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2. 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

3. 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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4. 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

5. 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

6. 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

7. 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

8. 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

9. 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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10. 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

11. 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

12. 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

14. 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

16. 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

17. 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

20. Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer

Author

Boer, S.M. de, Wortman, B.G., Bosse, T., Powell, M.E., Singh, N., Hollema, H., Wilson, G., Chowdhury, M.N., Mileshkin, L., Pyman, J., Katsaros, D., Carinelli, S., Fyles, A., McLachlin, C.M., Haie-Meder, C., Duvillard, P., Nout, R.A., Verhoeven-Adema, K.W., Putter, H., Creutzberg, C.L., Smit, V.T.H.B.M., PORTEC Study Grp, and Targeted Gynaecologic Oncology (TARGON)

Subjects
0301 basic medicine, Pathology, medicine.medical_treatment, Central Pathology Review, chemotherapy, radiation therapy, Carboplatin, law.invention, GRADING SYSTEMS, chemistry.chemical_compound, 0302 clinical medicine, POSTOPERATIVE RADIOTHERAPY, Randomized controlled trial, law, REPRODUCIBILITY, Antineoplastic Combined Chemotherapy Protocols, pathology review, Hematology, Middle Aged, OPEN-LABEL, STAGE-I, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, Adult, medicine.medical_specialty, Paclitaxel, CARCINOMA, endometrial carcinoma, high risk, DIAGNOSIS, 03 medical and health sciences, RADIATION-THERAPY, medicine, Humans, External beam radiotherapy, Aged, Radiotherapy, business.industry, Patient Selection, Endometrial cancer, Chemoradiotherapy, Adjuvant, Original Articles, medicine.disease, randomised trial, Endometrial Neoplasms, Clinical trial, INTEROBSERVER VARIABILITY, 030104 developmental biology, chemistry, EXTERNAL-BEAM RADIOTHERAPY, Cisplatin, business, Gynecological Tumors, Chemoradiotherapy
Abstract

Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ).Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70).Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved. This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138).

Published
2018

23. Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: A systematic review.

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

1 maart 2018, Item does not contain fulltext, BACKGROUND: In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to local recurrences should be helpful to select high risk patients and/or to develop strategies to prevent local recurrences. OBJECTIVE: This systematic review aims to evaluate the current knowledge on the incidence of local recurrences in vulvar carcinoma related to clinicopathologic and cell biologic variables. DATA SOURCES: Relevant studies were identified by an extensive online electronic search in July 2017. STUDY ELIGIBILITY CRITERIA: Studies reporting prognostic factors specific for local recurrences of vulvar carcinoma were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Two review authors independently performed data selection, extraction and assessment of study quality. The risk difference was calculated for each prognostic factor when described in two or more studies. RESULTS: Twenty-two studies were included; most of all were retrospective and mainly reported pathologic prognostic factors. Our review indicates an estimated annual local recurrence rate of 4% without plateauing. The prognostic relevance for local recurrence of vulvar carcinoma of all analyzed variables remains equivocal, including pathologic tumor free margin distance <8mm, presence of lichen sclerosus, groin lymph node metastases and a variety of primary tumor characteristics (grade of differentiation, tumor size, tumor focality, depth of invasion, lymphovascular space invasion, tumor localization and presence of human papillomavirus). CONCLUSIONS: Current quality of data on prognostic factors for local recurrences in vulvar carcinoma patients does not allow evidence-based clinical decision making. Further research on prognostic factors, applying state of the art methodology is needed to identify high-risk patients and to develop alternative primary and secondary prevention strategies.

Published
2018

24. Characteristics of Lynch syndrome associated ovarian cancer

Author

Woolderink, J.M., Bock, G.H. de, Hullu, J.A. de, Hollema, H., Zweemer, R.P., Slangen, B.F., Vasen, H.F., Mourits, M.J.E., Woolderink, J.M., Bock, G.H. de, Hullu, J.A. de, Hollema, H., Zweemer, R.P., Slangen, B.F., Vasen, H.F., and Mourits, M.J.E.

Abstract

Item does not contain fulltext

Published
2018

25. Characteristics of Lynch syndrome associated ovarian cancer

Author

Woolderink, J. M., De Bock, G. H., de Hullu, J. A., Hollema, H., Zweemer, R. P., Slangen, B. F.M., Gaarenstroom, K. N., van Beurden, M., van Doorn, H. C., Sijmons, R. H., Vasen, H. F.A., Mourits, M. J.E., Woolderink, J. M., De Bock, G. H., de Hullu, J. A., Hollema, H., Zweemer, R. P., Slangen, B. F.M., Gaarenstroom, K. N., van Beurden, M., van Doorn, H. C., Sijmons, R. H., Vasen, H. F.A., and Mourits, M. J.E.

Published
2018

26. Proteomic alterations in early stage cervical cancer

Author

Güzel, C. (Coşkun), Govorukhina, N. (Natalia), Wisman, G.B.A. (G Bea A.), Stingl, C. (Christoph), Dekker, L.J.M. (Lennard J.M.), Klip, H.G. (Harry G.), Hollema, H., Guryev, V. (Victor), Horvatovich, P.L. (Peter ), Zee, A.G.J. van der, Bischoff, R. (Rainer), Luider, T.M. (Theo), Güzel, C. (Coşkun), Govorukhina, N. (Natalia), Wisman, G.B.A. (G Bea A.), Stingl, C. (Christoph), Dekker, L.J.M. (Lennard J.M.), Klip, H.G. (Harry G.), Hollema, H., Guryev, V. (Victor), Horvatovich, P.L. (Peter ), Zee, A.G.J. van der, Bischoff, R. (Rainer), and Luider, T.M. (Theo)

