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1. Efficacy of a nurse-led sexual rehabilitation intervention for women with gynaecological cancers receiving radiotherapy: results of a randomised trial

Author

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

Published
2024
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2. Automated causal inference in application to randomized controlled clinical trials

Author

Wu, Jiqing, Horeweg, Nanda, de Bruyn, Marco, Nout, Remi A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C. H. W., Jobsen, Jan J., van der Steen-Banasik, Elzbieta M., Nijman, Hans W., Smit, Vincent T. H. B. M., Bosse, Tjalling, Creutzberg, Carien L., and Koelzer, Viktor H.

Subjects
Statistics - Methodology, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract

Randomized controlled trials (RCTs) are considered as the gold standard for testing causal hypotheses in the clinical domain. However, the investigation of prognostic variables of patient outcome in a hypothesized cause-effect route is not feasible using standard statistical methods. Here, we propose a new automated causal inference method (AutoCI) built upon the invariant causal prediction (ICP) framework for the causal re-interpretation of clinical trial data. Compared to existing methods, we show that the proposed AutoCI allows to efficiently determine the causal variables with a clear differentiation on two real-world RCTs of endometrial cancer patients with mature outcome and extensive clinicopathological and molecular data. This is achieved via suppressing the causal probability of non-causal variables by a wide margin. In ablation studies, we further demonstrate that the assignment of causal probabilities by AutoCI remain consistent in the presence of confounders. In conclusion, these results confirm the robustness and feasibility of AutoCI for future applications in real-world clinical analysis., Comment: Submitted to Nature Machine Intelligence. The code is publicly available via https://github.com/CTPLab/AutoCI

Published
2022

3. Nine Recommendations for Decision Aid Implementation from the Clinician Perspective

Author

Ankolekar, Anshu, Vanneste, Ben G. L., Gurp, Esther Bloemen-van, van Roermund, Joep, Berlanga, Adriana, Roumen, Cheryl, van Limbergen, Evert, Lutgens, Ludy, Marcelissen, Tom, Lambin, Philippe, Dekker, Andre, and Fijten, Rianne

Subjects
Computer Science - Computers and Society, J.3
Abstract

Background: Shared decision-making (SDM) aims to empower patients to take an active role in their treatment choices, supported by clinicians and patient decision aids (PDAs). The purpose of this study is to explore barriers and possible facilitators to SDM and a PDA in the prostate cancer trajectory. In the process we identify possible actions that organizations and individuals can take to support implementation in practice. Methods: We use the Ottawa Model of Research Use as a framework to determine the barriers and facilitators to SDM and PDAs from the perspective of clinicians. Semi-structured interviews were conducted with urologists (n=4), radiation oncologists (n=3), and oncology nurses (n=2), focusing on the current decision-making process experienced by these stakeholders. Questions included their attitudes towards SDM and PDAs, barriers to implementation and possible strategies to overcome them. Results: Time pressure and patient characteristics were cited as major barriers by 55% of the clinicians we interviewed. Structural factors such as external quotas for certain treatment procedures were also considered as barriers by 44% of the clinicians. Facilitating factors involved organizational changes to em-bed PDAs in the treatment trajectory, training in using PDAs as a tool for SDM, and clinician motivation by disseminating positive clinical outcomes. Our findings also suggest a role for external stakeholders such as healthcare insurers in creating economic incentives to facilitate implementation. Conclusion: Our findings highlight the importance of a multi-faceted implementation strategy to support SDM. While clinician motivation and patient activation are essential, structural/economic barriers may hamper implementation. Action must also be taken at the administrative and policy levels to foster a collaborative environment for SDM and, in the process, for PDAs.

Published
2020

4. 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, Barkey Wolf, Jurriaan, 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, Powell, Melanie E, 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

Published
2023
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5. Prediction of recurrence risk in endometrial cancer with multimodal deep learning

Author

Volinsky-Fremond, Sarah, primary, Horeweg, Nanda, additional, Andani, Sonali, additional, Barkey Wolf, Jurriaan, additional, Lafarge, Maxime W., additional, de Kroon, Cor D., additional, Ørtoft, Gitte, additional, Høgdall, Estrid, additional, Dijkstra, Jouke, additional, Jobsen, Jan J., additional, Lutgens, Ludy C. H. W., additional, Powell, Melanie E., additional, Mileshkin, Linda R., additional, Mackay, Helen, additional, Leary, Alexandra, additional, Katsaros, Dionyssios, additional, Nijman, Hans W., additional, de Boer, Stephanie M., additional, Nout, Remi A., additional, de Bruyn, Marco, additional, Church, David, additional, Smit, Vincent T. H. B. M., additional, Creutzberg, Carien L., additional, Koelzer, Viktor H., additional, and Bosse, Tjalling, additional

Published
2024
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6. A unified strategy to focal brachytherapy incorporating transperineal biopsy, image fusion, and real-time implantation with and without rectal spacer simulated in prostate phantoms.

Author

Vanneste, Ben G. L., Skouteris, Basile, Pinheiro, Luis Campos, Voncken, Robert, Van Limbergen, Evert J., Lutgens, Ludy, Fonteyne, Valérie, Van Praet, Charles, Lumen, Nicolaas, Sheu, Rendi, Stock, Richard, and Stone, Nelson N.

