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Article ; Online: Reproducibility of CT-based radiomic features against image resampling and perturbations for tumour and healthy kidney in renal cancer patients

Margherita Mottola / Stephan Ursprung / Leonardo Rundo / Lorena Escudero Sanchez / Tobias Klatte / Iosif Mendichovszky / Grant D Stewart / Evis Sala / Alessandro Bevilacqua

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 11

Abstract: Abstract Computed Tomography (CT) is widely used in oncology for morphological evaluation and diagnosis, commonly through visual assessments, often exploiting semi-automatic tools as well. Well-established automatic methods for quantitative imaging offer ...

Abstract	Abstract Computed Tomography (CT) is widely used in oncology for morphological evaluation and diagnosis, commonly through visual assessments, often exploiting semi-automatic tools as well. Well-established automatic methods for quantitative imaging offer the opportunity to enrich the radiologist interpretation with a large number of radiomic features, which need to be highly reproducible to be used reliably in clinical practice. This study investigates feature reproducibility against noise, varying resolutions and segmentations (achieved by perturbing the regions of interest), in a CT dataset with heterogeneous voxel size of 98 renal cell carcinomas (RCCs) and 93 contralateral normal kidneys (CK). In particular, first order (FO) and second order texture features based on both 2D and 3D grey level co-occurrence matrices (GLCMs) were considered. Moreover, this study carries out a comparative analysis of three of the most commonly used interpolation methods, which need to be selected before any resampling procedure. Results showed that the Lanczos interpolation is the most effective at preserving original information in resampling, where the median slice resolution coupled with the native slice spacing allows the best reproducibility, with 94.6% and 87.7% of features, in RCC and CK, respectively. GLCMs show their maximum reproducibility when used at short distances.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acceptability and potential impact on uptake of using different risk stratification approaches to determine eligibility for screening

Juliet A. Usher‐Smith / Laragh L. W. Harvey‐Kelly / Sabrina H. Rossi / Hannah Harrison / Simon J. Griffin / Grant D. Stewart

Health Expectations, Vol 24, Iss 2, Pp 341-

A population‐based survey

2021 Volume 351

Abstract: Abstract Background Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. Objectives To compare the public acceptability and potential impact on uptake of using different approaches to ... ...

Abstract	Abstract Background Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. Objectives To compare the public acceptability and potential impact on uptake of using different approaches to determine eligibility for screening. Design An online population‐based survey of 668 adults in the UK aged 45‐79 including a series of scenarios in the context of a potential kidney cancer screening programme in which eligibility was determined by age, sex, age and sex combined, a simple risk score (age, sex, body mass index, smoking status), a complex risk score additionally incorporating family history and lifestyle, or a genetic risk score. Outcome measures We used multi‐level ordinal logistic regression to compare acceptability and potential uptake within individuals and multivariable ordinal logistic regression differences between individuals. Results Using sex, age and sex, or the simple risk score were less acceptable than age (P < .0001). All approaches were less acceptable to women than men. Over 70% were comfortable waiting until they were older if the complex risk score or genetics indicated a low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. Conclusions Varying the starting age of screening based on estimated risk from models incorporating phenotypic or genetic risk factors would be acceptable to most individuals and may increase uptake. Patient or Public Contribution Two members of the public contributed to the development of the survey and have commented on this paper.
Keywords	acceptability ; public attitudes ; risk stratification ; screening ; Medicine (General) ; R5-920 ; Public aspects of medicine ; RA1-1270
Subject code	310
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reasons for intending to accept or decline kidney cancer screening

Juliet A Usher-Smith / Sabrina H Rossi / Grant D Stewart / Katie Mills / Charlotte Freer-Smith / Laragh Harvey-Kelly / Hannah Harrison

BMJ Open, Vol 11, Iss

thematic analysis of free text from an online survey

2021 Volume 5

Abstract: Objectives Kidney cancer has been identified as a disease for which screening might provide significant benefit for patients. The aim of this study was to understand in detail the facilitators and barriers towards uptake of a future kidney cancer ... ...

Abstract	Objectives Kidney cancer has been identified as a disease for which screening might provide significant benefit for patients. The aim of this study was to understand in detail the facilitators and barriers towards uptake of a future kidney cancer screening programme, and to compare these across four proposed screening modalities.Design An online survey including free-text responses.Setting UKParticipants 668 adultsPrimary and secondary outcome measures The survey assessed participants’ self-reported intention to take-up kidney cancer screening with four different test methods (urine test, blood test, ultrasound scan and low-dose CT). We conducted thematic analysis of 2559 free-text comments made within the survey using an inductive approach.Results We identified five overarching themes that influenced screening intention: ‘personal health beliefs’, ‘practicalities’, ‘opinions of the test’, ‘attitudes towards screening’ and ‘cancer apprehension’. Overall, participants considered the tests presented as simple to complete and the benefits of early detection to outweigh any drawbacks to screening. Dominant facilitators and barriers varied with patterns of intention to take up screening across the four tests. Most intended to take up screening by all four tests, and for these participants, screening was seen as a positive health behaviour. A significant minority were driven by practicalities and the risks of the tests offered. A smaller proportion intended to reject all forms of screening offered, often due to fear or worry about results and unnecessary medical intervention or a general negative view of screening.Conclusions Most individuals would accept kidney cancer screening by any of the four test options presented because of strong positive attitudes towards screening in general and the perceived simplicity of the tests. Providing information about the rationale for screening in general and the potential benefits of early detection will be important to optimise uptake among uncertain individuals.
Keywords	Medicine ; R
Subject code	150
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.

