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1. Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status

Author

Wang, Yuwei, Dackus, Gwen M. H. E., Rosenberg, Efraim H., Cornelissen, Sten, de Boo, Leonora W., Broeks, Annegien, Brugman, Wim, Chan, Terry W. S., van Diest, Paul J., Hauptmann, Michael, ter Hoeve, Natalie D., Isaeva, Olga I., de Jong, Vincent M. T., Jóźwiak, Katarzyna, Kluin, Roelof J. C., Kok, Marleen, Koop, Esther, Nederlof, Petra M., Opdam, Mark, Schouten, Philip C., Siesling, Sabine, van Steenis, Charlaine, Voogd, Adri C., Vreuls, Willem, Salgado, Roberto F., Linn, Sabine C., and Schmidt, Marjanka K.

Published
2024
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3. Automated Scoring of Nuclear Pleomorphism Spectrum with Pathologist-level Performance in Breast Cancer

Author

Mercan, Caner, Balkenhol, Maschenka, Salgado, Roberto, Sherman, Mark, Vielh, Philippe, Vreuls, Willem, Polonia, Antonio, Horlings, Hugo M., Weichert, Wilko, Carter, Jodi M., Bult, Peter, Christgen, Matthias, Denkert, Carsten, van de Vijver, Koen, van der Laak, Jeroen, and Ciompi, Francesco

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Nuclear pleomorphism, defined herein as the extent of abnormalities in the overall appearance of tumor nuclei, is one of the components of the three-tiered breast cancer grading. Given that nuclear pleomorphism reflects a continuous spectrum of variation, we trained a deep neural network on a large variety of tumor regions from the collective knowledge of several pathologists, without constraining the network to the traditional three-category classification. We also motivate an additional approach in which we discuss the additional benefit of normal epithelium as baseline, following the routine clinical practice where pathologists are trained to score nuclear pleomorphism in tumor, having the normal breast epithelium for comparison. In multiple experiments, our fully-automated approach could achieve top pathologist-level performance in select regions of interest as well as at whole slide images, compared to ten and four pathologists, respectively., Comment: 16 pages, 11 figures

Published
2020

4. External validation and clinical utility assessment of PREDICT breast cancer prognostic model in young, systemic treatment-naïve women with node-negative breast cancer

Author

Wang, Yuwei, Broeks, Annegien, Giardiello, Daniele, Hauptmann, Michael, Jóźwiak, Katarzyna, Koop, Esther A., Opdam, Mark, Siesling, Sabine, Sonke, Gabe S., Stathonikos, Nikolas, ter Hoeve, Natalie D., van der Wall, Elsken, van Deurzen, Carolien H.M., van Diest, Paul J., Voogd, Adri C., Vreuls, Willem, Linn, Sabine C., Dackus, Gwen M.H.E., and Schmidt, Marjanka K.

Published
2023
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7. Interobserver Variation in the Assessment of Immunohistochemistry Expression Levels in HER2-Negative Breast Cancer: Can We Improve the Identification of Low Levels of HER2 Expression by Adjusting the Criteria? An International Interobserver Study

Author

Baez-Navarro, Ximena, van Bockstal, Mieke R., Nawawi, Diënna, Broeckx, Glenn, Colpaert, Cecile, Doebar, Shusma C., Hogenes, Marieke C.H., Koop, Esther, Lambein, Kathleen, Peeters, Dieter J.E., Sinke, Renata H.J.A., Bastiaan van Brakel, Johannes, van der Starre-Gaal, José, van der Vegt, Bert, van de Vijver, Koen, Vreuls, Celien P.H., Vreuls, Willem, Westenend, Pieter J., and van Deurzen, Carolien H.M.

Published
2023
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8. Whole-Slide Mitosis Detection in H&E Breast Histology Using PHH3 as a Reference to Train Distilled Stain-Invariant Convolutional Networks

Author

Tellez, David, Balkenhol, Maschenka, Otte-Holler, Irene, van de Loo, Rob, Vogels, Rob, Bult, Peter, Wauters, Carla, Vreuls, Willem, Mol, Suzanne, Karssemeijer, Nico, Litjens, Geert, van der Laak, Jeroen, and Ciompi, Francesco

