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1. Association of persistent morbidity after radiotherapy with quality of life in locally advanced cervical cancer survivors

Author

Spampinato, Sofia, Tanderup, Kari, Lindegaard, Jacob C., Schmid, Maximilian P., Sturdza, Alina, Segedin, Barbara, Jürgenliemk-Schulz, Ina M., De Leeuw, Astrid, Bruheim, Kjersti, Mahantshetty, Umesh, Chargari, Cyrus, Rai, Bhavana, Cooper, Rachel, van der Steen-Banasik, Elzbieta, Sundset, Marit, Wiebe, Ericka, Villafranca, Elena, Van Limbergen, Erik, Pieters, Bradley R., Tee Tan, Li, Lutgens, Ludy C.H.W., Hoskin, Peter, Smet, Stéphanie, Pötter, Richard, Nout, Remi, Chopra, Supriya, and Kirchheiner, Kathrin

Published
2023
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2. Risk Factors for Late Persistent Fatigue After Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: An Analysis From the EMBRACE-I Study

Author

Smet, Stéphanie, Spampinato, Sofia, Pötter, Richard, Jürgenliemk-Schulz, Ina M., Nout, Remi A., Chargari, Cyrus, Mahantshetty, Umesh, Sturdza, Alina, Segedin, Barbara, Bruheim, Kjersti, Hoskin, Peter, Rai, Bhavana, Huang, Fleur, Cooper, Rachel, Van der Steen-Banasik, Elzbieta, Sundset, Marit, Van Limbergen, Erik, Tan, Li Tee, Lutgens, Ludy C.H.W., Villafranca, Elena, Pieters, Bradley R., Tanderup, Kari, and Kirchheiner, Kathrin

Published
2022
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3. Severity and Persistency of Late Gastrointestinal Morbidity in Locally Advanced Cervical Cancer: Lessons Learned From EMBRACE-I and Implications for the Future

Author

Spampinato, Sofia, Jensen, Nina B.K., Pötter, Richard, Fokdal, Lars U., Chargari, Cyrus, Lindegaard, Jacob C., Schmid, Maximilian P., Sturdza, Alina, Jürgenliemk-Schulz, Ina M., Mahantshetty, Umesh, Hoskin, Peter, Segedin, Barbara, Rai, Bhavana, Bruheim, Kjersti, Wiebe, Ericka, Van der Steen-Banasik, Elzbieta, Cooper, Rachel, Van Limbergen, Erik, Sundset, Marit, Pieters, Bradley R., Lutgens, Ludy C.H.W., Tan, Li Tee, Villafranca, Elena, Smet, Stéphanie, Jastaniyah, Noha, Nout, Remi A., Kirisits, Christian, Chopra, Supriya, Kirchheiner, Kathrin, Tanderup, Kari, and EMBRACE Collaborative Group

Published
2022
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4. Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy

Author

Wortman, Bastiaan G., Post, Cathalijne C.B., Powell, Melanie E., Khaw, Pearly, Fyles, Anthony, D'Amico, Romerai, Haie-Meder, Christine, Jürgenliemk-Schulz, Ina M., McCormack, Mary, Do, Viet, Katsaros, Dionyssios, Bessette, Paul, Baron, Marie Hélène, Nout, Remi A., Whitmarsh, Karen, Mileshkin, Linda, Lutgens, Ludy C.H.W., Kitchener, Henry C., Brooks, Susan, Nijman, Hans W., Astreinidou, Eleftheria, Putter, Hein, Creutzberg, Carien L., and de Boer, Stephanie M.

Published
2022
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5. Patients' and clinicians' preferences in adjuvant treatment for high-risk endometrial cancer: Implications for shared decision making

Author

Post, Cathalijne C.B., Mens, Jan Willem M., Haverkort, Marie A.D., Koppe, Friederike, Jürgenliemk-Schulz, Ina M., Snyers, An, Roeloffzen, Ellen M.A., Schaake, Eva E., Slot, Annerie, Stam, Tanja C., Beukema, Jannet C., van den Berg, Hetty A., Lutgens, Ludy C.H.W., Nijman, Hans W., de Kroon, Cornelis D., Kroep, Judith R., Stiggelbout, Anne M., and Creutzberg, Carien L.

