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2. Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Author

Fonseca, Nicolette M., Maurice-Dror, Corinne, Herberts, Cameron, Tu, Wilson, Fan, William, Murtha, Andrew J., Kollmannsberger, Catarina, Kwan, Edmond M., Parekh, Karan, Schönlau, Elena, Bernales, Cecily Q., Donnellan, Gráinne, Ng, Sarah W. S., Sumiyoshi, Takayuki, Vergidis, Joanna, Noonan, Krista, Finch, Daygen L., Zulfiqar, Muhammad, Miller, Stacy, Parimi, Sunil, Lavoie, Jean-Michel, Hardy, Edward, Soleimani, Maryam, Nappi, Lucia, Eigl, Bernhard J., Kollmannsberger, Christian, Taavitsainen, Sinja, Nykter, Matti, Tolmeijer, Sofie H., Boerrigter, Emmy, Mehra, Niven, van Erp, Nielka P., De Laere, Bram, Lindberg, Johan, Grönberg, Henrik, Khalaf, Daniel J., Annala, Matti, Chi, Kim N., and Wyatt, Alexander W.

Published
2024
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3. WNT Pathway Mutations in Metachronous Oligometastatic Castration-Sensitive Prostate Cancer

Author

Sutera, Philip, Deek, Matthew P., Van der Eecken, Kim, Shetty, Amol C., Chang, Jin Hee, Hodges, Theresa, Song, Yang, Verbeke, Sofie, Van Dorpe, Jo, Fonteyne, Valérie, De Laere, Bram, Mishra, Mark, Rana, Zaker, Molitoris, Jason, Ferris, Matthew, Ross, Ashley, Schaeffer, Edward, Roberts, Nicholas, Song, Daniel Y., DeWeese, Theodore, Pienta, Kenneth J., Antonarakis, Emmanuel S., Ost, Piet, and Tran, Phuoc T.

Published
2023
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5. Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genotyping

Author

Warner, Evan W., primary, Van der Eecken, Kim, additional, Murtha, Andrew J., additional, Kwan, Edmond M., additional, Herberts, Cameron, additional, Sipola, Joonatan, additional, Ng, Sarah W. S., additional, Chen, Xinyi E., additional, Fonseca, Nicolette M., additional, Ritch, Elie, additional, Schönlau, Elena, additional, Bernales, Cecily Q., additional, Donnellan, Gráinne, additional, Munzur, Aslı D., additional, Parekh, Karan, additional, Beja, Kevin, additional, Wong, Amanda, additional, Verbeke, Sofie, additional, Lumen, Nicolaas, additional, Van Dorpe, Jo, additional, De Laere, Bram, additional, Annala, Matti, additional, Vandekerkhove, Gillian, additional, Ost, Piet, additional, and Wyatt, Alexander W., additional

Published
2024
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7. AR and PI3K Genomic Profiling of Cell-free DNA Can Identify Poor Responders to Lutetium-177-PSMA Among Patients with Metastatic Castration-resistant Prostate Cancer

Author

Vanwelkenhuyzen, Jan, primary, Van Bos, Eva, additional, Van Bruwaene, Siska, additional, Lesage, Karl, additional, Maes, Alex, additional, Üstmert, Sezgin, additional, Lavent, Filip, additional, Beels, Laurence, additional, Grönberg, Henrik, additional, Ost, Piet, additional, Lindberg, Johan, additional, and De Laere, Bram, additional

Published
2023
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8. Consensus Statement on Circulating Biomarkers for Advanced Prostate Cancer

Author

Sumanasuriya, Semini, Omlin, Aurelius, Armstrong, Andrew, Attard, Gerhardt, Chi, Kim N., Bevan, Charlotte L., Shibakawa, Aki, IJzerman, Maarten J., De Laere, Bram, Lolkema, Martijn, Lorente, David, Luo, Jun, Mehra, Niven, Olmos, David, Scher, Howard, Soule, Howard, Stoecklein, Nikolas H., Terstappen, Leon W.M.M., Waugh, David, and de Bono, Johann S.

