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5. The Healthcare Redesign Student Experience: Qualitative and Quantitative Insights of Postgraduate Work-Integrated Learning

Author

Prior, Sarah Jane, Van Dam, Pieter Jan, Griffin, Phoebe E. J., Reeves, Nicole S., Kirkwood, Lea, Paton, Bronwyn, Giles, Amelia, and Peterson, Gregory M.

Abstract

A challenge for providers of work-integrated learning courses is delivering a meaningful learning experience for students, while collaborating with organisations to ensure adequate support. Evaluating student experience has traditionally been about collecting feedback on teaching methods, course content and learning outcomes, rather than the educational influence of student interactions with people, places and systems at their workplace. The aim of this mixed-methods study was to evaluate the student experience within a workplace-integrated healthcare redesign postgraduate course and understand how it affects student learning. Ninety-nine graduates of the course completed an online bespoke survey indicating their levels of satisfaction with the course, including delivery, support and goal achievement. In addition, 10 graduates participated in semi-structured interviews where they shared their overall experience with the course, including barriers and enablers to completion, the balance between academic requirements and workplace responsibilities, and the influence of educators on their achievements. The results suggested that social interaction, communication, and knowledge and skills development were highly valued by students, and that resourcing, course structure and organisational support were significant factors that influenced student outcomes. Cross-discipline interaction and networking opportunities further enhanced student learning. Study findings indicated that a blended model of learning involving workplace project-based activity and traditional academic delivery provided meaningful, practice-relevant learning opportunities and enriched the student experience.

Published
2022
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6. Publisher Correction: Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

Author

Powles, Thomas, Kockx, Mark, Rodriguez-Vida, Alejo, Duran, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., Szabados, Bernadett, Pous, Albert Font, Gravis, Gwenaelle, Herranz, Urbano Anido, Protheroe, Andrew, Ravaud, Alain, Maillet, Denis, Mendez, Maria Jose, Suarez, Cristina, Linch, Mark, Prendergast, Aaron, van Dam, Pieter-Jan, Stanoeva, Diana, Daelemans, Sofie, Mariathasan, Sanjeev, Tea, Joy S., Mousa, Kelly, Banchereau, Romain, and Castellano, Daniel

Published
2023
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7. Final Results of Neoadjuvant Atezolizumab in Cisplatin-ineligible Patients with Muscle-invasive Urothelial Cancer of the Bladder

Author

Szabados, Bernadett, Kockx, Mark, Assaf, Zoe June, van Dam, Pieter-Jan, Rodriguez-Vida, Alejo, Duran, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., Pous, Albert Font, Gravis, Gwenaelle, Herranz, Urbano Anido, Protheroe, Andrew, Ravaud, Alain, Maillet, Denis, Mendez, Maria Jose, Suarez, Cristina, Linch, Mark, Prendergast, Aaron, Tyson, Charlotte, Stanoeva, Diana, Daelemans, Sofie, Rombouts, Miche, Mariathasan, Sanjeev, Tea, Joy S., Mousa, Kelly, Sharma, Shruti, Aleshin, Alexey, Banchereau, Romain, Castellano, Daniel, and Powles, Thomas

Published
2022
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9. Leadership Education and Development: An Exploration of Australian Academic Educators' Perceptions of Leadership Education for Health and Human Service Sector Leaders.

Author

Fennell, Kate L., Van Dam, Pieter Jan, Stephens, Nicola, and Holloway, Adele

Subjects
EDUCATIONAL leadership, QUALITATIVE research, EDUCATION, UNIVERSITIES & colleges, LEADERS
Abstract

The purpose of this study was to explore the nature of postgraduate leadership courses and programs offered by Australian Higher Education Institutions for leaders and potential leaders in the Health & Human Service (H&HS) sector including structure, content, and teaching practices from the perspective of educators. Ten educators from a range of institutions were interviewed. Interview data was coded and analyzed using Inductive Content Analysis. Six global categories represent the broad range of experiences and perspectives of participants in this study. Findings demonstrate formal education has the potential to positively impact the development of leaders in the H&HS sector. [ABSTRACT FROM AUTHOR]

Published
2025
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14. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

Author

Powles, Thomas, Kockx, Mark, Rodriguez-Vida, Alejo, Duran, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., Szabados, Bernadett, Pous, Albert Font, Gravis, Gwenaelle, Herranz, Urbano Anido, Protheroe, Andrew, Ravaud, Alain, Maillet, Denis, Mendez, Maria Jose, Suarez, Cristina, Linch, Mark, Prendergast, Aaron, van Dam, Pieter-Jan, Stanoeva, Diana, Daelemans, Sofie, Mariathasan, Sanjeev, Tea, Joy S., Mousa, Kelly, Banchereau, Romain, and Castellano, Daniel