Abstract

Laser capture microdissection (LCM) allows the capture of cell types or welldefined structures in tissue. We compared in a semi-quantitative way the proteomes from an equivalent of 8,000 tumor cells from patients with squamous cell cervical cancer (SCC, n = 22) with healthy epithelial and stromal cells obtained from normal cervical tissue (n = 13). Proteins were enzymatically digested into peptides which were measured by high-resolution mass spectrometry and analyzed by "all-ornothing" analysis, Bonferroni, and Benjamini-Hochberg correction for multiple testing. By comparing LCM cell type preparations, 31 proteins were exclusively found in early stage cervical cancer (n = 11) when compared with healthy epithelium and stroma, based on criteria that address specificity in a restrictive "all-or-nothing" way. By Bonferroni correction for multiple testing, 30 proteins were significantly up-regulated between early stage cervical cancer and healthy control, including six members of the MCM protein family. MCM proteins are involved in DNA repair and expected to be participating in the early stage of cancer. After a less stringent Benjamini-Hochberg correction for multiple testing, we found that the abundances of 319 proteins were significantly different between early stage cervical cancer and healthy controls. Four proteins were confirmed in digests of whole tissue lysates by Parallel Reaction M

Published
2018
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27. Characteristics of Lynch syndrome associated ovarian cancer

Author

Divisie Beeld & Oncologie, MS Gynaecologische Oncologie, Cancer, Woolderink, J. M., De Bock, G. H., de Hullu, J. A., Hollema, H., Zweemer, R. P., Slangen, B. F.M., Gaarenstroom, K. N., van Beurden, M., van Doorn, H. C., Sijmons, R. H., Vasen, H. F.A., Mourits, M. J.E., Divisie Beeld & Oncologie, MS Gynaecologische Oncologie, Cancer, Woolderink, J. M., De Bock, G. H., de Hullu, J. A., Hollema, H., Zweemer, R. P., Slangen, B. F.M., Gaarenstroom, K. N., van Beurden, M., van Doorn, H. C., Sijmons, R. H., Vasen, H. F.A., and Mourits, M. J.E.

Published
2018

28. Proteomic alterations in early stage cervical cancer

Author

Güzel, Coskun, Govorukhina, NI, Wisman, GBA, Stingl, Christoph, Dekker, Lennard, Klip, HG, Hollema, H, Guryev, V, Horvatovich, PL, van der Zee, AGJ, Bischoff, R, Luider, Theo, Güzel, Coskun, Govorukhina, NI, Wisman, GBA, Stingl, Christoph, Dekker, Lennard, Klip, HG, Hollema, H, Guryev, V, Horvatovich, PL, van der Zee, AGJ, Bischoff, R, and Luider, Theo

Published
2018

29. Bacterial vaginosis in not important in the etiology of cervical neoplasia: a survey on women with dyskaryotic smears

Author

Peters, N., Leeuwen, A.M. van, Pieters, W.J.L.M., Hollema, H., Quint, W.G.V., and Burger, M.P.M.

Subjects
Cervix dysplasia -- Causes of, Vaginosis -- Complications, Health
Abstract

Bacterial vaginosis may not predispose women to develop cervical cancer. Bacterial vaginosis is a condition where bacteria take over the healthy flora of the vagina. Researchers identified bacterial vaginosis in 56 of 280 women (20%) with abnormal cervical Pap smears. Bacterial vaginosis was determined not to cause cervical human papillomavirus (HPV) infection or the development of abnormal cervical cells. Similar risk factors for both bacterial vaginosis and HPV infection, which can lead to cervical cancer, include smoking and the number of sexual partners. Other risk factors for bacterial vaginosis include age when sexual activity first began and the concurrent presence of Chlamydia trachomatis infection. The 20% rate of bacterial vaginosis may be normal among gynecology outpatients.

Published
1995

31. Less-favourable prognosis for low-risk endometrial cancer patients with a discordant pre- versus post-operative risk stratification

Author

Eggink, F.A., Mom, C.H., Bouwman, K., Boll, D., Becker, J.H., Creutzberg, C.L., Niemeijer, G.C., Driel, W.J. van, Reyners, A.K., Zee, A.G. van der, Bremer, G.L., Ezendam, N.P., Kruitwagen, R.F.P.M., Pijnenborg, J.M.A., Hollema, H., Nijman, H.W., Aa, M.A. van der, Eggink, F.A., Mom, C.H., Bouwman, K., Boll, D., Becker, J.H., Creutzberg, C.L., Niemeijer, G.C., Driel, W.J. van, Reyners, A.K., Zee, A.G. van der, Bremer, G.L., Ezendam, N.P., Kruitwagen, R.F.P.M., Pijnenborg, J.M.A., Hollema, H., Nijman, H.W., and Aa, M.A. van der

Abstract

Contains fulltext : 174766.pdf (publisher's version ) (Closed access), BACKGROUND: Pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival. METHODS: Patients diagnosed with EC within the first 6 months of the years 2005-2014 were selected from the Netherlands Cancer Registry (N = 7875). Pre- and post-operative risk stratifications were determined based on grade and/or histological subtype for 3784 eligible patients. RESULTS: A discordant risk stratification was found in 10% of patients: 4% (N = 155) had high pre- and low post-operative risk and 6% (N = 215) had low pre- and high post-operative risk. Overall survival of patients with high pre- and low post-operative risk was less favourable compared to those with a concordant low risk (80% versus 89%, p = 0.002). This difference remained significant when correcting for age, stage, surgical staging and adjuvant therapy (hazard ratio 1.80, 95% confidence interval 1.28-2.53, p = 0.001). Survival of patients with low pre- and high post-operative risk did not differ from those with a concordant high risk (64% versus 62%, p = 0.295). CONCLUSION: Patients with high pre- and low post-operative risk have a less favourable prognosis compared to patients with a concordant low risk. Pre-operative risk stratifications contain independent prognostic information and should be incorporated into clinical decision-making.

