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2. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Author

McCormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, PJ, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Lutgens, LCHW, Hollema, H, Pras, E, Snyers, A, Westerveld, GH, Jobsen, JJ, Slot, A, Mens, JM, Stam, TC, Van Triest, B, Van der Steen-Banasik, EM, De Winter, KAJ, Quinn, MA, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Colombo, A, Carinelli, S, Ferrero, A, Artioli, G, Davidson, C, McLachlin, CM, Ghatage, P, Rittenberg, PVC, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer, Stephanie M, Powell, Melanie E, Mileshkin, Linda, Katsaros, Dionyssios, Bessette, Paul, Haie-Meder, Christine, Ottevanger, Petronella B, Ledermann, Jonathan A, Khaw, Pearly, D'Amico, Romerai, Fyles, Anthony, Baron, Marie-Helene, Jürgenliemk-Schulz, Ina M, Kitchener, Henry C, Nijman, Hans W, Wilson, Godfrey, Brooks, Susan, Gribaudo, Sergio, Provencher, Diane, Hanzen, Chantal, Kruitwagen, Roy F, Smit, Vincent T H B M, Singh, Naveena, Do, Viet, Lissoni, Andrea, Nout, Remi A, Feeney, Amanda, Verhoeven-Adema, Karen W, Putter, Hein, and Creutzberg, Carien L

Published
2019
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10. High-Grade Serous Carcinoma at Risk-Reducing Salpingo-Oophorectomy in Asymptomatic Carriers of BRCA1/2 Pathogenic Variants: Prevalence and Clinical Factors.

Author

Stroot, I.A.S., Brouwer, J., Bart, J., Hollema, H., Stommel-Jenner, D.J., Wagner, M.M., Doorn, H.C. van, Hullu, J.A. de, Gaarenstroom, K.N., Beurden, M. van, Lonkhuijzen, L.R. van, Slangen, B.F.M., Zweemer, R.P., Gómez Garcia, E.B., Ausems, M.G., Boere, I.A., Engelen, K. van, Asperen, C.J. van, Schmidt, M.K., Wevers, M.R., Bock, G.H. de, Mourits, M.J., Stroot, I.A.S., Brouwer, J., Bart, J., Hollema, H., Stommel-Jenner, D.J., Wagner, M.M., Doorn, H.C. van, Hullu, J.A. de, Gaarenstroom, K.N., Beurden, M. van, Lonkhuijzen, L.R. van, Slangen, B.F.M., Zweemer, R.P., Gómez Garcia, E.B., Ausems, M.G., Boere, I.A., Engelen, K. van, Asperen, C.J. van, Schmidt, M.K., Wevers, M.R., Bock, G.H. de, and Mourits, M.J.

Abstract

Item does not contain fulltext, PURPOSE: To investigate the prevalence of and clinical factors associated with high-grade serous carcinoma (HGSC) at risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic BRCA1/2-pathogenic variant (PV) carriers. PATIENTS AND METHODS: We included BRCA1/2-PV carriers who underwent RRSO between 1995 and 2018 from the Hereditary Breast and Ovarian cancer in the Netherlands study. All pathology reports were screened, and histopathology reviews were performed for RRSO specimens with epithelial abnormalities or where HGSC developed after normal RRSO. We then compared clinical characteristics, including parity and oral contraceptive pill (OCP) use, for women with and without HGSC at RRSO. RESULTS: Of the 2,557 included women, 1,624 had BRCA1, 930 had BRCA2, and three had both BRCA1/2-PV. The median age at RRSO was 43.0 years (range: 25.3-73.8) for BRCA1-PV and 46.8 years (27.6-77.9) for BRCA2-PV carriers. Histopathologic review confirmed 28 of 29 HGSCs and two further HGSCs from among 20 apparently normal RRSO specimens. Thus, 24 (1.5%) BRCA1-PV and 6 (0.6%) BRCA2-PV carriers had HGSC at RRSO, with the fallopian tube identified as the primary site in 73%. The prevalence of HGSC in women who underwent RRSO at the recommended age was 0.4%. Among BRCA1/2-PV carriers, older age at RRSO increased the risk of HGSC and long-term OCP use was protective. CONCLUSION: We detected HGSC in 1.5% (BRCA1-PV) and 0.6% (BRCA2-PV) of RRSO specimens from asymptomatic BRCA1/2-PV carriers. Consistent with the fallopian tube hypothesis, we found most lesions in the fallopian tube. Our results highlight the importance of timely RRSO with total removal and assessment of the fallopian tubes and show the protective effects of long-term OCP.

