139 results on '"E. Van Nieuwenhuysen"'
Search Results
2. LIO-1: Initiale Phase 2 Erfahrung mit Lucitanib + Nivolumab bei Patientinnen mit persistierendem oder rezidiviertem Zervixkarzinom (NCT04042116; ENGOT-GYN3/AGO/LIO)
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F Heitz, A Oaknin, FJ Backes, E Van Nieuwenhuysen, RN Eskander, A González-Martín, V Makker, C Marth, M Patel, RT Penson, A Redondo, MJR Pérez, E Hamilton, P Wimberger, N Concin, J Go, K Wride, D Lepley, R Dusek, T Cameron, and S Pignata
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- 2022
3. Robot-assisted surgery for women with endometrial cancer: Surgical and oncologic outcomes within a Belgium gynaecological oncology group cohort
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E. Van Nieuwenhuysen, Ph Van Trappen, Annouschka Laenen, Ignace Vergote, K. Traen, F. Peeters, S. Ongaro, Frédéric Goffin, A. Kakkos, C. Ver Eecke, and Evelyn Despierre
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Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Hysterectomy ,03 medical and health sciences ,0302 clinical medicine ,Belgium ,Robotic Surgical Procedures ,Age groups ,Laparotomy ,medicine ,Humans ,Obesity ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,030219 obstetrics & reproductive medicine ,business.industry ,Endometrial cancer ,Gynaecological oncology ,Postoperative complication ,General Medicine ,Perioperative ,Length of Stay ,Middle Aged ,medicine.disease ,Conversion to Open Surgery ,Endometrial Neoplasms ,Surgery ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Stage I endometrial cancer - Abstract
Objective To evaluate surgical and oncologic outcomes of patients treated by robot-assisted surgery for endometrial cancer within the Belgium Gynaecological Oncology Group (BGOG). Study design We performed a retrospective analysis of women with clinically Stage I endometrial cancer who underwent surgical treatment from 2007 to 2018 in five institutions of the BGOG group. Results A total of 598 consecutive women were identified. The rate of conversion to laparotomy was low (0.8%). The mean postoperative Complication Common Comprehensive Index (CCI) score was 3.4. The rate of perioperative complications did not differ between age groups, however the disease-free survival was significantly lower in patients over 75 years compared to patients under 65 years of age (p=0.008). Per-operative complications, conversion to laparotomy rate, post-operative hospital stay, CCI score and disease-free survival were not impacted by increasing BMI. Conclusion Robot-assisted surgery for the surgical treatment of patients suffering from early-stage endometrial cancer is associated with favourable surgical and oncologic outcomes, particularly for unfavourable groups such as elderly and obese women, thus permitting a low morbidity minimally-invasive surgical approach for the majority of patients in expert centres.
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- 2021
4. 14P Unravelling the immune landscape of non-epithelial ovarian cancer
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T. Laga, A-S. Van Rompuy, P. Busschaert, S.J.A.R. Olbrecht, L. Loverix, F. Lodi, T. Baert, T. Van Gorp, I.B. Vergote, D. Lambrechts, and E. Van Nieuwenhuysen
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Cancer Research ,Oncology - Published
- 2023
5. 41P Phase I analysis of ubamatamab (MUC16xCD3 bispecific antibody) in patients with recurrent ovarian cancer
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K.N. Moore, D. O'Malley, E. Van Nieuwenhuysen, E. Hamilton, R.E. O'Cearbhaill, O. Yeku, S. Bouberhan, J.Y. Hou, M. Peterman, P. Goncalves, T. Schmidt, S-Y. Yoo, M. Zhu, I. Lowy, T. Rowlands, T. Uldrick, E.A. Miller, and J. Liu
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Cancer Research ,Oncology - Published
- 2023
6. Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies
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Y. Chai, S. Shacham, E Van Nieuwenhuysen, T.J. Unger, Anne L Kranich, T. Nottrup, Y. Landesman, Mansoor Raza Mirza, Morten Mau-Sørensen, Sileny Han, Charlotte Aaquist Haslund, Bente Lund, M. Kauffman, Ignace Vergote, J. Shah, A. Joshi, Marsha Crochiere, Nicole Concin, Tami Rashal, N. Au, Ulla Peen, and Z. Umajuridze
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Genital Neoplasms, Female ,Nausea ,Receptors, Cytoplasmic and Nuclear ,Phases of clinical research ,Selinexor ,Karyopherins ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endometrial cancer ,Ovarian cancer ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Adverse effect ,Aged ,Aged, 80 and over ,Cervical cancer ,business.industry ,Obstetrics and Gynecology ,Cancer ,Middle Aged ,Triazoles ,medicine.disease ,Progression-Free Survival ,Hydrazines ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,XPO1 ,Female ,Neoplasm Grading ,Neoplasm Recurrence, Local ,medicine.symptom ,business - Abstract
Background Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies. Methods In this phase 2 trial, patients received selinexor (35 or 50 mg/m2 twice-weekly [BIW] or 50 mg/m2 once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) ≥12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1–11), 2 (1–5), and 3 (1–6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m2 QW had fewer high-grade AEs with similar efficacy as BIW treatment. Conclusions Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care.
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- 2020
7. EPV255/#120 Tisotumab vedotin vs investigator’s choice chemotherapy in second- or third-line recurrent or metastatic cervical cancer (innovatv 301/ENGOT-CX12/GOG-3057, trial in progress)
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Ignace Vergote, Susana Banerjee, Domenica Lorusso, Bradley J. Monk, Anneke M. Westermann, K Madsen, Christian Marth, I. Soumaoro, Brian M. Slomovitz, S Jain, Nicoletta Colombo, Robert L. Coleman, Antonio González-Martín, Leslie M Randall, Paula Calvert, E Van Nieuwenhuysen, Linn Woelber, David Cibula, and Elsa Kalbacher
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Oncology ,medicine.medical_specialty ,Chemotherapy ,Third line ,business.industry ,Internal medicine ,medicine.medical_treatment ,medicine ,business ,Metastatic cervical cancer - Published
- 2021
8. 197TiP First-in-human (FIH) phase I/II study of ubamatamab, a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer (OC)
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K.N. Moore, S. Bouberhan, E. Hamilton, J. Liu, R.E. O'Cearbhaill, D. O'Malley, K. Papadimitriou, D. Schröder, E. Van Nieuwenhuysen, S-Y. Yoo, M. Peterman, P. Goncalves, T. Schmidt, M. Zhu, I. Lowy, T. Uldrick, and E.A. Miller
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Oncology ,Immunology and Allergy - Published
- 2022
9. 40 InnovaTV 301/ENGOT-cx12/GOG-3057: tisotumab vedotin vs investigator’s choice chemo in second- or third-line recurrent or metastatic cervical cancer
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I Soumaoro, E Van Nieuwenhuysen, K Madsen, Domenica Lorusso, Brian M. Slomovitz, Antonio González-Martín, Elsa Kalbacher, Ignace Vergote, Leslie M Randall, and S Jain
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Oncology ,Chemotherapy ,medicine.medical_specialty ,Bevacizumab ,business.industry ,medicine.medical_treatment ,Vinorelbine ,Gemcitabine ,Irinotecan ,Pemetrexed ,Internal medicine ,medicine ,Clinical endpoint ,Topotecan ,business ,medicine.drug - Abstract
Introduction/Background* Doublet chemotherapy (paclitaxel plus either platinum or topotecan) with bevacizumab (if eligible) is recommended for first-line treatment of recurrent or metastatic cervical cancer (r/mCC; Tewari 2014). In the second-line setting, there are limited data for available treatment options. Tisotumab vedotin (TV) is an investigational antibody-drug conjugate directed to tissue factor. In the phase 2 pivotal trial (innovaTV 204/ENGOT-cx6/GOG-3023) in r/mCC patients with disease progression on or after chemotherapy, TV demonstrated clinically meaningful and durable activity (objective response rate [ORR]: 24%; median duration of response [DOR]: 8.3 months) with a manageable and tolerable safety profile. Most adverse events associated with TV were mild to moderate. These findings support further investigation of TV in patients with r/mCC who progress on first-line treatment options. Methodology innovaTV 301/ENGOT-cx12/GOG-3057 (NCT04697628) is a global, randomized, open-label, phase 3 trial evaluating efficacy and safety of TV in patients with previously treated r/mCC. Eligible patients must be ≥18 years, have r/mCC, and have progressed after receiving 1–2 prior lines of therapy (either standard of care systemic chemotherapy doublet or platinum-based therapy with bevacizumab, if eligible). Approximately 482 patients will be randomized 1:1 to receive 21-day cycles of TV (2.0 mg/kg IV once every 3 weeks) or investigator’s choice of chemotherapy: topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint is overall survival. Key secondary endpoints are progression-free survival, ORR, time to response, DOR, safety, and quality of life outcomes. The study is enrolling and will have sites in the USA, Europe, Japan, Latin America, Taiwan, Singapore, and South Korea. Result(s)* Not applicable for trial in progress Conclusion* Not applicable for trial in progress
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- 2021
10. 1109 Quality of life and sexual functioning after treatment for locally advanced cervical cancer – CCRT versus NACT-S
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Ignace Vergote, M Tahapary, M-R Christiaens, T Van Gorp, E Van Nieuwenhuysen, R Salihi, Sileny Han, H Toelen, and Patrick Neven
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Cervical cancer ,medicine.medical_specialty ,Activities of daily living ,business.industry ,medicine.medical_treatment ,Brachytherapy ,Cancer ,medicine.disease ,Quality of life ,Internal medicine ,Sex life ,Concomitant ,medicine ,business ,Reproductive health - Abstract
Introduction/Background* Locally advanced cervical cancer can be treated by concomitant chemoradiation therapy (CCRT) followed by brachytherapy or by neo-adjuvant chemotherapy followed by surgery (NACT-S). Quality of life (QoL) and sexual health (SH) are important to evaluate after treatment considering the young mean age in affected women and relatively long 5-year survival. This study aims to compare differences in QoL and SH among women treated for locally advanced cervical cancer, after CCRT versus NACT-S. Methodology In this academic single centre cross-sectional questionnaire study, we included patients > 18 years with a history of locally advanced cervical cancer, who received either CCRT or NACT-S. QoL and SH were assessed using Dutch questionnaires including the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life core module 30 (QLQ-C30), the cervical cancer module 24 (QLQ-CX24), and sexual health questionnaire (SHQ-22). X2-test and T-test were performed to compare the two groups. Result(s)* We sent the questionnaires to 105 women who were treated at our centre in the period between 01-01-2002 and 31-12-2018. A total of 36 patients (34%; n=12 CCRT; n=24 NACT-S) returned the questionnaire and were included for analysis. Six patients in the NACT-S group also underwent adjuvant CCRT. When comparing the CCRT and NACT-S group, 58% vs. 54% did “not at all” feel limited in their daily activities. QoL on average scored 63% vs. 67% (P= 0.29), in the CCRT and NACTS group respectively. Patients were at least “quite a bit” or “very much” satisfied with their sex life in 25% vs. 54% in the CCRT and NACT-S group, respectively (P= 0.048). A total of 33% vs. 46% did “not at all” communicate with medical professionals about sexual issues in the CCRT and NACT-S group, respectively. Conclusion* QoL did not significantly differ when comparing the CCRT to the NACT-S group. Satisfaction with sexual life was higher in the NACT-S group. QoL and SH should receive more attention in patients with cervical cancer after treatment.