Subjects
ENDORECTAL ultrasonography, LOW dose rate brachytherapy, IMAGE fusion, RADIOISOTOPE brachytherapy, PROSTATE cancer, PROSTATE, RETENTION of urine, MAGNETIC resonance imaging, BIOPSY
Abstract

Purpose: To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer. Material and methods: Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (125I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer. Results: The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D2cc) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively. Conclusions: Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the nonspacer implants. Further validation of this concept is warranted in clinical trials. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Clinical Behavior and Molecular Landscape of Stage I p53-abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

Jamieson, Amy, primary, Vermij, Lisa, additional, Kramer, Claire J.H., additional, Jobsen, Jan J., additional, Jürgenliemk-Schulz, Ina, additional, Lutgens, Ludy, additional, Mens, Jan Willem, additional, Haverkort, Marie A.D., additional, Slot, Annerie, additional, Nout, Remi A., additional, Oosting, Jan, additional, Carlson, Joseph, additional, Howitt, Brooke E., additional, Ip, Philip P.C., additional, Lax, Sigurd F., additional, McCluggage, W. Glenn, additional, Singh, Naveena, additional, McAlpine, Jessica N., additional, Creutzberg, Carien L., additional, Horeweg, Nanda, additional, Gilks, C. Blake, additional, and Bosse, Tjalling, additional

Published
2023
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8. QPOLE: A Quick, Simple, and Cheap Alternative for POLE Sequencing in Endometrial Cancer by Multiplex Genotyping Quantitative Polymerase Chain Reaction

Author

Van den Heerik, Anne Sophie V.M., primary, Ter Haar, Natalja T., additional, Vermij, Lisa, additional, Jobsen, Jan J., additional, Brinkhuis, Mariel, additional, Roothaan, Suzan M., additional, Leon-Castillo, Alicia, additional, Ortoft, Gitte, additional, Hogdall, Estrid, additional, Hogdall, Claus, additional, Van Wezel, Tom, additional, Lutgens, Ludy C.H.W., additional, Haverkort, Marie A.D., additional, Khattra, Jas, additional, McAlpine, Jessica N., additional, Creutzberg, Carien L., additional, Smit, Vincent T.H.B.M., additional, Gilks, C. Blake, additional, Horeweg, Nanda, additional, and Bosse, Tjalling, additional

Published
2023
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9. Abstract 5695: Deep learning risk prediction model of distant recurrence from H&E endometrial cancer slides

Author

Fremond, Sarah, primary, Andani, Sonali, additional, Wolf, Jurriaan Barkey, additional, Ørtoft, Gitte, additional, Høgdall, Estrid, additional, Dijkstra, Jouke, additional, Jobsen, Jan J., additional, Jürgenliemk-Schulz, Ina M., additional, Lutgens, Ludy CHW, additional, Powell, Melanie E., additional, Singh, Naveena, additional, Mileshkin, Linda R., additional, Mackay, Helen J., additional, Leary, Alexandra, additional, Katsaros, Dionyssios, additional, Nijman, Hans W., additional, de Boer, Stephanie M., additional, Nout, Remi A., additional, Smit, Vincent T.H.B.M, additional, Creutzberg, Carien L., additional, Horeweg, Nanda, additional, Koelzer, Viktor H., additional, and Bosse, Tjalling, additional

Published
2023
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10. QPOLE:A Quick, Simple, and Cheap Alternative for POLE Sequencing in Endometrial Cancer by Multiplex Genotyping Quantitative Polymerase Chain Reaction

Author

Van den Heerik, Anne Sophie V.M., Ter Haar, Natalja T., Vermij, Lisa, Jobsen, Jan J., Brinkhuis, Mariel, Roothaan, Suzan M., Leon-Castillo, Alicia, Ortoft, Gitte, Hogdall, Estrid, Hogdall, Claus, Van Wezel, Tom, Lutgens, Ludy C.H.W., Haverkort, Marie A.D., Khattra, Jas, McAlpine, Jessica N., Creutzberg, Carien L., Smit, Vincent T.H.B.M., Gilks, C. Blake, Horeweg, Nanda, Bosse, Tjalling, Van den Heerik, Anne Sophie V.M., Ter Haar, Natalja T., Vermij, Lisa, Jobsen, Jan J., Brinkhuis, Mariel, Roothaan, Suzan M., Leon-Castillo, Alicia, Ortoft, Gitte, Hogdall, Estrid, Hogdall, Claus, Van Wezel, Tom, Lutgens, Ludy C.H.W., Haverkort, Marie A.D., Khattra, Jas, McAlpine, Jessica N., Creutzberg, Carien L., Smit, Vincent T.H.B.M., Gilks, C. Blake, Horeweg, Nanda, and Bosse, Tjalling