Published
2017

32. CD103+ tumor-infiltrating lymphocytes are tumor-reactive intraepithelial CD8+ T cells associated with prognostic benefit and therapy response in cervical cancer

Author

Komdeur, F.L., Prins, T.M., Wall, S. van de, Plat, A., Wisman, G.B., Hollema, H., Daemen, T., Church, D.N., Bruyn, M. de, Nijman, H.W., Komdeur, F.L., Prins, T.M., Wall, S. van de, Plat, A., Wisman, G.B., Hollema, H., Daemen, T., Church, D.N., Bruyn, M. de, and Nijman, H.W.

Abstract

Contains fulltext : 178711.pdf (Publisher’s version ) (Open Access), Human papilloma virus (HPV)-induced cervical cancer constitutively expresses viral E6/E7 oncoproteins and is an excellent target for T cell-based immunotherapy. However, not all tumor-infiltrating T cells confer equal benefit to patients, with epithelial T cells being superior to stromal T cells. To assess whether the epithelial T cell biomarker CD103 could specifically discriminate the beneficial antitumor T cells, association of CD103 with clinicopathological variables and outcome was analyzed in the TCGA cervical cancer data set (n = 304) and by immunohistochemistry (IHC) in an independent cohort (n = 460). Localization of CD103+ cells in the tumor was assessed by immunofluorescence. Furthermore, use of CD103 as a response biomarker was assessed in an in vivo E6/E7+ tumor model. Our results show that CD103 gene expression was strongly correlated with cytotoxic T cell markers (e.g. CD8/GZMB/PD1) in the TCGA series. In line with this, CD103+ cells in the IHC series co-expressed CD8 and were preferentially located in cervical tumor epithelium. High CD103+ cell infiltration was strongly associated with an improved prognosis in both series, and appeared to be a better predictor of outcome than CD8. Interestingly, the prognostic benefit of CD103 in both series seemed limited to patients receiving radiotherapy. In a preclinical mouse model, HPV E6/E7-targeted therapeutic vaccination in combination with radiotherapy increased the intratumoral number of CD103+ CD8+ T cells, providing a potential mechanistic basis for our results. In conclusion, CD103 is a promising marker for rapid assessment of tumor-reactive T cell infiltration of cervical cancers and a promising response biomarker for E6/E7-targeted immunotherapy.

Published
2017

34. The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in the tumour microenvironment

Author

HAG Hart- Vaatziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Versluis, M A C, Marchal, S, Plat, A, Bock, G.H., Hall, T., de Bruyn, K.M.T., Hollema, H., Nijman, Hans W, HAG Hart- Vaatziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Versluis, M A C, Marchal, S, Plat, A, Bock, G.H., Hall, T., de Bruyn, K.M.T., Hollema, H., and Nijman, Hans W

Published
2017

35. Less-favourable prognosis for low-risk endometrial cancer patients with a discordant pre-versus post-operative risk stratification

Author

Eggink, F. A., Mom, C. H., Bouwman, K., Boll, D., Becker, J. H., Creutzberg, C. L., Niemeijer, G. C., van Driel, W. J., Reyners, A. K., van der Zee, A. G., Bremer, G. L., Ezendam, N. P., Kruitwagen, R. F., Pijnenborg, J. M., Hollema, H., Nijman, H. W., van der Aa, M. A., Eggink, F. A., Mom, C. H., Bouwman, K., Boll, D., Becker, J. H., Creutzberg, C. L., Niemeijer, G. C., van Driel, W. J., Reyners, A. K., van der Zee, A. G., Bremer, G. L., Ezendam, N. P., Kruitwagen, R. F., Pijnenborg, J. M., Hollema, H., Nijman, H. W., and van der Aa, M. A.

Abstract

Background: Pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival.Methods: Patients diagnosed with EC within the first 6 months of the years 2005-2014 were selected from the Netherlands Cancer Registry (N = 7875). Pre-and post-operative risk stratifications were determined based on grade and/or histological subtype for 3784 eligible patients.Results: A discordant risk stratification was found in 10% of patients: 4% (N = 155) had high pre-and low post-operative risk and 6% (N = 215) had low pre-and high post-operative risk. Overall survival of patients with high pre-and low post-operative risk was less favourable compared to those with a concordant low risk (80% versus 89%, p = 0.002). This difference remained significant when correcting for age, stage, surgical staging and adjuvant therapy (hazard ratio 1.80, 95% confidence interval 1.28-2.53, p = 0.001). Survival of patients with low pre-and high post-operative risk did not differ from those with a concordant high risk (64% versus 62%, p = 0.295).Conclusion: Patients with high pre-and low post-operative risk have a less favourable prognosis compared to patients with a concordant low risk. Pre-operative risk stratifications contain independent prognostic information and should be incorporated into clinical decision-making. (C) 2017 Elsevier Ltd. All rights reserved.