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- 2021
11. 415 Single-cell map of the dynamic changes underlying platinum-based chemotherapy with or without bevacizumab in high-grade serous tubo-ovarian carcinoma
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A Vandestichele, T Van Gorp, Sileny Han, E Van Nieuwenhuysen, T Laga, Liselore Loverix, D Lambrechts, Ignace Vergote, Siel Olbrecht, A.S. Van Rompuy, Pieter Busschaert, and Thaïs Baert
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Chemotherapy ,Stromal cell ,Bevacizumab ,business.industry ,Angiogenesis ,medicine.medical_treatment ,medicine.disease ,Vascular endothelial growth factor ,Serous fluid ,chemistry.chemical_compound ,Vascular endothelial growth factor A ,chemistry ,Cancer research ,Carcinoma ,medicine ,business ,medicine.drug - Abstract
Introduction/Background* The vascular endothelial growth factor (VEGF) plays an import role in emergence and spread of high-grade serous tubo-ovarian carcinoma (HGSTOC). Bevacizumab, a monoclonal antibody targeting VEGFA, has therefore been added to first-line treatment of advanced HGSTOC. We here map the dynamics of different stromal components of the tumour microenvironment under chemotherapy with or without bevacizumab. Methodology We performed single-cell RNA-sequencing on 62,461 cells sampled from 6 HGSTOC patients before and after neo-adjuvant platin-based chemotherapy with or without bevacizumab. We identified 44 stromal cell subclusters on which we applied Mixed-effects modelling of Associations of Single Cells to identify cell populations associated with bevacizumab exposure and pathological response using the chemotherapeutic response score. Result(s)* Our study revealed diverse stromal cell subsets associated with bevacizumab exposure. The addition of bevacizumab to frontline chemotherapy increased the odds of endothelial cell (ECs) prevalence by a 3-fold (OR 2.91, 95%CI:2.36-3.58; p Conclusion* We here provide initial evidence on the mechanisms underlying early response to bevacizumab and frontline chemotherapy in HGSTOC, including tip cell impairment, reduced hypoxia and a decrease in regulatory T cells. However, bevacizumab exposure increased the influx of PDGFC-expressing macrophages capable to bypass VEGFA-dependent angiogenesis.
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- 2021
12. 199 Randomised Phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer
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Annouschka Laenen, E Falco, MJ Rubio Pérez, Salvatore Antonio Pignata, E Van Nieuwenhuysen, J Kerger, P Zola, E Guerra-Alia, Christine Gennigens, Mustafa Zelal Muallem, Jalid Sehouli, Pauline Wimberger, T Van Gorp, E Garcia Martinez, A Ferrero, Domenica Lorusso, I Braicu, Antonio Casado, Philip R. Debruyne, and Ignace Vergote
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Cervical cancer ,medicine.medical_specialty ,Chemotherapy ,Bevacizumab ,business.industry ,medicine.medical_treatment ,medicine.disease ,Placebo ,Gastroenterology ,Carboplatin ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Clinical endpoint ,Nintedanib ,business ,Febrile neutropenia ,medicine.drug - Abstract
Introduction/Background* Platinum in combination with paclitaxel (P) and bevacizumab is the standard of care in first-line recurrent/advanced cervical cancer (Tewari, NEJM 2020). Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. Methodology Double-blind phase II randomised study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin AUC 5-6 and paclitaxel 175mg/m2 q 3 weeks with oral nintedanib 200 mg BID/placebo. Stratification factor was primary advanced versus recurrent disease. The primary endpoint was progression-free survival (PFS) at 1,5 years with at least 87 events and α=0.15, β=80%, one sided, in favor of the nintedanib (N) versus control (C) arm. The study (NCT02009579) was performed according to the ENGOT model A. Result(s)* 120 patients (62 N, 58 C) were randomised between March 2014 and October 2018. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favour of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Subgroup analysis did not demonstrate a difference in PFS in the primary advanced setting, but in the recurrent setting the 1 year PFS was 22.8% and 14.9% for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Discontinuation of chemotherapy was similar in both groups. N was discontinued in 3% versus placebo in 1.6% of the patients. Dose reduction of N was necessary in 53% of the patients. Conclusion* The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.
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- 2021
13. 523MO Ubamatamab (REGN4018, MUC16xCD3 bispecific antibody) monotherapy in patients with recurrent ovarian cancer (OC): Phase I dose-escalation analysis
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E. Van Nieuwenhuysen, D. O'Malley, R.E. O'Cearbhaill, K.N. Moore, E.P. Hamilton, O. Yeku, S. Bouberhan, J.Y. Hou, S-Y. Yoo, J. Brouwer-Visser, H.K. Cheung, M. Peterman, P. Goncalves, T. Schmidt, M. Zhu, I. Lowy, T. Rowlands, T.S. Uldrick, E.A. Miller, and J.F. Liu
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Oncology ,Hematology - Published
- 2022
14. 615TiP NIRVANA-1: A multicentre randomized study comparing carboplatin-paclitaxel (CP) followed by niraparib (nira) to CP–bevacizumab (bev) followed by nira-bev in patients with FIGO stage III ovarian high-grade epithelial cancer and no residual disease after upfront surgery
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G. Freyer, A.J. Gonzalez Martin, F. Raspagliesi, J. Peron, E. Van Nieuwenhuysen, K. Hasegawa, M-C. Lim, and I.L. Ray-Coquard
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Oncology ,Hematology - Published
- 2022
15. Abstract P3-08-20: Clinical next-generation sequencing analysis in ER-positive HER2-negative metastatic breast cancer patients: Mutation frequency & clinical correlations
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I. Vanden Bempt, Ines Nevelsteen, Guiseppe Floris, J Goyens, H. Wildiers, K Punie, E Van Nieuwenhuysen, Patrick Neven, A Smeets, Ignace Vergote, S Vander Borght, and Sileny Han
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Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,Fulvestrant ,business.industry ,Cancer ,medicine.disease ,medicine.disease_cause ,Metastatic breast cancer ,Breast cancer ,Internal medicine ,Mutation (genetic algorithm) ,biology.protein ,Medicine ,PTEN ,KRAS ,Mutation frequency ,business ,medicine.drug - Abstract
Background: Clinical next-generation sequencing (NGS) has opened new perspectives on genome-driven therapy for metastatic breast cancer (MBC) through the identification of recurrent driver mutations. However, therapeutic relevance of the detection of these mutations with a potential impact on disease outcome and treatment resistance remains unclear. Patients and Methods: A monocentric retrospective study was performed to investigate mutation frequency and disease outcome in 86 metastatic breast cancers patients treated in UZ-Leuven and tested for the presence of mutations in representative formalin-fixed, paraffin-embedded tumor tissue using a routine diagnostic panel of 26 cancer genes (TruSight Tumor 26, Illumina, mean coverage 500X). It mainly concerned metastatic lesions (96.5%). Out of 86 patients, 63 had hormone receptor (HR) positive/ HER2-negative disease; 8 were HER2-positive and 15 triple negative as determined by immunohistochemistry (IHC)/Fluurescence in situ hybridization (FISH). The 63 ER-positive/ HER2-negative cases were selected for further investigation. Single-nucleotide variants and insertions/deletions were reported. Results: Overall, mutations (> 5% allelic frequency) were found in 60.3% of the cases. As expected, mutations in PIK3CA and TP53 were being most frequently encountered (35% and 19% respectively); variants in AKT1, KRAS and PTEN were less common (5%, 3% and 2% respectively). Focusing on ER-positive/HER2-negative cases, 13 out of 63 had a single PIK3CA mutation, 6 had a single TP53 mutation and 21 cases had more than 1 mutation. In 23 out of 63 cases, no potentially actionable mutation could be identified using the 26 cancer gene panel. Interestingly, we found a clinically relevant and statistically significant difference in median progression-free survival between patients harboring a TP53 mutation only (19,8 months (m), range 12.1 – 27.4) and those harboring a PIK3CA mutation only (84m, range 7.4 – 215.1) or patients without any detected mutation (45,3m, range 5.8 – 225.8). Similarly, overall survival was significantly worse for TP53 mutated cases compared with patients with a PIK3CA or no mutation at all. Finally, a brief comparison of MBC-therapies used in these different subgroups showed the interesting finding that none of 7 PIK3CA-mutated tumors treated with fulvestrant monotherapy showed treatment response. Conclusion: This small retrospective analysis showed that clinical sequencing using a small targeted NGS panel reveals mutations in 60.3% of MBC patients, with 40% being targetable. Besides predictive implications, detection of these mutations could also have major prognostic implications on distant metastasis free survival and overall survival. Citation Format: Goyens J, Punie K, Wildiers H, Smeets A, Vander Borght S, Floris G, Vergote I, Van Nieuwenhuysen E, Han S, Nevelsteen I, Neven P, Vanden Bempt I. Clinical next-generation sequencing analysis in ER-positive HER2-negative metastatic breast cancer patients: Mutation frequency & clinical correlations [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-20.
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- 2019
16. Abstract P4-08-25: Decentralized beta testing of MammaPrint and BluePrint NGS kit at University Hospitals Leuven and Curie Institute Paris
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Leonie J. M. J. Delahaye, Liesbet Vliegen, P Sintubin, Laurence Slembrouck, E Van Nieuwenhuysen, I. Vanden Bempt, C Helsmoortel, L Darrigues, S Vander Borght, EL Faron, Cécile Reyes, Sileny Han, H. Wildiers, Lynn Jongen, G Hoste, Annuska M. Glas, Patrick Neven, S Neijenhuis, V Raynal, L. Mittempergher, Anne Vincent Salomon, A Smeets, K Punie, Guiseppe Floris, Anke T. Witteveen, Mylène Bohec, Timothé Cynober, F Reyal, Ines Nevelsteen, Audrey Rapinat, and Cécile Laurent
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Concordance ,Cancer ,medicine.disease ,Beta testing ,University hospital ,Subtyping ,Breast cancer ,MammaPrint ,Internal medicine ,Invasive lobular carcinoma ,medicine ,business - Abstract
Background Many countries restrict patient material exchange to central diagnostic laboratories abroad, limiting access to assays like MammaPrint® (MP) and BluePrint® (BP). Both assays are microarray-based, with MP being prognostic for distant recurrence and BP for molecular subtyping of breast cancer (Luminal-, HER2-, and Basal-type). To increase accessibility, decentralization is required with Next Generation Sequencing (NGS) being the preferred testing platform given that most diagnostic laboratories have the technology in place. The aim of this beta testing study is to validate a previously developed and centrally validated MP and BP NGS kit for RNA samples in two large tertiary academic hospitals in Europe. Patients and Methods Patients with early breast cancer diagnosed at the Multidisciplinary Breast Center at University Hospitals Leuven and Curie Institute Paris were prospectively included between September 2017 and January 2018. Patients with bilateral breast cancer or presenting with more than 3 positive lymph nodes were excluded. Only patients with invasive ductal and invasive lobular carcinoma were included. Twenty tissue sections were cut from formalin-fixed, paraffin-embedded (FFPE) blocks; 10 tissue sections were analyzed at the local site using the MP and BP NGS kit, and 10 tissue sections were analyzed at Agendia using the same kit and procedure, as well as with the golden standard method (gene expression microarrays). Targeted RNA sequencing of the 70 MP and 80 BP signature genes was performed on Illumina MiSeq instruments. The raw NGS data generated at the local test sites was sent through a secure file transfer protocol server to Agendia for interpretation and comparison with microarray and NGS performed in the Agendia laboratories. We aimed for a minimum concordance rate between MP and BP outcome of 90% between each local site and Agendia's centralized site. Results In this study, 116 early breast cancer patients were included (73 from University Hospitals Leuven and 43 from Curie Institute). Out of these patients, 52% were MP Low Risk and 48% MP High Risk according to microarray. The patients had a BP luminal, HER2 or basal subtype in respectively 83%, 9% and 8%. Concordance between MP microarray obtained from Agendia and MP NGS obtained from the local sites was 91.4%. Concordance between MP High and Low Risk classification between NGS Leuven versus NGS Agendia was 92.1% and between NGS Curie versus NGS Agendia 95.3%. For BP subtype outcomes, the results from microarray versus NGS for all patients combined from both local sites gave a 98.3% concordance and NGS Agendia versus NGS from each local site gave a 100% concordance. Conclusion The MP and BP NGS kit was successfully validated in a decentralized setting, showing high concordance between results obtained at three different sites. There was a clear benefit of having well-trained NGS experienced diagnostic technical teams. The MP and BP NGS kit the first FFPE targeted RNA sequencing based multigene signature for breast cancer care, will provide a high and equal standard of MP and BP gene expression testing for breast cancer in a decentralized setting. Citation Format: Slembrouck L, Laurent C, Delahaye LJ, Mittempergher L, Vanden Bempt I, Vander Borght S, Darrigues L, Vliegen L, Sintubin P, Raynal V, Bohec M, Reyes C, Rapinat A, Helsmoortel C, Jongen L, Hoste G, Neven P, Wildiers H, Smeets A, Nevelsteen I, Punie K, Van Nieuwenhuysen E, Han S, Salomon AV, Faron EL, Cynober T, Witteveen AT, Neijenhuis S, Glas AM, Reyal F, Floris G. Decentralized beta testing of MammaPrint and BluePrint NGS kit at University Hospitals Leuven and Curie Institute Paris [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-25.