Abstract

PURPOSE: Detection of 11 pathogenic variants in the POLE gene in endometrial cancer (EC) is critically important to identify women with a good prognosis and reduce overtreatment. Currently, POLE status is determined by DNA sequencing, which can be expensive, relatively time-consuming, and unavailable in hospitals without specialized equipment and personnel. This may hamper the implementation of POLE-testing in clinical practice. To overcome this, we developed and validated a rapid, low-cost POLE hotspot test by a quantitative polymerase chain reaction (qPCR) assay, QPOLE. MATERIALS AND METHODS: Primer and fluorescence-labeled 5'-nuclease probe sequences of the 11 established pathogenic POLE mutations were designed. Three assays, QPOLE-frequent for the most common mutations and QPOLE-rare-1 and QPOLE-rare-2 for the rare variants, were developed and optimized using DNA extracted from formalin-fixed paraffin-embedded tumor tissues. The simplicity of the design enables POLE status assessment within 4-6 hours after DNA isolation. An interlaboratory external validation study was performed to determine the practical feasibility of this assay. RESULTS: Cutoffs for POLE wild-type, POLE-mutant, equivocal, and failed results were predefined on the basis of a subset of POLE mutants and POLE wild-types for the internal and external validation. For equivocal cases, additional DNA sequencing is recommended. Performance in 282 EC cases, of which 99 were POLE-mutated, demonstrated an overall accuracy of 98.6% (95% CI, 97.2 to 99.9), a sensitivity of 95.2% (95% CI, 90.7 to 99.8), and a specificity of 100%. After DNA sequencing of 8.8% equivocal cases, the final sensitivity and specificity were 96.0% (95% CI, 92.1 to 99.8) and 100%. External validation confirmed feasibility and accuracy. CONCLUSION: QPOLE is a qPCR assay that is a quick, simple, and reliable alternative for DNA sequencing. QPOLE detects all pathogenic variants in the exonuclease domain of the POLE gene. QPOLE will

Published
2023

11. Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

Jamieson, Amy, Vermij, Lisa, Kramer, Claire J.H., Jobsen, Jan J., Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A.D., Slot, Annerie, Nout, Remi A., Oosting, Jan, Carlson, Joseph, Howitt, Brooke E., Ip, Philip P.C., Lax, Sigurd F., McCluggage, W. Glenn, Singh, Naveena, McAlpine, Jessica N., Creutzberg, Carien L., Horeweg, Nanda, Gilks, C. Blake, Bosse, Tjalling, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J.H., Jobsen, Jan J., Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A.D., Slot, Annerie, Nout, Remi A., Oosting, Jan, Carlson, Joseph, Howitt, Brooke E., Ip, Philip P.C., Lax, Sigurd F., McCluggage, W. Glenn, Singh, Naveena, McAlpine, Jessica N., Creutzberg, Carien L., Horeweg, Nanda, Gilks, C. Blake, and Bosse, Tjalling

Abstract

PURPOSE: The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort. EXPERIMENTAL DESIGN: Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan-Meier method was used for survival analysis. RESULTS: We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, PIK3CA and PTEN mutations) but they also showed features of p53abn EC (TP53 mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients. CONCLUSIONS:A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence.

Published
2023

12. Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

MS Radiotherapie, Cancer, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J H, Jobsen, Jan J, Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A D, Slot, Annerie, Nout, Remi A, Oosting, Jan, Carlson, Joseph, Howitt, Brooke E, Ip, Philip P C, Lax, Sigurd F, McCluggage, W Glenn, Singh, Naveena, McAlpine, Jessica N, Creutzberg, Carien L, Horeweg, Nanda, Gilks, C Blake, Bosse, Tjalling, MS Radiotherapie, Cancer, Jamieson, Amy, Vermij, Lisa, Kramer, Claire J H, Jobsen, Jan J, Jürgemlienk-Schulz, Ina, Lutgens, Ludy, Mens, Jan Willem, Haverkort, Marie A D, Slot, Annerie, Nout, Remi A, Oosting, Jan, Carlson, Joseph, Howitt, Brooke E, Ip, Philip P C, Lax, Sigurd F, McCluggage, W Glenn, Singh, Naveena, McAlpine, Jessica N, Creutzberg, Carien L, Horeweg, Nanda, Gilks, C Blake, and Bosse, Tjalling

Published
2023

13. 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

MS Radiotherapie, Cancer, Fremond, Sarah, Andani, Sonali, Barkey Wolf, Jurriaan, 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., Powell, Melanie E., 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., Bosse, Tjalling, MS Radiotherapie, Cancer, Fremond, Sarah, Andani, Sonali, Barkey Wolf, Jurriaan, 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., Powell, Melanie E., 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

Published
2023

14. Evaluation of hyaluronic acid gel dissolution with hyaluronidase in an in-vitro prostate cancer model

Author

Vanneste, Ben G L, Lutgens, Ludy, Van Limbergen, Evert J, Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Radiotherapie OC (9)

Subjects
Medical physics. Medical radiology. Nuclear medicine, In-vitro, Oncology, Hyaluronic acid, R895-920, Technical Note, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hyaluronidase, Radiology, Nuclear Medicine and imaging, Prostate cancer radiotherapy, INJECTION, RC254-282, Rectum spacer
Abstract

Highlights • Hyaluronic acid (HA) is an implantable rectum spacer used to decrease rectal radiation dose in prostate cancer radiotherapy. • Hyaluronidase (HAS) is an enzyme that degrades HA, when wrongly positioned. • A ratio of HA:HAS of 1:2 has already a decrease of half of volume on the 2nd day., Aim To determine a dose response relationship of disintegration of a hyaluronic acid (HA) and hyaluronidase (HAS) used in prostate cancer radiotherapy. Materials and methods Five in-vitro models are applicated with 3 ml (ml) HA. For dissolution varying doses of HAS were used: 6 ml, 3 ml, 1.5 ml, and 0 ml. One ml contains 150 International Units (IU). Each HAS was added with saline till the complementary amount of 6 ml. One phantom was solely implanted with a HA 3 ml acting as a control. Length, width and height were measured on different time points: 1st day 4 times, 2nd day 3 times, third day 2 times, and then once daily during one week, with a final measurement 2 weeks after implantation. The experiments were performed in duplicate to exclude variations and confirm the results. Results The fastest dissolution was observed with the highest concentration of HAS, already observed at the first time point 2 h after implantation, with volume decrease of 50% on the second day, and less than 1 ml residue (33%) on day 4. The 2 other concentrations of HAS also showed a volume decrease, with less than 2 ml (66%) on day 4. All the applied quantities of HAS are observed with a residue of less than 1 ml after 7 days. After 14 days the control phantom and the saline filled one remains on steady state volume (3 ml). Conclusions A dose response was observed by HAS injection: highest volumes of HAS dissolute most swiftly. Using a ratio of HA:HAS of 1:2 results in a decrease to half of initial volume within 24 h. This is of special interest when used in clinical practice following erroneous positioning, and dissolution is urgently needed.