Published
2021
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6. MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study

Author

Chargari, Cyrus, Dumas, Isabelle, Lowe, Gerry, Swamidas, Jamema, Hudej, Robert, Paulsen Hellebust, Taran, Menon, Geetha, Oinam, Arun S., Bownes, Peter, Christiaens, Melissa, De Brabandere, Marisol, Janssen, Hilde, Oosterveld, Bernard, Koedooder, Kees, Langeland Marthinsen, Anne Beate, Sundset, Marit, Whitney, Diane, Ketelaars, Martijn, Lutgens, Ludy C.H.W., Reinniers, Brigitte, Mora, Itxa, Villafranca, Elena, Antal, Gergely, Hadjiev, Janaki, Bachand, Francois, Batchelar, Deidre, Erickson, Beth, Rownd, Jason, Jacobson, Geraldine, Kim, Yusung, Anttila, Maarit, Palmgren, Jan-Erik, An, Jusheng, Assenholt, Marianne Sanggaard, Banerjee, Susovan, Bentzen, Sören, Berger, Thomas, Dankulchai, Pittaya, Diendorfer, Tamara, Dilworth, Ian, Dimopoulos, Johannes, Dörr, Elke, Ecker, Stefan, Federico, Mario, Fidarova, Elena, Fortin, Israel, Georg, Petra, Gora, Joanna, Hegazy, Neamat, Jastaniyah, Noha, Jensen, Nina Boje Kibsgaard, Liederer, Thomas, Majercakova, Katarina, Misimovic, Dragan, Motisi, Laura, Najjari Jamal, Dina, Nkiwane, Karen, Schwartz-Vittrup, Anders, Serban, Monica, Smet, Stephanie, Spampinato, Sofia, Trnkova, Petra, Valgma, Margit, Westerveld, Henrike, Wong, Joyce Siu Yu, Yoshida, Kenji, Pötter, Richard, Tanderup, Kari, Schmid, Maximilian Paul, Jürgenliemk-Schulz, Ina, Haie-Meder, Christine, Fokdal, Lars Ulrik, Sturdza, Alina Emiliana, Hoskin, Peter, Mahantshetty, Umesh, Segedin, Barbara, Bruheim, Kjersti, Huang, Fleur, Rai, Bhavana, Cooper, Rachel, van der Steen-Banasik, Elzbieta, Van Limbergen, Erik, Pieters, Bradley Rumwell, Tan, Li-Tee, Nout, Remi Abubakar, De Leeuw, Astrid Agatha Catharina, Ristl, Robin, Petric, Primoz, Nesvacil, Nicole, Kirchheiner, Kathrin, Kirisits, Christian, and Lindegaard, Jacob Christian

Published
2021
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7. Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial

Author

Post, Cathalijne C.B., de Boer, Stephanie M., Powell, Melanie E., Mileshkin, Linda, Katsaros, Dionyssios, Bessette, Paul, Haie-Meder, Christine, Ottevanger, Nelleke (P.) B., Ledermann, Jonathan A., Khaw, Pearly, D'Amico, Romerai, Fyles, Anthony, Baron, Marie Hélène, Kitchener, Henry C., Nijman, Hans W., Lutgens, Ludy C.H.W., Brooks, Susan, Jürgenliemk-Schulz, Ina M., Feeney, Amanda, Goss, Geraldine, Fossati, Roldano, Ghatage, Prafull, Leary, Alexandra, Do, Viet, Lissoni, Andrea A., McCormack, Mary, Nout, Remi A., Verhoeven-Adema, Karen W., Smit, Vincent T.H.B.M., Putter, Hein, and Creutzberg, Carien L.