Published
2019
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18. Publisher Correction: Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

Author

Powles, Thomas, Kockx, Mark, Rodriguez-Vida, Alejo, Duran, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., Szabados, Bernadett, Pous, Albert Font, Gravis, Gwenaelle, Herranz, Urbano Anido, Protheroe, Andrew, Ravaud, Alain, Maillet, Denis, Mendez, Maria Jose, Suarez, Cristina, Linch, Mark, Prendergast, Aaron, van Dam, Pieter-Jan, Stanoeva, Diana, Daelemans, Sofie, Mariathasan, Sanjeev, Tea, Joy S., Mousa, Kelly, Banchereau, Romain, and Castellano, Daniel

Published
2020
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19. Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis

Author

Mayrhofer, Markus, De Laere, Bram, Whitington, Tom, Van Oyen, Peter, Ghysel, Christophe, Ampe, Jozef, Ost, Piet, Demey, Wim, Hoekx, Lucien, Schrijvers, Dirk, Brouwers, Barbara, Lybaert, Willem, Everaert, Els, De Maeseneer, Daan, Strijbos, Michiel, Bols, Alain, Fransis, Karen, Oeyen, Steffi, van Dam, Pieter-Jan, Van den Eynden, Gert, Rutten, Annemie, Aly, Markus, Nordström, Tobias, Van Laere, Steven, Rantalainen, Mattias, Rajan, Prabhakar, Egevad, Lars, Ullén, Anders, Yachnin, Jeffrey, Dirix, Luc, Grönberg, Henrik, and Lindberg, Johan

Published
2018
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22. Molecular, histopathological and radiological profiling of the histopathological growth patterns of liver metastases

Author

van Dam, Pieter-Jan, van Laere, Steven, and Vermeulen, Peter

Subjects
Human medicine
Abstract

The liver is the second most common organ for metastasis and liver metastasis is one of the leading causes of cancer-related mortality. There are currently no reliable biomarkers that impact clinical management in patients with liver metastases. Different histological growth patterns (HGP) have been described and reflect the biological heterogeneity of liver metastases: desmoplastic, pushing and replacement. In the desmoplastic HGP tumor cells are separated from the liver parenchyma by a layer of desmoplastic stroma containing new blood vessels resulting from sprouting angiogenesis. In the replacement HGP, the tumor cells replace the hepatocytes in the liver cell plates thereby co-opting sinusoidal blood vessels as a means of blood supply. The HGP have been shown to be prognostic in colorectal cancer and predictive for resistance to anti-VEGF and chemotherapy. This thesis describes a difference in immune infiltrate between the replacement and the desmoplastic HGP, showcasing a ‘desert’ and ‘excluded’ immune phenotype respectively. This introduces the HGP’s as a potential biomarker for immunotherapy. The HGP’s are currently scored on resection specimens. In order to use the histopathological growth patterns in routine clinical practice, non-invasive assessment is indispensable. Two retrospective studies using MRI and CT respectively showcase the potential of this approach. The first study using MRI on 26 liver metastases, Differences in rim presence, necrosis type, section analysis type and enhancement after contrast were detected. A classification tree was able to predict the histopathological growth pattern in 88.6% of liver metastases. In the second study using radiomics on CT images, differences in features were detected between colorectal desmoplastic and replacement liver metastases. The international consensus guidelines to score the HGP’s of liver metastases are introduced to allow for reproducible assessment of the HGP’s. Next, the prognostic importance of the HGP’s in two new solid tumor types, uveal and cutaneous melanoma, is described. In both tumor types, patients with the replacement HGP have a worse overall survival when compared to patients with the desmoplastic HGP. Finally, expression profiling of desmoplastic and replacement HGP reveals differences in the underlying biology. Our international, multicentric, prospective trial shows that the differences are due to differences in the tumor and not in the adjacent liver. The replacement HGP is characterized by signatures related to cell proliferation and energy metabolism while the desmoplastic HGP is defined by signatures of inflammation, immune cell signaling and angiogenesis.