Published
2018
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9. AR and PI3K Genomic Profiling of Cell-free DNA Can Identify Poor Responders to Lutetium-177-PSMA Among Patients with Metastatic Castration-resistant Prostate Cancer

Author

Vanwelkenhuyzen, Jan, Van Bos, Eva, Van Bruwaene, Siska, Lesage, Karl, Maes, Alex, Üstmert, Sezgin, Lavent, Filip, Beels, Laurence, Grönberg, Henrik, Ost, Piet, Lindberg, Johan, and De Laere, Bram

Subjects
Cell-free DNA, Liquid biopsy, Biomarker, Circulating tumour DNA, Lutetium-177-PSMA, Metastatic castration-resistant prostate cancer
Abstract

UNLABELLED: Lutetium-177 prostate-specific membrane antigen radioligands (177Lu-PSMA) are new therapeutic agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We evaluated the prognostic value of circulating tumour DNA (ctDNA) profiling in patients with mCRPC starting treatment with 177Lu-PSMA I&T. Between January 2020 and October 2022, patients with late-stage mCRPC (n = 57) were enrolled in a single-centre observational cohort study. Genomic alterations in the AR gene, PI3K signalling pathway, TP53, and TMPRSS2-ERG were associated with progression-free survival (PFS) on Kaplan-Meier and multivariable Cox regression analyses. Median PFS of 3.84 mo (95% confidence interval [CI] 3.3-5.4) was observed, and 21/56 (37.5%) evaluable patients experienced a prostate-specific antigen response of ≥50% during treatment. Among 46 patients who provided a blood sample for profiling before 177Lu-PSMA treatment. ctDNA was detected in 39 (84.8%); higher ctDNA was correlated with shorter PFS. Genomic structural rearrangements in the AR gene (hazard ratio [HR] 9.74, 95% confidence interval [CI] 2.4-39.5; p = 0.001) and alterations in the PI3K signalling pathway (HR 3.58, 95% CI 1.41-9.08; p = 0.007) were independently associated with poor 177Lu-PSMA prognosis on multivariable Cox regression. Prospective evaluation of these associations in biomarker-driven trials is warranted. PATIENT SUMMARY: We examined cell-free DNA in blood samples from patients with advanced metastatic prostate cancer who started treatment with lutetium-177-PSMA, a new radioligand therapy. We found that patients with genetic alterations in the androgen receptor gene or PI3K pathway genes did not experience a lasting benefit from lutetium-177-PSMA. ispartof: Eur Urol Open Sci vol:53 pages:63-66 ispartof: location:Netherlands status: Published online

Published
2023

11. Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial

Author

De Laere, Bram, Crippa, Alessio, Discacciati, Andrea, Larsson, Berit, Persson, Maria, Johansson, Susanne, D’hondt, Sanne, Bergström, R., Chellappa, Venkatesh, Mayrhofer, Markus, Banijamali, Mahsan, Kotsalaynen, Anastasijia, Schelstraete, Céline, Vanwelkenhuyzen, Jan Pieter, Hjälm-Eriksson, Marie, Pettersson, Linn, Ullén, Anders, Lumen, Nicolaas, Enblad, Gunilla, Thellenberg Karlsson, Camilla, Jänes, Elin, Sandzén, Johan, Schatteman, Peter, Nyre Vigmostad, Maria, Olsson, Martha, Ghysel, Christophe, Sautois, Brieuc, De Roock, Wendy, Van Bruwaene, Siska, Anden, Mats, Verbiene, Ingrida, De Maeseneer, Daan, Everaert, Els, Darras, Jochen, Aksnessether, Bjørg Y., Luyten, Daisy, Strijbos, Michiel, Mortezavi, Ashkan, Oldenburg, Jan, Ost, Piet, Eklund, Martin, Grönberg, Henrik, and Lindberg, Johan

Abstract

ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician’s choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician’s choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or ‘all’ patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician’s choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR(single-nucleotide variant/genomic structural rearrangement)-negative and TP53wild-type patients and TMPRSS2–ERGfusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician’s choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835.

Published
2024
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13. Differential impact of RB status on E2F1 reprogramming in human cancer

Author

McNair, Christopher, Xu, Kexin, Mandigo, Amy C., Benelli, Matteo, Leiby, Benjamin, Rodrigues, Daniel, Lindberg, Johan, Gronberg, Henrik, Crespo, Mateus, De Laere, Bram, Dirix, Luc, Visakorpi, Tapio, Li, Fugen, Feng, Felix Y., de Bono, Johann, Demichelis, Francesca, Rubin, Mark A., Brown, Myles, and Knudsen, Karen E.