Stephan Ursprung / Andrew N Priest / Fulvio Zaccagna / Wendi Qian / Andrea Machin / Grant D Stewart / Anne Y Warren / Timothy Eisen / Sarah J Welsh / Ferdia A Gallagher / Tristan Barrett

PLoS ONE, Vol 16, Iss 10, p e

2021 Volume 0258988

Abstract: Purpose To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. Method Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: ... ...

Abstract	Purpose To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. Method Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. Results 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). Conclusions Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. Trial registration EudraCtNo: 2005-004502-82.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma

Stephan Ursprung / Andrew N. Priest / Fulvio Zaccagna / Wendi Qian / Andrea Machin / Grant D. Stewart / Anne Y. Warren / Timothy Eisen / Sarah J. Welsh / Ferdia A. Gallagher / Tristan Barrett

PLoS ONE, Vol 16, Iss

2021 Volume 10

Abstract	Purpose To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. Method Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. Results 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). Conclusions Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. Trial registration EudraCtNo: 2005-004502-82.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Computerized image analysis of tumor cell nuclear morphology can improve patient selection for clinical trials in localized clear cell renal cell carcinoma

In Hwa Um / Lindesay Scott-Hayward / Monique Mackenzie / Puay Hoon Tan / Ravindran Kanesvaran / Yukti Choudhury / Peter D Caie / Min-Han Tan / Marie O'Donnell / Steve Leung / Grant D Stewart / David J Harrison

Journal of Pathology Informatics, Vol 11, Iss 1, Pp 35-

2020 Volume 35

Abstract: Background: Clinicopathological scores are used to predict the likelihood of recurrence-free survival for patients with clear cell renal cell carcinoma (ccRCC) after surgery. These are fallible, particularly in the middle range. This inevitably means ... ...

Abstract	Background: Clinicopathological scores are used to predict the likelihood of recurrence-free survival for patients with clear cell renal cell carcinoma (ccRCC) after surgery. These are fallible, particularly in the middle range. This inevitably means that a significant proportion of ccRCC patients who will not develop recurrent disease enroll into clinical trials. As an exemplar of using digital pathology, we sought to improve the predictive power of “recurrence free” designation in localized ccRCC patients, by precise measurement of ccRCC nuclear morphological features using computational image analysis, thereby replacing manual nuclear grade assessment. Materials and Methods: TNM 8 UICC pathological stage pT1-pT3 ccRCC cases were recruited in Scotland and in Singapore. A Leibovich score (LS) was calculated. Definiens Tissue studio® (Definiens GmbH, Munich) image analysis platform was used to measure tumor nuclear morphological features in digitized hematoxylin and eosin (H&E) images. Results: Replacing human-defined nuclear grade with computer-defined mean perimeter generated a modified Leibovich algorithm, improved overall specificity 0.86 from 0.76 in the training cohort. The greatest increase in specificity was seen in LS 5 and 6, which went from 0 to 0.57 and 0.40, respectively. The modified Leibovich algorithm increased the specificity from 0.84 to 0.94 in the validation cohort. Conclusions: CcRCC nuclear mean perimeter, measured by computational image analysis, together with tumor stage and size, node status and necrosis improved the accuracy of predicting recurrence-free in the localized ccRCC patients. This finding was validated in an ethnically different Singaporean cohort, despite the different H and E staining protocol and scanner used. This may be a useful patient selection tool for recruitment to multicenter studies, preventing some patients from receiving unnecessary additional treatment while reducing the number of patients required to achieve adequate power within neoadjuvant and adjuvant ...
Keywords	clear cell renal cell carcinoma ; computational image analysis ; leibovich score ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Pathology ; RB1-214
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Literature-Based Analysis of the Learning Curves of Laparoscopic Radical Prostatectomy

Daniel W. Good / Grant D. Stewart / Jens-Uwe Stolzenburg / Stuart A. McNeill

European Medical Journal Urology, Vol 2, Iss 1, Pp 90-

2014 Volume 96

Abstract: There is a trend for the increased adoption of minimally invasive techniques of radical prostatectomy (RP) – laparoscopic (LRP) and robotic assisted (RARP) – from the traditional open radical retropubic prostatectomy (ORP), popularised by Partin et al. ... ...