Published
2022

23. Efficacy, safety, and biomarker analysis of neoadjuvant avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx).

Author

Bex, Axel, primary, Abu-Ghanem, Yasmin, additional, Van Thienen, Johannes V., additional, Graafland, Niels, additional, Lagerveld, Brunolf, additional, Zondervan, Patricia, additional, Beerlage, Harrie, additional, van Moorselaar, Jeroen, additional, Kockx, Mark, additional, Van Dam, Pieter-Jan, additional, Szabados, Bernadett, additional, Blank, Christian U., additional, Powles, Thomas, additional, and Haanen, John B. A. G., additional

Published
2022
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25. Dynamic changes of PD-L1 and T-cell activation in ECLIPSE : A phase II study investigating preoperative immune combination strategies in untreated, operable ER+ primary breast cancer

Author

Schmid, Peter, Kockx, Mark, Kim, Sung-Bae, Wheatley, Duncan, Phillips, Melissa Mary, Hoffmann, Oliver, Blohmer, Jens U., Im, Seock-Ah, Schneeweiss, Andreas, Zamora, Esther, Waumans, Yannick, Van Dam, Pieter-Jan, Peeters, Dieter, Wimalasingham, Akhila, Marosics, Patricia, Prendergast, Aaron, Mousa, Kelly, Cortes, Javier, and Kuemmel, Sherko

Subjects
Medizin, ComputingMethodologies_GENERAL
Abstract

Poster-Abstract

Published
2021

26. A comprehensive analysis of baseline clinical characteristics and biomarkers associated with outcome in advanced melanoma patients treated with pembrolizumab

Author

Awada, Gil, Jansen, Yanina Y.J., Schwarze, Julia Katharina, Tijtgat, Jens, Hellinckx, Lennert, Gondry, Odrade, Vermeulen, Sim, Warren, Sarah, Schats, Kelly, Van Dam, Pieter Jan, Kockx, Mark, Keyaerts, Marleen, Everaert, Hendrik, Seremet, Teofila T.C., Rogiers, Anne, Neyns, Bart, Awada, Gil, Jansen, Yanina Y.J., Schwarze, Julia Katharina, Tijtgat, Jens, Hellinckx, Lennert, Gondry, Odrade, Vermeulen, Sim, Warren, Sarah, Schats, Kelly, Van Dam, Pieter Jan, Kockx, Mark, Keyaerts, Marleen, Everaert, Hendrik, Seremet, Teofila T.C., Rogiers, Anne, and Neyns, Bart

Abstract

Background: Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monother-apy has not been conducted. Methods: Survival data of patients with advanced melanoma who were treated with pembrolizumab in a single university hospital were collected. A multivariate Cox regression analysis was performed to correlate baseline clinical, laboratory, and radiologic characteristics and NanoString IO360 gene expression profiling (GEP) with survival. Results: 183 patients were included (stage IV 85.2%, WHO performance status ≥1 31.1%; pembrolizumab first-line 25.7%), of whom 112 underwent baseline18F-FDG-PET/CT imaging, 58 had circulating tumor DNA (ctDNA) assessments, and GEP was available in 27 patients. Active brain metastases, a higher number of metastatic sites, lower albumin and absolute lymphocyte count (ALC), higher C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, higher total metabolic tumor volume (TMTV), and higher ctDNA levels were associated with worse survival. Elevated lactate dehydrogenase (LDH) ≥ 2ULN (upper limit of normal), CRP ≥ 10ULN, or ALC < 750/mm3 delineate a subpopulation where treatment with pembrolizumab is futile. A TMTV ≥ 80 mL encompassed 17/21 patients with LDH ≥ 2ULN, CRP ≥ 10ULN, or ALC < 750/mm3. No significant associations were observed between baseline GEP scores and survival. Conclusion: Multiple baseline variables correlate with survival on pembrolizumab. TMTV is a more comprehensive baseline biomarker than CRP, LDH, or ALC in predicting the futility of pembrolizumab., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

27. Dynamic changes of the immune infiltrate after neoadjuvant avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx).

