Publications by authors named "Geertruida H de Bock"

297 Publications

Performance of a deep learning-based lung nodule detection system as an alternative reader in a Chinese lung cancer screening program.

Eur J Radiol 2021 Nov 24;146:110068. Epub 2021 Nov 24.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Radiology, Tianjin, People's Republic of China. Electronic address:

Objective: To evaluate the performance of a deep learning-based computer-aided detection (DL-CAD) system in a Chinese low-dose CT (LDCT) lung cancer screening program.

Materials And Methods: One-hundred-and-eighty individuals with a lung nodule on their baseline LDCT lung cancer screening scan were randomly mixed with screenees without nodules in a 1:1 ratio (total: 360 individuals). All scans were assessed by double reading and subsequently processed by an academic DL-CAD system. The findings of double reading and the DL-CAD system were then evaluated by two senior radiologists to derive the reference standard. The detection performance was evaluated by the Free Response Operating Characteristic curve, sensitivity and false-positive (FP) rate. The senior radiologists categorized nodules according to nodule diameter, type (solid, part-solid, non-solid) and Lung-RADS.

Results: The reference standard consisted of 262 nodules ≥ 4 mm in 196 individuals; 359 findings were considered false positives. The DL-CAD system achieved a sensitivity of 90.1% with 1.0 FP/scan for detection of lung nodules regardless of size or type, whereas double reading had a sensitivity of 76.0% with 0.04 FP/scan (P = 0.001). The sensitivity for detection of nodules ≥ 4 - ≤ 6 mm was significantly higher with DL-CAD than with double reading (86.3% vs. 58.9% respectively; P = 0.001). Sixty-three nodules were only identified by the DL-CAD system, and 27 nodules only found by double reading. The DL-CAD system reached similar performance compared to double reading in Lung-RADS 3 (94.3% vs. 90.0%, P = 0.549) and Lung-RADS 4 nodules (100.0% vs. 97.0%, P = 1.000), but showed a higher sensitivity in Lung-RADS 2 (86.2% vs. 65.4%, P < 0.001).

Conclusions: The DL-CAD system can accurately detect pulmonary nodules on LDCT, with an acceptable false-positive rate of 1 nodule per scan and has higher detection performance than double reading. This DL-CAD system may assist radiologists in nodule detection in LDCT lung cancer screening.
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http://dx.doi.org/10.1016/j.ejrad.2021.110068DOI Listing
November 2021

Community-based lung cancer screening by low-dose computed tomography in China: First round results and a meta-analysis.

Eur J Radiol 2021 Nov 1;144:109988. Epub 2021 Oct 1.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Department of Radiology, Tianjin, People's Republic of China. Electronic address:

Objective: To evaluate the efficiency of low-dose computed tomography (LDCT) screening for lung cancer in China by analyzing the baseline results of a community-based screening study accompanied with a meta-analysis.

Methods: A first round of community-based lung cancer screening with LDCT was conducted in Tianjin, China, and a systematic literature search was performed to identify LDCT screening and registry-based clinical studies for lung cancer in China. Baseline results in the community-based screening study were described by participant risk level and the lung cancer detection rate was compared with the pooled rate among the screening studies. The percentage of patients per stage was compared between the community-based study and screening and clinical studies.

Results: In the community-based study, 5523 participants (43.6% men) underwent LDCT. The lung cancer detection rate was 0.5% (high-risk, 1.2%; low-risk, 0.4%), with stage I disease present in 70.0% (high-risk, 50.0%; low-risk, 83.3%), and the adenocarcinoma present in 84.4% (high-risk, 61.5%; low-risk, 100%). Among all screen-detected lung cancer, women accounted for 8.3% and 66.7% in the high- and low-risk group, respectively. In the screening studies from mainland China, the lung cancer detection rate 0.6% (95 %CI: 0.3%-0.9%) for high-risk populations. The proportions with carcinoma in situ and stage I disease in the screening and clinical studies were 76.4% (95 %CI: 66.3%-85.3%) and 15.2% (95 %CI: 11.8%-18.9%), respectively.

Conclusions: The stage shift of lung cancer due to screening suggests a potential effectiveness of LDCT screening in China. Nearly 70% of screen-detected lung cancers in low-risk populations are identified in women.
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http://dx.doi.org/10.1016/j.ejrad.2021.109988DOI Listing
November 2021

Association of Deficits Identified by Geriatric Assessment With Deterioration of Health-Related Quality of Life in Patients Treated for Head and Neck Cancer.

JAMA Otolaryngol Head Neck Surg 2021 Oct 21. Epub 2021 Oct 21.

Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Importance: Accumulation of geriatric deficits, leading to an increased frailty state, makes patients susceptible for decline in health-related quality of life (HRQOL) after treatment for head and neck cancer (HNC).

Objective: To assess the association of single and accumulated geriatric deficits with HRQOL decline in patients after treatment for HNC.

Design, Setting, And Participants: Between October 2014 and May 2016, patients at a tertiary referral center were included in the Oncological Life Study (OncoLifeS), a prospective data biobank, and followed up for 2 years. A consecutive series of 369 patients with HNC underwent geriatric assessment at baseline; a cohort of 283 patients remained eligible for analysis, and after 2 years, 189 patients remained in the study. Analysis was performed between March and November 2020.

Interventions Or Exposures: Geriatric assessment included scoring of the Adult Comorbidity Evaluation 27, polypharmacy, Malnutrition Universal Screening Tool, Activities of Daily Living, Instrumental Activities of Daily Living (IADL), Timed Up & Go, Mini-Mental State Examination, 15-item Geriatric Depression Scale, marital status, and living situation.

Main Outcomes And Measures: The primary outcome measure was the Global Health Status/Quality of Life (GHS/QOL) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Differences between patients were evaluated using linear mixed models at 3 months after treatment (main effects, β [95% CI]) and declining course per year during follow-up (interaction × time, β [95% CI]), adjusted for baseline GHS/QOL scores, and age, sex, stage, and treatment modality.

Results: Among the 283 patients eligible for analysis, the mean (SD) age was 68.3 (10.9) years, and 193 (68.2%) were male. Severe comorbidity (β = -7.00 [-12.43 to 1.56]), risk of malnutrition (β = -6.18 [-11.55 to -0.81]), and IADL restrictions (β = -10.48 [-16.39 to -4.57]) were associated with increased GHS/QOL decline at 3 months after treatment. Severe comorbidity (β = -4.90 [-9.70 to -0.10]), IADL restrictions (β = -5.36 [-10.50 to -0.22]), restricted mobility (β = -6.78 [-12.81 to -0.75]), signs of depression (β = -7.08 [-13.10 to -1.06]), and living with assistance or in a nursing home (β = -8.74 [-15.75 to -1.73]) were associated with further GHS/QOL decline during follow-up. Accumulation of domains with geriatric deficits was a major significant factor for GHS/QOL decline at 3 months after treatment (per deficient domain β = -3.17 [-5.04 to -1.30]) and deterioration during follow-up (per domain per year β = -2.74 [-4.28 to -1.20]).