Published
2022

15. Automated causal inference in application to randomized controlled clinical trials

Author

Wu, Ji Q., Horeweg, Nanda, de Bruyn, Marco, Nout, Remi A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Jobsen, Jan J., van der Steen-Banasik, Elzbieta M., Nijman, Hans W., Smit, Vincent T.H.B.M., Bosse, Tjalling, Creutzberg, Carien L., Koelzer, Viktor H., Wu, Ji Q., Horeweg, Nanda, de Bruyn, Marco, Nout, Remi A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Jobsen, Jan J., van der Steen-Banasik, Elzbieta M., Nijman, Hans W., Smit, Vincent T.H.B.M., Bosse, Tjalling, Creutzberg, Carien L., and Koelzer, Viktor H.

Abstract

Randomized controlled trials (RCTs) are considered the gold standard for testing causal hypotheses in the clinical domain; however, the investigation of prognostic variables of patient outcome in a hypothesized cause–effect route is not feasible using standard statistical methods. Here we propose a new automated causal inference method (AutoCI) built on the invariant causal prediction (ICP) framework for the causal reinterpretation of clinical trial data. Compared with existing methods, we show that the proposed AutoCI allows one to clearly determine the causal variables of two real-world RCTs of patients with endometrial cancer with mature outcome and extensive clinicopathological and molecular data. This is achieved via suppressing the causal probability of non-causal variables by a wide margin. In ablation studies, we further demonstrate that the assignment of causal probabilities by AutoCI remains consistent in the presence of confounders. In conclusion, these results confirm the robustness and feasibility of AutoCI for future applications in real-world clinical analysis.

Published
2022

16. Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer

Author

Peters, Elke E.M., León-Castillo, Alicia, Smit, Vincent T.H.B.M., Boennelycke, Marie, Hogdall, Estrid, Hogdall, Claus, Creutzberg, Carien, Jürgenliemk-Schulz, Ina M., Jobsen, Jan J., Mens, Jan Willem M., Lutgens, Ludy C.H.W., Van Der Steen-Banasik, Elzbieta M., Ortoft, Gitte, Bosse, Tjalling, Nout, Remi, Peters, Elke E.M., León-Castillo, Alicia, Smit, Vincent T.H.B.M., Boennelycke, Marie, Hogdall, Estrid, Hogdall, Claus, Creutzberg, Carien, Jürgenliemk-Schulz, Ina M., Jobsen, Jan J., Mens, Jan Willem M., Lutgens, Ludy C.H.W., Van Der Steen-Banasik, Elzbieta M., Ortoft, Gitte, Bosse, Tjalling, and Nout, Remi

Abstract

Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P<0.001), respectively when 0, 1 to 3, or ≥4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (≥4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.

Published
2022

17. 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, Jurgenliemk-Schulz, Ina M., McCormack, Mary, Do, Viet, Katsaros, Dionyssios, Bessette, Paul, Baron, Marie Helene, 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., de Boer, Stephanie M., Wortman, Bastiaan G., Post, Cathalijne C. B., Powell, Melanie E., Khaw, Pearly, Fyles, Anthony, D'Amico, Romerai, Haie-Meder, Christine, Jurgenliemk-Schulz, Ina M., McCormack, Mary, Do, Viet, Katsaros, Dionyssios, Bessette, Paul, Baron, Marie Helene, 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.

Abstract

Purpose: Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer. Methods and Materials: Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis. Physician-reported AEs were graded using Common Terminology Criteria for Adverse Events v3.0. QoL was assessed by the European Organisation for Research and Treatment of Cancer QLQC30, CX24, and OV28 questionnaires. Data were compared between 3DCRT and IMRT. A P value of ≤ .01 was considered statistically significant due to the risk of multiple testing. For QoL, combined scores 1 to 2 (“not at all” and “a little”) versus 3 to 4 (“quite a bit” and “very much”) were compared between the techniques. Results: Of 658 evaluable patients, 559 received 3DCRT and 99 IMRT. Median follow-up was 74.6 months. During treatment no significant differences were observed, with a trend for more grade ≥3 AEs, mostly hematologic and gastrointestinal, after 3DCRT (37.7% vs 26.3%, P = .03). During follow-up, 15.4% (vs 4%) had grade ≥2 diarrhea, and 26.1% (vs 13.1%) had grade ≥2 hematologic AEs after 3DCRT (vs IMRT) (both P < .01). Among 574 (87%) patients evaluable for QoL, 494 received 3DCRT and 80 IMRT. During treatment, 37.5% (vs 28.6%) reported diarrhea after 3DCRT (vs IMRT) (P = .125); 22.1% (versus 10.0%) bowel urgency (P = 0039), and 18.2% and 8.6% abdominal cramps (P = .058). Other QoL scores showed no differences. Conclusions: IMRT resulted in fewer grade ≥3 AEs during treatment and significantly lower rates of grade ≥2 diarrhea and hematologic AEs during follow-up. Trends toward fewer patient-reported bowel urgency and abdominal cr