Author

Bex, Axel, primary, Abu-Ghanem, Yasmin, additional, Van Thienen, Johannes V., additional, Graafland, Niels, additional, Lagerveld, Brunolf, additional, Zondervan, Patricia, additional, Beerlage, Harrie, additional, van Moorselaar, Jeroen, additional, Kockx, Mark, additional, Van Dam, Pieter-Jan, additional, Szabados, Bernadett, additional, Blank, Christian U., additional, Powles, Thomas, additional, and Haanen, John B. A. G., additional

Published
2021
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29. Abstract PD14-06: Dynamic changes of PD-L1 and T-cell activation in ECLIPSE: A phase II study investigating preoperative immune combination strategies in untreated, operable ER+ primary breast cancer

Author

Schmid, Peter, primary, Kockx, Mark, additional, Kim, Sung-Bae, additional, Wheatley, Duncan, additional, Phillips, Melissa Mary, additional, Hoffmann, Oliver, additional, Blohmer, Jens U., additional, Im, Seock-Ah, additional, Schneeweiss, Andreas, additional, Zamora, Esther, additional, Waumans, Yannick, additional, Van Dam, Pieter-Jan, additional, Peeters, Dieter, additional, Wimalasingham, Akhila, additional, Marosics, Patricia, additional, Prendergast, Aaron, additional, Mousa, Kelly, additional, Cortes, Javier, additional, and Kuemmel, Sherko, additional

Published
2021
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31. A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab

Author

Awada, Gil, primary, Jansen, Yanina, additional, Schwarze, Julia Katharina, additional, Tijtgat, Jens, additional, Hellinckx, Lennert, additional, Gondry, Odrade, additional, Vermeulen, Sim, additional, Warren, Sarah, additional, Schats, Kelly, additional, van Dam, Pieter-Jan, additional, Kockx, Mark, additional, Keyaerts, Marleen, additional, Everaert, Hendrik, additional, Seremet, Teofila, additional, Rogiers, Anne, additional, and Neyns, Bart, additional

Published
2021
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34. Uncovering the immune-modulating role of anti-RANKL therapy for cervical cancer: Preliminary results.

Author

Van Dam, Peter, primary, Verhoeven, Yannick, additional, De Waele, Jorrit, additional, Jacobs, Julie, additional, Van Dam, Pieter-Jan, additional, Kockx, Mark, additional, Van de Vijver, Koen, additional, Lammens, Martin, additional, Wouters, An, additional, Smits, Evelien, additional, Lardon, Filip, additional, and Trinh, Xuan Bich, additional

Published
2020
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37. MHCI and FOXP3 predicting outcome to neoadjuvant atezolizumab in sequential urothelial cancer tissue.

Author

Szabados, Bernadett, primary, Kockx, Mark, additional, Van Dam, Pieter-Jan, additional, Rodriguez-Vida, Alejo, additional, Duran, Ignacio, additional, Crabb, Simon J., additional, Van Der Heijden, Michiel Simon, additional, Font, Albert, additional, Gravis, Gwenaelle, additional, Prendergast, Aaron, additional, Perdicchio, Maurizio, additional, Stanoeva, Diana, additional, Daelemans, Sofie, additional, Mariathasan, Sanjeev, additional, Tea, Joy S., additional, Mousa, Kelly, additional, Banchereau, Romain, additional, Castellano, Daniel, additional, and Powles, Thomas, additional

Published
2020
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38. Abstract P5-04-04: The spatial interactions between FOXP3+ Tregs, CD8+ cytotoxic T cells and tumor cells predict response to therapy and prognosis in inflammatory breast cancer

Author

Van Berckelaer, Christophe, primary, Rypens, Charlotte, additional, Van Laere, Steven, additional, Marien, Koen, additional, van Dam, Pieter-Jan, additional, Vermeulen, Peter, additional, Dirix, Luc, additional, Kockx, Mark, additional, Colpaert, Cecile, additional, and van Dam, Peter, additional

Published
2020
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39. HER-2 status of circulating tumor cells in a metastatic breast cancer cohort: A comparative study on characterization techniques

Author

Brouwer, Anja, primary, De Laere, Bram, additional, van Dam, Pieter-Jan, additional, Peeters, Dieter, additional, Van Haver, Jasper, additional, Sluydts, Ellen, additional, El Moussaoui, Ali, additional, Mendelaar, Pauline, additional, Kraan, Jaco, additional, Peeters, Marc, additional, Van Laere, Steven, additional, and Dirix, Luc, additional

Published
2019
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40. TP53 Outperforms Other Androgen Receptor Biomarkers to Predict Abiraterone or Enzalutamide Outcome in Metastatic Castration-Resistant Prostate Cancer