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- 2019
17. Abstract P5-09-05: Hereditary breast cancer beyond BRCA: Clinical and histopathological characteristics in patients with germline CHEK2, ATM, PALB2 and TP53-mutations
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Patrick Neven, Eric Legius, G Van Buggenhout, Guiseppe Floris, Sileny Han, Caroline Weltens, P D'Hoore, Patrick Berteloot, K Punie, A Smeets, E Van Nieuwenhuysen, H. Wildiers, Hilde Janssen, G Hoste, E. Van Limbergen, and Ines Nevelsteen
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Cancer Research ,Oncology ,business.industry ,PALB2 ,Cancer research ,Medicine ,In patient ,Tp53 mutation ,business ,CHEK2 ,Germline ,Hereditary Breast Cancer - Abstract
Background The introduction of multi-gene panel testing in the diagnosis of hereditary breast and ovarian cancer (HBOC) has led to an important increase in the detection of breast cancer predisposition genes other than BRCA1 and BRCA2. Methods All individuals who underwent HBOC-testing at our institution since the introduction of multi-gene panel testing were included (March 2016-August 2017). In this retrospective analysis, the BRCA Hereditary Cancer MASTR Plus® panel is used (Multiplicom, Belgium), with sequencing of BARD1, BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, TP53, MRE11A, RAD50, NBN, FAM175A, ATM, PALB2, STK11, MEN1, PTEN, CDH1, MUTYH, CHEK2, BLM, XRCC2, EPCAM, MLH1, MSH6, PMS2, MSH2. In breast cancer patients with a recurrent germline alteration, age and TNM stage at diagnosis, histological subtype, grade of differentiation and molecular surrogate subtype were recorded. Given the low numbers of TP53-carriers diagnosed by HBOC testing, also patients with a germline TP53-mutation diagnosed by targeted sequencing at our institution were included. Statistical analysis were performed with SPSS version 25. Results In 11.9 % of 2806 patients who underwent panel testing, a germline pathogenic alteration was detected. BRCA1 and BRCA2 were the most prevalent alterations, detected in respectively 3.35 and 2.92 % of patients. Germline alterations in CHEK2, ATM , PALB2 and TP53 were detected in respectively 2.5 %, 1.1 %, 0.5 % and 0.1 %. In 1 % of patients, germline alterations were retrieved that only contribute to ovarian cancer risk (BRIP, RAD51C, RAD51D). Germline DNA mismatch repair alterations were detected in 0.39 % of patients. The median age at onset of breast cancer in patients with germline CHEK2-, ATM-, PALB2- and TP53-mutations was 47, 53, 39 and 33 years respectively. The age of breast cancer diagnosis in patients with germline TP53-alterations was significantly younger compared to patients with CHEK2-mutations (p = 0.01), ATM-mutations (p = 0.01) and PALB2-mutations (p = 0.04). In situ carcinomas were diagnosed in respectively 9 %, 11 % and 11 % of patients with CHEK2-, PALB2- and TP53-mutations. Patients with CHEK2, ATM, PALB2 and TP53-alterations were diagnosed with ≥T3-tumors in respectively 13 %, 12 %, 33 % and 22 %. Nodal status at diagnosis was negative in 40-60 % in these 4 subgroups. Upfront metastatic disease was diagnosed only in 2/43 CHEK2-carriers. More than half of the breast cancer diagnoses were luminal tumors in CHEK2-, ATM- and PALB2-carriers, while cases with germline TP53-alterations only presented with luminal cancers in 22 % in our series. Conclusion Almost half of the pathogenic mutations detected in HBOC-genes are alterations in genes other than BRCA1 and BRCA2. CHEK2-mutations are by far the most prevalent, followed by ATM, PALB2 and TP53. The range of the CHEK2- and ATM-population was wider then expected at the lower-age boundary. The age of breast cancer diagnosis in patients with germline TP53-mutations was significantly younger compared to patients with CHEK2-, ATM- and PALB2-mutations. The distribution of the histological subtypes and grade of differentiation was not suggestive of a specific correlation with germline mutation status. Citation Format: Hoste G, D'Hoore P, Legius E, Van Buggenhout G, Floris G, Wildiers H, Han SN, Van Nieuwenhuysen E, Berteloot P, Smeets A, Nevelsteen I, Weltens C, Janssen H, Van Limbergen E, Neven P, Punie K. Hereditary breast cancer beyond BRCA: Clinical and histopathological characteristics in patients with germline CHEK2, ATM, PALB2 and TP53-mutations [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-05.
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- 2019
18. Abstract PD3-09: Efficacy of HER2 inhibitors in metastatic breast cancer by discordance in HER2 amplification status between primary and metastatic breast cancer
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Annouschka Laenen, Sileny Han, Guiseppe Floris, R Salihi, H. Wildiers, Nicole Concin, Patrick Neven, E Van Raemdonck, E Van Nieuwenhuysen, Patrick Berteloot, K Punie, and Ignace Vergote
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,Proportional hazards model ,business.industry ,Cancer ,medicine.disease ,Metastatic breast cancer ,Breast cancer ,Trastuzumab ,Internal medicine ,Biopsy ,medicine ,Nottingham Prognostic Index ,Pertuzumab ,skin and connective tissue diseases ,business ,neoplasms ,medicine.drug - Abstract
Purpose: In stage IV breast cancer (BC), discordance in the human epidermal growth factor receptor 2 (HER2) amplification status between primary and metastatic BC might affect efficacy of HER2-targeted agents. We studied progression free (PFS) and overall survival (OS) dependent on HER2 concordance in patients treated with a first line taxane-trastuzumab combination and later line trastuzumab-emtansine (T-DM1). Patients and Methods: This retrospective monocentric study included 76 patients with metastatic BC under treatment with trastuzumab in which a biopsy from both the primary and metastatic site was available. HER2 amplification status, sex-steroid receptor status, Nottingham prognostic index, distant metastasis-free interval and consecutive lines of therapy were retrieved from patients' reports. The Kaplan-Meier method was used for estimating PFS/OS and log-rank test for analyzing between group differences. A Cox model is used for testing difference between groups while correcting for Pertuzumab. Multivariable Cox regression is used to model OS as a function group, correcting for possible confounders. Results: Discordance in HER2 amplification status was seen in 30 out of 76 patients (39%), 11 patients lost HER2 amplification in the metastatic lesion (HER2lost) while 19 acquired HER2 amplification (HER2acquired). The other 46 patients had a HER2 amplification on both primary and metastatic site (HER2stable). The HER2lost group had a significant lower median PFS (PFS= 5.5 months) for taxane-trastuzumab, after correcting for pertuzumab, compared to the HER2stable group (PFS= 9 months, corrected p= 0.0146) and HER2acquired group (PFS=14 months, corrected p=0.0121). For T-DM1 treatment, both discordant groups, HER2acquired (PFS=1.1 months, p=0.0373) and HER2lost (PFS=1.5 months, p=0.0116), had a significant lower PFS compared to the HER2stable group (PFS=6.0 months). After correcting for possible confounders, HER2lost had a significant worse OS compared to HER2stable (HR 0.187, 95% CI 0.079 – 0.439) and HER2acquired (HR 0.147, 95% 0.058-0.378). Conclusion: Loss of HER2 amplification in metastatic lesions seems to have a negative predictive value for PFS on HER2-targeted agents and negative prognostic impact on OS. Acquiring of HER2 amplification was predictive for lower PFS on T-DM1 but wasn't predictive for lower PFS on taxane-trastuzumab. Citation Format: Van Raemdonck E, Berteloot P, Laenen A, Han S, Van Nieuwenhuysen E, Salihi R, Concin N, Vergote I, Floris G, Wildiers H, Punie K, Neven P. Efficacy of HER2 inhibitors in metastatic breast cancer by discordance in HER2 amplification status between primary and metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-09.
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- 2019
19. 723MO Tisotumab vedotin (TV) + carboplatin (Carbo) in first-line (1L) or + pembrolizumab (Pembro) in previously treated (2L/3L) recurrent or metastatic cervical cancer (r/mCC): Interim results of ENGOT-Cx8/GOG-3024/innovaTV 205 study
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I. Soumaoro, Bradley J. Monk, Anneke M. Westermann, Susana Banerjee, Domenica Lorusso, E. Gort, E Van Nieuwenhuysen, Leonardo Viana Nicacio, Salvatore Antonio Pignata, Mansoor Raza Mirza, A. Sadozye, F. Forget, Krishnansu S. Tewari, C. Mondrup Andreassen, B. Melichar, David M. O'Malley, D. Collins, Ignace Vergote, Roisin E. O'Cearbhaill, and Christine Gennigens
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Oncology ,medicine.medical_specialty ,business.industry ,First line ,Hematology ,Pembrolizumab ,Carboplatin ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Interim ,medicine ,Previously treated ,business ,Metastatic cervical cancer - Published
- 2021
20. Curative effect of second curettage for treatment of gestational trophoblastic disease - Results of the Belgian registry for gestational trophoblastic disease
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Katty Delbecque, Sileny Han, A. Vandewal, Etienne Marbaix, Michelle Nisolle, J.-Ch Noel, Frédéric Goffin, A.S. Van Rompuy, Philippe Delvenne, Ignace Vergote, E Van Nieuwenhuysen, Frédéric Kridelka, UCL - SSS/DDUV/CELL - Biologie cellulaire, UCL - (SLuc) Centre du cancer, and UCL - (SLuc) Service d'anatomie pathologique
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medicine.medical_specialty ,endocrine system ,medicine.medical_treatment ,Chorionic Gonadotropin ,Human chorionic gonadotropin ,Curettage ,Second curettage ,Molar pregnancy ,Belgium ,Pregnancy ,Medicine ,Humans ,Registries ,Gestational Trophoblastic Disease ,Gestational trophoblastic neoplasia ,Curative effect ,Chemotherapy ,business.industry ,Gestational trophoblastic disease ,Obstetrics and Gynecology ,Hydatidiform Mole ,medicine.disease ,Surgery ,Reproductive Medicine ,Uterine Neoplasms ,Population study ,Female ,business - Abstract
Objective We assessed the curative effect of a second curettage in patients with persistent hCG serum levels after first curettage for a gestational trophoblastic disease (GTD). Study Design This prospective observational study used the data of the Belgian register for GTD between July 2012 and January 2017. We analysed the data of patients who underwent a second curettage. We included 313 patients in the database. Primary endpoints were need for second curettage and chemotherapy. Results Thirty-seven patients of the study population (12 %) underwent a second curettage. 20 had persistent human chorionic gonadotropin hormone (hCG) elevation before second curettage. Of them, 9 patients (45 %) needed no further treatment afterwards. Eleven patients (55 %) needed further chemotherapy. Nine (82 %) were cured with single-agent chemotherapy and 2 patients (18 %) needed multi-agent chemotherapy. Of the 37 patients, patients with hCG levels below 5000 IU/L undergoing a second curettage were cured without chemotherapy in 65 % versus 45 % of patients with hCG level more than 5000 IU/L. Of the ten patients with a hCG level below 1000 IU/L, eight were cured without chemotherapy. Conclusions Patients with post-mole gestational trophoblastic neoplasia can benefit from a second curettage to avoid chemotherapy, especially when the hCG level is lower than 5000 IU/L.