Published
2021
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8. Persistence of Late Substantial Patient-Reported Symptoms (LAPERS) After Radiochemotherapy Including Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: A Report From the EMBRACE Study

Author

Vittrup, Anders S., Tanderup, Kari, Bentzen, Søren M., Jensen, Nina B.K., Spampinato, Sofia, Fokdal, Lars U., Lindegaard, Jacob C., Sturdza, Alina, Schmid, Maximilian, Segedin, Barbara, Jürgenliemk-Schulz, Ina M., Bruheim, Kjersti, Mahantshetty, Umesh, Haie-Meder, Christine, Rai, Bhavana, Cooper, Rachel, van der Steen-Banasik, Elzbieta, Sundset, Marit, Huang, Fleur, Nout, Remi A., Villafranca, Elena, Van Limbergen, Erik, Pieters, Bradley R., Tan, Li Tee, Lutgens, Ludy C.H.W., Hoskin, Peter, Pötter, Richard, and Kirchheiner, Kathrin

Published
2021
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9. 919: Randomised trial of nurse-led sexual rehabilitation after radiotherapy for gynaecological cancers

Author

Suvaal, Isabelle, Hummel, Lisanne B., Mens, Jan-Willem M., Tuijnman-Raasveld, Charlotte C., Tsonaka, Roula, Velema, Laura A., Westerveld, Henrike, Cnossen, Jeltsje, Snyers, An, Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Beukema, Jannet C., Haverkort, Dorien, Nowee, Marlies E., de Kroon, Cor D., van den Hout, Wilbert B., Creutzberg, Carien L., van Doorn, Lena E., and Kuile, Moniek M. ter

Published
2024
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11. Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

Author

Lindegaard, Jacob, Tanderup, Kari, Fokdal, Lars, Van Der Steen Banasik, Elzbieta, Haie-Meder, Christine, Dumas, Isabelle, Chargari, Cyrus, Nout, Remi A., Van Limbergen, Erik, Petrič, Primož, Segedin, Barbara, Hudej, Robert, Erickson, Beth, Hoskin, Peter, Lowe, Gerry, Mahantshetty, Umesh, Swamidas, Jamema, Shrivastava, Shyam Kishore, Jürgenliemk-Schulz, Ina M., De Leeuw, Astrid, Kirchheiner, Kathrin, Dörr, Wolfgang, Pötter, Richard, Lutgens, Ludy C.H.W., Hadjiev, Janaki, Cooper, Rachel, Bownes, Peter, Sundset, Marit, Bruheim, Kjersti, Hellebust, Taran Paulsen, Huang, Fleur, Menon, Geetha, Villafranca, Elena, Rai, Bhavana, Oinam, Arun S., Tan, Li Tee, Bachand, Francois, Jacobson, Geraldine, Anttila, Maarit, Pieters, Bradley, and Lindegaard, Jacob C.

Published
2016
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12. Interpretable deep learning model to predict the molecular classification of endometrial cancer from haematoxylin and eosin-stained whole-slide images: a combined analysis of the PORTEC randomised trials and clinical cohorts

Author

Fremond, Sarah, Andani, Sonali, Wolf, Jurriaan Barkey, Dijkstra, Jouke, Melsbach, Sinéad, Jobsen, Jan J., Brinkhuis, Mariel, Roothaan, Suzan, Jurgenliemk-Schulz, Ina, Lutgens, Ludy C.H.W., Nout, Remi A ., van der Steen-Banasik, Elzbieta M., de Boer, Stephanie M., Singh, Naveena, Mileshkin, Linda R., Mackay, Helen J., Leary, Alexandra, Nijman, Hans W., Smit, Vincent T.H.B.M, Creutzberg, Carien L., Horeweg, Nanda, Koelzer, Viktor H., and Bosse, Tjalling