Published
2023

14. A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study

Author

Reyners, A.K.L., de Munck, L., Erdkamp, F.L.G., Smit, W.M., Hoekman, K., Lalisang, R.I., de Graaf, H., Wymenga, A.N.M., Polee, M., Hollema, H., van Vugt, M.A.T.M., Schaapveld, M., and Willemse, P.H.B.

Published
2012
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19. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Author

de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, D'Amico, R, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Gribaudo, S, Provencher, D, Hanzen, C, Kruitwagen, R, Smit, V, Singh, N, Do, V, Lissoni, A, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Lutgens, L, Hollema, H, Pras, E, Snyers, A, Westerveld, G, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen-Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Colombo, A, Carinelli, S, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., D'Amico R., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Gribaudo S., Provencher D., Hanzen C., Kruitwagen R. F., Smit V. T. H. B. M., Singh N., Do V., Lissoni A., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Lutgens L. C. H. W., Hollema H., Pras E., Snyers A., Westerveld G. H., Jobsen J. J., Slot A., Mens J. M., Stam T. C., Van Triest B., Van der Steen-Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Colombo A., Carinelli S., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., Tubiana-Mathieu N., de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, D'Amico, R, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Gribaudo, S, Provencher, D, Hanzen, C, Kruitwagen, R, Smit, V, Singh, N, Do, V, Lissoni, A, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Lutgens, L, Hollema, H, Pras, E, Snyers, A, Westerveld, G, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen-Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Colombo, A, Carinelli, S, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., D'Amico R., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Gribaudo S., Provencher D., Hanzen C., Kruitwagen R. F., Smit V. T. H. B. M., Singh N., Do V., Lissoni A., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Lutgens L. C. H. W., Hollema H., Pras E., Snyers A., Westerveld G. H., Jobsen J. J., Slot A., Mens J. M., Stam T. C., Van Triest B., Van der Steen-Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Colombo A., Carinelli S., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., and Tubiana-Mathieu N.

Abstract

Background: The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. Methods: In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I–III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0–2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. Findings: Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the rad

Published
2019

20. 263 Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

Author

Paijens, ST, primary, Vledder, A, additional, Loiero, D, additional, Duiker, EW, additional, Bart, J, additional, Hendriks, AM, additional, Jalving, M, additional, Workel, HH, additional, Hollema, H, additional, Werner, N, additional, Plat, A, additional, Wisman, GBA, additional, Yigit, R, additional, Arts, H, additional, Kruse, AJ, additional, de Lange, NM, additional, Koelzer, VH, additional, de Bruyn, M, additional, and Nijman, HW, additional

Published
2021
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21. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial

Author

de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, Colombo, A, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Carinelli, S, Provencher, D, Hanzen, C, Lutgens, L, Smit, V, Singh, N, Do, V, D'Amico, R, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Kruitwagen, R, Hollema, H, Pras, E, Snyers, A, Stalpers, L, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen - Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Gribaudo, S, Lissoni, A, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., Colombo A., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Carinelli S., Provencher D., Hanzen C., Lutgens L. C. H. W., Smit V. T. H. B. M., Singh N., Do V., D'Amico R., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Kruitwagen R. F. P. M., Hollema H., Pras E., Snyers A., Stalpers L., Jobsen J. J., Slot A., Mens J. -W. M., Stam T. C., Van Triest B., Van der Steen - Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Gribaudo S., Lissoni A. A., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., Tubiana-Mathieu N., de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, Colombo, A, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Carinelli, S, Provencher, D, Hanzen, C, Lutgens, L, Smit, V, Singh, N, Do, V, D'Amico, R, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Kruitwagen, R, Hollema, H, Pras, E, Snyers, A, Stalpers, L, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen - Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Gribaudo, S, Lissoni, A, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, Tubiana-Mathieu, N, de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., Colombo A., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Carinelli S., Provencher D., Hanzen C., Lutgens L. C. H. W., Smit V. T. H. B. M., Singh N., Do V., D'Amico R., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Kruitwagen R. F. P. M., Hollema H., Pras E., Snyers A., Stalpers L., Jobsen J. J., Slot A., Mens J. -W. M., Stam T. C., Van Triest B., Van der Steen - Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Gribaudo S., Lissoni A. A., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., and Tubiana-Mathieu N.