Published
2022

18. Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer

Author

MS Radiotherapie, Cancer, Peters, Elke E.M., León-Castillo, Alicia, Smit, Vincent T.H.B.M., Boennelycke, Marie, Hogdall, Estrid, Hogdall, Claus, Creutzberg, Carien, Jürgenliemk-Schulz, Ina M., Jobsen, Jan J., Mens, Jan Willem M., Lutgens, Ludy C.H.W., Van Der Steen-Banasik, Elzbieta M., Ortoft, Gitte, Bosse, Tjalling, Nout, Remi, MS Radiotherapie, Cancer, Peters, Elke E.M., León-Castillo, Alicia, Smit, Vincent T.H.B.M., Boennelycke, Marie, Hogdall, Estrid, Hogdall, Claus, Creutzberg, Carien, Jürgenliemk-Schulz, Ina M., Jobsen, Jan J., Mens, Jan Willem M., Lutgens, Ludy C.H.W., Van Der Steen-Banasik, Elzbieta M., Ortoft, Gitte, Bosse, Tjalling, and Nout, Remi

Published
2022

19. 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

MS Radiotherapie, Cancer, 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., de Boer, Stephanie M., MS Radiotherapie, Cancer, 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

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

Author

MS Radiotherapie, Cancer, 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, Kirchheiner, Kathrin, MS Radiotherapie, Cancer, 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

21. Automated causal inference in application to randomized controlled clinical trials

Author

MS Radiotherapie, Cancer, Wu, Ji Q., Horeweg, Nanda, de Bruyn, Marco, Nout, Remi A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Jobsen, Jan J., van der Steen-Banasik, Elzbieta M., Nijman, Hans W., Smit, Vincent T.H.B.M., Bosse, Tjalling, Creutzberg, Carien L., Koelzer, Viktor H., MS Radiotherapie, Cancer, Wu, Ji Q., Horeweg, Nanda, de Bruyn, Marco, Nout, Remi A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Jobsen, Jan J., van der Steen-Banasik, Elzbieta M., Nijman, Hans W., Smit, Vincent T.H.B.M., Bosse, Tjalling, Creutzberg, Carien L., and Koelzer, Viktor H.

Published
2022

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

Author

MS Radiotherapie, Cancer, 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, EMBRACE Collaborative Group, Collaborative Group, MS Radiotherapie, Cancer, 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, Collaborative Group

Published
2022

23. Meeting Report: Synopsis of Partial-Body Radiation Diagnostic Biomarkers and Medical Management of Radiation Injury Workshop

Author

Prasanna, Pataje G. S., Blakely, William F., Bertho, Jean-Marc, Chute, John P., Cohen, Eric P., Goans, Ronald E., Grace, Marcy B., Lillis-Hearne, Patricia K., Lloyd, David C., Lutgens, Ludy C. H. W., Meineke, Viktor, Ossetrova, Natalia I., Romanyukha, Alexander, Saba, Julie D., Weisdorf, Daniel J., Wojcik, Andrzej, Yukihara, Eduardo G., and Pellmar, Terry C.

Published
2010
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24. Long-term toxicity and health-related quality of life after adjuvant chemoradiotherapy or radiotherapy alone for high-risk endometrial cancer in the randomised PORTEC-3 trial

Author

Post, C, de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, N, Ledermann, J, Khaw, P, D'Amico, R, Fyles, A, Baron, M, Kitchener, H, Nijman, H, Lutgens, L, Brooks, S, Jürgenliemk-Schulz, I, Feeney, A, Goss, G, Fossati, R, Ghatage, P, Leary, A, Do, V, Lissoni, A, Mccormack, M, Nout, R, Verhoeven-Adema, K, Smit, V, Putter, H, Creutzberg, C, 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, Creutzberg, Carien L, Post, C, de Boer, S, Powell, M, Mileshkin, L, Katsaros, D, Bessette, P, Haie-Meder, C, Ottevanger, N, Ledermann, J, Khaw, P, D'Amico, R, Fyles, A, Baron, M, Kitchener, H, Nijman, H, Lutgens, L, Brooks, S, Jürgenliemk-Schulz, I, Feeney, A, Goss, G, Fossati, R, Ghatage, P, Leary, A, Do, V, Lissoni, A, Mccormack, M, Nout, R, Verhoeven-Adema, K, Smit, V, Putter, H, Creutzberg, C, 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

Abstract

Background: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiotherapy versus pelvic radiotherapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL). Patients and methods: 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiotherapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiotherapy alone. Toxicity was graded using CTCAE v3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28-subscales and compared to normative-data. An as-treated analysis was performed. Results: Median follow up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade ≥2 AE were scored for 78 (38%) patients who had received chemoradiotherapy versus 46 (24%) who had received radiotherapy (p=0.008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, p=0.18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade ≥2 persisted after chemoradiotherapy in 6% (vs 0% after radiotherapy, p<0.001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, p<0.001 at 3 years; 24% vs 9%, p=0.002 at 5 years). Until 3 years, more patients who had chemoradiotherapy reported limb weakness (21% vs 5%, p<0.001) and lower physical (79 vs 87, p<0.001) and role functioning (78 vs 88, p<0.001) scores. Both treatment groups reported similar long-term global health/QOL scores, which were better than those of the normative-population. Conclusion: This study shows a long-lasting, clinically relevant, negative impact of chemoradiotherapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and

Published
2021

25. 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., Creutzberg, Carien L., 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.