Conclusions And Relevance: In this prospective cohort study, geriatric deficits were significantly associated with HRQOL decline after treatment for HNC. Therefore, geriatric assessment may aid decision-making, indicate interventions, and reduce loss of HRQOL.

Trial Registration: trialregister.nl Identifier: NL7839.
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http://dx.doi.org/10.1001/jamaoto.2021.2837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532038PMC
October 2021

Home-based Physical Activity to Alleviate Fatigue in Cancer Survivors: A Systematic Review and Meta-analysis.

Med Sci Sports Exerc 2021 Dec;53(12):2661-2674

Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, Groningen, THE NETHERLANDS.

Purpose: Physical activity (PA) affects fatigue and mental health in cancer survivors favorably, but participation in PA interventions tends to be low. More participants may be reached by home-based PA owing to greater accessibility and self-monitoring. This systematic review therefore evaluated the effects of home-based PA of low to moderate intensity on symptoms of fatigue, depression, and anxiety among cancer survivors.

Methods: PubMed, CINAHL, PsycINFO, and Web of Science were systematically searched for randomized controlled trials. We included investigations of home-based PA interventions in adults treated curatively for cancer and evaluating fatigue, depression, or anxiety as outcomes. We performed a random-effect meta-analysis for the effects of PA interventions on fatigue in the short and long terms. Subgroup analyses were performed for the frequency of counseling. Standardized mean differences (SMD) and 95% confidence intervals are reported.

Results: Eleven articles comprising 1066 participants were included: 77% had a history of breast cancer; 14%, ovarian cancer; 4%, colorectal cancer; 4%, prostate cancer; and 1%, "other" cancer (not specified). Concerning the outcomes, nine articles reported on fatigue and two reported on depression or anxiety. Meta-analyses showed a significant effect of home-based PA on fatigue immediately after the intervention (SMD = 0.22 [0.06-0.37]), at 3 months' follow-up (SMD = 0.27 [0.04-0.51]), and at 6-9 months' follow-up (SMD = 0.31 [0.08-0.55]). PA interventions that used frequent counseling were associated with larger improvements in fatigue than those using no or infrequent counseling.

Conclusions: Home-based PA interventions can reduce fatigue among adult cancer survivors for up to 9 months, and frequent counseling may improve the benefits of these interventions.
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http://dx.doi.org/10.1249/MSS.0000000000002735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594505PMC
December 2021

Type 2 Diabetes Mellitus and Clinicopathological Tumor Characteristics in Women Diagnosed with Breast Cancer: A Systematic Review and Meta-Analysis.

Cancers (Basel) 2021 Oct 5;13(19). Epub 2021 Oct 5.

Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Poor prognosis caused by type 2 diabetes mellitus (T2DM) in women with breast cancer is conferred, while the association between T2DM and breast tumor aggressiveness is still a matter of debate. This study aimed to clarify the differences in breast cancer characteristics, including stage, size, lymph node status, grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2), between patients with and without pre-existing T2DM. PubMed, Embase, and Web of Science were searched for studies from 1 January 2010 to 2 July 2021. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by using a random effects model. T2DM was significantly associated with tumor stages III/IV versus cancers in situ and stages I/II (pooled ORs (pOR), 95% CI: 1.19; 1.04-1.36, = 0.012), tumor size >20 versus ≤20 mm (pOR, 95% CI: 1.18; 1.04-1.35, = 0.013), and lymph node invasion versus no involvement (pOR, 95% CI: 1.26; 1.05-1.51, = 0.013). These findings suggest that women with T2DM are at a higher risk of late-stage tumors, large tumor sizes, and invasive lymph nodes at breast cancer diagnosis.
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http://dx.doi.org/10.3390/cancers13194992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508341PMC
October 2021

Preferences and Experiences Regarding the Use of the Self-Sampling Device in hrHPV Screening for Cervical Cancer.

Patient 2021 Sep 24. Epub 2021 Sep 24.

Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Huispostcode FA40, PO BOX 30 001, 9700 RB, Groningen, The Netherlands.

Background: To improve participation in the Dutch cervical cancer screening, a self-sampling device (SSD) was introduced in 2017 into the Dutch population-based screening programme (PBS) for the early detection of cervical cancer. The aim of this study was to gather potential preferences and experiences that might influence a woman's decision to use the SSD in the Dutch PBS.

Methods: A scoping review was performed in the PubMed database. Studies that assessed preferences and experiences of women regarding the SSD were included, and preferences and experiences were extracted. In addition, in a qualitative study, the list of potential preferences and experiences specific for the Dutch PBS was extended based on semi-structured interviews with SSD users as well as non-SSD users who recently participated in the PBS, analysed in a structured manner by translating full sentences to key words.

Results: Ninety-eight studies were included in the scoping review and 16 interviews were performed. Frequently mentioned reasons for using the SSD, in both the interviews and the literature, were practicality and comfort. Frequently mentioned reasons for not using the SSD were fear of not performing the SSD procedure correctly and doubts on whether the results of the high-risk human papillomavirus (hrHPV) test will be reliable. A new positive experience elicited in the interviews was accessibility. Negative preferences and experiences were not being aware the SSD was an option, and the inconvenience that after an hrHPV-positive test result of the SSD, an additional smear test at the GP is necessary.

Conclusion: Several preferences and experiences play a role in the choice whether or not to use the SSD. Based on the currently found preferences and experiences, an app will be developed in order to assess which of these are the most important for women participating in the Dutch population-based cervical screening programme.
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http://dx.doi.org/10.1007/s40271-021-00550-yDOI Listing
September 2021

Improved precision of noise estimation in CT with a volume-based approach.

Eur Radiol Exp 2021 Sep 10;5(1):39. Epub 2021 Sep 10.

Department of Radiology, EB44, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

Assessment of image noise is a relevant issue in computed tomography (CT). Noise is routinely measured by the standard deviation of density values (Hounsfield units, HU) within a circular region of interest (ROI). We explored the effect of a spherical volume of interest (VOI) on noise measurements. Forty-nine chronic obstructive pulmonary disease patients underwent CT with clinical protocol (regular dose [RD], volumetric CT dose index [CTDIvol] 3.04 mGy, 64-slice unit), and ultra-low dose (ULD) protocol (median CTDIvol 0.38 mGy, dual-source unit). Noise was measured in 27 1-cm ROIs and 27 0.75-cm VOIs inside the trachea. Median true noise was 21 HU (range 17-29) for RD-CT and 33 HU (26-39) for ULD-CT. The VOI approach resulted in a lower mean distance between limits of agreement compared to ROI: 5.9 versus 10.0 HU for RD-CT (-40%); 4.7 versus 9.9 HU for ULD-CT (-53%). Mean systematic bias barely changed: -1.6 versus -0.9HU for RD-CT; 0.0 to 0.4HU for ULD-CT. The average measurement time was 6.8 s (ROI) versus 9.7 (VOI), independent of dose level. For chest CT, measuring noise with a VOI-based instead of a ROI-based approach reduces variability by 40-53%, without a relevant effect on systematic bias and measurement time.
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http://dx.doi.org/10.1186/s41747-021-00237-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429536PMC
September 2021

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 Nov 6;30(11):2114-2121. Epub 2021 Sep 6.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Background: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer.