Abstract

Background: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. Methods: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. Results: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1–73·1). 5-year overall survival was 81·8% (95% CI

Published
2018

22. Loss of MSH2 protein expression is a risk factor in early stage cervical cancer

Author

Nijhuis, E.R., Nijman, H.W., Oien, K.A., Bell, A., Hoor, K.A. ten, Reesink-Peters, N., Boezen, H.M., Hollema, H., and van der Zee, A.G.J.

Subjects
Cervical cancer -- Diagnosis, Cervical cancer -- Research, Cervical cancer -- Risk factors, Tumor staging -- Diagnosis, Tumor staging -- Research, Gene expression -- Research, Gene expression -- Health aspects, Health
Published
2007

23. Germline BRCA-Associated Endometrial Carcinoma Is a Distinct Clinicopathologic Entity

Author

Jonge, M.M. de, Ritterhouse, L.L., Kroon, C.D. de, Vreeswijk, M.P.G., Segal, J.P., Puranik, R., Rookus, M.A., Hogervorst, F.B.L., Leeuwen, F.E. van, Adank, M.A., Schmidt, M.K., Jenner, D.J., Collee, J.M., Ouweland, A.M.W. van den, Hooning, M.J., Boere, I.A., Asperen, C.J. van, Devilee, P., Luijt, R.B. van der, Cronenburg, T.C.T.E.F. van, Wevers, M.R., Mensenkamp, A.R., Ausems, M.G.E.M., Koudijs, M.J., Meijers-Heijboer, H.E.J., Os, T.A.M. van, Engelen, K. van, Gille, J.J.P., Gomez-Garcia, E.B., Blok, M.J., Boer, M. de, Oosterwijk, J.C., Hout, A.H. van der, Mourits, M.J., Bock, G.H. de, Siesling, S., Verloop, J., Broek, E.C. van den, Hollema, H., Smit, V.T.H.B.M., Howitt, B.E., Bosse, T., HEBON Grp, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Life Course Epidemiology (LCE), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Promovendi ODB, Clinical Genetics, and Medical Oncology

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, MAINTENANCE THERAPY, TAMOXIFEN TREATMENT, PROGNOSIS, Germline, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Carcinoma, BREAST-CANCER, RISK, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], business.industry, MUTATIONS, Endometrial cancer, WOMEN, Histology, medicine.disease, OVARIAN, UTERINE SEROUS CARCINOMA, 030104 developmental biology, 030220 oncology & carcinogenesis, CLEAR-CELL, Ovarian cancer, business, Cohort study, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Purpose: Whether endometrial carcinoma (EC) should be considered part of the gBRCA1/2-associated hereditary breast and ovarian cancer (HBOC) syndrome is topic of debate. We sought to assess whether ECs occurring in gBRCA carriers are enriched for clinicopathologic and molecular characteristics, thereby supporting a causal relationship. Experimental Design: Thirty-eight gBRCA carriers that developed EC were selected from the nationwide cohort study on hereditary breast and ovarian cancer in the Netherlands (HEBON), and these were supplemented with four institutional cases. Tumor tissue was retrieved via PALGA (Dutch Pathology Registry). Nineteen morphologic features were scored and histotype was determined by three expert gynecologic pathologists, blinded for molecular analyses (UCM-OncoPlus Assay including 1213 genes). ECs with LOH of the gBRCA-wild-type allele (gBRCA/LOHpos) were defined “gBRCA-associated,” those without LOH (gBRCA/LOHneg) were defined “sporadic.” Results: LOH could be assessed for 40 ECs (30 gBRCA1, 10 gBRCA2), of which 60% were gBRCA/LOHpos. gBRCA/LOHpos ECs were more frequently of nonendometrioid (58%, P = 0.001) and grade 3 histology (79%, P < 0.001). All but two were in the TP53-mutated TCGA-subgroup (91.7%, P < 0.001). In contrast, gBRCA/LOHneg ECs were mainly grade 1 endometrioid EC (94%) and showed a more heterogeneous distribution of TCGA-molecular subgroups: POLE-mutated (6.3%), MSI-high (25%), NSMP (62.5%), and TP53-mutated (6.3%). Conclusions: We provide novel evidence in favor of EC being part of the gBRCA-associated HBOC-syndrome. gBRCA-associated ECs are enriched for EC subtypes associated with unfavorable clinical outcome. These findings have profound therapeutic consequences as these patients may benefit from treatment strategies such as PARP inhibitors. In addition, it should influence counseling and surveillance of gBRCA carriers.