Published
2017

36. Corrigendum to 'Less-favourable prognosis for low-risk endometrial cancer patients with a discordant pre- versus post-operative risk stratification' (vol 78, pg 82, 2017)

Author

Eggink, F. A., Mom, C. H., Bouwman, K., Boll, D., Becker, J. H., Creutzberg, C. L., Niemeijer, G. C., van Driel, W. J., Reyners, A. K., van der Zee, A. G., Bremer, G. L., Ezendam, N. P., Kruitwagen, R. F., Pijnenborg, J. M., Hollema, H., Nijman, H. W., van der Aa, M. A., Eggink, F. A., Mom, C. H., Bouwman, K., Boll, D., Becker, J. H., Creutzberg, C. L., Niemeijer, G. C., van Driel, W. J., Reyners, A. K., van der Zee, A. G., Bremer, G. L., Ezendam, N. P., Kruitwagen, R. F., Pijnenborg, J. M., Hollema, H., Nijman, H. W., and van der Aa, M. A.

Published
2017

37. P003 Implementation of High Throughput Parallel Sequencing in a Diagnostic Setting: Multiplexed Amplicon Sequencing of the Breast Cancer Genes BRCA1 and 2

Author

Zogopoulos G, Tomi Pastinen, Sivanandan K, Vaca F, Kinoshita T, Johannes B, Leguis E, Jansen-van der Weide M, Learn L, Godlewski D, Ed Saunders, Montserrat Rué, Vaisman A, de Bock G, Ángel Segura, Sabbaghian N, Mohammad Amin Kerachian, Pelletier S, Metcalfe K, Lilge L, Stockle E, Cheng S, Burger C, Woike A, Michelle Guy, Ragone A, Y. J. Bignon, Bronkhorst Y, Patricia N. Tonin, Lima M, Mieke Kriege, Karsan A, Zweemer R, Prady C, Beattie M, Panchal S, Kathleen Claes, van Zon P, Diane Provencher, Ummels A, Kang I, Shumak R, Arcusa Â, Yosr Hamdi, Alonso Mc, Dolman L, Houssami N, Olivier Delattre, Yannick Bidet, Claude Houdayer, Mercedes Durán, Ganschow P, Isabel Chirivella, Domingo S, Rebsamen M, Giustina Simone, Orland Diez, Chapman J, An tSaoir C, Jeanna McCuaig, Blayney J, Bosdet I, Treacy R, Esther Darder, Ando J, Luc Dehaspe, García-Casado Z, Duffy J, Harkin D, Z Kote-Jarai, Kasamatsu T, Ulf Kristoffersson, Membrez, Priston M, Noreau-Heisz D, Trivedi A, Begoña Graña, Ghadirian P, Ashuryk O, Consol López, Wenzel L, Vogel R, Joseph G, Poll A, Kennedy R, Patton S, Pérez C, Mónica Cornet, Panighetti A, Cassart P, Burke K, Mes-Masson A, Llacuachaqui M, Marc Tischkowitz, Wong N, Arcand S, Kotsopoulos J, Meschino W, Hall A, Marles S, Docking R, Haroun I, Marie Plante, Rachel Laframboise, Daniel Sinnett, Luce J, Sekiguchi I, Edenir Inêz Palmero, de Winter J, Christopher J. Lord, Hamel N, Pruski-Clark J, Lee D, Rusnak A, Carson N, Marta Santamariña, Knoppers B, Oakhill K, Bruce R. Rosen, Pierre O. Chappuis, Bruce Poppe, Stanislaw C, Catts Z, Brood M, van der Wall E, Yip C, Christine Walsh, Hoodfar E, Pressman A, Andrulis I, Alicia Barroso, D. Leongamornlert, Gillian Mitchell, Akira Hirasawa, Shen Z, Sameer Parpia, Horgan M, van Echtelt J, Chun K, Lubinski J, Rebecca Sutphen, Terespolsky D, Richard D, McDyer F, Floquet A, Lambo R, Bathurst L, Brown G, Kidd M, Nicolas Sevenet, Mourits M, Vencken P, Tatiana Popova, Garcia N, Armel S, van Amstel H, Valentini A, Ellen Warner, Hofland N, Hanna D, Kim J, Osann K, Enmore M, Loranger K, Sulivan I, J. Oliveira, Meijers H, Jansen R, Edmundo Carvalho Mauad, Kirkpatrick R, Danilo V Viana, Ian G. Campbell, Mil S, E J Sawyer, J. Balmaña, Samra Turajlic, Graham G, Alonso C, Inanc Birol, Sinclair F, van Tuil M, Pascual Bolufer, Micheli R, Andrew R. Green, Junyent N, Whittaker J, Monnerat C, Rhéaume J, Livingston D, Chan S, L. Ramadan, Lee R, Katarzyna Durda, De Leeneer K, Grados C, Côté C, Kyle B. Matchett, Robert Winqvist, Bonner D, Brunella Pilato, Mohd Taib N, Judy Garber, Kleiderman E, Murakami S, Sharifi N, Kimberley Hill, Desbiens C, Robert Royer, Jasperson K, Hsieh S, De Summa S, Dominique Stoppa-Lyonnet, de Lima J, Stuart McIntosh, Shakeri M, Wendy Kohlmann, Albert-Green A, de Hullu J, Pasick R, Avard D, Pathania S, van der Groep P, Laura Fachal, Bruno Zeitouni, Susan M. Domchek, Davey S, Richard Marais, Powell C, Hans J. J. P. Gille, Greenberg R, Kamata H, Cina, Gaarenstroom K, Lakhal Chaieb M, Kavanagh L, Gaelle Benais-Pont, Sun P, Jansen L, Matthew Parker, Barjhoux L, Russ H, Simon J. Furney, Willems A, Robb L, David E. Goldgar, Young S, Natalia Campacci, Mark G. Thomas, Doug Easton, Klugman S, Barrault M, Calvo N, Adriana C. Flora, Littell R, Narod S, Fragoso, N. Bosch, Finch A, Paul M. Wilkerson, Teo S, Tomasz Huzarski, Manuel Salto-Tellez, Moseley M, Davis S, Olga M. Sinilnikova, Iturbe A, Joan Brunet, Tierney M, Tsai E, Navarro de Souza A, Leclerc M, Lorenzo Manti, Gutiérrez-Enríquez S, Milewski