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Manual counting of mitotic tumor cells in tissue sections constitutes one of the strongest prognostic markers for breast cancer. This procedure, however, is time-consuming and error-prone. We developed a method to automatically detect mitotic figures in breast cancer tissue sections based on convolutional neural networks (CNNs). Application of CNNs to hematoxylin and eosin (H&E) stained histological tissue sections is hampered by: (1) noisy and expensive reference standards established by pathologists, (2) lack of generalization due to staining variation across laboratories, and (3) high computational requirements needed to process gigapixel whole-slide images (WSIs). In this paper, we present a method to train and evaluate CNNs to specifically solve these issues in the context of mitosis detection in breast cancer WSIs. First, by combining image analysis of mitotic activity in phosphohistone-H3 (PHH3) restained slides and registration, we built a reference standard for mitosis detection in entire H&E WSIs requiring minimal manual annotation effort. Second, we designed a data augmentation strategy that creates diverse and realistic H&E stain variations by modifying the hematoxylin and eosin color channels directly. Using it during training combined with network ensembling resulted in a stain invariant mitosis detector. Third, we applied knowledge distillation to reduce the computational requirements of the mitosis detection ensemble with a negligible loss of performance. The system was trained in a single-center cohort and evaluated in an independent multicenter cohort from The Cancer Genome Atlas on the three tasks of the Tumor Proliferation Assessment Challenge (TUPAC). We obtained a performance within the top-3 best methods for most of the tasks of the challenge., Comment: Accepted to appear in IEEE Transactions on Medical Imaging

Published
2018
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10. Long-term trends in incidence, characteristics and prognosis of screen-detected and interval cancers in women participating in the Dutch breast cancer screening programme

Author

Ten Velde, Daniëlle E, Duijm, Lucien E M, van der Sangen, Maurice J C, Schipper, Robert-Jan, Tjan-Heijnen, Vivianne C G, Vreuls, Willem, Strobbe, Luc J A, Voogd, Adri C, Ten Velde, Daniëlle E, Duijm, Lucien E M, van der Sangen, Maurice J C, Schipper, Robert-Jan, Tjan-Heijnen, Vivianne C G, Vreuls, Willem, Strobbe, Luc J A, and Voogd, Adri C

Abstract

BACKGROUND: No studies are available in which changes over time in characteristics and prognosis of patients with interval breast cancers (ICs) and screen-detected breast cancers (SDCs) have been compared. The aim was to study these trends between 1995 and 2018. METHODS: All women with invasive SDCs (N?=?4290) and ICs (N?=?1352), diagnosed in a southern mammography screening region in the Netherlands, were included and followed until date of death or 31 December 2022. RESULTS: The 5-year overall survival rate of women with SDCs increased from 91.4% for those diagnosed in 1995-1999 to 95.0% for those diagnosed in 2013-2018 (P?

Published
2024

11. Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status

Author

Pathologie, Cancer, Pathologie Pathologen staf, Wang, Yuwei, Dackus, Gwen M H E, Rosenberg, Efraim H, Cornelissen, Sten, de Boo, Leonora W, Broeks, Annegien, Brugman, Wim, Chan, Terry W S, van Diest, Paul J, Hauptmann, Michael, Ter Hoeve, Natalie D, Isaeva, Olga I, de Jong, Vincent M T, Jóźwiak, Katarzyna, Kluin, Roelof J C, Kok, Marleen, Koop, Esther, Nederlof, Petra M, Opdam, Mark, Schouten, Philip C, Siesling, Sabine, van Steenis, Charlaine, Voogd, Adri C, Vreuls, Willem, Salgado, Roberto F, Linn, Sabine C, Schmidt, Marjanka K, Pathologie, Cancer, Pathologie Pathologen staf, Wang, Yuwei, Dackus, Gwen M H E, Rosenberg, Efraim H, Cornelissen, Sten, de Boo, Leonora W, Broeks, Annegien, Brugman, Wim, Chan, Terry W S, van Diest, Paul J, Hauptmann, Michael, Ter Hoeve, Natalie D, Isaeva, Olga I, de Jong, Vincent M T, Jóźwiak, Katarzyna, Kluin, Roelof J C, Kok, Marleen, Koop, Esther, Nederlof, Petra M, Opdam, Mark, Schouten, Philip C, Siesling, Sabine, van Steenis, Charlaine, Voogd, Adri C, Vreuls, Willem, Salgado, Roberto F, Linn, Sabine C, and Schmidt, Marjanka K

Published
2024

19. The dilemma of recalling well-circumscribed masses in a screening population: A narrative literature review and exploration of Dutch screening practice.