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- 2021
21. Features of durable response and treatment efficacy for capecitabine monotherapy in advanced breast cancer: real-world evidence from a large single-centre cohort
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Ignace Vergote, Hans Wildiers, Paul Clement, Kevin Punie, Sileny Han, E Van Nieuwenhuysen, Ann Smeets, Benoit Beuselinck, Caroline Weltens, Hilde Janssen, Patrick Berteloot, J Menten, Patrick Neven, Annouschka Laenen, C Remmerie, Guiseppe Floris, S. Thijssen, Ines Nevelsteen, and T Van Gorp
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Population ,Capecitabine monotherapy ,Breast Neoplasms ,Durable response ,Metastasis ,Capecitabine ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Neoplasm Invasiveness ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,business.industry ,Hazard ratio ,Carcinoma, Ductal, Breast ,Cancer ,Retrospective cohort study ,General Medicine ,Middle Aged ,Metastatic breast cancer ,medicine.disease ,Prognosis ,Survival Rate ,Carcinoma, Lobular ,030104 developmental biology ,Treatment efficacy ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug ,Follow-Up Studies - Abstract
PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p
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- 2020
22. 51P The development of a predictive model for risk results of the 70-gene signature
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Patrick Neven, A Smeets, Ivey Sebastian, A.A. Martinez, A-S Van Rompuy, Ines Nevelsteen, E Van Nieuwenhuysen, Laurence Slembrouck, Guiseppe Floris, Caroline Weltens, Sileny Han, K Punie, H. Wildiers, and I. Vanden Bempt
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Oncology ,business.industry ,Medicine ,Hematology ,Computational biology ,Gene signature ,business - Published
- 2021
23. Analysis of 108 patients with endometrial carcinoma using the PROMISE classification and additional genetic analyses for MMR-D
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T Van Gorp, I. Vanden Bempt, Jasper Victoor, E Van Nieuwenhuysen, A.S. Van Rompuy, Patrick Neven, Hilde Brems, S. Timmerman, Sileny Han, Ignace Vergote, and Annouschka Laenen
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Oncology ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,MLH1 ,DNA Mismatch Repair ,Germline mutation ,Endometrial cancer ,Internal medicine ,PMS2 ,Humans ,Medicine ,Poly-ADP-Ribose Binding Proteins ,Aged ,Neoplasm Staging ,ProMisE ,Aged, 80 and over ,business.industry ,Obstetrics and Gynecology ,Microsatellite instability ,DNA Polymerase II ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Lynch syndrome ,digestive system diseases ,Endometrial Neoplasms ,MSH6 ,DNA Repair Enzymes ,MSH2 ,Molecular classification ,Female ,Microsatellite Instability ,DNA mismatch repair ,Tumor Suppressor Protein p53 ,MutL Protein Homolog 1 ,business - Abstract
OBJECTIVES: To apply the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) to a consecutive series of endometrial cancer (EC) patients diagnosed at a tertiary referral center and assign EC specimens to one of four molecular subgroups using immunohistochemistry (IHC) for p53/mismatch repair protein expression and sequencing for Polymerase Epsilon Exonuclease Domain Mutations (POLE-EDM). Mismatch Repair Deficient (MMR-D) cases were more thoroughly investigated to identify underlying somatic or germline genetic defects. METHODS: Hundred-and eight consecutive endometrial cancer patients, diagnosed between March 2017 and April 2019, were subjected to immunohistochemical and molecular analysis, according to ProMisE. IHC for p53 and the mismatch repair proteins (MLH1, PMS2, MSH6 and PMS2) was performed. All patients were also tested for POLE-EDM by Sanger sequencing. In addition, tumor and corresponding normal tissue of cases with abnormal MMR IHC were tested by PCR for microsatellite instability (MSI) (MSI analysis system, Promega). Hypermethylation of MLH1 promotor was tested with (methylation specific) multiplex ligation dependent probe amplification. MMR-D cases were subjected to germline mutation analysis of the mismatch repair genes, using next generation sequencing on MiSeq (Illumina) with the BRCA Hereditary Cancer MASTR Plus, (Multiplicom/Agilent), RNA mutation analysis and MLPA. RESULTS: FIGO classification was stage IA (n = 54), IB (n = 22) II(n = 8), III(n = 18) and IV(n = 6). Of the 33 patients with MMR-D on IHC (31%), 26 showed MLH1 promotor hypermethylation as the probable cause of MMR-D. The remaining 7 patients without MLH1 promotor hypermethylation were referred for germline analysis of Lynch syndrome. Six patients carried a pathogenic germline mutation in one of the mismatch repair genes: MSH6(n = 3), PMS2(n = 1), MLH1(n = 1) and MSH2 (n = 1). Pathogenic POLE-EDM were identified in 7 (6%) patients. Multiple molecular features (POLE-EDM + MMR-D or POLE-EDM + p53 abnormal) were observed in 4 patients (4%). A high concordance between MMR-D and microsatellite instability was observed in our cohort. In cases of a genetic defect in the MMR genes, we do note a large proportion of cases exhibiting microsatellite instability. On the contrary a hypermutation state, as seen in POLE EDM, does not result in accompanied phenotypic changes in MSI status. CONCLUSION: The ProMisE classification proved to be an efficient and easily implementable system. Future research should elucidate the precise biological and prognostic meaning of the cases with multiple molecular markers. ispartof: GYNECOLOGIC ONCOLOGY vol:157 issue:1 pages:245-251 ispartof: location:United States status: published
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- 2020
24. EP1193 Value of radiotherapy in the management of Paget's disease of the vulva: a retrospective study of 31 patients
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S Han, E Van Nieuwenhuysen, M Christiaens, A S Van Rompuy, Ignace Vergote, C Nawara, T Van Gorp, P Neven, and E Van Limbergen
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medicine.medical_specialty ,Adjuvant radiotherapy ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,Disease ,Perineum ,Surgery ,Resection ,Vulva ,Paget s disease ,Radiation therapy ,medicine.anatomical_structure ,medicine ,business - Abstract
Introduction/Background Surgical treatment is mutilating and resection often results in involved margins. As a consequence, local recurrences are frequent after surgery. Methodology Retrospective study of patients with vulvar Paget9s disease treated in our hospital between 1993 and 2018. Results Thirty-one consecutive patients with vulvar Paget9s disease were included, whereof twenty patients were irradiated in the primary or recurrent setting. Radiotherapy on the vulva and perineum was performed at a median dose of 60 Gy in fractions of 2 Gy. The median follow-up after radiotherapy was 75 months. Eight (26%) patients underwent as primary treatment radiotherapy only. Only one (13%) had a recurrence (after four months) and was operated. Fifteen (48%) patients had surgery as only primary treatment; five (33%) of them had a recurrence. Four of these had, after 3 or 4 surgical interventions, radiotherapy for recurrence. Only one of these 4, had a relapse after 85 months. Eight (26%) patients had as primary treatment surgery followed by adjuvant radiotherapy (due to positive margins), one (13%) of these recurred and died of disease. Conclusion Surgery is the most commonly used therapy for vulvar Paget9s disease, even though it is difficult to excise the disease adequately and often multiple surgeries are necessary. According to our experience, radiotherapy is a good adjuvant treatment option in patients with vulvar Paget9s disease with positive resection margins. Moreover, in our experience, primary radiotherapy seemed to be a safe alternative to surgery, that can prevent patients with Paget9s disease of the vulva to undergo mutilating and often repeated surgery. Disclosure Nothing to disclose
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- 2019
25. P115 Quality-of-life analysis in the randomized phase II CLIO trial comparing olaparib with standard chemotherapy in platinum-resistant recurrent ovarian cancer
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D Lambrechts, P. Berteloot, A Vanderstichele, E Van Nieuwenhuysen, P Busschaert, T. Van Gorp, Nicole Concin, T Callewaert, Ignace Vergote, Sileny Han, and P Neven
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Oncology ,Chemotherapy ,medicine.medical_specialty ,business.industry ,Nausea ,medicine.medical_treatment ,medicine.disease ,Gemcitabine ,Olaparib ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Topotecan ,Progression-free survival ,medicine.symptom ,business ,Adverse effect ,Ovarian cancer ,medicine.drug - Abstract
Introduction/Background Patients with relapsed ovarian cancer receive multiple lines of chemotherapy, each negatively affecting their health-related quality of life (HRQOL). The CLIO trial randomized patients with platinum-resistant relapsed ovarian cancer (PROC) to treatment with olaparib versus standard chemotherapy (paclitaxel weekly, or pegylated liposomal doxorubicin, or gemcitabine or topotecan). Olaparib showed a favorable response rate compared with chemotherapy (Vanderstichele A et al., ASCO 2019). We aimed to assess HRQOL and quality-adjusted survival measures including Q-TWIST (quality-adjusted time without symptoms and toxicities of treatment) and QAPFS (quality-adjusted progression free survival). Methodology EORTC questionnaires QLQ-C30 and QLQ-OV28 were administered at baseline and every three months until end of treatment. Scoring of HRQOL focused on abdominal/gastrointestinal symptoms. Overall survival was partitioned into three health states to calculate Q-TWIST: time with grade ≥2 nausea, vomiting and fatigue (toxicity), time without toxicities (twist) and relapse. Each health state was adjusted by a utility weight derived from the QLQ-C30 global health status. QAPFS calculation was based on Q-TWIST, but excluded relapse status. Results In CLIO, we randomized 100 PROC patients 2:1 towards olaparib (n=67) and chemotherapy (n=33). Baseline compliance rate of questionnaires was 83% (88% olaparib vs. 73% chemotherapy). There was no significant difference in abdominal/gastrointestinal symptoms between both arms (p=0.4). In the olaparib-arm, significant differences were observed between responders and non-responders (p=0.001). Adverse events (AEs) of grade ≥3 occurred in 60% and 52% of patients in the olaparib and chemotherapy arm respectively (p=0.521). The difference in Q-TWIST was 35.6 days (95%CI: -121.5–27.8) in favour of chemotherapy. The difference in QAPFS was 23.8 days (95% CI: -42.2–63.5) in favour of olaparib. Conclusion In PROC patients, olaparib monotherapy showed similar HRQOL compared to standard chemotherapy. There were no significant differences in abdominal/gastrointestinal symptoms, Q-TWIST and QAPFS between the two treatment arms. Disclosure The presenting author, T. Callewaert, has no conflict of interest.