B, Simon S. McDade, Kaplan C, Buckley N, Eva Esteban-Cardeñosa, Richter S, Shimizu C, Li J, Elena Castro, Iwanka Kozarewa, Harley I, Atocha Romero, Carlos E. Andrade, Carole Verny-Pierre, Barouk E, Vian D, Montserrat Baiget, Chan J, Sandra Bonache, Andrew Y Shuen, van der Merwe N, Kaklewski K, Mohar A, Tamura C, Heale E, Rooyadeh M, van Asperen C, Gemma Llort, Alan Mackay, Denroche R, Seelaus C, Zbuk K, McCluggage W, van der Luijt R, Maaike P.G. Vreeswijk, Edelweiss M, Crossan G, Arseneau J, Ambus I, Verheul H, Rodrigo Augusto Depieri Michelli, Juul T. Wijnen, Gross-Lester J, Britta Weigelt, Pedro Pérez-Segura, Richard A. Moore, Cornelissen C, Larouche G, McAlpine J, Daniel Nava Rodrigues, Trim L, Furnival J, Elser C, Muszyńka M, Adriana Lasa, Tuya Pal, Greuter. M, Ng K, Dorval M, Bresee C, Reimnitz G, Gaëtan MacGrogan, Perry Maxwell, Barnadas A, Hwang E, Powell B, Knapke S, Griskevicius. L, Alvarez R, Mester J, Anne-Bine Skytte, Eladio Velasco, Vidal S, Australie K, Leunen K, Ben-Yishay M, Van Houdt J, Phuah S, Amy E Taylor, Pinto R, Fonseca T, Champine M, Gammon A, Hollema H, Menko F, Feng B, David Olmos, Chong G, Tomasz Byrski, Patrick J. Morrison, Gregoire J, André Lopes Carvalho, Don B. Plewes, Rabeneck L, Carrol J, Alan Ashworth, Terlinge A, A Jakubowska, Odette Mariani, Setareh Moghadasi, Reitsma W, Rothenmund H, Herrera L, Anna Tenés, Angel Izquierdo, Asunción Torres, Stawicka M, Goh C, Hirst M, Drummond J, Osorio A, Ostrovsky R, Jeffrey N. Weitzel, Gareth W. Irwin, Fehniger J, Sugano K, Spriggs E, Dęniak T, Volenik A, Thorne H, Piccinin C, Amie Blanco, Jinno H, Robert A. Holt, Stephen B. Fox, Julia J. Gorski, Gilpin C, Herschorn S, Vega A, E. Page, Hamet P, McKenna D, Fabrice Bonnet, Yoshida T, Kienan I. Savage, Petzel S, Elizabeth Bancroft, Schneider S, Warwick L, Stewart S, William D. Foulkes, Colizza K, Bell K, Demsky R, Malgorzata Tymrakiewicz, Caldés T, Fons G, Bowen D, Côté S, Clouston D, Kitagawa Y, Gordon Glendon, Jenny Lester, Kinney A, Nelson E, Silke Hollants, Macrae L, Cajal T, Andrew J. Mungall, Ferrell B, Creighton B, Bressler L, Uy P, Makishima K, Haffaf Z, Ramūnas Janavičius, Einstein G, Zakalik D, Chiarelli A, Cantu D, Croce S, Kalloger S, Lin F, Ian O. Ellis, Benedito Mauro Rossi, R A Wilkinson, Mulligan J, Murphy J, Vadaparampil S, Smith E, Slangen B, Loiselle C, Iqbal J, Palma L, Cooper K, Jorge S. Reis-Filho, Chen. L, Quinten Waisfisz, Haneda E, Banks P, Vermeulen K, Visser B, Montalbán G, McCabe N, Honeyford J, Naseri S, Ng J, Ali A, Sandrine Viala, Mensa I, Kamarainen O, Guerra C, Mazzola E, David A. Schwartz, Marjanka K. Schmidt, Simon R, Fergus J. Couch, Margreet G. E. M. Ausems, Anne Vincent-Salomon, Olinski R, Zewald R, Moreno R, Semple J, McPherson J, Lamers E, Kharbanda A, Kessler L, Biemans D, Au A, Bordeleau L, Jean Feunteun, Mar Infante, Mullan P, Rudaitis, Molenda A, Rachael Natrajan, Pawar, Boman B, Kok T, Andrew A. Brown, Geller M, Monfared N, Bart J, Murata P, Crawford N, Butterfield Y, Bargalló J, Katherine L. Tucker, Cook-Wiens G, Rhodes A, Elodie Manié, Rubio E, Oram L, Shandiz F, Hayden R, Crawford B, Parmigiani G, Harkin P, Müller C, Grant M, Maryou B. Lambros, Thong M, Grzegorz Sukiennicki, Wouts J, Haddock P, Ramon y Cajal T, Kenneth C. Anderson, Michel Longy, Batiste W, Carroll J, Matte C, Hojyo T, Zhao Y, Caroline Seynaeve, Wai P, Simard J, Hurley K, Bolton D, Karlan B, Javier Benítez, Miriam Masas, Tołczko-Grabarek A, de Dueñas E, Geneviève Michils, Moncoutier, Nancy Uhrhammer, MacDonald D, Keyserlingk J, Osher D, Gilks C, Christopher T. Elliott, Scharf L, Gabram-Mendola S, Grondin K, Dohany L, van Diest P, Joris Vermeesch, Jan C. Oosterwijk, M’Baïlara K, DePuit M, Jacek Gronwald, Stefania Tommasi, de la Hoya M, Bouchard K, Black L, Lui M, Soucy P, Rosalind A. Eeles, Gert Matthijs, Graham T, Andrea Eisen, Bacha O, Alvaro N.A. Monteiro, Yoon S, Caron T, Smith D, Marc-Henri Stern, Hampson E, Kurz R, Gaasbeek W, Mundt E, Angela Velasco, Quinn J, Jocelyne Chiquette, Marquez T, Adam B. Murphy, Bakker J, Neus Gadea, Anita Grigoriadis, Aoki D, Dean S, Looi L, Paradiso A, Agostina Stradella, K. Govindasami, Lovell N, Eva Tomiak, Siesling S, Belanger M, Feilotter H, Knight J, Emmanuel Barillot, Huang M, Raquel Andrés, Kang P, Somerman C, Gackowski D, Rimel B, Nakamura S, McClellan K, Barrros E, Henriette Roed Nielsen, Rui Manuel Reis, Greening S, Ayme A, Carmen Guillen, de Vries E, and Katarzyna Jaworska

