Fat suppression quality in diffusion-weighted imaging of the breast is best in women with a high amount of fibroglandular tissue. • High image quality of diffusion-weighted imaging in women with a high amount of FGT in MRI supports that the technical feasibility of DWI can be explored in the additional screening of women with mammographically dense breasts.

Long-term effects of the interruption of the Dutch breast cancer screening program due to COVID-19: A modelling study.

Due to COVID-19, the Dutch breast cancer screening program was interrupted for three months with uncertain long-term effects. The aim of this study was to estimate the long-term impact of this interruption on delay in detection, tumour size of screen-detected breast cancers, and interval cancer rate. After validation, the micro-simulation model SiMRiSc was used to calculate the effects of interruption of the breast cancer screening program for three months and for hypothetical interruptions of six and twelve months. A scenario without interruption was used as reference. Outcomes considered were tumour size of screen-detected breast cancers and interval cancer rate. Women of 55-59 and 60-64 years old at time of interruption were considered. Uncertainties were estimated using a sensitivity analysis. The three-month interruption had no clinically relevant long-term effect on the tumour size of screen-detected breast cancers. A 19% increase in interval cancer rate was found between last screening before and first screening after interruption compared to no interruption. Hypothetical interruptions of six and twelve months resulted in larger increases in interval cancer rate of 38% and 78% between last screening before and first screening after interruption, respectively, and an increase in middle-sized tumours in first screening after interruption of 26% and 47%, respectively. In conclusion, the interruption of the Dutch screening program is not expected to result in a long-term delay in detection or clinically relevant change in tumour size of screen-detected cancers, but only affects the interval cancer rate between last screening before and first screening after interruption.

Multi-source data approach for personalized outcome prediction in lung cancer screening: update from the NELSON trial.

Trials show that low-dose computed tomography (CT) lung cancer screening in long-term (ex-)smokers reduces lung cancer mortality. However, many individuals were exposed to unnecessary diagnostic procedures. This project aims to improve the efficiency of lung cancer screening by identifying high-risk participants, and improving risk discrimination for nodules. This study is an extension of the Dutch-Belgian Randomized Lung Cancer Screening Trial, with a focus on personalized outcome prediction (NELSON-POP). New data will be added on genetics, air pollution, malignancy risk for lung nodules, and CT biomarkers beyond lung nodules (emphysema, coronary calcification, bone density, vertebral height and body composition). The roles of polygenic risk scores and air pollution in screen-detected lung cancer diagnosis and survival will be established. The association between the AI-based nodule malignancy score and lung cancer will be evaluated at baseline and incident screening rounds. The association of chest CT imaging biomarkers with outcomes will be established. Based on these results, multisource prediction models for pre-screening and post-baseline-screening participant selection and nodule management will be developed. The new models will be externally validated. We hypothesize that we can identify 15-20% participants with low-risk of lung cancer or short life expectancy and thus prevent ~140,000 Dutch individuals from being screened unnecessarily. We hypothesize that our models will improve the specificity of nodule management by 10% without loss of sensitivity as compared to assessment of nodule size/growth alone, and reduce unnecessary work-up by 40-50%.

BRCA1/2 testing rates in epithelial ovarian cancer: a focus on the untested patients.

BACKGROUND: Since 2015, Dutch guidelines have recommended BRCA1/2 pathogenic variant testing for all patients with epithelial ovarian cancer. Recently, recommendations shifted from germline testing to the tumor-first approach, in which tumor tissue is tested first, and subsequent germline testing is performed only in those with BRCA1/2 tumor pathogenic variants or a positive family history. Data on testing rates and on characteristics of patients missing out on testing remain scarce. OBJECTIVE: To evaluate BRCA1/2 testing rates in patients with epithelial ovarian cancer and compare testing rates of germline testing (performed from 2015 until mid-2018) versus tumor-first testing (implemented mid-2018). METHODS: A consecutive series of 250 patients diagnosed with epithelial ovarian cancer between 2016 and 2019 was included from the OncoLifeS data-biobank of the University Medical Center Groningen, the Netherlands. Testing rates were analyzed for the overall study population and for germline testing (period I) and tumor-first testing (period II) separately. Characteristics of tested and untested patients were compared and predictors for receiving testing were assessed with multivariable logistic regression. RESULTS: Median age was 67.0 years (IQR 59.0-73.0) and 173 (69.2%) patients were diagnosed with high-grade serous carcinoma. Overall, 201 (80.4%) patients were tested. In period I, 137/171 (80.1%) patients were tested and in period II this was 64/79 (81.0%). Patients with non-high-grade serous carcinoma were significantly less likely to receive BRCA1/2 testing than patients with high-grade serous carcinoma (OR=0.23, 95% CI 0.11 to 0.46, p<0.001). CONCLUSIONS: The results show that BRCA1/2 testing rates are suboptimal and suggest that clinicians may not be choosing to test patients with epithelial ovarian cancer with non-high-grade serous ovarian carcinoma, although guidelines recommend BRCA1/2 testing in all patients with epithelial ovarian cancer. Suboptimal testing rates limit optimization of care for patients with epithelial ovarian cancer and counseling of potentially affected relatives.