Abstract

Background Endometrial cancer can be molecularly classified into POLEmut, mismatch repair deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP) subgroups. We aimed to develop an interpretable deep learning pipeline for whole-slide-image-based prediction of the four molecular classes in endometrial cancer (im4MEC), to identify morpho-molecular correlates, and to refine prognostication. Methods This combined analysis included diagnostic haematoxylin and eosin-stained slides and molecular and clinicopathological data from 2028 patients with intermediate-to-high-risk endometrial cancer from the PORTEC-1 (n=466), PORTEC-2 (n=375), and PORTEC-3 (n=393) randomised trials and the TransPORTEC pilot study (n=110), the Medisch Spectrum Twente cohort (n=242), a case series of patients with POLEmut endometrial cancer in the Leiden Endometrial Cancer Repository (n=47), and The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma cohort (n=395). PORTEC-3 was held out as an independent test set and a four-fold cross validation was performed. Performance was measured with the macro and class-wise area under the receiver operating characteristic curve (AUROC). Whole-slide images were segmented into tiles of 360 μm resized to 224 × 224 pixels. im4MEC was trained to learn tile-level morphological features with self-supervised learning and to molecularly classify whole-slide images with an attention mechanism. The top 20 tiles with the highest attention scores were reviewed to identify morpho-molecular correlates. Predictions of a nuclear classification deep learning model serve to derive interpretable morphological features. We analysed 5-year recurrence-free survival and explored prognostic refinement by molecular class using the Kaplan-Meier method. Findings im4MEC attained macro-average AUROCs of 0·874 (95% CI 0·856–0·893) on four-fold cross-validation and 0·876 on the independent test set. The class-wise AUROCs were 0·849 for POLEmut (n=51), 0·844 for MMRd (n=134), 0·883 for NSMP (n=120), and 0·928 for p53abn (n=88). POLEmut and MMRd tiles had a high density of lymphocytes, p53abn tiles had strong nuclear atypia, and the morphology of POLEmut and MMRd endometrial cancer overlapped. im4MEC highlighted a low tumour-to-stroma ratio as a potentially novel characteristic feature of the NSMP class. 5-year recurrence-free survival was significantly different between im4MEC predicted molecular classes in PORTEC-3 (log-rank p, The Lancet Digital Health, 5 (2), ISSN:2589-7500

Published
2023

13. Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial

Author

de Boer, Stephanie M., Nout, Remi A., Jürgenliemk-Schulz, Ina M., Jobsen, Jan J., Lutgens, Ludy C.H.W., van der Steen-Banasik, Elzbieta M., Mens, Jan Willem M., Slot, Annerie, Stenfert Kroese, Marika C., Oerlemans, Simone, Putter, Hein, Verhoeven-Adema, Karen W., Nijman, Hans W., and Creutzberg, Carien L.

Published
2015
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14. Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer.

Author

Horeweg, Nanda, Nout, Remi A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Jobsen, Jan J., Haverkort, Marie A.D., Mens, Jan Willem M., Slot, Annerie, Wortman, Bastiaan G., de Boer, Stephanie M., Stelloo, Ellen, Verhoeven-Adema, Karen W., Putter, Hein, Smit, Vincent T.H.B.M., Bosse, Tjalling, Creutzberg, Carien L., Creutzberg, C.L., Koper, P.C.M., van Putten, W.L.J., and Dercksen, R.

Published
2023
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17. Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data

Author

Nout, Remi A., Putter, Hein, Jürgenliemk-Schulz, Ina M., Jobsen, Jan J., Lutgens, Ludy C.H.W., van der Steen-Banasik, Elzbieta M., Mens, Jan Willem M., Slot, Annerie, Stenfert Kroese, Marika C., Nijman, Hans W., van de Poll-Franse, Lonneke V., and Creutzberg, Carien L.

Published
2012
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23. Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration

Author

Lutgens, Ludy C.H.W., Blijlevens, Nicole M.A., Deutz, Nicolaas E.P., Donnelly, J. Peter, Lambin, Philippe, and de Pauw, Ben E.

Subjects
Citrulline -- Research, Citrulline -- Analysis, Permeability -- Research, Permeability -- Analysis, Intestinal mucosa -- Complications and side effects, Intestinal mucosa -- Research, Intestinal mucosa -- Care and treatment, Intestinal mucosa -- Analysis, Small intestine cancer -- Research, Small intestine cancer -- Care and treatment, Small intestine cancer -- Diagnosis, Small intestine cancer -- Analysis, Health
Published
2005