Subjects
Retinoblastoma -- Research -- Development and progression, Prostate cancer -- Development and progression -- Analysis -- Research, Transcription factors -- Physiological aspects, Health care industry
Abstract

The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1 -mediated cell cycle regulation. For multiple tumor types, loss of RB function is associated with poor clinical outcome. RB action is abrogated either by direct depletion or through inactivation of RB function; however, the basis for this selectivity is unknown. Here, analysis of tumor samples and cell-free DNA from patients with advanced prostate cancer showed that direct RB loss was the preferred pathway of disruption in human disease. While RB loss was associated with lethal disease, RB-deficient tumors had no proliferative advantage and exhibited downstream effects distinct from cell cycle control. Mechanistically, RB loss led to E2F1 cistrome expansion and different binding specificity, alterations distinct from those observed after functional RB inactivation. Additionally, identification of protumorigenic transcriptional networks specific to RB loss that were validated in clinical samples demonstrated the ability of RB loss to differentially reprogram E2F1 in human cancers. Together, these findings not only identify tumor-suppressive functions of RB that are distinct from cell cycle control, but also demonstrate that the molecular consequence of RB loss is distinct from RB inactivation. Thus, these studies provide insight into how RB loss promotes disease progression, and identify new nodes for therapeutic intervention., Introduction The function of the retinoblastoma tumor suppressor (RB) in preventing tumor development relies in large part on the capacity of this transcriptional corepressor to modulate E2F family transcription factor [...]

Published
2018
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14. Genomic determinants of patterns of failure in metachronous oligometastatic castration-sensitive prostate cancer.

Author

Sutera, Philip, primary, Van der Eecken, Kim, additional, Shetty, Amol, additional, Song, Yang, additional, Hodges, Theresa, additional, Verbeke, Sofie, additional, Van Dorpe, Jo, additional, Fonteyne, Valerie, additional, De Laere, Bram, additional, Mishra, Mark V., additional, Rana, Zaker Hamid, additional, Molitoris, Jason K., additional, Ferris, Matthew J., additional, Roberts, Nicholas J, additional, Song, Daniel Y., additional, DeWeese, Theodore L., additional, Pienta, Kenneth J., additional, Deek, Matthew, additional, Ost, Piet, additional, and Tran, Phuoc T., additional

Published
2023
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16. 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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18. Unsupervised detection of fragment length signatures of circulating tumor DNA using non-negative matrix factorization

Author

Renaud, Gabriel, primary, Nørgaard, Maibritt, additional, Lindberg, Johan, additional, Grönberg, Henrik, additional, De Laere, Bram, additional, Jensen, Jørgen Bjerggaard, additional, Borre, Michael, additional, Andersen, Claus Lindbjerg, additional, Sørensen, Karina Dalsgaard, additional, Maretty, Lasse, additional, and Besenbacher, Søren, additional

Published
2022
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19. Abstract 41: Multi-focal genomic dissection of synchronous primary and metastatic tissue from de novo metastatic prostate cancer

Author

Warner, Evan, primary, Van der Eecken, Kim, additional, Murtha, Andrew J., additional, Kwan, Edmond M., additional, Ng, Sarah W., additional, Chen, Xinyi E., additional, Bernales, Cecily Q., additional, Donnellan, Grainne, additional, Schonlau, Elena, additional, Verbeke, Sofie, additional, Lumen, Nicolaas, additional, Van Dorpe, Jo, additional, Vandekerkhove, Gillian, additional, Ritch, Elie, additional, Annala, Matti, additional, De Laere, Bram, additional, Ost, Piet, additional, and Wyatt, Alexander W., additional

Published
2022
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20. Author response: Unsupervised detection of fragment length signatures of circulating tumor DNA using non-negative matrix factorization

Author

Renaud, Gabriel, primary, Nørgaard, Maibritt, additional, Lindberg, Johan, additional, Grönberg, Henrik, additional, De Laere, Bram, additional, Jensen, Jørgen Bjerggaard, additional, Borre, Michael, additional, Andersen, Claus Lindbjerg, additional, Sørensen, Karina Dalsgaard, additional, Maretty, Lasse, additional, and Besenbacher, Søren, additional

Published
2022
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23. Increased pathway complexity is a prognostic biomarker in metastatic castration-resistant prostate cancer