Methods: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year.

Results: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00-1.40) for ≤2 years, 1.57 (1.32-1.88) for 2 to 4 years, and 2.09 (1.73-2.52) for >4 years. The HR was 0.90 (0.79-1.03) for an additional year of thiazide-like diuretic use.

Conclusions: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed.

Impact: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0620DOI Listing
November 2021

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

J Clin Oncol 2021 Nov 25;39(32):3623-3632. Epub 2021 Aug 25.

James Cook University Hospital, South Tees NHS Foundation Trust, Middlesbrough, United Kingdom.

Purpose: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN).

Methods: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences.

Results: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL.

Conclusion: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.
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http://dx.doi.org/10.1200/JCO.21.00006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577685PMC
November 2021

A contrast-enhanced-CT-based classification tree model for classifying malignancy of solid lung tumors in a Chinese clinical population.

J Thorac Dis 2021 Jul;13(7):4407-4417

Department of Radiology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Tianjin, China.

Background: To develop and validate a contrast-enhanced CT based classification tree model for classifying solid lung tumors in clinical patients into malignant or benign.

Methods: Between January 2015 and October 2017, 827 pathologically confirmed solid lung tumors (487 malignant, 340 benign; median size, 27.0 mm, IQR 18.0-39.0 mm) from 827 patients from a dedicated Chinese cancer hospital were identified. Nodules were divided randomly into two groups, a training group (575 cases) and a testing group (252 cases). CT characteristics were collected by two radiologists, and analyzed using a classification and regression tree (CART) model. For validation, we used the decision analysis threshold to evaluate the classification performance of the CART model and radiologist's diagnosis (benign; malignant) in the testing group.

Results: Three out of 19 characteristics [margin (smooth; slightly lobulated/lobulated/spiculated), and shape (round/oval; irregular), subjective enhancement (no/uniform enhancement; heterogeneous enhancement)] were automatically generated by the CART model for classifying solid lung tumors. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the CART model is 98.5%, 58.1%, 80.6%, 98.6%, 79.8%, and 90.4%, 54.7%, 82.4% 98.5%, 74.2% for the radiologist's diagnosis by using three-threshold decision analysis.

Conclusions: Tumor margin and shape, and subjective tumor enhancement were the most important CT characteristics in the CART model for classifying solid lung tumors as malignant. The CART model had higher discriminatory power than radiologist's diagnosis. The CART model could help radiologists making recommendations regarding follow-up or surgery in clinical patients with a solid lung tumor.
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http://dx.doi.org/10.21037/jtd-21-588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339765PMC
July 2021

Lung Nodule Detectability of Artificial Intelligence-assisted CT Image Reading in Lung Cancer Screening.

Curr Med Imaging 2021 Aug 6. Epub 2021 Aug 6.

Department of Radiology, Shanghai General Hospital of Nanjing Medical University, Haining Rd.100, Shanghai 200080. China.

Background: Artificial intelligence (AI)-based automatic lung nodule detection system improves the detection rate of nodules. It is important to evaluate the clinical value of AI system by comparing AI-assisted nodule detection with actu-al radiology reports.

Objective: To compare the detection rate of lung nodules between the actual radiology reports and AI-assisted reading in lung cancer CT screening.

Methods: Participants in chest CT screening from November to December 2019 were retrospectively included. In the real-world radiologist observation, 14 residents and 15 radiologists participated to finalize radiology reports. In AI-assisted reading, one resident and one radiologist reevaluated all subjects with the assistance of an AI system to lo-cate and measure the detected lung nodules. A reading panel determined the type and number of detected lung nodules between these two methods.

Results: In 860 participants (57±7 years), the reading panel confirmed 250 patients with >1 solid nodule, while radiolo-gists observed 131, lower than 247 by AI-assisted reading (p<0.001). The panel confirmed 111 patients with >1 non-solid nodule, whereas radiologist observation identified 28, lower than 110 by AI-assisted reading (p<0.001). The accuracy and sensitivity of radiologist observation for solid nodules were 86.2% and 52.4%, lower than 99.1% and 98.8% by AI-assisted reading, respectively. These metrics were 90.4% and 25.2% for non-solid nodules, lower than 98.8% and 99.1% by AI-assisted reading, respectively.

Conclusion: Comparing with the actual radiology reports, AI-assisted reading greatly improves the accuracy and sensi-tivity of nodule detection in chest CT, which benefits lung nodule detection, especially for non-solid nodules.
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http://dx.doi.org/10.2174/1573405617666210806125953DOI Listing
August 2021

Diet quality indices and gastrointestinal cancer risk: results from the Lifelines study.

Eur J Nutr 2021 Aug 2. Epub 2021 Aug 2.

Department of Epidemiology, FA40 University Medical Centre Groningen, University of Groningen, PO 30.001, Groningen, 9700 RB, The Netherlands.

Objective: To investigate the long-term association between four dietary quality indices and the risk of gastrointestinal (GI) cancer.

Methods: Baseline details of the dietary intake of participants, assessed by a single food frequency questionnaire from the prospective Lifelines population-based cohort were translated to diet quality scores using several dietary and dietary-lifestyle indices. Incident cases of GI cancer were then assessed by linkage to the Dutch nationwide histo-cytopathology registry. The association between GI cancer risk and diet quality (defined as higher quintiles on dietary indices compared to the first quintile) was assessed by multivariable Cox proportional hazard models.

Results: We included 72,695 participants aged 51.20 ± 8.71 years with a median follow-up to cancer diagnosis of 8 years (interquartile range 2 years). During follow-up, 434 colorectal cancers and 139 upper GI cancers were diagnosed. There was a significant reduction in colorectal cancer risk for high categories in the American Cancer Society (ACS) Index (hazard ratio 0.62; 95% CI 0.46-0.84). However, high dietary index scores were not associated with strong beneficial effects on upper GI cancer risk.

Conclusion: High quintiles on the ACS Index were associated with a significantly reduced risk of colorectal cancer. This index may be of use in a colorectal cancer prevention program.
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http://dx.doi.org/10.1007/s00394-021-02648-3DOI Listing
August 2021

Assessment of the Benefits and Cost-Effectiveness of Population-Based Breast Cancer Screening in Urban China: A Model-Based Analysis.

Int J Health Policy Manag 2021 Jul 4. Epub 2021 Jul 4.

Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: To decrease the burden of breast cancer (BC), the Chinese government recently introduced biennial mammography screening for women aged 45-70 years. In this study, we assess the effectiveness and cost-effectiveness of implementing this programme in urban China using a micro-simulation model.

Methods: The 'Simulation Model on radiation Risk and breast cancer Screening' (SiMRiSc) was applied, with parameters updated based on available data for the Chinese population. The base scenario was biennial mammography screening for women aged 45-70 years, and this was compared to a reference population with no screening. Seven alternative scenarios were then simulated by varying the screening intervals and participant ages. This analysis was conducted from a societal perspective. The discounted incremental cost-effectiveness ratio (ICER) was compared to a threshold of triple the gross domestic product (GDP) per life years gained (LYG), which was 30 785 USD/LYG. Univariate sensitivity analyses were conducted to evaluate model robustness. In addition, a budget impact analysis was performed by comparing biennial screening with no screening at a time horizon of 10 years.

Results: Compared with no screening, the base scenario was cost-effective in urban China, giving a discounted average cost-effectiveness ratio (ACER) of 17 309 USD/LYG. The model was most sensitive to the cost of mammography per screen, followed by mean size of self-detected tumours, mammographic breast density and the cumulative lifetime risk of BC. The efficient frontier showed that at a threshold of 30 785 USD/LYG, the base scenario was the optimal scenario with a discounted ICER of 25 261 USD/LYG. Over 10 years, screening would incur a net cost of almost 38.1 million USD for a city with 1 million citizens.

Conclusion: Compared to no screening, biennial mammography screening for women aged from 45-70 is cost-effective in urban China.
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http://dx.doi.org/10.34172/ijhpm.2021.62DOI Listing
July 2021

Machine-Learning-Derived Nomogram Based on 3D Radiomic Features and Clinical Factors Predicts Progression-Free Survival in Lung Adenocarcinoma.

Front Oncol 2021 23;11:692329. Epub 2021 Jun 23.

Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: To establish a machine-learning-derived nomogram based on radiomic features and clinical factors to predict post-surgical 2-year progression-free survival (PFS) in patients with lung adenocarcinoma.

Methods: Patients with >2 years post-surgical prognosis results of lung adenocarcinoma were included in Hospital-1 for model training (n = 100) and internal validation (n = 50), and in Hospital-2 for external testing (n = 50). A total of 1,672 radiomic features were extracted from 3D segmented CT images. The Rad-score was established using random survival forest by accumulating and weighting the top-20 imaging features contributive to PFS. A nomogram for predicting PFS was established, which comprised the Rad-score and clinical factors highly relevant to PFS.

Results: In the training, internal validation, and external test groups, 69/100 (69%), 37/50 (74%) and 36/50 (72%) patients were progression-free at two years, respectively. According to the Rad-score, the integral of area under the curve (iAUC) for discriminating high and low risk of progression was 0.92 (95%CI: 0.77-1.0), 0.70 (0.41-0.98) and 0.90 (0.65-1.0), respectively. The C-index of Rad-score was 0.781 and 0.860 in the training and external test groups, higher than 0.707 and 0.606 for TNM stage, respectively. The nomogram integrating Rad-score and clinical factors (lung nodule type, cM stage and histological type) achieved a C-index of 0.845 and 0.837 to predict 2-year PFS, respectively, significantly higher than by only radiomic features (all p < 0.01).

Conclusion: The nomogram comprising CT-derived radiomic features and risk factors showed a high performance in predicting post-surgical 2-year PFS of patients with lung adenocarcinoma, which may help personalize the treatment decisions.
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http://dx.doi.org/10.3389/fonc.2021.692329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260977PMC
June 2021

Glycemic Control for Colorectal Cancer Survivors Compared to Those without Cancer in the Dutch Primary Care for Type 2 Diabetes: A Prospective Cohort Study.

Cancers (Basel) 2021 Jun 2;13(11). Epub 2021 Jun 2.

Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Cancer survivors with diabetes tend to have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. We aimed to investigate whether glycemic control differs between colorectal cancer (CRC) survivors and those without cancer, among patients with type 2 diabetes being treated in the Dutch primary care. The Zwolle Outpatient Diabetes project Integrating Available Care database was linked with the Dutch Cancer Registry ( = 71,648, 1998-2014). The cases were those with stage 0-III CRC, and the controls were those without cancer history. The primary and secondary outcomes were the probability of reaching the glycated hemoglobin (HbA1c) target and the mean of HbA1c during follow-up, respectively. Mixed linear modeling was applied, where the status of CRC was a time-varying variable. Among the 57,330 patients included, 705 developed CRC during follow-up. The mean probability of reaching the HbA1c target during follow-up was 73% versus 74% ( = 0.157) for CRC survivors versus those without cancer, respectively. The mean HbA1c was 51.1 versus 50.8 mmol/mol ( = 0.045) among CRC survivors versus those without cancer, respectively. We observed a clinically comparable glycemic control among the CRC survivors without cancer, indicating that glycemic control for CRC survivors can be delegated to primary care professionals.
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http://dx.doi.org/10.3390/cancers13112767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199666PMC
June 2021

Differences in Prostate Cancer Incidence and Mortality in Lower Saxony (Germany) and Groningen Province (Netherlands): Potential Impact of Prostate-Specific Antigen Testing.

Front Oncol 2021 28;11:681006. Epub 2021 May 28.

University Hospital for Urology, Klinikum Oldenburg, Department of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.

Background: Prostate cancer (PCa) is the most frequent cancer among men in Europe. Differences in PCa incidence around the world can be partly explained by variations in recommendations for prostate-specific antigen (PSA), particularly for early detection. For example, the PSA testing policy is more conservative in the Netherlands than in Germany. To better understand the relationship between PSA testing recommendations and PCa incidence, stage distribution, and mortality, we compared these variables over time between Lower Saxony in northwestern Germany and the neighboring province of Groningen in the Netherlands.

Methods: Population data, tumor stage- and age group-specific PCa incidence (ICD-10 C61) and mortality rates for Lower Saxony and Groningen were obtained from the Lower Saxony Epidemiological Cancer Registry, the Netherlands Comprehensive Cancer Organization, and Statistics Netherlands for 2003-2012. Incidence and mortality rates per 100,000 person-years were age-standardized (ASR, old European standard). Trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR) for specific age groups were assessed using joinpoint regression.

Results: The mean annual PCa ASIR between 2003 and 2012 was on average 19.9% higher in Lower Saxony than in Groningen (120.5 vs. 100.5 per 100,000), while the mean annual ASMR was on average 24.3% lower in Lower Saxony than in Groningen (21.5 vs. 28.4 per 100,000). Between 2003 and 2012, the average annual percentage change (AAPC) in PCa incidence rates did not change significantly in either Lower Saxony (-1.8%, 95% CI -3.5, 0.0) or Groningen (0.2%, 95% CI -5.0, 5.7). In contrast, the AAPC in mortality rate decreased significantly during the same time period in Lower Saxony (-2.5%, 95% CI -3.0, -2.0) but not in Groningen (0.1%, 95% CI -2.4, 2.6).