Abstract

Background: Decision making regarding adjuvant therapy for high-risk endometrial cancer is complex. The aim of this study was to determine patients' and clinicians' minimally desired survival benefit to choose chemoradiotherapy over radiotherapy alone. Moreover, influencing factors and importance of positive and negative treatment effects (i.e. attribute) were investigated. Methods: Patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy and multidisciplinary gynaecologic oncology clinicians completed a trade-off questionnaire based on PORTEC-3 trial data. Results: In total, 171 patients and 63 clinicians completed the questionnaire. Median minimally desired benefit to make chemoradiotherapy worthwhile was significantly higher for patients versus clinicians (10% vs 5%, p = 0.02). Both patients and clinicians rated survival benefit most important during decision making, followed by long-term symptoms. Older patients (OR 0.92 [95%CI 0.87–0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12–0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05–1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8–91.7]; p < 0.001) had higher preference for chemoradiotherapy. Conclusions: There is a considerable difference in minimally desired survival benefit of chemoradiotherapy in high-risk endometrial cancer among and between patients and clinicians. Overall, endometrial cancer patients needed higher benefits than clinicians before preferring chemoradiotherapy.

Published
2021

26. Phase II study of definitive chemoradiation for locally advanced squamous cell cancer of the vulva:An efficacy study

Author

van Triest, Baukelien, Rasing, Marnix, van der Velden, Jacobus, de Hullu, Joanne, Witteveen, Petronella O., Beukema, Jannet C., van der Steen-Banasik, Elsbieta, Westerveld, Henrike, Snyers, An, Peters, Max, Creutzberg, Carien L., Nout, Remi A., Lutgens, Ludy, Jürgenliemk-Schulz, Ina, van Triest, Baukelien, Rasing, Marnix, van der Velden, Jacobus, de Hullu, Joanne, Witteveen, Petronella O., Beukema, Jannet C., van der Steen-Banasik, Elsbieta, Westerveld, Henrike, Snyers, An, Peters, Max, Creutzberg, Carien L., Nout, Remi A., Lutgens, Ludy, and Jürgenliemk-Schulz, Ina

Abstract

Objective: To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival. Methods: In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated. Results: 52 patients with mainly T2/T3 disease were treated according to the study protocol in 10 centers in the Netherlands from 2007 to 2019. Full dose radiotherapy (tumor dose of 64.8Gy) was delivered in 92% and full dose capecitabine in 69% of patients. Most prevalent acute ≥ grade 3 toxicities were regarding skin/mucosa and pain (54% and 37%). Late ≥grade 3 toxicity was reported for skin/mucosa (10%), fibrosis (4%), GI incontinence (4%) and stress fracture or osteoradionecrosis (4%). Twelve weeks after treatment, local clinical complete response (cCR) and regional control (RC) rates were 62% and 75%, respectively. After 2 years, local cCR persisted in 22 patients (42%) and RC was 58%. Thirty patients (58%) had no evidence of disease at end of follow-up (median 35 months). In 9 patients (17%) extensive surgery with stoma formation was needed. Progression free survival was 58%, 51% and 45% and overall survival was 76%, 66%, 52% at 1,2, and 5 years. Conclusions: Definitive capecitabine-based chemoradiation as alternative for extensive surgery is feasible in locally advanced vulvar cancer and results in considerable locoregional control with acceptable survival rates with manageable acute and late toxicity.

Published
2021

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

Author

MS Radiotherapie, Cancer, 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., Creutzberg, Carien L., MS Radiotherapie, Cancer, 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

28. 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

MS Radiotherapie, Cancer, 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, Creutzberg, Carien L., MS Radiotherapie, Cancer, 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

29. Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer

Author

MS Radiotherapie, Cancer, Post, Cathalijne C.B., Stelloo, Ellen, Smit, Vincent T.H.B.M., Ruano, Dina, Tops, Carli M., Vermij, Lisa, Rutten, Tessa A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Jobsen, Jan J., Nout, Remi A., Crosbie, Emma J., Powell, Melanie E., Mileshkin, Linda, Leary, Alexandra, Bessette, Paul, Putter, Hein, de Boer, Stephanie M., Horeweg, Nanda, Nielsen, Maartje, Wezel, Tom van, Bosse, Tjalling, Creutzberg, Carien L., MS Radiotherapie, Cancer, Post, Cathalijne C.B., Stelloo, Ellen, Smit, Vincent T.H.B.M., Ruano, Dina, Tops, Carli M., Vermij, Lisa, Rutten, Tessa A., Jürgenliemk-Schulz, Ina M., Lutgens, Ludy C.H.W., Jobsen, Jan J., Nout, Remi A., Crosbie, Emma J., Powell, Melanie E., Mileshkin, Linda, Leary, Alexandra, Bessette, Paul, Putter, Hein, de Boer, Stephanie M., Horeweg, Nanda, Nielsen, Maartje, Wezel, Tom van, Bosse, Tjalling, and Creutzberg, Carien L.