Subjects
Oncology, Education and Communication, medicine.medical_specialty, endocrine system diseases, medicine.diagnostic_test, business.industry, Psycho-Oncology, medicine.disease, Meeting Abstracts, Transcriptome, Basic Research, Clinical Management, Germline mutation, Breast cancer, Applied Research, Internal medicine, Mutation (genetic algorithm), medicine, Genetic Counselling, Human genome, skin and connective tissue diseases, business, Ovarian cancer, Comparative genomic hybridization, Fluorescence in situ hybridization
Abstract

Background: Germline mutation screening of BRCA1 and BRCA2 genes is performed in suspected familial breast cancer cases, but a causative mutation is found in only 30% of patients. The development of additional methods to identify good candidates for BRCA1 and BRCA2 analysis would therefore increase the efficacy of diagnostic mutation screening. With this in mind, we developed a study to determine molecular signatures of BRCA1—or BRCA2—mutated breast cancers. Materials and Methods: Array-cgh (comparative genomic hybridization) and transcriptomic analysis were performed on a series of 103 familial breast cancers. The series included 7 breast cancers with a BRCA1 mutation and 5 breast cancers with a BRCA2 mutation. The remaining 91 cases were obtained from 73 families selected on the basis of at least 3 affected first-degree relatives or at least 2 affected first-degree relatives with breast cancer at an average age of 45 years. Array-cgh analyses were performed on a 4407 BAC-array (CIT-V8) manufactured by IntegraGen. Transcriptomic analyses were performed using an Affymetrix Human Genome U133 Plus 2.0 chip. Results: Using supervised clustering analyses we identified two transcriptomic signatures: one for BRCA1-mutated breast cancers consisting of 600 probe sets and another for BRCA2-mutated breast cancers also consisting of 600 probes sets. We also defined cgh-array signatures, based on the presence of specific genomic rearrangements, one for BRCA1-mutated breast cancers and one for BRCA2-mutated breast cancers. Conclusions: This study identified molecular signatures of breast cancers with BRCA1 or BRCA2 germline mutations. Genes present in these signatures could be exploited to find new markers for such breast cancers. We also identified specific genomic rearrangements in these breast cancers, which could be screened for in a diagnostic setting using fluorescence in situ hybridization, thus improving patient selection for BRCA1 and BRCA2 molecular genetic analysis.

Published
2009

38. Population Pharmacokinetics and Pharmacodynamics of Paclitaxel and Carboplatin in Ovarian Cancer Patients: A Study by the European Organization for Research and Treatment of Cancer-Pharmacology and Molecular Mechanisms Group and New Drug Development Group

Author

Joerger, M., Huitema, A. D. R., Richel, D. J., Dittrich, C., Pavlidis, Nicholas, Briassoulis, E. Ch, Vermorken, J. B., Strocchi, E., Martoni, A., Sorio, R., Sleeboom, H. P., Izquierdo, M. A., Jodrell, D. I., Calvert, H., Boddy, A. V., Hollema, H., Féty, R., Vijgh, W. J. F. Van Der, Hempel, G., Chatelut, E., Karlsson, M., Wilkins, J., Tranchand, B., Schrijvers, A. H. G. J., Twelves, C., Beijnen, J. H., Schellens, J. H. M., Faculteit Medische Wetenschappen/UMCG, Targeted Gynaecologic Oncology (TARGON), CCA -Cancer Center Amsterdam, Oncology, and Pavlidis, Nicholas [0000-0002-2195-9961]

Subjects
Neutrophil count, Cancer Research, Peripheral neuropathy, medicine.medical_treatment, GYNECOLOGIC-ONCOLOGY-GROUP, Pharmacology, Gastroenterology, Ovarian neoplasms, Dexamethasone, Carboplatin, Multiple cycle treatment, chemistry.chemical_compound, Deep vein thrombosis, Antineoplastic agents, Antineoplastic Combined Chemotherapy Protocols, Priority journal, Ovarian Neoplasms, education.field_of_study, Predictive marker, Nausea, Blood toxicity, COMBINATION PACLITAXEL, CHEMOTHERAPY, Ondansetron, Europe, Treatment Outcome, Oncology, Paclitaxel, Area Under Curve, Drug dose reduction, Disease Progression, Paclitaxel/*pharmacokinetics/*pharmacology, Carboplatin/*pharmacokinetics/*pharmacology, Female, Human, Adult, Diarrhea, medicine.medical_specialty, Neutropenia, CARCINOMA, Ovary cancer, Vomiting, Metoclopramide, Population, Drug response, Antineoplastic Agents, Major clinical study, Side effect, Article, Granisetron, Ileus, Predictive Value of Tests, Antineoplastic combined chemotherapy protocols, Internal medicine, Thrombocyte count, 3-HOUR INFUSION, medicine, Humans, BREAST-CANCER, Clemastine, education, Aged, Chemotherapy, Ovarian Neoplasms/*drug therapy/*genetics/*pathology, business.industry, Antineoplastic Agents/therapeutic use, medicine.disease, Thrombocytopenia, PHASE-III, RANDOMIZED-TRIAL, Cancer combination chemotherapy, MODEL, Kinetics, Pharmacodynamics, chemistry, TIME-COURSE, Drug Design, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Aminotransferase blood level, business, Ovarian cancer
Abstract