Author

De Laere, Bram, Crippa, Alessio, Mortezavi, Ashkan, Ghysel, Christophe, Rajan, Prabhakar, Eklund, Martin, Wyatt, Alexander, Dirix, Luc, Ost, Piet, Gronberg, Henrik, and Lindberg, Johan

Subjects
Human medicine
Abstract

Simple Summary Circulating tumour DNA profiling can cost-efficiently accelerate biomarker discovery within oncology trials. However, biomarker identification in metastatic castration-resistant prostate cancer is confounded by a heterogeneous genomic landscape with few commonly-perturbed genes and a large number of infrequently mutated, yet potentially biologically-relevant, cancer drivers. Hence, large sample sizes are required for the stratified evaluation of these infrequent perturbations. To circumvent this issue, we investigated whether grouping genomic alterations with other events within the same cellular pathways would offer increased precision for biomarker discovery. We undertook an individual patient-level pooled analysis of 342 patients with metastatic castration-resistant prostate cancer-initiating abiraterone acetate or enzalutamide. We found that the total number of altered pathways, which we termed the pathway complexity index (PCI) was associated with a poor prognosis. Since genomic profiling is now standard practice in interventional oncology trials, our findings highlight the importance of comprehensive genomic profiling for biomarker discovery and utilization. Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease, characterized by common and rare driver gene alterations that provide a selective growth advantage for progressing tumour cells. We hypothesized that the number of distinct gene driver alteration-affected pathways or gene classes was associated with poor prognosis in patients initiating androgen receptor signalling inhibitors (ARSi). We performed a post hoc analysis of an amalgamated baseline circulating tumour DNA (ctDNA) mutational landscape dataset of ARSi-treated men with mCRPC (n = 342). We associated the detected hotspot, pathogenic, and/or high impact protein function-affecting perturbations in 39 genes into 13 pathways. Progression-free (PFS) and overall survival (OS) were analysed using Kaplan-Meier curves and multivariate Cox regression models. Driver gene alterations were detected in 192/342 (56.1%) evaluable patients. An increased number of affected pathways, coined pathway complexity index (PCI), resulted in a decremental PFS and OS, and was independently associated with prognosis once >= 3 pathway or gene classes were affected (PFS HR (95%CI): 1.7 (1.02-2.84), p = 0.04, and OS HR (95%CI): 2.5 (1.06-5.71), p = 0.04). Additionally, visceral disease and baseline PSA and plasma ctDNA levels were independently associated with poor prognosis. Elevated PCI is associated with poor ARSi outcome and supports comprehensive genomic profiling to better infer mCRPC prognosis.

Published
2021

25. Discovering fragment length signatures of circulating tumor DNA using Non-negative Matrix Factorization

Author

Renaud, Gabriel, primary, Nørgaard, Maibritt, additional, Lindberg, Johan, additional, Grönberg, Henrik, additional, De Laere, Bram, additional, Jensen, Jørgen Bjerggaard, additional, Borre, Michael, additional, Andersen, Claus Lindbjerg, additional, Sørensen, Karina Dalsgaard, additional, Maretty, Lasse, additional, and Besenbacher, Søren, additional

Published
2021
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28. The ProBio Trial: Molecular Biomarkers for Advancing Personalized Treatment Decision in Patients with Metastatic Castration-Resistant Prostate Cancer

Author

Crippa, Alessio, primary, De Laere, Bram, additional, Discacciati, Andrea, additional, Larsson, Berit, additional, Connor, Jason T., additional, Gabriel, Erin E, additional, Thellenberg, Camilla, additional, Jänes, Elin, additional, Enblad, Gunilla, additional, Ullen, Anders, additional, Hjälm-Eriksson, Marie, additional, Oldenburg, Jan, additional, Ost, Piet, additional, Lindberg, Johan, additional, Eklund, Martin, additional, and Grönberg, Henrik, additional

Published
2020
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30. 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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32. AR splice variants in circulating tumor cells of patients with castration‐resistant prostate cancer: relation with outcome to cabazitaxel

Author

Sieuwerts, Anieta M., primary, Onstenk, Wendy, additional, Kraan, Jaco, additional, Beaufort, Corine M., additional, Van, Mai, additional, De Laere, Bram, additional, Dirix, Luc Y., additional, Hamberg, Paul, additional, Beeker, Aart, additional, Meulenbeld, Hielke J., additional, Creemers, Geert‐Jan, additional, Weerden, Wytske M., additional, Jenster, Guido W., additional, Nieuweboer, Annemieke J. M., additional, Mathijssen, Ron H. J., additional, Wit, Ronald, additional, Martens, John W. M., additional, and Sleijfer, Stefan, additional