Author

De Laere, Bram, primary, Oeyen, Steffi, additional, Mayrhofer, Markus, additional, Whitington, Tom, additional, van Dam, Pieter-Jan, additional, Van Oyen, Peter, additional, Ghysel, Christophe, additional, Ampe, Jozef, additional, Ost, Piet, additional, Demey, Wim, additional, Hoekx, Lucien, additional, Schrijvers, Dirk, additional, Brouwers, Barbara, additional, Lybaert, Willem, additional, Everaert, Els G., additional, De Maeseneer, Daan, additional, Strijbos, Michiel, additional, Bols, Alain, additional, Fransis, Karen, additional, Beije, Nick, additional, de Kruijff, Inge E., additional, van Dam, Valerie, additional, Brouwer, Anja, additional, Goossens, Dirk, additional, Heyrman, Lien, additional, Van den Eynden, Gert G., additional, Rutten, Annemie, additional, Del Favero, Jurgen, additional, Rantalainen, Mattias, additional, Rajan, Prabhakar, additional, Sleijfer, Stefan, additional, Ullén, Anders, additional, Yachnin, Jeffrey, additional, Grönberg, Henrik, additional, Van Laere, Steven J., additional, Lindberg, Johan, additional, and Dirix, Luc Y., additional

Published
2019
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41. Phase i clinical trial of decitabine (5-aza-2'-deoxycytidine) administered by hepatic arterial infusion in patients with unresectable liver-predominant metastases

Author

Jansen, Yanina Y.J., Verset, Gontran, Schats, Kelly, Van Dam, Pieter Jan, Seremet, Teofila T.C., Kockx, Mark, Van Laethem, Jean-Luc, Neyns, Bart, Jansen, Yanina Y.J., Verset, Gontran, Schats, Kelly, Van Dam, Pieter Jan, Seremet, Teofila T.C., Kockx, Mark, Van Laethem, Jean-Luc, and Neyns, Bart

Abstract

DNA demethylating agents may increase the immunogenicity of malignant tumours and increase the efficacy of subsequent treatment with immune check point inhibitors. We investigated the safety of administrating the demethylating agent decitabine by hepatic arterial infusionin patients with unresectable liver meta stases from solid tumours in a dose escalation phase I clinical trial. A total of nine eligible patients were enrolled and initiated study treatment at three different dose levels (two patients at 10, four at 15 and six at a dose level of 20mg decitabine/m2/day) (per protocol there was no intent to escalate the dose above the median tolerated intravenous dose level). Decitabine was administered as a 1-hour hepatic arterial infusion on five consecutive days every 4 weeks. Intrapatient dose escalation was applied in five patients. Grades 1 and 2 haematological toxicity was the most frequent treatment-related adverse event. None of the patients experienced treatment-limiting adverse events. Expression analysis of 30 cancer test is antigens (CTA) in pretreatment and post-treatment biopsies from patients indicated an increased expression of 21 CTAs after treatment. There were no objective tumour responses on study treatment or during post study exposure to immune checkpoint therapy in four patients with uveal melanoma liver metastases. We conclude that the investigate d hepatic arterial administration regimen for decitabine can be safely applied, and a dose level of 20 mg/m2/day on five consecutive days every 4 weeks can be considered for further investigation in combinatorial immunotherapy regimens., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

42. Integrating patient complexity into health policy: a conceptual framework.

Author

Maree, Peter, Hughes, Roger, Radford, Jan, Stankovich, Jim, and Van Dam, Pieter Jan

Subjects
HEALTH policy, MEDICAL quality control, HEALTH services accessibility, MATHEMATICAL models, PATIENT-centered care, CONCEPTUAL structures, QUALITY assurance, THEORY, POLICY sciences, INTEGRATED health care delivery, PATIENT-professional relations, NEEDS assessment
Abstract

Objective: Clinicians across all health professions increasingly strive to add value to the care they deliver through the application of the central tenets of people-centred care (PCC), namely the 'right care', in the 'right place', at the 'right time' and 'tailored to the needs of communities'. This ideal is being hampered by a lack of a structured, evidence-based means to formulate policy and value the commissioning of services in an environment of increasing appreciation for the complex health needs of communities. This creates significant challenges for policy makers, commissioners and providers of health services. Communities face a complex intersection of challenges when engaging with healthcare. Increasingly, complexity is gaining prominence as a significant factor in the delivery of PCC. Based on the World Health Organization (WHO) components of health policy, this paper proposes a policy framework that enables policy makers, commissioners and providers of health care to integrate a model of complexity into policy, subsequent service planning and development of models of care. Methods: The WHO components of health policy were used as the basis for the framework. Literature was drawn on to develop a policy framework that integrates complexity into health policy. Results: Within the framework, complexity is juxtaposed between the WHO components of 'vision', 'priorities' and 'roles'. Conclusion: This framework, supported by the literature, provides a means for policy makers and health planners to conduct analyses of and for policy. Further work is required to better model complexity in a manner that integrates consumer needs and provider capabilities. What is known about the topic?: There is a growing body of evidence regarding patient complexity and its impact on the delivery of health services, but there is little consideration of patient complexity in policy, which is an important consideration for service provision. What does this paper add?: This paper presents an argument for the inclusion of patient complexity in health policy and provides a framework for how that might occur. What are the implications for practitioners?: The inclusion of patient complexity in policy could provide a means for policy makers to consider the factors that contribute to patient complexity in service provision decisions. [ABSTRACT FROM AUTHOR]