Author

Geertse, T.D., Waal, D. van der, Vreuls, Willem, Tetteroo, Eric, Duijm, Lucien E. M., Pijnappel, Ruud M., Broeders, M.J., Geertse, T.D., Waal, D. van der, Vreuls, Willem, Tetteroo, Eric, Duijm, Lucien E. M., Pijnappel, Ruud M., and Broeders, M.J.

Abstract

01 juni 2023, Item does not contain fulltext, BACKGROUND: In Dutch breast cancer screening, solitary, new or growing well-circumscribed masses should be recalled for further assessment. This results in cancers detected but also in false positive recalls, especially at initial screening. The aim of this study was to determine characteristics of well-circumscribed masses at mammography and identify potential methods to improve the recall strategy. METHODS: A systematic literature search was performed using PubMed. In addition, follow-up data were retrieved on all 8860 recalled women in a Dutch screening region from 2014 to 2019. RESULTS: Based on 15 articles identified in the literature search, we found that probably benign well-circumscribed masses that were kept under surveillance had a positive predictive value (PPV) of 0-2%. New or enlarging solitary well-circumscribed masses had a PPV of 10-12%. In general the detected carcinomas had a favorable prognosis. In our exploration of screening practice, 25% of recalls (2133/8860) were triggered by a well-circumscribed mass. Those recalls had a PPV of 2.0% for initial and 10.6% for subsequent screening. Most detected carcinomas had a favorable prognosis as well. CONCLUSION: To recognize malignancies presenting as well-circumscribed masses, identifying solitary, new or growing lesions is key. This information is missing at initial screening since prior examinations are not available, leading to a low PPV. Access to prior clinical examinations may therefore improve this PPV. In addition, given the generally favorable prognosis of screen-detected malignant well-circumscribed masses, one may opt to recall these lesions at subsequent screening, if grown, rather than at initial screening.

Published
2023

20. External validation and clinical utility assessment of PREDICT breast cancer prognostic model in young, systemic treatment-naïve women with node-negative breast cancer

Author

Pathologie Pathologen staf, Pathologie Support, Speerpunt Cancer, Cancer, Pathologie, MS MOD, Pathologie Research, Pathologie Opleiding, Wang, Yuwei, Broeks, Annegien, Giardiello, Daniele, Hauptmann, Michael, Jóźwiak, Katarzyna, Koop, Esther A., Opdam, Mark, Siesling, Sabine, Sonke, Gabe S., Stathonikos, Nikolas, ter Hoeve, Natalie D., van der Wall, Elsken, van Deurzen, Carolien H.M., van Diest, Paul J., Voogd, Adri C., Vreuls, Willem, Linn, Sabine C., Dackus, Gwen M.H.E., Schmidt, Marjanka K., Pathologie Pathologen staf, Pathologie Support, Speerpunt Cancer, Cancer, Pathologie, MS MOD, Pathologie Research, Pathologie Opleiding, Wang, Yuwei, Broeks, Annegien, Giardiello, Daniele, Hauptmann, Michael, Jóźwiak, Katarzyna, Koop, Esther A., Opdam, Mark, Siesling, Sabine, Sonke, Gabe S., Stathonikos, Nikolas, ter Hoeve, Natalie D., van der Wall, Elsken, van Deurzen, Carolien H.M., van Diest, Paul J., Voogd, Adri C., Vreuls, Willem, Linn, Sabine C., Dackus, Gwen M.H.E., and Schmidt, Marjanka K.

Published
2023

21. The dilemma of recalling well-circumscribed masses in a screening population: A narrative literature review and exploration of Dutch screening practice

Author

MS Radiologie, Cancer, Geertse, Tanya D., van der Waal, Daniëlle, Vreuls, Willem, Tetteroo, Eric, Duijm, Lucien E.M., Pijnappel, Ruud M., Broeders, Mireille J.M., MS Radiologie, Cancer, Geertse, Tanya D., van der Waal, Daniëlle, Vreuls, Willem, Tetteroo, Eric, Duijm, Lucien E.M., Pijnappel, Ruud M., and Broeders, Mireille J.M.

Published
2023

23. Confocal laser microscopy for assessment of surgical margins during radical prostatectomy.

Author

Baas, Diederik J.H., Vreuls, Willem, Sedelaar, J.P. Michiel, Vrijhof, Henricus J.E.J., Hoekstra, Robert J., Zomer, Saskia F., van Leenders, Geert J.L.H., van Basten, Jean‐Paul A., and Somford, Diederik M.