Conclusions: Higher PCa incidence and lower PCa-related mortality was detected in Lower Saxony than in Groningen. Although recommendations on PSA testing may play a role, the assessed data could not offer obvious explanations to the observed differences. Therefore, further investigations including data on the actual use of PSA testing, other influences (e.g., dietary and ethnic factors), and better data quality are needed to explain differences between the regions.
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http://dx.doi.org/10.3389/fonc.2021.681006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194402PMC
May 2021

Frailty and restrictions in geriatric domains are associated with surgical complications but not with radiation-induced acute toxicity in head and neck cancer patients: A prospective study.

Oral Oncol 2021 07 7;118:105329. Epub 2021 Jun 7.

Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, PO box 30.001, 9700 RB, Groningen, the Netherlands.

Objectives: We aimed to evaluate the association between frailty screening and geriatric assessment (GA) on short term adverse events in patients treated for head and neck cancer (HNC) for the first time in a prospective study.

Materials And Methods: Newly diagnosed HNC patients undergoing curative treatment were prospectively included in OncoLifeS, a data biobank. Prior to the start of treatment, frailty was assessed with a GA, Groningen Frailty Indicator (GFI) and Geriatric-8 (G8). The GA included comorbidity (Adult Comorbidity Evaluation - 27), nutritional status (Malnutrition Universal Screening Tool), functional status ((instrumental) Activities of Daily Living), mobility (Timed Up & Go), psychological (Geriatric Depression Scale 15) and cognitive (Mini Mental State Examination) measures. Clinically relevant postoperative complications (Clavien-Dindo ≥ grade 2) and acute radiation-induced toxicity (Common Terminology Criteria for Adverse Events version 4.0 ≥ grade 2) were defined as outcome measures. Univariable and multivariable logistic regression analyses were performed, yielding odds ratios (ORs) and 95% confidence intervals (95%CIs).

Results: Of the 369 included patients, 259 patients were eligible for analysis. Postoperative complications occurred in 41/148 (27.7%) patients and acute radiation-induced toxicity was present in 86/160 (53.7%) patients. Number of deficit domains of GA (OR = 1.71, 95%CI = 1.14-2.56), GFI (OR = 2.54, 95%CI = 1.02-6.31) and G8 (OR5.59, 95%CI = 2.14-14.60) were associated with postoperative complications, but not with radiation-induced toxicity.

Conclusion: Frailty and restrictions in geriatric domains were associated with postoperative complications, but not with radiation-induced acute toxicity in curatively treated HNC patients. The results of this prospective study further emphasizes the importance of geriatric evaluation, particularly before surgery.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105329DOI Listing
July 2021

A Classification Approach for Cancer Survivors from Those Cancer-Free, Based on Health Behaviors: Analysis of the Lifelines Cohort.

Cancers (Basel) 2021 May 12;13(10). Epub 2021 May 12.

Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Health behaviors affect health status in cancer survivors. We hypothesized that nonlinear algorithms would identify distinct key health behaviors compared to a linear algorithm and better classify cancer survivors. We aimed to use three nonlinear algorithms to identify such key health behaviors and compare their performances with that of a logistic regression for distinguishing cancer survivors from those without cancer in a population-based cohort study. We used six health behaviors and three socioeconomic factors for analysis. Participants from the Lifelines population-based cohort were binary classified into a cancer-survivors group and a cancer-free group using either nonlinear algorithms or logistic regression, and their performances were compared by the area under the curve (AUC). In addition, we performed case-control analyses (matched by age, sex, and education level) to evaluate classification performance only by health behaviors. Data were collected for 107,624 cancer free participants and 2760 cancer survivors. Using all variables resulted an AUC of 0.75 ± 0.01, using only six health behaviors, the logistic regression and nonlinear algorithms differentiated cancer survivors from cancer-free participants with AUCs of 0.62 ± 0.01 and 0.60 ± 0.01, respectively. The main distinctive classifier was age. Though not relevant to classification, the main distinctive health behaviors were body mass index and alcohol consumption. In the case-control analyses, algorithms produced AUCs of 0.52 ± 0.01. No key health behaviors were identified by linear and nonlinear algorithms to differentiate cancer survivors from cancer-free participants in this population-based cohort.
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http://dx.doi.org/10.3390/cancers13102335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151639PMC
May 2021

The Role of Socio-Demographic Factors in the Coverage of Breast Cancer Screening: Insights From a Quantile Regression Analysis.

Front Public Health 2021 15;9:648278. Epub 2021 Apr 15.

Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

In Flanders, breast cancer (BC) screening is performed in a population-based breast cancer screening program (BCSP), as well as in an opportunistic setting. Women with different socio-demographic characteristics are not equally covered by BC screening. To evaluate the role of socio-demographic characteristics on the lowest 10th and highest 90th quantile levels of BC screening coverage. The 2017 neighborhood-level coverage rates of 8,690 neighborhoods with women aged 50-69 and eligible for BCSP and opportunistic screening were linked to socio-demographic data. The association between socio-demographic characteristics and the coverage rates of BCSP and opportunistic screening was evaluated per quantile of coverage using multivariable quantile regression models, with specific attention to the lowest 10th and highest 90th quantiles. The median coverage in the BCSP was 50%, 33.5% in the 10th quantile, and 64.5% in the 90th quantile. The median coverage of the opportunistic screening was 12, 4.2, and 24.8% in the 10th and 90th quantile, respectively. A lower coverage of BCSP was found in neighborhoods with more foreign residents and larger average household size, which were considered indicators for a lower socioeconomic status (SES). However, a higher average personal annual income, which was considered an indicator for a higher SES, was also found in neighborhoods with lower coverage of BCSP. For these neighborhoods, that have a relatively low and high SES, the negative association between the percentage of foreign residents, average household size, and average personal annual income and the coverage in the BCSP had the smallest regression coefficient and 95% confidence interval (CI) values were -0.75 (95% CI: -0.85, -0.65), -13.59 (95% CI: -15.81, -11.37), and -1.05 (95% CI: -1.18, -0.92), respectively, for the 10th quantile. The neighborhoods with higher coverage of opportunistic screening had a relatively higher average personal annual income, with the largest regression coefficient of 1.72 (95% CI: 1.59, 1.85) for the 90th quantile. Women from relatively low and high SES neighborhoods tend to participate less in the BCSP, whereas women with a relatively high SES tend to participate more in opportunistic screening. For women from low SES neighborhoods, tailored interventions are needed to improve the coverage of BCSP.
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http://dx.doi.org/10.3389/fpubh.2021.648278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082021PMC
May 2021

Prediction of Incident Cancers in the Lifelines Population-Based Cohort.

Cancers (Basel) 2021 04 28;13(9). Epub 2021 Apr 28.

Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Cancer incidence is rising, and accurate prediction of incident cancers could be relevant to understanding and reducing cancer incidence. The aim of this study was to develop machine learning (ML) models that could predict an incident diagnosis of cancer. Participants without any history of cancer within the Lifelines population-based cohort were followed for a median of 7 years. Data were available for 116,188 cancer-free participants and 4232 incident cancer cases. At baseline, socioeconomic, lifestyle, and clinical variables were assessed. The main outcome was an incident cancer during follow-up (excluding skin cancer), based on linkage with the national pathology registry. The performance of three ML algorithms was evaluated using supervised binary classification to identify incident cancers among participants. Elastic net regularization and Gini index were used for variables selection. An overall area under the receiver operator curve (AUC) <0.75 was obtained, the highest AUC value was for prostate cancer (random forest AUC = 0.82 (95% CI 0.77-0.87), logistic regression AUC = 0.81 (95% CI 0.76-0.86), and support vector machines AUC = 0.83 (95% CI 0.78-0.88), respectively); age was the most important predictor in these models. Linear and non-linear ML algorithms including socioeconomic, lifestyle, and clinical variables produced a moderate predictive performance of incident cancers in the Lifelines cohort.
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http://dx.doi.org/10.3390/cancers13092133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125183PMC
April 2021

Preoperative Inflammatory Markers as a Predictor of Three-Year Overall Survival in Older Cancer Patients Undergoing Oncologic Surgery.

Cancers (Basel) 2021 Apr 11;13(8). Epub 2021 Apr 11.

Department of Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.

Oncologic surgery results in substantially higher morbidity and mortality rates in older patients compared to younger patients, yet little is known about the relation between the preoperative inflammatory state and postoperative outcome in the specific group of older cancer patients. The aim of this study was to examine whether preoperative inflammatory markers could be a predictor of overall survival in older patients undergoing elective surgery for a solid malignant tumor. Patients 65 years and older undergoing surgery for a solid malignant tumor were included in a prospective cohort study. Inflammatory markers C-reactive protein (CRP), interleukin-1 beta (IL-1β), IL-6, IL10, IL-12 and tumor necrosis factor-alpha (TNF-α) were measured in plasma samples preoperatively. The main outcome was overall survival three years after surgery. Between 2010 and 2016, 328 patients with a median age of 71.5 years (range 65-89) were included. A significantly higher mortality rate three years after surgery, was found in patients with high preoperative plasma levels of CRP and IL-6 ( = 0.013 and = 0.046, respectively). In multivariate analysis, corrected for variables such as age, disease stage, frailty, comorbidities, type of surgery and complications, a preoperative plasma level of CRP ≥ 10 mg/L was an independent prognostic factor for inferior overall survival three years after surgery (multivariate hazard ratio 1.50, 95% confidence interval 1.04-2.16, = 0.031). Also, for the specific group of patients with colorectal cancer, a preoperative plasma level of CRP ≥ 10 mg/L was a prognostic factor for inferior survival three years after surgery (multivariate hazard ratio 2.40, 95% confidence interval 1.20-4.81, = 0.014). Preoperative elevated plasma level of CRP is an independent unfavorable prognostic factor for overall survival three years after oncologic surgery. This gives more insight into the relationship between inflammation and survival in older cancer patients, and might contribute to risk stratification for poor outcome after surgery in older cancer patients.
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http://dx.doi.org/10.3390/cancers13081824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069748PMC
April 2021

Simultaneous Identification of and Mutations in Patients with Non-Small Cell Lung Cancer by Machine Learning-Derived Three-Dimensional Radiomics.

Cancers (Basel) 2021 Apr 10;13(8). Epub 2021 Apr 10.

Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Haining Rd.100, Shanghai 200080, China.

Purpose: To develop a machine learning-derived radiomics approach to simultaneously discriminate epidermal growth factor receptor (), Kirsten rat sarcoma viral oncogene (), Erb-B2 receptor tyrosine kinase 2 (), and tumor protein 53 () genetic mutations in patients with non-small cell lung cancer (NSCLC).

Methods: This study included consecutive patients from April 2018 to June 2020 who had histologically confirmed NSCLC, and underwent pre-surgical contrast-enhanced CT and post-surgical next-generation sequencing (NGS) tests to determine the presence of , , , and mutations. A dedicated radiomics analysis package extracted 1672 radiomic features in three dimensions. Discriminative models were established using the least absolute shrinkage and selection operator to determine the presence of , , , and mutations, based on radiomic features and relevant clinical factors.

Results: In 134 patients (63.6 ± 8.9 years), the 20 most relevant radiomic features (13 for ) to mutations were selected to construct models. The areas under the curve (AUCs) of the combined model (radiomic features and relevant clinical factors) for discriminating and mutations were 0.78 (95% CI: 0.70-0.86), 0.81 (0.69-0.93), 0.87 (0.78-0.95), and 0.84 (0.78-0.91), respectively. In particular, the specificity to exclude mutations was 0.96 (0.87-0.99). The sensitivity to determine , , and mutations ranged from 0.82 (0.69-90) to 0.92 (0.62-0.99).

Conclusions: Machine learning-derived 3D radiomics can simultaneously discriminate the presence of , , , and mutations in patients with NSCLC. This noninvasive and low-cost approach may be helpful in screening patients before invasive sampling and NGS testing.
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http://dx.doi.org/10.3390/cancers13081814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070114PMC
April 2021

Seasonal prevalence and characteristics of low-dose CT detected lung nodules in a general Dutch population.

Sci Rep 2021 04 28;11(1):9139. Epub 2021 Apr 28.

Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

We investigated whether presence and characteristics of lung nodules in the general population using low-dose computed tomography (LDCT) varied by season. Imaging in Lifelines (ImaLife) study participants who underwent chest LDCT-scanning between October 2018 and October 2019 were included in this sub-study. Hay fever season (summer) was defined as 1st April to 30th September and Influenza season (winter) as 1st October to 31st March. All lung nodules with volume of ≥ 30 mm (approximately 3 mm in diameter) were registered. In total, 2496 lung nodules were found in 1312 (38%) of the 3456 included participants (nodules per participant ranging from 1 to 21, median 1). In summer, 711 (54%) participants had 1 or more lung nodule(s) compared to 601 (46%) participants in winter (p = 0.002). Of the spherical, perifissural and left-upper-lobe nodules, relatively more were detected in winter, whereas of the polygonal-, irregular-shaped and centrally-calcified nodules, relatively more were detected in summer. Various seasonal diseases with inflammation as underlying pathophysiology may influence presence and characteristics of lung nodules. Further investigation into underlying pathophysiology using short-term LDCT follow-up could help optimize the management strategy for CT-detected lung nodules in clinical practice.
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http://dx.doi.org/10.1038/s41598-021-88328-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080793PMC
April 2021

Human-recognizable CT image features of subsolid lung nodules associated with diagnosis and classification by convolutional neural networks.