Published
2021
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43. Replacement and desmoplastic histopathological growth patterns : a pilot study of prediction of outcome in patients with uveal melanoma liver metastases

Author

Barnhill, Raymond, Vermeulen, Peter, Daelemans, Sofie, van Dam, Pieter‐Jan, Roman‐Roman, Sergio, Servois, Vincent, Hurbain, Ilse, Gardrat, Sophie, Raposa, Graça, Nicolas, André, Dendale, Rémi, Pierron, Gaëlle, Desjardins, Laurence, Cassoux, Nathalie, Piperno‐Neumann, Sophie, Mariani, Pascale, Lugassy, Claire, Université Paris Descartes - Paris 5 (UPD5), Institut Curie [Paris], HistoGeneX, University of Antwerp (UA), Center of Operation Research and Econometrics [Louvain] (CORE), Université Catholique de Louvain = Catholic University of Louvain (UCL), Département de recherche translationnelle, Université Paris sciences et lettres (PSL), Sorbonne Université (SU), BioImaging Cell and Tissue Core Facility (PICT-IBiSA), Département de chirurgie, Institut Curie, Université Catholique de Louvain (UCL), and PSL Research University (PSL)

Subjects
Adult, Male, Uveal Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pilot Projects, liver, replacement, metastasis, Humans, vascular co‐option, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Melanoma, angiotropism, Aged, Comparative Genomic Hybridization, histopathological growth patterns, Liver Neoplasms, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Original Articles, Middle Aged, Prognosis, vascular co-option, Progression-Free Survival, Survival Rate, desmoplastic, Original Article, Female, Human medicine, uveal melanoma
Abstract

International audience; Up to 50% of uveal melanomas (UM) metastasise to the liver within 10 years of diagnosis, and these almost always prove rapidly fatal. As histopathological growth patterns (HGPs) of liver metastases of the replacement and desmoplastic type, particularly from colon and breast carcinoma, may import valuable biological and prognostic information, we have studied HGP in a series of 41 UM liver metastases originating from 41 patients from the period 2006-2017. Twenty patients underwent enucleation while 21 had radiation therapy. Analysis of UM by array comparative genomic hybridisation revealed: 25 (64%) patients with high risk (monosomy3/8q gain); 13 (33%) intermediate risk (M3/8normal or disomy3/8q gain); and 1 low risk (disomy3/8normal). The principal HGP was replacement in 30 (73%) cases and desmoplastic in 11 (27%) cases. Cases with replacement demonstrated striking vascular co-option/angiotropism. With the development of liver metastasis, only the replacement pattern, largest primary tumour diameter, and R2 (incomplete resection) status predicted diminished overall survival (OS; p < 0.041, p < 0.017, p < 0.047, respectively). On multivariate analysis, only HGP (hazard ratio; HR = 6.51, p = 0.008) and resection status remained significant. The genomic high-risk variable had no prognostic value at this stage of liver metastasis. Chi-square test showed no association of HGP with monosomy 3 or 8q gain. Eighteen of 41 (44%) patients are alive with disease and 23 (56%) patients died with follow-up ranging from 12 to 318 months (mean: 70 months, median: 47 months). In conclusion, we report for the first time the frequency of the replacement and desmoplastic HGPs in liver UM metastases resected from living patients, and their potential important prognostic value for UM patients, as in other solid cancers. These results may potentially be utilised to develop radiological correlates and therapeutic targets for following and treating patients with UM metastases.