Purpose: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 μmol/L (tC > 0.05−0.2) predicts neutropenia. The objective of this study was to build a population pharmacokinetic-pharmacodynamic model of paclitaxel/carboplatin in ovarian cancer patients. Experimental Design: One hundred thirty-nine ovarian cancer patients received paclitaxel (175 mg/m2) over 3 h followed by carboplatin area under the concentration-time curve 5 mg/mL*min over 30 min. Plasma concentration-time data were measured, and data were processed using nonlinear mixed-effect modeling. Semiphysiologic models with linear or sigmoidal maximum response and threshold models were adapted to the data. Results: One hundred five patients had complete pharmacokinetic and toxicity data. In 34 patients with measurable disease, objective response rate was 76%. Neutrophil and thrombocyte counts were adequately described by an inhibitory linear response model. Paclitaxel tC > 0.05 was significantly higher in patients with a complete (91.8 h) or partial (76.3 h) response compared with patients with progressive disease (31.5 h; P = 0.02 and 0.05, respectively). Patients with paclitaxel tC > 0.05 > 61.4 h (mean value) had a longer time to disease progression compared with patients with paclitaxel tC > 0.05 < 61.4 h (89.0 versus 61.9 weeks; P = 0.05). Paclitaxel tC > 0.05 was a good predictor for severe neutropenia (P = 0.01), whereas carboplatin exposure (Cmax and area under the concentration-time curve) was the best predictor for thrombocytopenia (P < 10−4). Conclusions: In this group of patients, paclitaxel tC > 0.05 is a good predictive marker for severe neutropenia and clinical outcome, whereas carboplatin exposure is a good predictive marker for thrombocytopenia.

Published
2007

39. Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy

Author

Wouters, M. C. A., Komdeur, F. L., Workel, H. H., Brunekreeft, K. L., Plat, A., Klip, H. G., Eggink, F. A., Wisman, G. B. A., Arts, H. J. G., Oonk, M. H. M., Mourits, M. J. E., Yigit, R., Versluis, M., Duiker, E. W., Edwin Bremer, Helfrich, W., Hollema, H., Nijman, H. W., Bruyn, M., Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Translational Immunology Groningen (TRIGR)

Published
2015

41. A role of MLH3 in hereditary nonpolyposis colorectal cancer

Author

Hofstra, R.M.W., Wu, Y., Berends, M.J.W., Sijmons, R.H., Mensink, R.G.J., Verlind, E., Kooi, K.A., van der Sluis, T., Kempinga, C., van der Zee, A.G.J., Hollema, H., Kleibeuker, J.H., and Buys, C.H.C.M.

Subjects
Human genetics -- Research, Genetic disorders -- Research, Colorectal cancer -- Genetic aspects, Biological sciences
Published
2001

42. Germline hMLH3 mutations in patients with suspected HNPCC

Author

Wu, Y., Berends, M.J.W, Mensink, R.G.J, Verlind, E., Sijmons, R.H., van der Zee, A.G.J., Hollema, H., Kleibeuker, J.H., Buys, C.H.C.M., and Hofstra, R.M.W.

Subjects
Genetic research -- Analysis, Colorectal cancer -- Research, Gene mutations -- Research, Biological sciences
Published
2000

43. Predictors of colorectal neoplasia after polypectomy: based on initial and consecutive findings

Author

van Enckevort, C. C. G., de Graaf, A. P. J., Hollema, H., Sluiter, W. J., Kleibeuker, J. H., Koornstra, J. J., Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)

Subjects
Adenoma, endocrine system diseases, SOCIETY TASK-FORCE, BOWEL PREPARATION, SCREENING COLONOSCOPY, polypectomy, colorectal neoplasms, CANCER, PREVENTION, digestive system diseases, SURVEILLANCE COLONOSCOPY, stomatognathic diseases, colonoscopy, ADENOMA CHARACTERISTICS, surveillance, RISK-FACTORS, FOLLOW-UP, RECURRENCE
Abstract

Background: Colorectal adenoma patients are kept under surveillance because of the risk of developing metachronous neoplasia. The aim is to determine predictors of neoplasia development after polypectomy. Methods: It is an observational cohort study. 433 Patients who had >= 1 adenoma removed between 1988 and 2004 were included, with follow-up until 2010. Multivariate analysis of patient and adenoma characteristics was performed at initial colonoscopy and at consecutive positive examinations. The main outcome measured was the development of metachronous (advanced) adenomas during follow-up. Results: Median follow-up was 85 months. Multivariate analysis identified male sex, >= 3 adenomas, high-grade dysplasia and age >= 55 years as risk factors for metachronous lesions at first surveillance. Analysis using life expectancy as a timescale showed >= 3 adenomas to be the only predictive factor. The time to second or third metachronous adenoma did not depend on the number of adenomas. Patients with >= 3 adenomas were five years older at the time of their first polypectomy compared with those with fewer adenomas, but of the same age at the first recurrence. Prevalence of high-grade dysplasia was associated with age and high-grade dysplasia in the prior adenoma independent of time interval. Conclusions: Adenoma development after polypectomy occurs in a regular and repetitive way. Our data suggest that only the interval between the initial colonoscopy and the first follow-up colonoscopy should be based on initial findings, i.e. number of adenomas, and that subsequent colonoscopies can be planned at predetermined intervals.