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- 2019
26. EP1218 Outcome in 186 patients with cervical cancer stage IB1 treated with radical hysterectomy without adjuvant radiochemotherapy, unless presenting with metastatic lymph nodes
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T Van Gorp, E Van Nieuwenhuysen, A-S Van Rompuy, M-R Christiaens, J Haesen, Patrick Neven, Ignace Vergote, R Salihi, and Sileny Han
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Cervical cancer ,medicine.medical_specialty ,Chemotherapy ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,medicine.disease ,Gastroenterology ,medicine.anatomical_structure ,Internal medicine ,Adjuvant therapy ,Medicine ,Stage (cooking) ,Radical Hysterectomy ,business ,Cervix ,Adjuvant - Abstract
Introduction/Background Lymphovascular space invasion (LVSI), deep stromal invasion (DSI) and large tumor size have been identified as predictors for intermediate risk for recurrence. Adjuvant radiotherapy (RT) has been advocated in these patients (Sedlis Gynecol Oncol 1999,73:177). However, it is still controversial whether adjuvant radiochemotherapy (RCT) improves overall survival (OS). Methodology All consecutive patients (1997–2017) with cervical cancer FIGO (2009) stage IB1 (≤ 4cm) treated in our department were included. Intermediate risk for recurrence was defined as presence of two of the following factors in patients with negative lymph nodes: LVSI, DSI (>10 mm) and large tumor size (>2cm). Results Two hundred-and-one patients were included into the study, of which 186 patients underwent primary surgery and 15 patients received a fertility sparing treatment (table 1). Mean time of follow-up was 11 years (IQR 6–15). Postoperatively, 24 patients received adjuvant therapy due to presence of positive lymph nodes, positive section margins or vaginal intra-epithelial neoplasia: RCT (n=16), RT (n=7) or chemotherapy (n=1). None of the patients with intermediate risk factors according underwent adjuvant RT/RCT. Disease recurrence was observed in 23 patients (11%). The recurrences were local (n=14), distant (n=2) or both local and distant (n=7). Ten patients died of disease. The 5-year OS was 93% and the 5-year progression-free-survival (PFS) was 89%. Cox proportional hazards models showed that intermediate risk factors did not significantly influence OS or PFS. Conclusion Recurrence rate was rather low (11%), despite the fact that only 12% of the patients with cervix cancer stage IB1 received postoperative radio(chemo)therapy. Intermediate risk factors such as LVSI, DSI (>10 mm) or tumor size >2 cm did not predict recurrence nor survival. Future studies are needed to elucidate whether adjuvant radiotherapy is needed in the current era with better survival than in the nineties when the GOG99 (Sedlis et al.) was performed. Disclosure Nothing to disclose.
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- 2019
27. EP877 Intestinal (sub)obstruction in ovarian cancer patients: management, complications and survival
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T Van Gorp, Ignace Vergote, J Jansen, Patrick Neven, E Van Nieuwenhuysen, and Sileny Han
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medicine.medical_specialty ,business.industry ,Exploratory laparotomy ,medicine.medical_treatment ,Cancer ,medicine.disease ,Gastrostomy ,Surgery ,Bowel obstruction ,Parenteral nutrition ,Ascites ,Medicine ,medicine.symptom ,business ,Ovarian cancer ,Cohort study - Abstract
Introduction/Background We aimed to describe management, complications and survival of malignant bowel obstruction (MBO) in epithelial tubo-ovarian cancer patients. Our primary objective was overall survival, measured in days. MBO complications and management were considered secondary endpoints. Methodology Retrospective monocentric cohort study at the University Hospitals Leuven, Belgium, between January 1st, 2012 until December 31rd, 2016. All primary epithelial tubo-ovarian cancer patients with MBO were identified. The standard conservative approach of MBO in the University Hospitals Leuven is presented in table 1. Results 452 patient files were searched from which 48 patients were included in this study with a total of 84 MBO episodes, (median 1 per patient; range 1–5). Median time interval between two MBO episodes was 59 days (range 2–626). Median hospitalization time was 11 days (range 0–74) per episode. Median time interval between cancer diagnosis and first MBO episode was 342 days (range 0–1155). Further characteristics are noted in table 2. Two complications were registered bowel perforation and bowel ischemia, each in one episode. Conservative treatment was applied in 73 (87%) episodes, including gastrostomy in 3 (4%) episodes. Operative treatment was necessary in 11 (13%) episodes, including exploratory laparoscopy in 2 (2%) episodes and exploratory laparotomy in 9 (11%) episodes. Only one case of postoperative peritonitis was reported. Total parenteral nutrition (TPN) was administered in 15 (31%) patients only. During the study period 35 patients died within a median time interval of 101 days (range 3–917) since the first MBO (figure 1). There was no significant difference in survival between patient groups regarding TPN use, ascites and obstruction at cancer diagnosis. Conclusion Tubo-ovarian cancer patients with MBO have poor prognosis: 73% of our study population died within a relatively short time interval since the first MBO. The majority of patients with MBO were treated conservatively. Disclosure Nothing to disclose.
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- 2019
28. P88 Analysis of 93 patients with endometrial cancer using the PROMISE classification and additional genetic analyses for MSI and POLE-EDM
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Hilde Brems, I. Vanden Bempt, T Van Gorp, S. Timmerman, E Van Nieuwenhuysen, Ignace Vergote, Sileny Han, A-S Van Rompuy, and Patrick Neven
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Oncology ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,business.industry ,Endometrial cancer ,Microsatellite instability ,medicine.disease ,digestive system diseases ,Lynch syndrome ,MSH6 ,Germline mutation ,Internal medicine ,medicine ,PMS2 ,DNA mismatch repair ,Multiplex ligation-dependent probe amplification ,business - Abstract
Introduction/Background Recent research has distinguished various molecular classifications for endometrial carcinoma (EC). The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMise, Talhouk, BJC 2015,113:299) classification consists of immunohistochemistry (IHC) (p53 and mismatch repair proteins) and PCR sequencing for Polymerase Epsylon-Extracellular-Domain-Mutations (POLE-EDM). Methodology Ninety-three consecutive endometrial cancer patients, diagnosed between March 2017 and November 2018, were subjected to molecular and immunohistochemical analyses, according to ProMise. IHC for p53 and the mismatch repair proteins (MLH1, PMS2, MSH6 and PMS2) was performed. All patients were also tested for POLE-EDM using PCR, followed by Sanger sequencing (exon 9, 11, 13 and 14). In addition to the ProMise testing, all tumors and corresponding normal tissue of patients with mismatch repair deficient staining on IHC, were tested with PCR using the Microsatellite Instability (MSI) kit (MSI analysis system, Promega). Hypermethylation of MLH1 promotor and the presence of the BRAF p.V600E missense mutation was tested with (methylation specific) multiplex ligation dependent probe amplification. Results FIGO classification was stage IA(n=45), IB(n=17)) II(n=8), III(n=17) and IV(n=6). Classification according to histological type is presented in table 1. Of the 28 patients with MMR-D (Mismatch Repair-Deficiency) on IHC, 22(79%) showed hypermethylation as the probable cause of MMR-D. The remaining 6 patients were referred for germline analysis of Lynch syndrome. Five patients carried a pathogenic germline mutation in one of the mismatch repair genes: MSH6(n=3), PMS2(n=1), MLH1(n=1). In one patient no germline mutation was identified, hypothesizing a somatic cause. POLE-EDM was identified in 6 (6%) patients. Double positive status (POLE-EDM+MMR-D or POLE-EDM+p53 abnormal) was observed in 4 patients (4%) (table1). Conclusion The ProMise classification proved to be an efficient and easily implementable system. In the group with MMR-D, hypermethylation was the cause in 79%. POLE-EDM was identified in 6% of the patients, but its role needs to be clarified in non-endometrioid tumors. Disclosure Nothing to disclose.
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- 2019
29. TP53 mutations in cell-free DNA as early markers of therapeutic response in platinum-resistant relapsed ovarian cancer (PROC): a prospective translational analysis of the phase II GANNET53 clinical trial
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Sven Mahner, Pauline Wimberger, Jalid Sehouli, Eric Pujade-Lauraine, Alain G. Zeimet, Ute M. Moll, Florence Joly, P Combe, S Darb-Esfahani, Ioana Braicu, Regina Berger, E Van Nieuwenhuysen, Ignace Vergote, Christian Marth, Frédéric Selle, I.L. Ray-Coquard, P Busschaert, P. Harter, Robert Zeillinger, Barbara Schmalfeldt, A Vanderstichele, Nicole Concin, D Lambrechts, and Atanas Ignatov
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Oncology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Cancer ,medicine.disease ,Tp53 mutation ,Clinical trial ,Serous fluid ,Internal medicine ,Biopsy ,medicine ,Ovarian cancer ,business ,Genotyping ,Platinum resistant - Abstract
Introduction/Background Detecting tumor-specific genetic alterations in cell-free DNA (cfDNA) obtained from cancer patients allows for a quantification of the tumoral fraction, i.e. the circulating tumor DNA (ctDNA). Previous studies in metastatic cancer patients showed that early changes of this fraction during therapy are indicative of therapeutic response. We tested this hypothesis on cfDNA samples collected in the GANNET53 clinical trial (FP7, funded by the European Commission, grant no 602602). Methodology Patients with high-grade serous/endometrioid and/or undifferentiated PROC were recruited for treatment with weekly paclitaxel with or without Hsp90-inhibitor ganetespib. Archival biopsy samples were used for tumor TP53 genotyping. CfDNA was prospectively collected prior to treatment at baseline (cycle 1 day 1, C1D1), 24 hours later (cycle 1 day 2, C1D2) and after 4 and 8 weeks, at day 1 of cycle 2 (C2D1) and 3 (C3D1) respectively. Targeted TP53 resequencing was performed on cfDNA and allelic frequencies of the known TP53 variant (TP53 VAF) were quantified and correlated with clinical outcome. Results For 125 of the 133 randomized patients, at least 1 C1D1 cfDNA sample was available. For 119 tumor samples, TP53 genotyping was successful and identified deleterious TP53 mutations in 106 patients (89.1%). The median ctDNA level was 1.82% (IQR:0.17–8.34%) at C1D1 which decreased significantly after 4–8 weeks of therapy. Overall, ctDNA was detectable in 64.6% (64/99) of baseline samples. Baseline CA125 did not differ between cases with and without detectable ctDNA at C1D1. Detection of ctDNA at C1D1 (HR 2.3; 95%CI:1.4–3.9), C1D2 (HR 2.2; 95%CI:1.3–3.9) and C2D1 (HR 2.8; 95%CI:1.6–4.9) predicted a worse overall survival. A subgroup of patients for whom TP53 ctDNA was undetectable at C2D1 or C3D1 (14/64) had a high overall response rate of 64.2%. Conclusion Quantification of TP53 mutations in cfDNA of PROC patients has prognostic value at baseline. Favorable early changes during treatment may predict therapeutic response. Disclosure The presenting author, A.Vanderstichele, has no conflict of interest.