Published
2019

24. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer

Author

Niessen, R.C., Berends, M.J.W., Wu, Y., Sijmons, R.H., Hollema, H., Ligtenberg, M.J.L., de Walle, H.E.K., de Vries, E.G.E., Karrenbeld, A., Buys, C.H.C.M., van der Zee, A.G.J., Hofstra, R.M.W., and Kleibeuker, J.H.

Subjects
Gene mutations -- Research, Gene mutations -- Physiological aspects, Colorectal cancer -- Research, Colorectal cancer -- Genetic aspects, Colorectal cancer -- Diagnosis, Health
Published
2006

25. Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

Author

Paijens, S. T., primary, Vledder, A., additional, Loiero, D., additional, Duiker, E. W., additional, Bart, J., additional, Hendriks, A. M., additional, Jalving, M., additional, Workel, H. H., additional, Hollema, H., additional, Werner, N., additional, Plat, A., additional, Wisman, G. B. A., additional, Yigit, R., additional, Arts, H., additional, Kruse, A. J., additional, de Lange, N.M., additional, Koelzer, V. H., additional, de Bruyn, M., additional, and Nijman, H. W., additional

Published
2021
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26. Detection of telomerase, its components, and human papillomavirus in cervical scrapings as a tool for triage in women with cervical dysplasia. (Original Article)

Author

Reesink-Peters, N., Helder, M.N., Wisman, G.B.A., Knol, A.J., Koopmans, S., Boezen, H.M., Schuuring, E., Hollema, H., Vries, E.G.E. de, Jong, S. de, and Zee, A.G.J. van der

Subjects
Papillomavirus infections -- Physiological aspects -- Risk factors, Cervical cancer -- Risk factors, Telomerase -- Physiological aspects, Health, Physiological aspects, Risk factors
Abstract

Aim: To examine whether the detection of either telomerase and its components or high risk human papillomavirus (HPV) are of value in predicting the presence of cervical intraepithelial neoplasia (CIN) [...]

Published
2003

27. The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium. (Original Article)

Author

Mourits, M.J.E., Hoor, K.A. Ten, Zee, A.G.J. van der, Willemse, P.H.B., Vries, E.G.E. de, and Hollema, H.

Subjects
Tamoxifen -- Physiological aspects -- Health aspects, Epithelium -- Physiological aspects -- Health aspects, Estrogen -- Receptors, Postmenopausal women -- Health aspects -- Physiological aspects, Progesterone -- Receptors, Health
Abstract

Aim: To study the effects of tamoxifen on the proliferation index and oestrogen receptor (ER) and progesterone receptor (PR) expression in postmenopausal endometrium. Methods: A total of 125 endometrial specimens [...]

Published
2002

28. Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation. (Cancer)

Author

Rijcken, F.E.M., Hollema, H., and Kleibeuker, J.H.

Subjects
Adenoma -- Development and progression -- Genetic aspects, Colorectal cancer -- Genetic aspects -- Development and progression, Health, Development and progression, Genetic aspects
Abstract

Background: Hereditary non-palyposis colorectal cancer (HNPCC) is thought to arise from adenomas. HNPCC mostly occurs in the proximal colon. We investigated whether this proximal preponderance is due to a proximal [...]