Published
2014

45. Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters

Author

Versluis, MA, de Jong, RA, Plat, A, Bosse, T, Smit, VT, Mackay, H, Powell, M, Leary, A, Mileshkin, L, Kitchener, HC, Crosbie, EJ, Edmondson, RJ, Creutzberg, CL, Hollema, H, Daemen, T, de Bock, GH, Nijman, HW, Versluis, MA, de Jong, RA, Plat, A, Bosse, T, Smit, VT, Mackay, H, Powell, M, Leary, A, Mileshkin, L, Kitchener, HC, Crosbie, EJ, Edmondson, RJ, Creutzberg, CL, Hollema, H, Daemen, T, de Bock, GH, and Nijman, HW

Abstract

BACKGROUND: Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort. METHODS: We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype. RESULTS: Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71 vs 0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort. CONCLUSIONS: In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful.

Published
2015

46. Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters

Author

Versluis, M A, primary, de Jong, R A, additional, Plat, A, additional, Bosse, T, additional, Smit, V T, additional, Mackay, H, additional, Powell, M, additional, Leary, A, additional, Mileshkin, L, additional, Kitchener, H C, additional, Crosbie, E J, additional, Edmondson, R J, additional, Creutzberg, C L, additional, Hollema, H, additional, Daemen, T, additional, de Bock, G H, additional, and Nijman, H W, additional

Published
2015
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47. Detecting cervical cancer by quantitative promoter hypermethylation assay on cervical scrapings: A feasibility study

Author

Reesink-Peters, N., Wisman, G. B. A., Jéronimo, C., Tokumaru, C. Y., Cohen, Y., Dong, S. M., Klip, H. G., Buikema, H. J., Albert Suurmeijer, Hollema, H., Boezen, H. M., Sidransky, D., Zee, A. G. J., Targeted Gynaecologic Oncology (TARGON), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Life Course Epidemiology (LCE), and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
SMEAR, AGE, CARCINOMA, TISSUE, MULTIPLE GENES, TUMOR-SUPPRESSOR, NEOPLASIA, DNA METHYLATION, DISEASE, SERUM
Abstract

Current morphology-based cervical cancer screening is associated with significant false-positive and false-negative results. Tumor suppressor gene hypermethylation is frequently present in cervical cancer. It is unknown whether a cervical scraping reflects the methylation status of the underlying epithelium, and it is therefore unclear whether quantitative hypermethylation specific PCR (QMSP) on cervical scrapings could be used as a future screening method augmenting the current approach. Cervical scrapings and paired fresh frozen cervical tissue samples were obtained from 53 cervical cancer patients and 45 controls. All scrapings were morphologically scored and analyzed with QMSP for the genes APC, DAPK, MGMT, and GSTP1. To adjust for DNA input, hypermethylation ratios were calculated against DNA levels of a reference gene. Hypermethylation ratios of paired fresh frozen tissue samples and scrapings of cervical cancer patients and controls were strongly related (Spearman correlation coefficient, 0.80 for APC, 0.98 for DAPK, and 0.83 for MGMT; P

Published
2004

48. Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus

Author

Heeren, PAM, Kloppenberg, FWH, Hollema, H, Mulder, NH, Nap, RE, Plukker, JTM, Faculteit Medische Wetenschappen/UMCG, Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
esophageal carcinoma, NEOADJUVANT CHEMOTHERAPY, apoptotic markers, PROTEIN EXPRESSION, SURGERY, chemotherapy response, PROGNOSTIC-SIGNIFICANCE, PHASE-II, PREOPERATIVE CHEMORADIATION, ADVANCED CANCER, THERAPY, SQUAMOUS-CELL CARCINOMAS, CHEMORADIOTHERAPY
Abstract

Background: Cell cycle regulating proteins (p53/p21) and proliferation index Ki-67 have been associated with prognosis and response to chemotherapy. The aim of this study was to determine the significance of these molecular markers on tumor response and prognostic effect in a group of esophageal cancer patients treated with neoadjuvant chemotherapy. Patients and Methods: Immunohistochemical expression of p53/p21 and Ki-67 was examined in pretreatment biopsy specimen of 30 patients, in phase II neoadjuvant studies for locally advanced adenocarcinoma of the esophagus, who underwent surgery. Seven patients (23%) had progressive disease. Resection was achieved in all responders (n=23; 77%) and histochemical expression of the above-mentioned proliferating markers was examined in pre-treatment and resection specimens after chemotherapy. Results: Responders had a significantly better survival compared to non-responders (p=0.001). Expression of p53, p21 and high Ki-67 in pre-treatment specimens was 73% (22/30), 63% (19/30) and 30% (10/30), respectively and was not related to response to chemotherapy. However, alteration in expression of p53-positivity in the pre-treatment specimens to p53-negativity in the resection specimens and p21-negativity to p21-positivity in 6 of the 23 (26%) resected tumors was correlated with better response and survival (p=0.011). Conclusion: Data from this study showed that alteration of p53 and p21 expression rather than the initial expression seems to be related to chemotherapy response and overall survival in patients with esophageal adenocarcinoma.

Published
2004

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