Abstract	There is a trend for the increased adoption of minimally invasive techniques of radical prostatectomy (RP) – laparoscopic (LRP) and robotic assisted (RARP) – from the traditional open radical retropubic prostatectomy (ORP), popularised by Partin et al. Recently there has been a dramatic expansion in the rates of RARP being performed, and there have been many early reports postulating that the learning curve for RARP is shorter than for LRP. The aim of this study was to review the literature and analyse the length of the LRP learning curves for the various outcome measures: perioperative, oncologic, and functional outcomes. A broad search of the literature was performed in November 2013 using the PubMed database. Only studies of real patients and those from 2004 until 2013 were included; those on simulators were excluded. In total, 239 studies were identified after which 13 were included. The learning curve is a heterogeneous entity, depending entirely on the criteria used to define it. There is evidence of multiple learning curves; however the length of these is dependent on the definitions used by the authors. Few studies use the more rigorous definition of plateauing of the curve. Perioperative learning curve takes approximately 150-200 cases to plateau, oncologic curve approximately 200 cases, and the functional learning curve up to 700 cases to plateau (700 for potency, 200 cases for continence). In this review, we have analysed the literature with respect to the learning curve for LRP. It is clear that the learning curve is long. This necessitates centralising LRP to high volume centres such that surgeons, trainees, and patients are able to utilise the benefits of LRP.
Keywords	laparoscopic radical prostatectomy ; Learning curve ; prostate cancer ; Medicine ; R
Subject code	370
Language	English
Publishing date	2014-05-01T00:00:00Z
Publisher	European Medical Journal
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma

Saiful E. Syafruddin / Paulo Rodrigues / Erika Vojtasova / Saroor A. Patel / M. Nazhif Zaini / Johanna Burge / Anne Y. Warren / Grant D. Stewart / Tim Eisen / Dóra Bihary / Shamith A. Samarajiwa / Sakari Vanharanta

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 13

Abstract: Super enhancers are frequently involved in the dysregulation of gene expression in cancer. Here, in kidney cancer, a super enhancer is shown to drive the expression of KLF6, which alters the expression of lipid metabolism genes and promotes tumorigenesis. ...

Abstract	Super enhancers are frequently involved in the dysregulation of gene expression in cancer. Here, in kidney cancer, a super enhancer is shown to drive the expression of KLF6, which alters the expression of lipid metabolism genes and promotes tumorigenesis.
Keywords	Science ; Q
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 13

Abstract	Super enhancers are frequently involved in the dysregulation of gene expression in cancer. Here, in kidney cancer, a super enhancer is shown to drive the expression of KLF6, which alters the expression of lipid metabolism genes and promotes tumorigenesis.
Keywords	Science ; Q
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Efficacy of Sunitinib Treatment of Renal Cancer Cells Is Associated with the Protein PHAX In Vitro

Rafia S. Al-Lamki / Nicholas J. Hudson / John R. Bradley / Anne Y. Warren / Tim Eisen / Sarah J. Welsh / Antony C. P. Riddick / Fiach C. O’Mahony / Arran Turnbull / Thomas Powles / SCOTRRCC Collaborative / Antonio Reverter / David J. Harrison / Grant D. Stewart

Biology, Vol 9, Iss 74, p

2020 Volume 74

Abstract: Anti-angiogenic agents, such as the multi-tyrosine kinase inhibitor sunitinib, are key first line therapies for metastatic clear cell renal cell carcinoma (ccRCC), but their mechanism of action is not fully understood. Here, we take steps towards ... ...

Abstract	Anti-angiogenic agents, such as the multi-tyrosine kinase inhibitor sunitinib, are key first line therapies for metastatic clear cell renal cell carcinoma (ccRCC), but their mechanism of action is not fully understood. Here, we take steps towards validating a computational prediction based on differential transcriptome network analysis that phosphorylated adapter RNA export protein (PHAX) is associated with sunitinib drug treatment. The regulatory impact factor differential network algorithm run on patient tissue samples suggests PHAX is likely an important regulator through changes in genome-wide network connectivity. Immunofluorescence staining of patient tumours showed strong localisation of PHAX to the microvasculature consistent with the anti-angiogenic effect of sunitinib. In normal kidney tissue, PHAX protein abundance was low but increased with tumour grade (G1 vs. G3/4; p < 0.01), consistent with a possible role in cancer progression. In organ culture, ccRCC cells had higher levels of PHAX protein expression than normal kidney cells, and sunitinib increased PHAX protein expression in a dose dependent manner (untreated vs. 100 µM; p < 0.05). PHAX knockdown in a ccRCC organ culture model impacted the ability of sunitinib to cause cancer cell death ( p < 0.0001 untreated vs. treated), suggesting a role for PHAX in mediating the efficacy of sunitinib.
Keywords	renal cancer ; kidney cancer ; sunitinib ; PHAX ; organ culture ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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