Published
2019
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33. 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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34. 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

35. Genomic Determinants Associated with Modes of Progression and Patterns of Failure in Metachronous Oligometastatic Castration-sensitive Prostate Cancer

Author

Sutera, Philip, Song, Yang, Shetty, Amol C., English, Keara, Van der Eecken, Kim, Guler, Ozan Cem, Wang, Jarey, Cao, Yufeng, Bazyar, Soha, Verbeke, Sofie, Van Dorpe, Jo, Fonteyne, Valérie, De Laere, Bram, Mishra, Mark, Rana, Zaker, Molitoris, Jason, Ferris, Matthew, Kiess, Ana, Song, Daniel Y., DeWeese, Theodore, Pienta, Kenneth J., Barbieri, Christopher, Marchionni, Luigi, Ren, Lei, Sawant, Amit, Simone, Nicole, Berlin, Alejandro, Onal, Cem, Tran, Phuoc T., Ost, Piet, and Deek, Matthew P.

Abstract

For patients with metachronous oligometastatic castration-sensitive prostate cancer, tumor genomics may play a role in the mode of progression and pattern of failure after initial therapy for metastatic disease. Specifically, patients with TP53and RB1mutations have a higher likelihood of progression, and TP53, SPOP, and WNT pathway mutations may have a role in metastatic organotropism directing the likelihood of bone and visceral disease progression.

Published
2024
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36. 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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37. An In-Depth Evaluation of the Validity and Logistics Surrounding the Testing of AR-V7 mRNA Expression in Circulating Tumor Cells

Author

Sieuwerts, Anieta M., primary, Mostert, Bianca, additional, van der Vlugt-Daane, Michelle, additional, Kraan, Jaco, additional, Beaufort, Corine M., additional, Van, Mai, additional, Prager, Wendy J.C., additional, De Laere, Bram, additional, Beije, Nick, additional, Hamberg, Paul, additional, Westgeest, Hans M., additional, Tascilar, Metin, additional, Dirix, Luc Y., additional, Onstenk, Wendy, additional, de Wit, Ronald, additional, Lolkema, Martijn P., additional, Mathijssen, Ron H.J., additional, Martens, John W.M., additional, and Sleijfer, Stefan, additional

Published
2018
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38. Consensus statement on circulating biomarkers for advanced prostate cancer.

Author

Sumanasuriya, Semini, primary, Omlin, Aurelius Gabriel, additional, Armstrong, Andrew J., additional, Attard, Gerhardt, additional, Chi, Kim N., additional, Bevan, Charlotte L, additional, Waugh, David J., additional, Ijzerman, Maarten J, additional, De Laere, Bram, additional, Lolkema, Martijn P., additional, Lorente, David, additional, Luo, Jun, additional, Mehra, Niven, additional, Olmos, David, additional, Scher, Howard I., additional, Soule, Howard R., additional, Stoecklein, Nikolas H., additional, Terstappen, Leon W M M, additional, and De Bono, Johann S., additional

Published
2018
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39. 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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40. Differential impact of RB status on E2F1 reprogramming in human cancer

Author

McNair, Christopher, primary, Xu, Kexin, additional, Mandigo, Amy C., additional, Benelli, Matteo, additional, Leiby, Benjamin, additional, Rodrigues, Daniel, additional, Lindberg, Johan, additional, Gronberg, Henrik, additional, Crespo, Mateus, additional, De Laere, Bram, additional, Dirix, Luc, additional, Visakorpi, Tapio, additional, Li, Fugen, additional, Feng, Felix Y., additional, de Bono, Johann, additional, Demichelis, Francesca, additional, Rubin, Mark A., additional, Brown, Myles, additional, and Knudsen, Karen E., additional

Published
2017
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41. 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, primary, van Dam, Pieter-Jan, additional, Whitington, Tom, additional, Mayrhofer, Markus, additional, Diaz, Emanuela Henao, additional, Van den Eynden, Gert, additional, Vandebroek, Jean, additional, Del-Favero, Jurgen, additional, Van Laere, Steven, additional, Dirix, Luc, additional, Grönberg, Henrik, additional, and Lindberg, Johan, additional

Published
2017
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42. Circulating tumour cells and survival in abiraterone- and enzalutamide-treated patients with castration-resistant prostate cancer.