Subjects
*SURGICAL margin, *LASER microscopy, *RADICAL prostatectomy, *CONFOCAL microscopy, *RETROPUBIC prostatectomy, *SURGERY
Abstract

Objective: To evaluate the feasibility of confocal laser microscopy (CLM) for intraoperative margin assessment as faster alternative to neurovascular structure‐adjacent frozen‐section examination (NeuroSAFE) during robot‐assisted radical prostatectomy (RARP). Patients and Methods: Surgical margins were assessed during 50 RARP procedures in patients scheduled for NeuroSAFE. Posterolateral sections were cut and imaged with CLM and further processed to conform with the NeuroSAFE protocol. Secondary resection (SR) was performed in case a positive surgical margin (PSM) was observed with NeuroSAFE. Afterwards, the CLM images were non‐blinded assessed for the presence of PSMs. The accuracy of both NeuroSAFE and CLM was compared with conventional histopathology. Agreement for detection of PSMs between NeuroSAFE and CLM was evaluated with Cohen's kappa coefficient. Procedure times were compared with a Wilcoxon signed‐ranks test. Results: In total, 96 posterolateral sections of RP specimens were evaluated for the presence of PSMs. CLM identified 15 (16%) PSMs and NeuroSAFE identified 14 (15%) PSMs. CLM had a calculated sensitivity, specificity, positive predictive value and negative predictive value of 86%, 96%, 80% and 98% respectively for the detection of PSMs compared to definite pathology. After SR, residual tumour was found in six of 13 cases (46%), which were all identified by both techniques. There was a substantial level of agreement between CLM and NeuroSAFE (κ = 0.80). The median procedure time for CLM was significantly shorter compared to NeuroSAFE (8 vs 50 min, P < 0.001). The main limitation of this study was the non‐blinded assessment of the CLM images. Conclusions: Compared to NeuroSAFE, CLM is a promising technique for intraoperative margin assessment and is able to reduce the time of intraoperative margin assessment. [ABSTRACT FROM AUTHOR]

Published
2023
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25. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

Author

de Jong, Vincent M.T., primary, Wang, Yuwei, additional, ter Hoeve, Natalie D., additional, Opdam, Mark, additional, Stathonikos, Nikolas, additional, Jóźwiak, Katarzyna, additional, Hauptmann, Michael, additional, Cornelissen, Sten, additional, Vreuls, Willem, additional, Rosenberg, Efraim H., additional, Koop, Esther A., additional, Varga, Zsuzsanna, additional, van Deurzen, Carolien H.M., additional, Mooyaart, Antien L., additional, Córdoba, Alicia, additional, Groen, Emma J., additional, Bart, Joost, additional, Willems, Stefan M., additional, Zolota, Vasiliki, additional, Wesseling, Jelle, additional, Sapino, Anna, additional, Chmielik, Ewa, additional, Ryska, Ales, additional, Broeks, Annegien, additional, Voogd, Adri C., additional, Loi, Sherene, additional, Michiels, Stefan, additional, Sonke, Gabe S., additional, van der Wall, Elsken, additional, Siesling, Sabine, additional, van Diest, Paul J., additional, Schmidt, Marjanka K., additional, Kok, Marleen, additional, Dackus, Gwen M.H.E., additional, Salgado, Roberto, additional, and Linn, Sabine C., additional

Published
2022
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26. Interobserver variation in the assessment of HER2 low expression in breast cancer: can we improve by adjusting criteria? An international interobserver study.

Author

Navarro, Ximena Baez, primary, Bockstal, Mieke Rosalie van, additional, Nawawi, Diënna, additional, Broeckx, Glenn, additional, Colpaert, Cecile, additional, Doebar, Shusma Charlane, additional, Hogenes, Marieke C.H., additional, Koop, Esther, additional, Lambein, Kathleen, additional, Peeters, Dieter J.E., additional, Sinke, Renata, additional, Brakel, Johannes Bastiaan van, additional, Starre-Gaal, José van der, additional, Vegt, Bert Van der, additional, de Vijver, Koen Van, additional, Vreuls, Celien P.H., additional, Vreuls, Willem, additional, Westenend, Pieter, additional, and Deurzen, Carolien van, additional

Published
2022
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27. Deep learning for fully-automated nuclear pleomorphism scoring in breast cancer

Author

Mercan, C., Balkenhol, M.C.A., Salgado, Roberto, Sherman, Mark, Vielh, Philippe, Vreuls, Willem, Bult, P., Bokhorst, J.M., Laak, J.A.W.M. van der, Ciompi, F., Mercan, C., Balkenhol, M.C.A., Salgado, Roberto, Sherman, Mark, Vielh, Philippe, Vreuls, Willem, Bult, P., Bokhorst, J.M., Laak, J.A.W.M. van der, and Ciompi, F.