Published
2021

30. Phase II study of definitive chemoradiation for locally advanced squamous cell cancer of the vulva: An efficacy study

Author

Onderzoek Radiotherapie, Cancer, MS Radiotherapie, MS Medische Oncologie, Arts-assistenten Radiotherapie, van Triest, Baukelien, Rasing, Marnix, van der Velden, Jacobus, de Hullu, Joanne, Witteveen, Petronella O., Beukema, Jannet C., van der Steen-Banasik, Elsbieta, Westerveld, Henrike, Snyers, An, Peters, Max, Creutzberg, Carien L., Nout, Remi A., Lutgens, Ludy, Jürgenliemk-Schulz, Ina, Onderzoek Radiotherapie, Cancer, MS Radiotherapie, MS Medische Oncologie, Arts-assistenten Radiotherapie, van Triest, Baukelien, Rasing, Marnix, van der Velden, Jacobus, de Hullu, Joanne, Witteveen, Petronella O., Beukema, Jannet C., van der Steen-Banasik, Elsbieta, Westerveld, Henrike, Snyers, An, Peters, Max, Creutzberg, Carien L., Nout, Remi A., Lutgens, Ludy, and Jürgenliemk-Schulz, Ina

Published
2021

31. Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer

Author

Post, Cathalijne C B, primary, Stelloo, Ellen, additional, Smit, Vincent T H B M, additional, Ruano, Dina, additional, Tops, Carli M, additional, Vermij, Lisa, additional, Rutten, Tessa A, additional, Jürgenliemk-Schulz, Ina M, additional, Lutgens, Ludy C H W, additional, Jobsen, Jan J, additional, Nout, Remi A, additional, Crosbie, Emma J, additional, Powell, Melanie E, additional, Mileshkin, Linda, additional, Leary, Alexandra, additional, Bessette, Paul, additional, Putter, Hein, additional, de Boer, Stephanie M, additional, Horeweg, Nanda, additional, Nielsen, Maartje, additional, Wezel, Tom van, additional, Bosse, Tjalling, additional, and Creutzberg, Carien L, additional

Published
2021
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33. Confirmation of thermal dose as a predictor of local control in cervical carcinoma patients treated with state-of-the-art radiation therapy and hyperthermia

Author

Kroesen, Michiel, Mulder, Hendrik T., van Holthe, Jeanette M.L., Aangeenbrug, Aleida A., Mens, Jan Willem M., van Doorn, Helena C., Paulides, Margarethus M., Oomen-de Hoop, Esther, Vernhout, Rene M., Lutgens, Ludy C., van Rhoon, Gerard C., Franckena, Martine, Kroesen, Michiel, Mulder, Hendrik T., van Holthe, Jeanette M.L., Aangeenbrug, Aleida A., Mens, Jan Willem M., van Doorn, Helena C., Paulides, Margarethus M., Oomen-de Hoop, Esther, Vernhout, Rene M., Lutgens, Ludy C., van Rhoon, Gerard C., and Franckena, Martine

Abstract

Background: Addition of deep hyperthermia results in improved local control (LC) and overall survival (OS) compared to radiotherapy alone in patients with cervical carcinoma. Previously, we showed that the thermal dose of hyperthermia significantly correlates with LC and disease specific survival (DSS). Over the last decade, new radiation techniques were introduced resulting in improved LC. Aim: To validate the effect of thermal dose in a more recent cohort of patients treated with modern radiotherapy techniques, including image guided brachytherapy (IGBT). Methods: We analyzed primary cervical carcinoma patients treated with a combination of radiotherapy and deep hyperthermia between 2005 and 2016 at our institute. Data on patient, tumor and treatment were collected including the thermal dose parameters TRISE and CEM43T90. Follow-up data on LC, disease free survival, DSS, OS as well as late toxicity data were collected. Data were analyzed using the Cox proportional hazard and Kaplan–Meier analyses. Results: 227 patients were included. In multivariate analysis, histology, FIGO stage, lymphadenopathy, TRISE, CEM43T90 and IGBT had a significant effect on LC. In the patients treated with IGBT, the thermal dose parameter TRISE remained to have a significant effect on LC in univariate analysis. Conclusions: The positive association between thermal dose and clinical outcome is replicated in an independent, recent cohort of cervical carcinoma patients. Importantly, in patients receiving IGBT, the effect of thermal dose on clinical outcome is still observed.

Published
2019

34. 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

35. 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

MS Radiotherapie, Cancer, 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., Stam, Tanja C., PORTEC study group, MS Radiotherapie, Cancer, 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., Stam, Tanja C., and PORTEC study group

Published
2018

38. Author Correction: Prediction of recurrence risk in endometrial cancer with multimodal deep learning

Author

Volinsky-Fremond, Sarah, Horeweg, Nanda, Andani, Sonali, Barkey Wolf, Jurriaan, Lafarge, Maxime W., de Kroon, Cor D., Ørtoft, Gitte, Høgdall, Estrid, Dijkstra, Jouke, Jobsen, Jan J., Lutgens, Ludy C. H. W., Powell, Melanie E., Mileshkin, Linda R., Mackay, Helen, Leary, Alexandra, Katsaros, Dionyssios, Nijman, Hans W., de Boer, Stephanie M., Nout, Remi A., de Bruyn, Marco, Church, David, Smit, Vincent T. H. B. M., Creutzberg, Carien L., Koelzer, Viktor H., and Bosse, Tjalling

Published
2024
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39. Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer—Combined Analysis of the PORTEC Cohorts

Author

Stelloo, Ellen, primary, Nout, Remi A., additional, Osse, Elisabeth M., additional, Jürgenliemk-Schulz, Ina J., additional, Jobsen, Jan J., additional, Lutgens, Ludy C., additional, van der Steen-Banasik, Elzbieta M., additional, Nijman, Hans W., additional, Putter, Hein, additional, Bosse, Tjalling, additional, Creutzberg, Carien L., additional, and Smit, Vincent T.H.B.M., additional

Published
2016
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41. 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., Nout, Remi A., 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.