Author

De Laere, Bram, primary, Van Oyen, Peter, additional, Ghysel, Christophe, additional, Ost, Piet, additional, Demey, Wim, additional, Hoekx, Lucien, additional, Schrijvers, Dirk L., additional, Brouwers, Barbara Anna Henk, additional, Lybaert, Willem, additional, Everaert, Els Grieta, additional, Ampe, Jozef, additional, Van Kerckhove, Piet, additional, De Maeseneer, Daan Joost, additional, Strijbos, Michiel Hendrik, additional, Bols, Alain, additional, Fransis, Karen, additional, Van den Eynden, Gert, additional, Vandebroek, Jean, additional, Van Laere, Steven J, additional, and Dirix, Luc Yves, additional

Published
2017
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43. 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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45. Patients with metastatic hormone receptor-positive breast cancer express PIK3CA oncogene mutational heterogeneity in circulating tumor cells

Author

De Laere, Bram, primary, JE Peeters, Dieter, additional, Brouwer, Anja, additional, Salgado, Roberto, additional, A van Dam, Peter, additional, Rutten, Annemie, additional, den Eynden, Gert Van, additional, Denkert, Carsten, additional, Teuwen, Laure-Anne, additional, Vermeulen, Peter B, additional, J Van Laere, Steven, additional, and Y Dirix, Luc, additional

Published
2016
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46. Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells

Author

Onstenk, Wendy, primary, Sieuwerts, Anieta M., additional, Kraan, Jaco, additional, Van, Mai, additional, Nieuweboer, Annemieke J.M., additional, Mathijssen, Ron H.J., additional, Hamberg, Paul, additional, Meulenbeld, Hielke J., additional, De Laere, Bram, additional, Dirix, Luc Y., additional, van Soest, Robert J., additional, Lolkema, Martijn P., additional, Martens, John W.M., additional, van Weerden, Wytske M., additional, Jenster, Guido W., additional, Foekens, John A., additional, de Wit, Ronald, additional, and Sleijfer, Stefan, additional

Published
2015
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50. An In-Depth Evaluation of the Validity and Logistics Surrounding the Testing of AR-V7mRNA Expression in Circulating Tumor Cells

Author

Sieuwerts, Anieta M., Mostert, Bianca, van der Vlugt-Daane, Michelle, Kraan, Jaco, Beaufort, Corine M., Van, Mai, Prager, Wendy J.C., De Laere, Bram, Beije, Nick, Hamberg, Paul, Westgeest, Hans M., Tascilar, Metin, Dirix, Luc Y., Onstenk, Wendy, de Wit, Ronald, Lolkema, Martijn P., Mathijssen, Ron H.J., Martens, John W.M., and Sleijfer, Stefan

Abstract

Recent reports have emphasized the clinical relevance of detecting AR-V7in circulating tumor cells (CTCs). Our aim was to set up a validated multicenter pipeline to measure AR-V7by quantitative RT-PCR (RT-qPCR) in RNA isolated from CellSearch-enriched CTCs to provide an AR-V7–positive or AR-V7–negative score in a clinically acceptable time range. CellSearch-enirched CTCs from patients with metastatic castration–resistant prostate cancer were characterized by RT-qPCR. After optimization, it was prospectively tested whether it was possible to report the AR-V7status within 11 days (PRELUDE study). In the range of the RNA equivalent of 0.2 to 12 VCaP cells, the CV for AR-V7was 9% (n = 37). The limit of detection was 0.3, and the limit of quantitation was 3 cells in the final RT-qPCR. No differences were observed between AR-V7data generated by five technicians or in two different laboratories. For the 45 patients in PRELUDE, 13 patients were ineligible, 22 patients were AR-V7negative, and 10 were AR-V7positive. The median time to inform the physician of the test result was 7 days (range, 2 to 11 days). This assay can establish the AR-V7status in CTCs from patients with metastatic castration–resistant prostate cancer. Furthermore, it was possible to provide an AR-V7outcome within 11 days, indicating that it may be used to choose between an anti–androgen receptor or taxane-based cabazitaxel treatment.

Published
2018
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