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- 2019
30. P78 Robot-assisted management of endometrial cancer in belgium: an analysis of 615 patients by the belgian and luxembourg gynaecological oncology group
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Frédéric Goffin, A. Kakkos, Evelyn Despierre, Frédéric Kridelka, Annouschka Laenen, Koen Traen, P Van Trappen, E. Van Nieuwenhuysen, S. Ongaro, Frederik Peeters, C. Ver Eecke, Ignace Vergote, and T Van Gorp
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medicine.medical_specialty ,Hysterectomy ,business.industry ,Endometrial cancer ,medicine.medical_treatment ,Postoperative complication ,Perioperative ,medicine.disease ,Surgery ,Serous fluid ,medicine ,Stage (cooking) ,Prospective cohort study ,business ,Complication - Abstract
Introduction/Background The aim of this prospective study was to report perioperative outcomes, disease-free and overall survival of robot-assisted management of patients with endometrial cancer, treated in 5 centers in Belgium. Methodology Patients undergoing surgery between August 2007 and December 2018 (n=615) were prospectively collected. Results Median age was 68 years (range, 31–92), median BMI 28 kg/m2 (range, 17–61). Five-hundred-ninety-nine patients underwent robot-assisted hysterectomy and bilateral salpingo-oophorectomy. In addition, full pelvic lymphadenectomy was performed in 151 (25%), and pelvic sentinel nodes biopsies only in 181 patients (29%). Sixteen patients were referred for robotic node staging after hysterectomy performed elsewhere. Histological types were endometrioid (n=512, 84%), serous (n=43, 7%), clear cell (n=8, 1%), mucinous (n=3, 0.5%), squamous (n=2, 0.3%) and carcinosarcoma (n=20, 3%). FIGO stage was: IA (61%), IB (24%), II (4%), IIIA (2%), IIIB (0,3%), IIIC (8%), IV (1%). Metastatic pelvic nodes were found in 43 (7%), positive para-aortic nodes in 3 (0,4%), pelvic and para-aortic nodal metastases in 7 patients (1,2%). Median number of removed pelvic and para-aortic nodes was 15 (range, 0–64) and 10 (range 1–47), respectively. Median estimated blood loss was 50 mL (range 0– 1000), median skin-to-skin time 150 minutes (range 55–480) and conversion rate 0.8% (n=5). Intra-operative complications occurred in 5% (n=30). At least one postoperative complication occurred in 15% (n=89). Median follow-up was 27 months (range, 1–131). Recurrence occurred in 63 patients (11%) and 38 patients (6%) died of endometrial cancer. The 2- and 5-year recurrence-free survival rates were 89% and 84%, respectively. The 2- and 5-year overall survival rates were 92% and 83%, respectively. Conclusion This study confirms the feasibility and safety of robot-assisted management of endometrial cancer with a low complication, conversion and recurrence rate. Disclosure Nothing to disclose.
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- 2019
31. Palbociclib in highly pretreated metastatic ER-positive HER2-negative breast cancer
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Benoit Beuselinck, I. Lefever, Nicole Concin, Ignace Vergote, Hans Wildiers, G Hoste, Patrick Berteloot, E Van Nieuwenhuysen, R Salihi, Sileny Han, Patrick Neven, and Kevin Punie
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Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pyridines ,Receptor, ErbB-2 ,medicine.drug_class ,Antineoplastic Agents ,Breast Neoplasms ,Kaplan-Meier Estimate ,Palbociclib ,Piperazines ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Endocrine system ,Neoplasm Metastasis ,Protein Kinase Inhibitors ,Aged ,Neoplasm Staging ,Aged, 80 and over ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Metastatic breast cancer ,Treatment Outcome ,030104 developmental biology ,Receptors, Estrogen ,Estrogen ,030220 oncology & carcinogenesis ,Retreatment ,Toxicity ,Female ,Neoplasm Grading ,business ,Progressive disease - Abstract
We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC). Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment. The efficacy and safety analysis was performed in 82 patients who had received at least one dose of palbociclib and who had at least 6-month follow-up at the data cut-off point. The primary objective was the evaluation of efficacy of the combination of palbociclib and endocrine therapy with clinical benefit as primary endpoint, defined as the absence of progressive disease and being on treatment for at least 6 months. Secondary objectives were the evaluation of toxicity and the identification of potential predictors for clinical benefit. The median age of the patients was 67.1 years (range 34.8–85.9) at the time of inclusion. The average duration of treatment was 5.6 months (range 1–19), with a median progression-free survival of 3.17 (95% CI 2.76–4.70) months. At the data cut-off point, 10 patients were still on treatment with palbociclib. In this highly pretreated setting, 34 patients experienced no progressive disease within 6 months, resulting in an overall clinical benefit rate (CBR) of 41.5%. 20.7% (17/82) showed stable disease for ≥ 9 months and 13.4% for ≥ 12 months. None of the investigated predicting factors were significantly associated with clinical benefit at 6 months. For 43.9% of the patients, treatment delay or dose reduction was indicated. Palbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.
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- 2018
32. Expression III: patients’ expectations and preferences regarding physician–patient relationship and clinical management—results of the international NOGGO/ENGOT-ov4-GCIG study in 1830 ovarian cancer patients from European countries
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A. du Bois, Jean-Emmanuel Kurtz, M. Keller, M. Jedryka, Florence Joly, Sabrina Chiara Cecere, Gennaro Cormio, Jalid Sehouli, Michael Friedlander, Antonio Casado, Catalin Vlad, Radoslav Chekerov, Daniel Reimer, E Van Nieuwenhuysen, Rolf Richter, Ignace Vergote, Cesar Mendiola, Alain G. Zeimet, G. Oskay-Özcelik, S Alavi, M. Maciejewski, and Patriciu Achimas-Cadariu
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Adult ,medicine.medical_specialty ,Patients ,medicine.medical_treatment ,MEDLINE ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Internal medicine ,Recurrent disease ,Humans ,Medicine ,Physician patient relationship ,030212 general & internal medicine ,Aged ,Ovarian Neoplasms ,Health Services Needs and Demand ,Physician-Patient Relations ,Chemotherapy ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Europe ,Clinical trial ,Oncology ,030220 oncology & carcinogenesis ,Doctor–patient relationship ,Female ,business ,Ovarian cancer - Abstract
Backround The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician–patient relationship and treatment. Patients and methods A questionnaire was developed based on the experiences of the national German survey ‘Expression II’, and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version. Results From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: ‘the therapy should not induce alopecia’ (42%), ‘there must be more done to counter fatigue’ (34.5%) and ‘the therapy should be more effective’ (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included. Conclusion This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient’s age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.
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- 2018
33. Breast cancer subtype and survival by parity and time since last birth
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Ann Smeets, Sileny Han, H. De Mulder, Annouschka Laenen, Kevin Punie, Patrick Neven, C Remmerie, Ines Nevelsteen, E Van Nieuwenhuysen, Ignace Vergote, Hans Wildiers, A Poppe, Hanne Lefrère, E. Van Limbergen, and Giuseppe Floris
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Adult ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Patient characteristics ,Breast Neoplasms ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Pregnancy ,Biomarkers, Tumor ,Clinical endpoint ,Humans ,Medicine ,Neoplasm Metastasis ,Reproductive History ,Triple negative ,Neoplasm Staging ,business.industry ,Obstetrics ,Confounding ,Breast cancer subtype ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,Cohort study - Abstract
Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome. We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000–Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders. Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p
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- 2018
34. Abstract P5-14-06: The effect of adjuvant chemotherapy in a large consecutive series of ER-pos HER-2 negative early breast cancers
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H. Wildiers, Guiseppe Floris, Sileny Han, E Van Nieuwenhuysen, Patrick Neven, Lynn Jongen, Patrick Berteloot, K Punie, Ines Nevelsteen, A Smeets, and B. Van Calster
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Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Series (stratigraphy) ,Adjuvant chemotherapy ,business.industry ,Internal medicine ,medicine ,business - Abstract
Background: The last EBCTCG-overview reported, in general, a significant better breast cancer outcome if adjuvant chemotherapy was added to surgery and endocrine therapy in ER-pos breast cancers, but the precise indication for adjuvant chemotherapy in this population remains controversial. We study the effect of adjuvant chemotherapy on breast cancer outcome in consecutive patients with an ER-pos HER-2 negative breast cancer treated with adjuvant antihormonal therapy. Methods: Data were collected prospectively from consecutive patients with non-metastatic breast cancer that were primary operated between 2000 and 2012 at the University Hospitals Leuven (Belgium). A Propensity Score (PS) weighted analysis was performed to estimate the average treatment effect (ATE). The primary endpoint was recurrence free interval (RFI). Secondary endpoints were distant recurrence free interval (D-RFI) and breast cancer specific survival (BCSS). Covariates used to generate the propensity score and to include in the PS weighted analysis were age at diagnosis, body mass index, tumor size, grade, pN, lymph vessel invasion, PR, and radiotherapy. Cause-specific hazard models were fitted, using death not from breast cancer as competing risk. Treatment heterogeneity was examined by evaluating interactions of each covariate with adjuvant chemotherapy, using the Bonferroni-Holm method to correct for multiple testing. Results: In the total cohort of 5609 patients, 4282 had a hormone sensitive HER-2 neg breast cancer and 4121 (96.2%) of these received adjuvant antihormonal therapy. Adjuvant chemotherapy was given in 1179/4121 patients (29%). Median follow-up was 8.5 years. Due to very strong differences between patients with and without adjuvant chemotherapy, a restricted PS weighted analysis was used according to a recent recommendation in the statistical literature. This analysis is based on 1750 patients with a PS between 0.1 and 0.9. In this group, 807 (46%) received adjuvant chemotherapy, 211 (12%) observed an event for RFI, 167 (10%) for D-RFI, and 108 (6%) for BCSS. Adjuvant chemotherapy was associated with better prognosis: the adjusted cumulative incidence of recurrence within 5 years was 9.7% without and 5.3% with adjuvant chemotherapy. The adjusted hazard ratio for RFI was 0.50 (95% CI 0.33-0.74). There were no strong interactions with adjuvant chemotherapy. Results for D-RFI and BCSS were similar. Conclusion: Based on PS analysis to reduce confounding and chemotherapy indication bias, we observed clear benefit from adjuvant chemotherapy in ER-pos HER-2 negative breast cancers. Citation Format: Van Calster B, Neven P, Wildiers H, Punie K, Jongen L, Han S, Berteloot P, Van Nieuwenhuysen E, Nevelsteen I, Smeets A, Floris G. The effect of adjuvant chemotherapy in a large consecutive series of ER-pos HER-2 negative early breast cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-14-06.
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- 2017
35. Abstract P6-09-32: The association of breast cancer subtype and breast cancer survival with parity and time since last birth
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Ignace Vergote, Annouschka Laenen, C Remmerie, E. Van Limbergen, H. De Mulder, A Poppe, A Smeets, Guiseppe Floris, H. Wildiers, Patrick Neven, Ines Nevelsteen, K Punie, and E Van Nieuwenhuysen
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Oncology ,Cancer Research ,medicine.medical_specialty ,Pregnancy ,Chemotherapy ,business.industry ,Receptor expression ,medicine.medical_treatment ,Estrogen receptor ,medicine.disease ,Breast cancer ,Internal medicine ,Progesterone receptor ,medicine ,business ,Triple-negative breast cancer ,Cohort study - Abstract
Background: Pregnancy affects breast cancer risk but it's influence on breast cancer subtype and prognosis remains controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome in women aged ≤50 years at diagnosis. Patients and Methods: A retrospective multivariate cohort study including all premenopausal women aged ≤50 years (N=1306) at diagnosis and primarily treated with surgery (N=1176) or neo-adjuvant chemotherapy (N=130) at University Hospitals Leuven (Jan. 2000 – Dec. 2009); local and systemic therapies were consistent with guidelines when treated. Tumor subtypes were defined by tumor grade and receptor expression for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) amplification; ER+PR+/-HER-2- cases were Luminal A- like if grade 1-2 and Luminal B like if grade 3; HER-2+ cases were Luminal HER-2 if ER+ and HER-2 like if ER-; triple negative breast cancer (TNBC) were ER-PR-HER-2-. Outcome endpoints were breast cancer subtype, disease free (DFS) and distant disease free survival (DDFS) by parity and in parous women comparing short ( Results: Breast cancer subtypes didn't differ between nulliparous and parous women but subtypes differed significantly in parous women by time interval since last birth (p Conclusion: After correction for age at diagnosis, parity does not but recent birth does affect breast cancer subtype. Such tumors are proportionally more likely ER-negative namely TNBC and HER-2 like. We observed a trend for better DFS for parous women. The prognostic value of time since last birth is mostly due to tumor characteristics and age at time of diagnosis. Citation Format: De Mulder H, Laenen A, Wildiers H, Punie K, Poppe A, Remmerie C, Nevelsteen I, Smeets A, Van Nieuwenhuysen E, Van Limbergen E, Floris G, Vergote I, Neven P. The association of breast cancer subtype and breast cancer survival with parity and time since last birth [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-32.