Published
2018
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44. Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis

Author

Mayrhofer, Markus, primary, De Laere, Bram, additional, Whitington, Tom, additional, Van Oyen, Peter, additional, Ghysel, Christophe, additional, Ampe, Jozef, additional, Ost, Piet, additional, Demey, Wim, additional, Hoekx, Lucien, additional, Schrijvers, Dirk, additional, Brouwers, Barbara, additional, Lybaert, Willem, additional, Everaert, Els, additional, De Maeseneer, Daan, additional, Strijbos, Michiel, additional, Bols, Alain, additional, Fransis, Karen, additional, Oeyen, Steffi, additional, van Dam, Pieter-Jan, additional, Van den Eynden, Gert, additional, Rutten, Annemie, additional, Aly, Markus, additional, Nordström, Tobias, additional, Van Laere, Steven, additional, Rantalainen, Mattias, additional, Rajan, Prabhakar, additional, Egevad, Lars, additional, Ullén, Anders, additional, Yachnin, Jeffrey, additional, Dirix, Luc, additional, Grönberg, Henrik, additional, and Lindberg, Johan, additional

Published
2018
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45. Comprehensive Profiling of the Androgen Receptor in Liquid Biopsies from Castration-resistant Prostate Cancer Reveals Novel Intra-AR Structural Variation and Splice Variant Expression Patterns

Author

De Laere, Bram, van Dam, Pieter-Jan, Whitington, Tom, Mayrhofer, Markus, Henao Diaz, Emanuela, van den Eynden, Gert, Del-Favero, Jurgen, van Laere, Steven, Dirix, Luc, Grönberg, Henrik, Lindberg, Johan, Diaz, Emanuela Henao, and Vandebroek, Jean

Subjects
0301 basic medicine, Oncology, Male, medicine.medical_specialty, Pathology, Time Factors, Antineoplastic Agents, Hormonal, DNA Copy Number Variations, Protein Conformation, Urology, Gene Dosage, Pilot Projects, Kaplan-Meier Estimate, Gene dosage, Disease-Free Survival, Transcriptome, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, Point Mutation, Protein Isoforms, Genetic Predisposition to Disease, Liquid biopsy, business.industry, Gene Expression Profiling, Liquid Biopsy, Genetic Variation, medicine.disease, Androgen receptor, Gene expression profiling, Prostatic Neoplasms, Castration-Resistant, 030104 developmental biology, Phenotype, Treatment Outcome, Gene Expression Regulation, Drug Resistance, Neoplasm, Receptors, Androgen, 030220 oncology & carcinogenesis, Hormonal therapy, Feasibility Studies, Human medicine, business, Blood drawing
Abstract

Background Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7–negative. Objective To investigate if a comprehensive liquid biopsy–based AR profile may improve patient stratification in the context of second-line endocrine therapy. Design, setting, and participants Peripheral blood was collected from patients with CRPC ( n =30) before initiation of a new line of systemic therapy. We performed profiling of circulating tumour DNA via low-pass whole-genome sequencing and targeted sequencing of the entire AR gene, including introns. Targeted RNA sequencing was performed on enriched circulating tumour cell fractions to assess the expression levels of seven AR splice variants (ARVs). Outcome measurements and statistical analysis Somatic AR variations, including copy-number alterations, structural variations, and point mutations, were combined with ARV expression patterns and correlated to clinicopathologic parameters. Results and limitations Collectively, any AR perturbation, including ARV, was detected in 25/30 patients. Surprisingly, intra-AR structural variation was present in 15/30 patients, of whom 14 expressed ARVs. The majority of ARV-positive patients expressed multiple ARVs, with AR-V3 the most abundantly expressed. The presence of any ARV was associated with progression-free survival after second-line endocrine treatment (hazard ratio 4.53, 95% confidence interval 1.424–14.41; p =0.0105). Six out of 17 poor responders were AR-V7–negative, but four carried other AR perturbations. Conclusions Comprehensive AR profiling, which is feasible using liquid biopsies, is necessary to increase our understanding of the mechanisms underpinning resistance to endocrine treatment. Patient summary Alterations in the androgen receptor are associated with endocrine treatment outcomes. This study demonstrates that it is possible to identify different types of alterations via simple blood draws. Follow-up studies are needed to determine the effect of such alterations on hormonal therapy.