Abstract

Contains fulltext : 285275.pdf (Publisher’s version ) (Open Access)

Published
2022

28. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

Author

Pathologie Support, Pathologie Pathologen staf, Cancer, Speerpunt Cancer, Pathologie, Pathologie Opleiding, de Jong, Vincent M T, Wang, Yuwei, Ter Hoeve, Natalie D, Opdam, Mark, Stathonikos, Nikolas, Jóźwiak, Katarzyna, Hauptmann, Michael, Cornelissen, Sten, Vreuls, Willem, Rosenberg, Efraim H, Koop, Esther A, Varga, Zsuzsanna, van Deurzen, Carolien H M, Mooyaart, Antien L, Córdoba, Alicia, Groen, Emma J, Bart, Joost, Willems, Stefan M, Zolota, Vasiliki, Wesseling, Jelle, Sapino, Anna, Chmielik, Ewa, Ryska, Ales, Broeks, Annegien, Voogd, Adri C, Loi, Sherene, Michiels, Stefan, Sonke, Gabe S, van der Wall, Elsken, Siesling, Sabine, van Diest, Paul J, Schmidt, Marjanka K, Kok, Marleen, Dackus, Gwen M H E, Salgado, Roberto, Linn, Sabine C, Pathologie Support, Pathologie Pathologen staf, Cancer, Speerpunt Cancer, Pathologie, Pathologie Opleiding, de Jong, Vincent M T, Wang, Yuwei, Ter Hoeve, Natalie D, Opdam, Mark, Stathonikos, Nikolas, Jóźwiak, Katarzyna, Hauptmann, Michael, Cornelissen, Sten, Vreuls, Willem, Rosenberg, Efraim H, Koop, Esther A, Varga, Zsuzsanna, van Deurzen, Carolien H M, Mooyaart, Antien L, Córdoba, Alicia, Groen, Emma J, Bart, Joost, Willems, Stefan M, Zolota, Vasiliki, Wesseling, Jelle, Sapino, Anna, Chmielik, Ewa, Ryska, Ales, Broeks, Annegien, Voogd, Adri C, Loi, Sherene, Michiels, Stefan, Sonke, Gabe S, van der Wall, Elsken, Siesling, Sabine, van Diest, Paul J, Schmidt, Marjanka K, Kok, Marleen, Dackus, Gwen M H E, Salgado, Roberto, and Linn, Sabine C

Published
2022

29. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

Author

de Jong, Vincent M T, Wang, Yuwei, Ter Hoeve, Natalie D, Opdam, Mark, Stathonikos, Nikolas, Jóźwiak, Katarzyna, Hauptmann, Michael, Cornelissen, Sten, Vreuls, Willem, Rosenberg, Efraim H, Koop, Esther A, Varga, Zsuzsanna, van Deurzen, Carolien H M, Mooyaart, Antien L, Córdoba, Alicia, Groen, Emma J, Bart, Joost, Willems, Stefan M, Zolota, Vasiliki, Wesseling, Jelle, Sapino, Anna, Chmielik, Ewa, Ryska, Ales, Broeks, Annegien, Voogd, Adri C, Loi, Sherene, Michiels, Stefan, Sonke, Gabe S, van der Wall, Elsken, Siesling, Sabine, et al, and University of Zurich

Subjects
10049 Institute of Pathology and Molecular Pathology, 610 Medicine & health
Published
2022
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30. False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

Author

Koomen, Bregje M, Vreuls, Willem, de Boer, Mirthe, de Ruiter, Emma J, Hoelters, Juergen, Vink, Aryan, Willems, Stefan M, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
DOCETAXEL, CARCINOMA, FORMALIN, SP263 antibody, NIVOLUMAB, programmed cell death-ligand 1, tissue fixation, PD-L1 EXPRESSION, immunohistochemistry, RELIABILITY, cytology, non-small-cell lung carcinoma, BLOCK, FIXATION, immunotherapy, IHC
Abstract

Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT.