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- 2017
36. Treatment efficacy and predictors of durable response to capecitabine monotherapy in advanced breast cancer: Real-world evidence from a large single-centre cohort
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H. Wildiers, Sileny Han, Ignace Vergote, S. Thijssen, Patrick Neven, E Van Nieuwenhuysen, Patrick Berteloot, K Punie, Benoit Beuselinck, and T Van Gorp
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Advanced breast ,Cancer ,medicine.disease ,Real world evidence ,Treatment efficacy ,Capecitabine ,Single centre ,Internal medicine ,Cohort ,medicine ,business ,medicine.drug - Published
- 2020
37. 817P Response to olaparib monotherapy in relapsed ovarian cancer by HRR gene mutational status and HRD scarring analysis: Results from the randomized phase II CLIO trial
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Ignace Vergote, Siel Olbrecht, R. Schepers, Adriaan Vanderstichele, D. Goossens, E Van Nieuwenhuysen, C. De Vogelaere, Patrick Neven, Liselore Loverix, T Van Gorp, Pieter Busschaert, Patrick Berteloot, Sileny Han, Diether Lambrechts, and L. Heyrman
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Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,Olaparib ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Mutational status ,Ovarian cancer ,business ,Gene - Published
- 2020
38. Phase III PAOLA-1/ENGOT-ov25 trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian cancer (OC) treated with platinum-based chemotherapy (PCh) plus bev
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Edgar Petru, Eric Pujade-Lauraine, Alexander Burges, Alain Lortholary, C. Lefeuvre-Plesse, Sandro Pignata, Domenica Lorusso, Keiichi Fujiwara, Antonio González-Martín, J. Maenpaa, Nicoletta Colombo, Frédéric Selle, E.M. Guerra Alia, P. Harter, Paul Buderath, David Pérol, E Van Nieuwenhuysen, N de Gregorio, I.L. Ray-Coquard, and Alexandra Leary
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Oncology ,medicine.medical_specialty ,Chemotherapy ,Bevacizumab ,business.industry ,medicine.medical_treatment ,Hematology ,medicine.disease ,Chemotherapy regimen ,Olaparib ,chemistry.chemical_compound ,chemistry ,Maintenance therapy ,Response Evaluation Criteria in Solid Tumors ,Internal medicine ,medicine ,Progression-free survival ,business ,Ovarian cancer ,medicine.drug - Published
- 2019
39. Ovarian cancer in children and adolescents: A rare disease that needs more attention
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N. Van Damme, A. Uyttebroeck, Ignace Vergote, An Coosemans, N. Storme, E Van Nieuwenhuysen, and Thaïs Baert
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Ovarian Neoplasms ,Gynecology ,medicine.medical_specialty ,Pediatrics ,030219 obstetrics & reproductive medicine ,Adolescent ,endocrine system diseases ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,Malignancy ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Epidemiology ,medicine ,Humans ,Female ,Ovarian mass ,Child ,Ovarian cancer ,business ,Rare disease - Abstract
Ovarian cancer is rare in childhood. This explains why there are only scattered reports on it in the literature and why there is a lack of specific pediatric treatment. This paper gives an overview of the Belgian data from 2004 to 2013 and reviews the literature. To index ovarian masses and malignancies in children better in the future, worldwide data collection should be improved and reproducible definitions of 'childhood', 'malignancy' and 'ovarian mass' need to be adopted. publisher: Elsevier articletitle: Ovarian cancer in children and adolescents: A rare disease that needs more attention journaltitle: Maturitas articlelink: http://dx.doi.org/10.1016/j.maturitas.2016.03.003 content_type: article copyright: © 2016 Elsevier Ireland Ltd. All rights reserved. ispartof: Maturitas vol:88 pages:3-8 ispartof: location:Ireland status: published
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- 2016
40. HIPEC: HOPE or HYPE in the fight against advanced ovarian cancer?
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Ignace Vergote, Jalid Sehouli, Sven Mahner, Luis Chiva, P. Harter, A. du Bois, E Van Nieuwenhuysen, Antonio González-Martín, and Christina Fotopoulou
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Oncology ,Ovarian Neoplasms ,Advanced ovarian cancer ,medicine.medical_specialty ,Systemic and surgical treatment ,business.industry ,Revolutionary new knowledge ,MEDLINE ,Hematology ,Hyperthermia, Induced ,Carcinoma, Ovarian Epithelial ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Carcinoma ,Humans ,Female ,030212 general & internal medicine ,business - Abstract
Undergoing an era of revolutionary new knowledge and advances in the systemic and surgical treatment of peritoneally disseminated epithelial ovarian cancer (EOC), we never before have been confronted with such a plethora of novel targeted agents, genetically based treatment strategies and cutting edge surgical techniques that enrich our armamentarium in the fight against this deadly disease [1–3]. Still, our art as clinicians is to put all this new body of knowledge into the right context so that we can help our patients without compromising their care through an enthusiastic effort of implementing new therapeutic
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- 2018
41. Efficacy of CDK 4/6 inhibition after fulvestrant in metastatic breast cancer
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E. Van Limbergen, Sileny Han, R Salihi, Ignace Vergote, H. Wildiers, Patrick Berteloot, K Punie, A Smeets, Benoit Beuselinck, I. Lefever, Hilde Janssen, G Hoste, Patrick Neven, Caroline Weltens, Ines Nevelsteen, E Van Nieuwenhuysen, and Nicole Concin
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Cancer Research ,Oncology ,biology ,Fulvestrant ,business.industry ,Cyclin-dependent kinase ,biology.protein ,Cancer research ,Medicine ,business ,medicine.disease ,Metastatic breast cancer ,medicine.drug - Published
- 2018
42. Abstract P4-02-07: Comparison of breast cancer molecular subtyping by Immunohistochemistry and by BluePrint® next generation RNA sequencing-based test at University Hospitals Leuven and Curie Institute Paris
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Laurence Slembrouck, S Vander Borght, A Vincent-Salomon, V Raynal, H. Wildiers, Lynn Jongen, Guiseppe Floris, F Reyal, Liesbet Vliegen, Lorenza Mittempergher, G Hoste, Lauren Darrigues, C Helsmoortel, Ines Nevelsteen, LJ Delahaye, Anke T. Witteveen, S Neijenhuis, P Sintubin, Patrick Neven, A Smeets, Audrey Rapinat, E Laas-Faron, Annuska M. Glas, K Punie, Christophe Laurent, E Van Nieuwenhuysen, Mylène Bohec, I. Vanden Bempt, Cécile Reyes, and Sileny Han
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Oncology ,Cancer Research ,medicine.medical_specialty ,Microarray ,business.industry ,Concordance ,Cancer ,RNA ,Estrogen receptor ,medicine.disease ,Subtyping ,Breast cancer ,Internal medicine ,medicine ,Immunohistochemistry ,business - Abstract
Background MammaPrint® (MP) and BluePrint® (BP) are microarray-based tests with MP being prognostic for distant recurrence and BP enabling stratification into breast cancer molecular subtypes (Luminal, HER2, Basal-type). Recently, a CE marked MP and BP targeted RNA Next Generation Sequencing (NGS)-based kit was developed at Agendia and validated at University Hospitals Leuven and Curie Institute Paris. Here we compare breast cancer molecular subtype stratification defined by immunohistochemistry (IHC) and by MP and BP NGS- and microarray- based tests. Patients and Methods In this study, 124 primary operable invasive breast cancer patients were included at University Hospitals Leuven and at Curie Institute (n=80 Leuven; n=44 Curie) with the following histological subtypes: ductal-NOS (n=100), lobular (n=16), mucinous (n=3), tubular (n=2), others (n=3). Patients with bilateral breast cancer or with >3 positive lymph nodes were excluded. Surrogate breast cancer subtypes based on IHC were defined as follows: luminal if ≥10% estrogen receptor (ER) expression; triple negative if Results Concordance between IHC and MP/BP NGS subtyping was 75.0% (93/124), while concordance between MP/BP on NGS and microarray was 89.5% (111/124). MP/BP NGS subtyping identified more low risk Luminal A tumors compared to IHC (54.0%, (67/124) vs 44.3% (55/124)). Notably, concordance was excellent for triple-negative and, to less extent for HER2 driven tumors (Luminal B-like-HER2 positive and HER2+). IHC vs. MP/BP NGS molecular subtyping (n=124) MP/BP NGSIHCLuminal ALuminal BHER2-positiveBasalTotalLuminal A-like4690055Luminal B-like, HER2-negative16210037Luminal B-like, HER2-positive565016HER2-positive00303Triple negative0101213Total6737812124Microarray vs MP/BP NGS molecular subtyping (n=124) MP/BP NGSMicroarrayLuminal ALuminal BHER2 positiveBasalTotalLuminal A6040064Luminal B7310038HER2-positive028010Basal0001212Total6737812124 Conclusion This study shows a discordance of 25.0% between IHC and BP/MP NGS subtyping. This is in line with previous findings where IHC was compared to molecular subtyping based on microarray (Viale 2017, Whitworth 2014) underlining the complementarity of genomic testing in early stage breast cancer. Moreover, we observed a high concordance between NGS and microarray molecular subtyping, which suggests a successful translation of the MP/BP microarray test to a MP/BP NGS test. Citation Format: Darrigues L, Slembrouck L, Mittempergher L, Delahaye LJ, Vanden Bempt I, Vander Borght S, Vliegen L, Sintubin P, Raynal V, Bohec M, Reyes C, Rapinat A, Helsmoortel C, Jongen L, Hoste G, Neven P, Wildiers H, Smeets A, Nevelsteen I, Punie K, Van Nieuwenhuysen E, Han S, Laurent C, Vincent-Salomon A, Laas-Faron E, Witteveen AT, Neijenhuis S, Glas AM, Floris G, Reyal F. Comparison of breast cancer molecular subtyping by Immunohistochemistry and by BluePrint® next generation RNA sequencing-based test at University Hospitals Leuven and Curie Institute Paris [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-07.