Published
2016

46. Circulating tumor cells and survival in abiraterone‐ and enzalutamide‐treated patients with castration‐resistant prostate cancer

Author

De Laere, Bram, primary, Oeyen, Steffi, additional, Van Oyen, Peter, additional, Ghysel, Christophe, additional, Ampe, Jozef, additional, Ost, Piet, additional, Demey, Wim, additional, Hoekx, Lucien, additional, Schrijvers, Dirk, additional, Brouwers, Barbara, additional, Lybaert, Willem, additional, Everaert, Els, additional, Van Kerckhove, Piet, additional, De Maeseneer, Daan, additional, Strijbos, Michiel, additional, Bols, Alain, additional, Fransis, Karen, additional, Beije, Nick, additional, de Kruijff, Inge, additional, van Dam, Valerie, additional, Brouwer, Anja, additional, van Dam, Pieter‐Jan, additional, Van den Eynden, Gert, additional, Rutten, Annemie, additional, Sleijfer, Stefan, additional, Vandebroek, Jean, additional, Van Laere, Steven, additional, and Dirix, Luc, additional

Published
2018
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47. International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

Author

van Dam, Pieter-Jan, primary, van der Stok, Eric P, additional, Teuwen, Laure-Anne, additional, Van den Eynden, Gert G, additional, Illemann, Martin, additional, Frentzas, Sophia, additional, Majeed, Ali W, additional, Eefsen, Rikke L, additional, Coebergh van den Braak, Robert R J, additional, Lazaris, Anthoula, additional, Fernandez, Maria Celia, additional, Galjart, Boris, additional, Laerum, Ole Didrik, additional, Rayes, Roni, additional, Grünhagen, Dirk J, additional, Van de paer, Michelle, additional, Sucaet, Yves, additional, Mudhar, Hardeep Singh, additional, Schvimer, Michael, additional, Nyström, Hanna, additional, Kockx, Mark, additional, Bird, Nigel C, additional, Vidal-Vanaclocha, Fernando, additional, Metrakos, Peter, additional, Simoneau, Eve, additional, Verhoef, Cornelis, additional, Dirix, Luc Y, additional, Van Laere, Steven, additional, Gao, Zu-hua, additional, Brodt, Pnina, additional, Reynolds, Andrew R, additional, and Vermeulen, Peter B, additional

Published
2017
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49. Prevalence and heterogeneity of androgen receptor splice variants and intra-AR structural variation in patient with castration-resistant prostate cancer.

Author

Dirix, Luc Yves, primary, De Laere, Bram, additional, van Dam, Pieter-Jan, additional, Whitington, Tom, additional, Mayrhofer, Markus, additional, Henao Diaz, Emanuela, additional, Van den Eynden, Gert, additional, Vandebroek, Jean, additional, Del-Favero, Jurgen, additional, Van Laere, Steven J, additional, Gronberg, Henrik, additional, and Lindberg, Johan, additional

Published
2017
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50. International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

Author

van Dam, Pieter-Jan, van der Stok, Eric P., Teuwen, Laure-Anne, Van den Eynden, Gert G., Illemann, Martin, Frentzas, Sophia, Majeed, Ali W., Eefsen, Rikke L., van den Braak, Robert R. J. Coebergh, Lazaris, Anthoula, Fernandez, Maria Celia, Galjart, Boris, Laerum, Ole Didrik, Rayes, Roni, Grunhagen, Dirk J., Van de Paer, Michelle, Sucaet, Yves, Mudhar, Hardeep Singh, Schvimer, Michael, Nyström, Hanna, Kockx, Mark, Bird, Nigel C., Vidal-Vanaclocha, Fernando, Metrakos, Peter, Simoneau, Eve, Verhoef, Cornelis, Dirix, Luc Y., Van Laere, Steven, Gao, Zu-hua, Brodt, Pnina, Reynolds, Andrew R., Vermeulen, Peter B., van Dam, Pieter-Jan, van der Stok, Eric P., Teuwen, Laure-Anne, Van den Eynden, Gert G., Illemann, Martin, Frentzas, Sophia, Majeed, Ali W., Eefsen, Rikke L., van den Braak, Robert R. J. Coebergh, Lazaris, Anthoula, Fernandez, Maria Celia, Galjart, Boris, Laerum, Ole Didrik, Rayes, Roni, Grunhagen, Dirk J., Van de Paer, Michelle, Sucaet, Yves, Mudhar, Hardeep Singh, Schvimer, Michael, Nyström, Hanna, Kockx, Mark, Bird, Nigel C., Vidal-Vanaclocha, Fernando, Metrakos, Peter, Simoneau, Eve, Verhoef, Cornelis, Dirix, Luc Y., Van Laere, Steven, Gao, Zu-hua, Brodt, Pnina, Reynolds, Andrew R., and Vermeulen, Peter B.

Abstract

Background: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. Methods: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. Results: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006). Conclusions: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.

Published
2017
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