Published
2021

31. Incidence of significant prostate cancer after negative MRI and systematic biopsy in the FUTURE trial.

Author

Exterkate, Leonie, Wegelin, Olivier, Barentsz, Jelle O., van der Leest, Marloes G., Kummer, J. Alain, Vreuls, Willem, de Bruin, Peter C., Witjes, J. Alfred, van Melick, Harm H.E., and Somford, Diederik M.

Subjects
PROSTATE cancer, DIGITAL rectal examination, MAGNETIC resonance imaging, PROSTATE-specific antigen, DISEASE risk factors, BIOPSY
Abstract

Objectives: To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow‐up in patients with negative systematic biopsy (SB) followed by non‐suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. Patients and Methods: A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate‐specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging‐Reporting and Data System (PI‐RADS) ≤2 on mpMRI entered biochemical follow‐up. Follow‐up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow‐up compared to the expected number in the general population (standardized incidence ratio [SIR]). Results: In total, 431 patients had non‐suspicious mpMRI and entered biochemical follow‐up. After a median (interquartile range) follow‐up of 41 (23–57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3–7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI‐RADS ≥3) were significant predictive factors for csPCa. Conclusion: After negative prior biopsy and non‐suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image‐guided risk‐adapted diagnostic surveillance strategies is warranted. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Failure of Stereotactic Core Needle Biopsy in Women Recalled for Suspicious Calcifications at Screening Mammography: Frequency, Causes and Final Outcome in a Multi-institutional, Observational Follow-up Study

Author

Duijm, Lucien EM, primary, Strobbe, Luc J, additional, Smallenburg, Vivian van Breest, additional, Vreuls, Willem, additional, Boerman, Thom, additional, Beek, Hermen C van, additional, de Coul-Froger, Clemence L op, additional, Setz-Pels, Wikke, additional, and Voogd, Adri C, additional

Published
2021
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34. False-negative programmed death-ligand 1 immunostaining in ethanol-fixed endobronchial ultrasound-guided transbronchial needle aspiration specimens of non-small-cell lung cancer patients

Author

Pathologie Opleiding, Cancer, Pathologie Pathologen staf, Circulatory Health, Koomen, Bregje M, Vreuls, Willem, de Boer, Mirthe, de Ruiter, Emma J, Hoelters, Juergen, Vink, Aryan, Willems, Stefan M, Pathologie Opleiding, Cancer, Pathologie Pathologen staf, Circulatory Health, Koomen, Bregje M, Vreuls, Willem, de Boer, Mirthe, de Ruiter, Emma J, Hoelters, Juergen, Vink, Aryan, and Willems, Stefan M

Published
2021

36. Histological subtypes in triple negative breast cancer are associated with specific information on survival

Author

Balkenhol, Maschenka C. A., Vreuls, Willem, Wauters, Carla A. P., Mol, Suzanne J. J., van der Laak, Jeroen, Bult, Peter, Balkenhol, Maschenka C. A., Vreuls, Willem, Wauters, Carla A. P., Mol, Suzanne J. J., van der Laak, Jeroen, and Bult, Peter

Abstract

Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC. A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed. Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18-3.03; p = 0.008; OS HR 1.94; 95% CI 1.28-2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes. In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients., Funding Agencies|Radboud University Medical Center Institute for Health Sciences (RIHS)

Published
2020
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40. Deep learning assisted mitotic counting for breast cancer

Author

Balkenhol, M.C.A., Tellez, D., Vreuls, Willem, Clahsen, Pieter C., Pinckaers, J.H.F.M., Ciompi, F., Bult, P., Laak, J.A.W.M. van der, Balkenhol, M.C.A., Tellez, D., Vreuls, Willem, Clahsen, Pieter C., Pinckaers, J.H.F.M., Ciompi, F., Bult, P., and Laak, J.A.W.M. van der

Abstract

Contains fulltext : 209656.pdf (Publisher’s version ) (Open Access)

Published
2019

42. The FUTURE Trial : A Multicenter Randomised Controlled Trial on Target Biopsy Techniques Based on Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer in Patients with Prior Negative Biopsies

Author

Wegelin, Olivier, Exterkate, Leonie, van der Leest, Marloes, Kummer, Jean A, Vreuls, Willem, de Bruin, Peter C, Bosch, J L H Ruud, Barentsz, Jelle O, Somford, Diederik M, van Melick, Harm H E, Wegelin, Olivier, Exterkate, Leonie, van der Leest, Marloes, Kummer, Jean A, Vreuls, Willem, de Bruin, Peter C, Bosch, J L H Ruud, Barentsz, Jelle O, Somford, Diederik M, and van Melick, Harm H E