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- 2019
43. Abstract P3-03-32: Monocentric experience with the sentinel lymph node biopsy prior to neoadjuvant chemotherapy in clinically lymph node negative early breast cancer
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C. Van Ongeval, Patrick Berteloot, K Punie, A Smeets, Hilde Janssen, M Delameilleure, Sileny Han, Guiseppe Floris, Machteld Keupers, Ignace Vergote, E. Van Limbergen, Caroline Weltens, R. Prevos, Ines Nevelsteen, Patrick Neven, E Van Nieuwenhuysen, G Hoste, R Salihi, and H. Wildiers
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Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Sentinel lymph node ,Axillary Lymph Node Dissection ,Cancer ,Retrospective cohort study ,medicine.disease ,medicine.anatomical_structure ,Breast cancer ,Oncology ,Seroma ,Biopsy ,medicine ,Radiology ,business ,Lymph node - Abstract
Background In patients with clinically lymph node negative (cN0) early breast cancer (EBC) treated with neoadjuvant chemotherapy (NACT), the sentinel lymph node biopsy (SLNB) can be performed before or after NACT. We report safety of axillary staging performing the SLNB prior to NACT in cN0 EBC and estimate NACT-induced downstaging to ypN0 in previously NACT-treated cN1 EBC, to make an assumption for avoiding axillary lymph node dissection (ALND) if SLNB was done after NACT. Patients and Methods Monocentric retrospective study of consecutive triple negative (TNBC) and HER-2 amplified BC patients treated with standard NACT. cN0 patients had SLNB before NACT followed by local therapy. Axillary lymph node dissection (ALND) post-NACT was performed in all cN1 and in cN0 cases with a positive or failed SLNB. Using descriptive statistics, we here report SLNB-detection and SLNB-positive rate, SLNB-operative complications, complete tumor regression in the breast (ypT0/is) and disease-free survival (DFS) for cN0 cases and NACT-induced downstaging to ypN0 in previously NACT-treated cN1 EBC. Results We included 245 NACT-treated patients; 119 cN0 and 126 cN1. SLNB-detection rate in cN0 cases was 99,2%; 25 or 21% had ≥ 1 involved SLN, 21.8% experienced SLNB related-complications (e.g. infection, seroma, hematoma) leading to NACT-delay in 3 and interruption in 1 patient. Median start of NACT after SLNB was 7 days (range 1-20 days). In patients with a positive SLNB, there were no additional involved nodes in the ALND. In 5 of these patients, therapy response in a lymph node was described. Complete tumor regression in the breast (ypT0/is) was 52% in SLNB-positive and 59,1% in SLNB-negative cN0 cases. NACT-induced ypN0 was 61% in cN1 cases. At 30 months of median follow-up (range 1-86 months), DFS was 93,2% (4.2% metastatic; no axillary relapse) in cN0 cases. Median DFS was better for patients with complete tumor regression in the breast as compared to those with partial response; 95.6% and 90% respectively. Conclusion In conclusion, performing SLNB before NACT in cN0 cases is a safe and accurate method. While some pN1(sn) could have avoid ALND by NACT-induced axillary down-staging, based on our assumption, long term follow-up is needed to conclude whether SLNB after NACT is safe. Keywords: Breast cancer, neoadjuvant chemotherapy, timing sentinel lymph node biopsy Citation Format: Delameilleure M, Smeets A, Nevelsteen I, Han S, Van Nieuwenhuysen E, Berteloot P, Hoste G, Salihi R, Van Ongeval C, Keupers M, Prevos R, Wildiers H, Punie K, Van Limbergen E, Weltens C, Janssen H, Floris G, Vergote I, Neven P. Monocentric experience with the sentinel lymph node biopsy prior to neoadjuvant chemotherapy in clinically lymph node negative early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-32.
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- 2019
44. Results of a phase 2 trial of selinexor, an oral selective inhibitor of nuclear export (SINE) in 114 patients with gynaecological cancers
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J. Meade, Ignace Vergote, Anne L Kranich, G. Wright, Sharon Shacham, Trine Juhler-Nøttrup, Z Ujmajuridze, E Van Nieuwenhuysen, Charlotte Aaquist Haslund, Y. Landesman, Patrick Berteloot, Morten Mau-Sørensen, Tami Rashal, Jean-Richard Saint-Martin, Patrick Neven, M. Raza Mirza, Michael Kauffman, M. Crochiere, H. Havsteen, and Bente Lund
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Gynecology ,Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Nuclear export signal ,business ,030217 neurology & neurosurgery - Published
- 2016
45. Preoperative c-reactive protein and thrombocyte count as potential markers for longterm survival in ovarian cancer
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Ignace Vergote, Hannah Woopen, Jalid Sehouli, Adriaan Vanderstichele, Sven Mahner, Maria Luisa Gasparri, P. Benedetti Panici, Patrick Achimas, Elena-Ioana Braicu, Michael D. Mueller, Andrea Papadia, Linn Woelber, E Van Nieuwenhuysen, Rolf Richter, I. Ruscito, Nicole Concin, A Berger, Bogdan Fetica, J. Zimmer, and Joanna Glajzer
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medicine.medical_specialty ,biology ,business.industry ,C-reactive protein ,Hematology ,medicine.disease ,Gastroenterology ,Oncology ,Thrombocyte count ,Internal medicine ,biology.protein ,Medicine ,business ,Ovarian cancer - Published
- 2018
46. Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium
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Weiva Sieh, Alice S. Whittemore, Satoyo Hosono, Francesmary Modugno, Ellen L. Goode, Joseph H. Rothstein, Elisa V. Bandera, Penelope M. Webb, Hoda Anton-Culver, Brooke L. Fridley, A. du Bois, Mary Anne Rossing, Ignace Vergote, Melissa C. Larson, Argyrios Ziogas, Sharon E. Johnatty, Sandrina Lambrechts, Jolanta Lissowska, Claus Høgdall, Jennifer A. Doherty, Keitaro Matsuo, Joellen M. Schildkraut, Allan Jensen, Anna H. Wu, Suzanne C. Dixon, N. Wentzensen, Roberta B. Ness, Rebecca Sutphen, M. W. Beckmann, Jillian Hung, Diether Lambrechts, Lorna Rodriguez-Rodriguez, Christina M. Nagle, Harvey A. Risch, Ira Schwaab, Daniel W. Cramer, Kathryn L. Terry, Robert A. Vierkant, Lisa E. Paddock, L A Brinton, K. Moysich, M. T. Goodman, Peter A. Fasching, E Van Nieuwenhuysen, Florian Heitz, Estrid Høgdall, Lene Lundvall, P. Harter, Celeste Leigh Pearce, Kristine G. Wicklund, Susanne K. Kjaer, Rachel Palmieri Weber, Hannah P. Yang, Sian Fereday, Jenny Chang-Claude, Valerie McGuire, and Anna deFazio
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Oncology ,obesity ,Cancer Research ,medicine.medical_specialty ,ovarian cancer-specific survival ,Epidemiology ,overall survival ,Kaplan-Meier Estimate ,Carcinoma, Ovarian Epithelial ,Disease-Free Survival ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Ovarian carcinoma ,medicine ,Humans ,Neoplasms, Glandular and Epithelial ,Progression-free survival ,030304 developmental biology ,Ovarian Neoplasms ,2. Zero hunger ,Gynecology ,0303 health sciences ,business.industry ,Hazard ratio ,Cancer ,medicine.disease ,3. Good health ,Serous fluid ,ovarian cancer ,030220 oncology & carcinogenesis ,Meta-analysis ,Female ,business ,Ovarian cancer ,Body mass index ,progression-free survival - Abstract
© 2015 Cancer Research UK. All rights reserved. Background: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. Methods: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. Results: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ≥35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m -2) and endometrioid subtypes (pHR: 1.08 per 5 kg m -2), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m -2) subtype, but only the association with high-grade serous cancers was significant. Conclusions: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.
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- 2015
47. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer
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C B Gilks, Anna H. Wu, Natalia Antonenkova, Weiva Sieh, Angela Brooks-Wilson, Liisa M. Pelttari, Ingo B. Runnebaum, Argyrios Ziogas, John R. McLaughlin, Arto Leminen, Jennifer A. Doherty, Aben Kkh., Jacek Gronwald, Diana Eccles, Kirsten B. Moysich, Jonathan Tyrer, Valerie McGuire, Julie M. Cunningham, Georgia Chenevix-Trench, Agnieszka Timorek, Penelope M. Webb, Estrid Høgdall, Shelley S. Tworoger, Allan Jensen, Stuart MacGregor, Line Bjørge, Matthias W. Beckmann, Joellen M. Schildkraut, Sara H. Olson, Adriaan Vanderstichele, Shan Wang-Gohrke, Jan Gawełko, Elizabeth M. Poole, Anja Rudolph, Francesmary Modugno, Marc T. Goodman, Usha Menon, Hoda Anton-Culver, Celeste Leigh Pearce, Kristine G. Wicklund, Hildebrandt Mat., Karen Lu, Elisa V. Bandera, Ignace Vergote, Peter A. Fasching, Susanne K. Kjaer, Honglin Song, Catherine M. Phelan, Pharoah Pdp., Simon A. Gayther, Fanny Dao, Maria Bisogna, Dong Liang, Massuger Lfag., Linda S. Cook, Steven A. Narod, Andrew Berchuck, Lukasz Szafron, Harvey A. Risch, Robert P. Edwards, Peter Hillemanns, Diether Lambrechts, Matthias Dürst, Stacey J. Winham, Rikki Cannioto, Alice S. Whittemore, Stacey A. Missmer, Jan Lubinski, Jolanta Kupryjanczyk, Susan J. Ramus, Jodie N. Painter, Nicolas Wentzensen, Brooke L. Fridley, Katharina Bischof, Agnieszka Dansonka-Mieszkowska, Mary Anne Rossing, Thilo Dörk, Natalia Bogdanova, Reidun K. Kopperud, Helga B. Salvesen, Nhu D. Le, Yi Lu, Britton Trabert, Terry K. Morgan, Stefanie Burghaus, Douglas A. Levine, Graham G. Giles, Kathryn L. Terry, Roberta B. Ness, Anna Jakubowska, Dale R. Nyholt, E Van Nieuwenhuysen, Gabriel Cuellar-Partida, Lambertus A. Kiemeney, Fiona Bruinsma, Ralf Bützow, Louise A. Brinton, Grant W. Montgomery, Alexander Hein, Xifeng Wu, Daniel W. Cramer, Joseph H. Rothstein, Andrew P. Morris, Joseph L. Kelley, Heli Nevanlinna, Jolanta Lissowska, Ellen L. Goode, Krina T. Zondervan, Ursula Eilber, Aleksandra Gentry-Maharaj, Jenny Chang-Claude, Lu, Yi, Cuellar-Partida, Gabriel, Painter, Jodie N, Nyholt, Dale R, MacGregor, Stuart, Lee, Sang Hong, Australian Ovarian Cancer Study, and International Endogene Consortium (IEC)
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endometriosis ,Oncology ,Risk ,medicine.medical_specialty ,endocrine system diseases ,genetic association studies ,Serous carcinoma ,Endometriosis ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Medizinische Fakultät ,Internal medicine ,Genetics ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Molecular Biology ,Genetics (clinical) ,Genetic Association Studies ,030304 developmental biology ,Genetic association ,Oligonucleotide Array Sequence Analysis ,Ovarian Neoplasms ,0303 health sciences ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Association Studies Articles ,General Medicine ,ovarian neoplasms ,medicine.disease ,3. Good health ,Serous fluid ,ovarian cancer ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,030220 oncology & carcinogenesis ,Clear cell carcinoma ,Female ,Ovarian cancer ,genetic predisposition - Abstract
Contains fulltext : 153959.pdf (Publisher’s version ) (Closed access) Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
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- 2015
48. Vanucizumab (VAN) in combination with atezolizumab (ATEZO) for platinum-resistant recurrent ovarian cancer (PROC): Results from a single arm extension phase of the phase I study BP28179
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P. Gerber, Simona Rossomanno, Oliver Krieter, Izolda Franjkovic, Florian Heil, Alexandra Leary, Ana Oaknin, I.L. Ray-Coquard, Tapan K. Nayak, V. Rodriguez Freixinos, E Van Nieuwenhuysen, P. Toussaint, A. Sahbi, Ignace Vergote, Angelika Lahr, Christophe Massard, Lorena Fariñas-Madrid, Christophe Boetsch, Nicole Concin, and K. Longauer
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,Surgery ,Phase i study ,03 medical and health sciences ,030104 developmental biology ,Recurrent Ovarian Cancer ,Atezolizumab ,Internal medicine ,Phase (matter) ,medicine ,business ,Platinum resistant - Published
- 2017
49. 2777 Lavage of the uterine cavity for early and differential diagnosis of serous ovarian cancer
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Elisabeth Maritschnegg, Isaac Kinde, Luis Diaz, Yuxuan Wang, Reinhard Horvat, Kenneth W. Kinzler, Ignace Vergote, Nina Pecha, Bert Vogelstein, Nickolas Papadopoulos, Paul Speiser, R Zeillinger, and E. Van Nieuwenhuysen
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Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,medicine.anatomical_structure ,business.industry ,Internal medicine ,medicine ,Serous ovarian cancer ,Uterine cavity ,Differential diagnosis ,business - Published
- 2015
50. An outline of a national health education programme
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M E, Van Nieuwenhuysen
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Black or African American ,South Africa ,Black People ,Humans ,Preventive Medicine ,Health Education ,White People - Published
- 1966
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