Eur Radiol 2021 Oct 13;31(10):7303-7315. Epub 2021 Apr 13.

Radiology Department, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Haining Rd.100, Shanghai, 200080, China.

Objectives: The interpretability of convolutional neural networks (CNNs) for classifying subsolid nodules (SSNs) is insufficient for clinicians. Our purpose was to develop CNN models to classify SSNs on CT images and to investigate image features associated with the CNN classification.

Methods: CT images containing SSNs with a diameter of ≤ 3 cm were retrospectively collected. We trained and validated CNNs by a 5-fold cross-validation method for classifying SSNs into three categories (benign and preinvasive lesions [PL], minimally invasive adenocarcinoma [MIA], and invasive adenocarcinoma [IA]) that were histologically confirmed or followed up for 6.4 years. The mechanism of CNNs on human-recognizable CT image features was investigated and visualized by gradient-weighted class activation map (Grad-CAM), separated activation channels and areas, and DeepDream algorithm.

Results: The accuracy was 93% for classifying 586 SSNs from 569 patients into three categories (346 benign and PL, 144 MIA, and 96 IA in 5-fold cross-validation). The Grad-CAM successfully located the entire region of image features that determined the final classification. Activated areas in the benign and PL group were primarily smooth margins (p < 0.001) and ground-glass components (p = 0.033), whereas in the IA group, the activated areas were mainly part-solid (p < 0.001) and solid components (p < 0.001), lobulated shapes (p < 0.001), and air bronchograms (p < 0.001). However, the activated areas for MIA were variable. The DeepDream algorithm showed the image features in a human-recognizable pattern that the CNN learned from a training dataset.

Conclusion: This study provides medical evidence to interpret the mechanism of CNNs that helps support the clinical application of artificial intelligence.

Key Points: • CNN achieved high accuracy (93%) in classifying subsolid nodules on CT images into three categories: benign and preinvasive lesions, MIA, and IA. • The gradient-weighted class activation map (Grad-CAM) located the entire region of image features that determined the final classification, and the visualization of the separated activated areas was consistent with radiologists' expertise for diagnosing subsolid nodules. • DeepDream showed the image features that CNN learned from a training dataset in a human-recognizable pattern.
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http://dx.doi.org/10.1007/s00330-021-07901-1DOI Listing
October 2021

Determinants of Population-Based Cancer Screening Performance at Primary Healthcare Institutions in China.

Int J Environ Res Public Health 2021 03 23;18(6). Epub 2021 Mar 23.

Department of Epidemiology and Health statistics, Tianjin Medical University, Tianjin 300070, China.

Background: For a decade, most population-based cancer screenings in China are performed by primary healthcare institutions. To assess the determinants of performance of primary healthcare institutions in population-based breast, cervical, and colorectal cancer screening in China.

Methods: A total of 262 primary healthcare institutions in Tianjin participated in a survey on cancer screening. The survey consisted of questions on screening tests, the number of staff members and training, the introduction of the screening programs to residents, the invitation of residents, and the number of performed screenings per year. Logistic regression models were used to analyze the determinants of performance of an institution to fulfil the target number of screenings.

Results: In 58% and 61% of the institutions between three and nine staff members were dedicated to breast and cervical cancer screening, respectively, whereas in 71% of the institutions ≥10 staff members were dedicated to colorectal cancer screening. On average 60% of institutions fulfilled the target number of breast and cervical cancer screenings, whereas 93% fulfilled the target number for colorectal cancer screening. The determinants of performance were rural districts for breast (OR = 5.16 (95%CI: 2.51-10.63)) and cervical (OR = 4.17 (95%CI: 2.14-8.11)) cancer screenings, and ≥3 staff members dedicated to cervical cancer screening (OR = 2.34 (95%CI: 1.09-5.01)).

Conclusions: Primary healthcare institutions in China perform better in colorectal than in breast and cervical cancer screening, and institutions in rural districts perform better than institutions in urban districts. Increasing the number of staff members on breast and cervical cancer screening could improve the performance of population-based cancer screening.
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http://dx.doi.org/10.3390/ijerph18063312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005057PMC
March 2021

Fatigue among Long-Term Breast Cancer Survivors: A Controlled Cross-Sectional Study.

Cancers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, PO Box 196, 9700 AD Groningen, The Netherlands.

Background: Fatigue is the most common and persistent symptom among women in the first five years after a breast cancer diagnosis. However, long-term prevalence of fatigue, among breast cancer survivors, needs further investigation.

Aim: To compare fatigue experienced by long-term breast cancer survivors with that in a reference population and to evaluate the determinants of that fatigue.

Design And Setting: A cross-sectional cohort study of 350 breast cancer survivors ≥5 years after diagnosis and a reference population of 350 women matched by age and general practitioner.

Method: Fatigue was measured using the Multidimensional Fatigue Inventory (MFI-20), and a sum score of >60 (multidimensional fatigue) was the primary outcome. Logistic regression was applied to compare the prevalence of multidimensional fatigue between the survivor and reference populations, adjusted for body mass index (BMI) and for cardiovascular and psychological variables. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated. Logistic regression was applied to evaluate the determinants of multidimensional fatigue among the survivors.

Results: Breast cancer survivors (median 10 years after diagnosis), more often experienced multidimensional fatigue than the reference population (26.6% versus 15.4%; OR, 2.0 [95%CI, 1.4-2.9]), even after adjusting for confounders. The odds of multidimensional fatigue were also higher among survivors with symptoms of depression (32.2% versus 2.7%; OR, 17.0 [95%CI, 7.1-40.5]) or anxiety (41.9% versus 10.1%; OR, 6.4 [95%CI, 3.6-11.4]).

Conclusion: One in four breast cancer survivors experience multidimensional fatigue and fatigue occurs more frequently than in women of the same age and general practitioner. This fatigue appears to be associated with symptoms of depression and anxiety.
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http://dx.doi.org/10.3390/cancers13061301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001130PMC
March 2021

Endometrial Cancer Risk in Women With Germline BRCA1 or BRCA2 Mutations: Multicenter Cohort Study.

J Natl Cancer Inst 2021 Sep;113(9):1203-1211

Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.

Background: Endometrial cancer (EC) risk in BReast CAncer gene 1/2 (BRCA1/2) mutation carriers is uncertain; therefore, we assessed this in a large Dutch nationwide cohort study.

Methods: We selected 5980 BRCA1/2 (3788 BRCA1, 2151 gBRCA2, 41 both BRCA1/BRCA2) and 8451 non-BRCA1/2 mutation carriers from the Hereditary Breast and Ovarian cancer study, the Netherlands cohort. Follow-up started at the date of the nationwide Dutch Pathology Registry coverage (January 1, 1989) or at the age of 25 years (whichever came last) and ended at date of EC diagnosis, last follow-up, or death (whichever came first). EC risk in BRCA1/2 mutation carriers was compared with 1) the general population, estimating standardized incidence ratios (SIRs) based on Dutch population-based incidence rates; and 2) non-BRCA1/2 mutation carriers, using Cox-regression analyses, expressed as hazard ratio (HR). Statistical tests were 2-sided.