Published
2019

43. The FUTURE Trial: A Multicenter Randomised Controlled Trial on Target Biopsy Techniques Based on Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer in Patients with Prior Negative Biopsies

Author

Cancer, MS HOD, Wegelin, Olivier, Exterkate, Leonie, van der Leest, Marloes, Kummer, Jean A, Vreuls, Willem, de Bruin, Peter C, Bosch, J L H Ruud, Barentsz, Jelle O, Somford, Diederik M, van Melick, Harm H E, Cancer, MS HOD, Wegelin, Olivier, Exterkate, Leonie, van der Leest, Marloes, Kummer, Jean A, Vreuls, Willem, de Bruin, Peter C, Bosch, J L H Ruud, Barentsz, Jelle O, Somford, Diederik M, and van Melick, Harm H E

Published
2019

44. Deep learning assisted mitotic counting for breast cancer

Author

Balkenhol, Maschenka C. A., Tellez, David, Vreuls, Willem, Clahsen, Pieter C., Pinckaers, Hans, Ciompi, Francesco, Bult, Peter, van der Laak, Jeroen, Balkenhol, Maschenka C. A., Tellez, David, Vreuls, Willem, Clahsen, Pieter C., Pinckaers, Hans, Ciompi, Francesco, Bult, Peter, and van der Laak, Jeroen

Abstract

As part of routine histological grading, for every invasive breast cancer the mitotic count is assessed by counting mitoses in the (visually selected) region with the highest proliferative activity. Because this procedure is prone to subjectivity, the present study compares visual mitotic counting with deep learning based automated mitotic counting and fully automated hotspot selection. Two cohorts were used in this study. Cohort A comprised 90 prospectively included tumors which were selected based on the mitotic frequency scores given during routine glass slide diagnostics. This pathologist additionally assessed the mitotic count in these tumors in whole slide images (WSI) within a preselected hotspot. A second observer performed the same procedures on this cohort. The preselected hotspot was generated by a convolutional neural network (CNN) trained to detect all mitotic figures in digitized hematoxylin and eosin (Hamp;E) sections. The second cohort comprised a multicenter, retrospective TNBC cohort (n = 298), of which the mitotic count was assessed by three independent observers on glass slides. The same CNN was applied on this cohort and the absolute number of mitotic figures in the hotspot was compared to the averaged mitotic count of the observers. Baseline interobserver agreement for glass slide assessment in cohort A was good (kappa 0.689; 95% CI 0.580-0.799). Using the CNN generated hotspot in WSI, the agreement score increased to 0.814 (95% CI 0.719-0.909). Automated counting by the CNN in comparison with observers counting in the predefined hotspot region yielded an average kappa of 0.724. We conclude that manual mitotic counting is not affected by assessment modality (glass slides, WSI) and that counting mitotic figures in WSI is feasible. Using a predefined hotspot area considerably improves reproducibility. Also, fully automated assessment of mitotic score appears to be feasible without introducing additional bias or variability., Funding Agencies|Radboud University Medical Center Institute for Health Sciences (RIHS)

Published
2019
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45. Quantitative Third Harmonic Generation Microscopy for Assessment of Glioma in Human Brain Tissue

Author

Pathologie Support, Pathologie, Pathologie Pathologen staf, Zhang, Zhiqing, de Munck, Jan C., Verburg, Niels, Rozemuller, Annemieke J., Vreuls, Willem, Cakmak, Pinar, van Huizen, Laura M.G., Idema, Sander, Aronica, Eleonora, de Witt Hamer, Philip C., Wesseling, Pieter, Groot, Marie Louise, Pathologie Support, Pathologie, Pathologie Pathologen staf, Zhang, Zhiqing, de Munck, Jan C., Verburg, Niels, Rozemuller, Annemieke J., Vreuls, Willem, Cakmak, Pinar, van Huizen, Laura M.G., Idema, Sander, Aronica, Eleonora, de Witt Hamer, Philip C., Wesseling, Pieter, and Groot, Marie Louise

Published
2019

46. Genotyping of in Formalin-Fixed Paraffin-Embedded Tissues and Serum Samples From Patients With Invasive Aspergillosis