26. 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, Stephanie M., Powell, Melanie E., Mileshkin, Linda, Katsaros, Dionyssios, Bessette, Paul, Haie-Meder, Christine, Ottevanger, Petronella B., Ledermann, Jonathan A., Khaw, Pearly, Colombo, Alessandro, Fyles, Anthony, Baron, Marie Helene, Jürgenliemk-Schulz, Ina M., Kitchener, Henry C., Nijman, Hans W., Wilson, Godfrey, Brooks, Susan, Carinelli, Silvestro, Provencher, Diane, Hanzen, Chantal, Lutgens, Ludy C.H.W., Smit, Vincent T.H.B.M., Singh, Naveena, Do, Viet, D'Amico, Romerai, Nout, Remi A., Feeney, Amanda, Verhoeven-Adema, Karen W., Putter, Hein, Creutzberg, Carien L., McCormack, Mary, Whitmarsh, Karen, Allerton, Rozenn, Gregory, Deborah, Symonds, Paul, Hoskin, Peter J., Adusumalli, Madhavi, Anand, Anjana, Wade, Robert, Stewart, Alexandra, Taylor, Wendy, Kruitwagen, Roy F.P.M., Hollema, Harry, Pras, Elizabeth, Snyers, An, Stalpers, Lukas, Jobsen, Jan J., Slot, Annerie, Mens, Jan Willem M., and Stam, Tanja C.

Subjects
Canada, Time Factors, Endometrial Neoplasms/mortality, Clinical Trial, Phase III, Risk Factors, Paclitaxel/administration & dosage, Journal Article, Humans, Comparative Study, Aged, Neoplasm Staging, Gynecologic Surgical Procedures/adverse effects, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Research Support, Non-U.S. Gov't, Australia, Carboplatin/administration & dosage, Chemoradiotherapy, Adjuvant/adverse effects, Middle Aged, Europe, Multicenter Study, Treatment Outcome, Oncology, Randomized Controlled Trial, Carcinoma, Endometrioid/mortality, Lymph Node Excision, Female, Radiotherapy, Adjuvant, Dose Fractionation, Radiation, Neoplasm Grading, Cisplatin/administration & dosage, 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/m 2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m 2) 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

29. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer – A pooled analysis of PORTEC 1 and 2 trials.

Author

Bosse, Tjalling, Peters, Elke E.M., Creutzberg, Carien L., Jürgenliemk-Schulz, Ina M., Jobsen, Jan J., Mens, Jan Willem M., Lutgens, Ludy C.H.W., van der Steen-Banasik, Elzbieta M., Smit, Vincent T.H.B.M., and Nout, Remi A.

Subjects
*DISEASE relapse, *TREATMENT effectiveness, *CONFIDENCE intervals, *RESEARCH methodology, *MULTIVARIATE analysis, *RADIOISOTOPE brachytherapy, *SURVIVAL, *ENDOMETRIAL tumors, *PROPORTIONAL hazards models, *RETROSPECTIVE studies, *DESCRIPTIVE statistics, *PROGNOSIS
Abstract

Background Lymph-vascular space invasion (LVSI) is an important adverse prognostic factor in endometrial cancer (EC). However, its role in relation to type of recurrence and adjuvant treatment is not well defined, and there is significant interobserver variation. This study aimed to quantify LVSI and correlate this to risk and type of recurrence. Methods In the post operative radiation therapy in endometrial carcinoma (PORTEC)-trials stage I EC patients were randomised to receive external beam radiotherapy (EBRT) versus no additional treatment after surgery (PORTEC-1, n = 714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n = 427). In tumour samples of 926 (81.2%) patients with endometrioid tumours LVSI was quantified using 2-, 3- and 4-tiered scoring systems. Cox proportional hazard models were used for time-to-event analysis. Results Any degree of LVSI was identified in 129 cases (13.9%). Substantial LVSI ( n = 44, 4.8%) using the 3-tiered approach had the strongest impact on the risk of distant metastasis (hazard ratio (HR) 4.5 confidence interval (CI) 2.4–8.5). In multivariate analysis (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4–16), distant metastasis (HR 3.6 CI 1.9–6.8) and overall survival (HR 2.0 CI 1.3–3.1). Only EBRT (HR 0.3 CI 0.1–0.8) reduced the risk of pelvic regional recurrence. Conclusions Substantial LVSI, in contrast to focal or no LVSI, was the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis and overall survival. Therapeutic decisions should be based on the presence of substantial, not ‘any’ LVSI. Adjuvant EBRT and/or chemotherapy should be considered for stage I EC with substantial LVSI. [ABSTRACT FROM AUTHOR]

Published
2015
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