Results: Fifty-eight BRCA1/2 and 33 non-BRCA1/2 mutation carriers developed EC over 119 296 and 160 841 person-years, respectively (SIR = 2.83, 95% confidence interval [CI] = 2.18 to 3.65; and HR = 2.37, 95% CI = 1.53 to 3.69, respectively). gBRCA1 mutation carriers showed increased risks for EC overall (SIR = 3.51, 95% CI = 2.61 to 4.72; HR = 2.91, 95% CI = 1.83 to 4.66), serous-like EC (SIR = 12.64, 95% CI = 7.62 to 20.96; HR = 10.48, 95% CI = 2.95 to 37.20), endometrioid EC (SIR = 2.63, 95% CI = 1.80 to 3.83; HR = 2.01, 95% CI = 1.18 to 3.45), and TP53-mutated EC (HR = 15.71, 95% CI = 4.62 to 53.40). For BRCA2 mutation carriers, overall (SIR = 1.70, 95% CI = 1.01 to 2.87) and serous-like EC risks (SIR = 5.11, 95% CI = 1.92 to 13.63) were increased compared with the general population. Absolute risks by 75 years remained low (overall EC = 3.0%; serous-like EC = 1.1%).

Conclusions: BRCA1/2 mutation carriers have a two- to threefold increased risk for EC, with highest risk observed for the rare subgroups of serous-like and p53-abnormal EC in BRCA1 mutation carriers.
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http://dx.doi.org/10.1093/jnci/djab036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418438PMC
September 2021

Diagnostic accuracy of follow-up tests for detecting colorectal cancer recurrences in primary care: A systematic review and meta-analysis.

Eur J Cancer Care (Engl) 2021 Sep 11;30(5):e13432. Epub 2021 Mar 11.

Department of General Practice & Elderly Care Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Introduction: Traditionally, follow-up of colorectal cancer (CRC) is performed in secondary care. In new models of care, the screening part care could be replaced to primary care. We aimed to synthesise evidence on the diagnostic accuracy of commonly used screeners in CRC follow-up applicable in primary care: carcinoembryonic antigen (CEA), ultrasound and physical examination.

Methods: Medline, EMBASE, Cochrane Trial Register and Web of Science databases were systematically searched. Studies were included if they provided sufficient data for a 2 × 2 contingency tables. QUADAS-2 was used to assess methodological quality. We performed bivariate random effects meta-analysis, generated a hypothetical cohort, and reported sensitivity and specificity.

Results: We included 12 studies (n = 3223, median recurrence rate 19.6%). Pooled estimates showed a sensitivity for CEA (≤ 5 μg/l) of 59% [47%-70%] and a specificity of 89% [80%-95%]. Only few studies reported sensitivities and specificities for ultrasound (36-70% and 97-100%, respectively) and clinical examination (23% and 27%, respectively).

Conclusion: In practice, GPs could perform CEA screening. Radiological examination in a hospital setting should remain part of the surveillance strategy. Personalised algorithms accounting for recurrence risk and changes of CEA-values over time might add to the diagnostic value of CEA in primary care.
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http://dx.doi.org/10.1111/ecc.13432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518902PMC
September 2021

Post-discharge Telemonitoring of Physical Activity, Vital Signs, and Patient-Reported Symptoms in Older Patients Undergoing Cancer Surgery.

Ann Surg Oncol 2021 Oct 27;28(11):6512-6522. Epub 2021 Feb 27.

Department of Surgical Oncology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

Background: Postoperative home monitoring could potentially detect complications early, but evidence in oncogeriatric surgery is scarce. Therefore, we evaluated whether post-discharge physical activity, vital signs, and patient-reported symptoms are related to post-discharge complications and hospital readmissions in older patients undergoing cancer surgery.

Methods: In this observational cohort study, we monitored older patients (≥65 years of age) undergoing cancer surgery, for 2 weeks post-discharge using tablet-based applications and connected devices. Outcome measures were post-discharge complications and readmissions; physical activity and patient-reported symptoms over time; and threshold violations for physical activity (step count <1000 steps/day), vital signs (temperature <36°C or >38°C; blood pressure <100/60 mmHg or >150/100 mmHg; heart rate <50 bpm or >100 bpm; weight -5% or +5% of weight at discharge); and patient-reported symptoms (pain score greater than the previous day; presence of dyspnea, vomiting, dizziness, fever).

Results: Of 58 patients (mean age 72 years), 24 developed a post-discharge complication and 13 were readmitted. Measured parameters indicated 392 threshold violations out of 5379 measurements (7.3%) in 40 patients, mostly because of physical inactivity. Patients with readmissions had lower physical activity at discharge and at day 9 after discharge and violated a physical activity threshold more often. Patients with post-discharge complications had a higher median pain score compared with patients without these adverse events. No differences in threshold violations of other parameters were observed between patients with and without post-discharge complications and readmissions.

Conclusion: Our results show the potential of telemonitoring older patients after cancer surgery but confirm that detecting post-discharge complications is complex and multifactorial.
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http://dx.doi.org/10.1245/s10434-021-09707-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914037PMC
October 2021

Informing policy makers on the efficiency of population level tobacco control interventions in Asia: A systematic review of model-based economic evaluations.

J Glob Health 2020 Dec;10(2):020437

University of Groningen, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, the Netherlands.

Background: Economic evaluations of tobacco control interventions support decisions regarding resource allocation in public health policy. Our systematic review was aimed at identifying potential bias in decision models used to estimate the long-term costs and effects of population-based tobacco control interventions in Asia.

Methods: We included studies conducted in Asian countries and using a modelling technique to evaluate the economic impacts of one or more population-based tobacco interventions in line with the Framework Convention on Tobacco Control (FCTC). We assessed the structure, input parameters, and risk of bias for each model, and performed a narrative synthesis of the included studies.

Results: Nine model-based economic evaluation studies of population-based tobacco interventions were identified. About 60% of the criteria for reporting quality were met in all studies, indicating that reporting generally lacked transparency. The studies were highly heterogeneous in terms of the scope, types, and structures of their models and the quality of input parameters. One-third of the models applied in the studies scored a high risk of bias, with problems mostly falling into the following categories: model type, time horizons, and smoking transition probabilities.

Conclusions: More data are needed to provide high-quality evidence regarding the cost-effectiveness of tobacco control policies in Asia. Strong evidence at the country level hinges on the availability of accurate estimates of the effects of the interventions, the relative risks of smoking, and the price elasticity of the demand for tobacco. Simple transfers of models built in Western populations do not suffice.

Protocol Registration: PROSPERO CRD 42019141679.
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http://dx.doi.org/10.7189/jogh.10.020437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750019PMC
December 2020
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