Author

de Groot, Theun, Hagen, Ferry, Vreuls, Willem, Verweij, Paul E, Chowdhary, Anuradha, Meis, Jacques F, Westerdijk Fungal Biodiversity Institute, and Westerdijk Fungal Biodiversity Institute - Medical Mycology

Abstract

Invasive aspergillosis (IA) is a deep tissue infection with a high mortality occurring mostly in immunocompromised patients. To investigate the pathology of patients with IA it may be important to determine the genotype of the invasive isolate of Aspergillus, however available tissues for study are often formalin fixed paraffin embedded (FFPE). Although DNA has been successfully isolated from such tissues for species identification, genotyping of Aspergillus species on such tissues has not yet been performed. In this study we aimed to determine the genotype of Aspergillus fumigatus in FFPE tissue and serum samples from five patients with invasive aspergillosis using nine highly polymorphic short tandem repeat (STRAf) loci. FFPE lung and bronchial biopsies from all patients were successfully typed. By comparing the latter result with non-FFPE materials from non-sterile samples such as sputum, bronchoalveolar lavage and lung abscess, we found identical genotypes within three patients, while the two other patients had a dominant genotype shared among all sample types. Genotyping of serum samples was successful in two serum samples with galactomannan ratios of 4 and 5.6, but failed in serum samples with galactomannan levels

Published
2018

47. Trends in frequency and outcome of high‐risk breast lesions at core needle biopsy in women recalled at biennial screening mammography, a multiinstitutional study

Author

Luiten, Jacky D., primary, Korte, Bram, additional, Voogd, Adri C., additional, Vreuls, Willem, additional, Luiten, Ernest J.T., additional, Strobbe, Luc J., additional, Rutten, Matthieu J.C.M., additional, Plaisier, Menno L., additional, Lohle, Paul N., additional, Hooijen, Marianne J.H., additional, Tjan‐Heijnen, Vivianne C.G., additional, and Duijm, Lucien E.M., additional

Published
2019
Full Text
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48. Quantitative Third Harmonic Generation Microscopy for Assessment of Glioma in Human Brain Tissue

Author

Zhang, Zhiqing, primary, de Munck, Jan C., additional, Verburg, Niels, additional, Rozemuller, Annemieke J., additional, Vreuls, Willem, additional, Cakmak, Pinar, additional, van Huizen, Laura M. G., additional, Idema, Sander, additional, Aronica, Eleonora, additional, de Witt Hamer, Philip C., additional, Wesseling, Pieter, additional, and Groot, Marie Louise, additional

Published
2019
Full Text
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49. The FUTURE Trial: A Multicenter Randomised Controlled Trial on Target Biopsy Techniques Based on Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer in Patients with Prior Negative Biopsies

Author

Wegelin, Olivier, primary, Exterkate, Leonie, additional, van der Leest, Marloes, additional, Kummer, Jean A., additional, Vreuls, Willem, additional, de Bruin, Peter C., additional, Bosch, J.L.H.Ruud, additional, Barentsz, Jelle O., additional, Somford, Diederik M., additional, and van Melick, Harm H.E., additional

Published
2019
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50. From Detection of Individual Metastases to Classification of Lymph Node Status at the Patient Level: The CAMELYON17 Challenge

Author

Bandi, Peter, primary, Geessink, Oscar, additional, Manson, Quirine, additional, Van Dijk, Marcory, additional, Balkenhol, Maschenka, additional, Hermsen, Meyke, additional, Ehteshami Bejnordi, Babak, additional, Lee, Byungjae, additional, Paeng, Kyunghyun, additional, Zhong, Aoxiao, additional, Li, Quanzheng, additional, Zanjani, Farhad Ghazvinian, additional, Zinger, Svitlana, additional, Fukuta, Keisuke, additional, Komura, Daisuke, additional, Ovtcharov, Vlado, additional, Cheng, Shenghua, additional, Zeng, Shaoqun, additional, Thagaard, Jeppe, additional, Dahl, Anders B., additional, Lin, Huangjing, additional, Chen, Hao, additional, Jacobsson, Ludwig, additional, Hedlund, Martin, additional, cetin, Melih, additional, Halici, Eren, additional, Jackson, Hunter, additional, Chen, Richard, additional, Both, Fabian, additional, Franke, Jorg, additional, Kusters-Vandevelde, Heidi, additional, Vreuls, Willem, additional, Bult, Peter, additional, van Ginneken, Bram, additional, van der Laak, Jeroen, additional, and Litjens, Geert, additional

Published
2019
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