Published
2002

31. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial

Author

de Boer S. M., Powell M. E., Mileshkin L., Katsaros D., Bessette P., Haie-Meder C., Ottevanger P. B., Ledermann J. A., Khaw P., Colombo A., Fyles A., Baron M. -H., Jurgenliemk-Schulz I. M., Kitchener H. C., Nijman H. W., Wilson G., Brooks S., Carinelli S., Provencher D., Hanzen C., Lutgens L. C. H. W., Smit V. T. H. B. M., Singh N., Do V., D'Amico R., Nout R. A., Feeney A., Verhoeven-Adema K. W., Putter H., Creutzberg C. L., McCormack M., Whitmarsh K., Allerton R., Gregory D., Symonds P., Hoskin P. J., Adusumalli M., Anand A., Wade R., Stewart A., Taylor W., Kruitwagen R. F. P. M., Hollema H., Pras E., Snyers A., Stalpers L., Jobsen J. J., Slot A., Mens J. -W. M., Stam T. C., Van Triest B., Van der Steen - Banasik E. M., De Winter K. A. J., Quinn M. A., Kolodziej I., Pyman J., Johnson C., Capp A., Fossati R., Gribaudo S., Lissoni A. A., Ferrero A., Artioli G., Davidson C., McLachlin C. M., Ghatage P., Rittenberg P. V. C., Souhami L., Thomas G., Duvillard P., Berton-Rigaud D., Tubiana-Mathieu N., de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, P, Ledermann, J, Khaw, P, Colombo, A, Fyles, A, Baron, M, Jurgenliemk-Schulz, I, Kitchener, H, Nijman, H, Wilson, G, Brooks, S, Carinelli, S, Provencher, D, Hanzen, C, Lutgens, L, Smit, V, Singh, N, Do, V, D'Amico, R, Nout, R, Feeney, A, Verhoeven-Adema, K, Putter, H, Creutzberg, C, Mccormack, M, Whitmarsh, K, Allerton, R, Gregory, D, Symonds, P, Hoskin, P, Adusumalli, M, Anand, A, Wade, R, Stewart, A, Taylor, W, Kruitwagen, R, Hollema, H, Pras, E, Snyers, A, Stalpers, L, Jobsen, J, Slot, A, Mens, J, Stam, T, Van Triest, B, Van der Steen - Banasik, E, De Winter, K, Quinn, M, Kolodziej, I, Pyman, J, Johnson, C, Capp, A, Fossati, R, Gribaudo, S, Lissoni, A, Ferrero, A, Artioli, G, Davidson, C, Mclachlin, C, Ghatage, P, Rittenberg, P, Souhami, L, Thomas, G, Duvillard, P, Berton-Rigaud, D, and Tubiana-Mathieu, N

Subjects
Canada, Antineoplastic Combined Chemotherapy Protocol, Paclitaxel, Time Factor, Risk Factor, Australia, Chemoradiotherapy, Adjuvant, Middle Aged, Carboplatin, Europe, Treatment Outcome, Gynecologic Surgical Procedures, Lymph Node Excision, Endometrial Neoplasm, Female, Radiotherapy, Adjuvant, Dose Fractionation, Radiation, Cisplatin, Neoplasm Grading, Carcinoma, Endometrioid, Aged, Human, Neoplasm Staging, New Zealand
Abstract

Background: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. Methods: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. Results: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1–73·1). 5-year overall survival was 81·8% (95% CI 77·5–86·2) with chemoradiotherapy versus 76·7% (72·1–81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54–1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3–79·9) versus 68·6% (63·1–73·4; HR 0·71, 95% CI 0·53–0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p

Published
2018

41. Margin status revisited in vulvar squamous cell carcinoma

Author

Grootenhuis, N.C. te, Pouwer, A.W., Bock, G.H. de, Hollema, H., Bulten, J., Zee, A.G. van der, Hullu, J.A. de, Oonk, M.H., Grootenhuis, N.C. te, Pouwer, A.W., Bock, G.H. de, Hollema, H., Bulten, J., Zee, A.G. van der, Hullu, J.A. de, and Oonk, M.H.

Abstract

Item does not contain fulltext

Published
2019

42. Measuring the depth of invasion in vulvar squamous cell carcinoma: interobserver agreement and pitfalls

Author

Pouwer, AFW, Bult, P, Otte, I, Brand, M, van der Horst, J, Harterink, LJV, Van de Vijver, KK, Guerra, E, Aliredjo, RP, Bosch, S L, Grefte, JMM, Zomer, S, Hollema, H, de Heus, B, Satumalaij, S, Graham, Patricia, IntHout, J, de Hullu, JA, Bulten, J, Pouwer, AFW, Bult, P, Otte, I, Brand, M, van der Horst, J, Harterink, LJV, Van de Vijver, KK, Guerra, E, Aliredjo, RP, Bosch, S L, Grefte, JMM, Zomer, S, Hollema, H, de Heus, B, Satumalaij, S, Graham, Patricia, IntHout, J, de Hullu, JA, and Bulten, J

Published
2019

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