Published
2015

42. Nomograms for prediction of outcome with or without adjuvant radiation therapy for patients with endometrial cancer : A pooled analysis of PORTEC-1 and PORTEC-2 trials

Author

Creutzberg, Carien L., Van Stiphout, Ruud G.P.M., Nout, Remi A., Lutgens, Ludy C.H.W., Jürgenliemk-Schulz, Ina M., Jobsen, Jan J, Smit, Vincent T.H.B.M., Lambin, Philippe, Creutzberg, Carien L., Van Stiphout, Ruud G.P.M., Nout, Remi A., Lutgens, Ludy C.H.W., Jürgenliemk-Schulz, Ina M., Jobsen, Jan J, Smit, Vincent T.H.B.M., and Lambin, Philippe

Published
2015

43. 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., Jurgenliemk-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, Creutzberg, Carien L., De Boer, Stephanie M., Nout, Remi A., Jurgenliemk-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

44. 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

MS Radiotherapie, Cancer, 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., Nout, Remi A., MS Radiotherapie, Cancer, 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.

Published
2015

45. Nomograms for prediction of outcome with or without adjuvant radiation therapy for patients with endometrial cancer: A pooled analysis of PORTEC-1 and PORTEC-2 trials

Author

MS Radiotherapie, Cancer, Creutzberg, Carien L., Van Stiphout, Ruud G.P.M., Nout, Remi A., Lutgens, Ludy C.H.W., Jürgenliemk-Schulz, Ina M., Jobsen, Jan J, Smit, Vincent T.H.B.M., Lambin, Philippe, MS Radiotherapie, Cancer, Creutzberg, Carien L., Van Stiphout, Ruud G.P.M., Nout, Remi A., Lutgens, Ludy C.H.W., Jürgenliemk-Schulz, Ina M., Jobsen, Jan J, Smit, Vincent T.H.B.M., and Lambin, Philippe

Published
2015

46. 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

MS Radiotherapie, Cancer, De Boer, Stephanie M., Nout, Remi A., Jurgenliemk-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, Creutzberg, Carien L., MS Radiotherapie, Cancer, De Boer, Stephanie M., Nout, Remi A., Jurgenliemk-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

47. Critical assessment of intramodality 3D ultrasound imaging for prostate IGRT compared to fiducial markers

Author

van der Meer, Skadi, Bloemen-van Gurp, Esther, Hermans, Jolanda, Voncken, Robert, Heuvelmans, Denys, Gubbels, Carol, Fontanarosa, Davide, Visser, Peter, Lutgens, Ludy, van Gils, Francis, Verhaegen, Frank, van der Meer, Skadi, Bloemen-van Gurp, Esther, Hermans, Jolanda, Voncken, Robert, Heuvelmans, Denys, Gubbels, Carol, Fontanarosa, Davide, Visser, Peter, Lutgens, Ludy, van Gils, Francis, and Verhaegen, Frank

Abstract

Purpose: A quantitative 3D intramodality ultrasound (US) imaging system was verified for daily in-room prostate localization, and compared to prostate localization based on implanted fiducial markers (FMs). Methods: Thirteen prostate patients underwent multiple US scans during treatment. A total of 376 US-scans and 817 matches were used to determine the intra- and interoperator variability. Additionally, eight other patients underwent daily prostate localization using both US and electronic portal imaging (EPI) with FMs resulting in 244 combined US-EPI scans. Scanning was performed with minimal probe pressure and a correction for the speed of sound aberration was performed. Uncertainties of both US and FM methods were assessed. User variability of the US method was assessed. Results: The overall US user variability is 2.6 mm. The mean differences between US and FM are: 2.5 ± 4.0 mm (LR), 0.6 ± 4.9 mm (SI), and −2.3 ± 3.6 mm (AP). The intramodality character of this US system mitigates potential errors due to transducer pressure and speed of sound aberrations. Conclusions: The overall accuracy of US (3.0 mm) is comparable to our FM workflow (2.2 mm). Since neither US nor FM can be considered a gold standard no conclusions can be drawn on the superiority of either method. Because US imaging captures the prostate itself instead of surrogates no invasive procedure is required. It requires more effort to standardize US imaging than FM detection. Since US imaging does not involve a radiation burden, US prostate imaging offers an alternative for FM EPI positioning.

Published
2013

48. Prostate IGRT using quantitative 3D ultrasound imaging: Intramodality US vs. MV imaging of implanted markers (Conference Abstract)

Author

van der Meer, Skadi, Bloemen-van Gurp, Esther, Fontanarosa, Davide, Visser, Peter, Lutgens, Ludy, van Gils, Francis, Verhaegen, Frank, van der Meer, Skadi, Bloemen-van Gurp, Esther, Fontanarosa, Davide, Visser, Peter, Lutgens, Ludy, van Gils, Francis, and Verhaegen, Frank

Abstract

To allow for high precision radiotherapy, imaging prior to a radiation session is performed in Image Guided Radiotherapy (IGRT). Electronic portal imaging (EPI) can visualise bony anatomy and fiducial markers (FM). However, for prostate cancer, visualising the organ itself is more desirable. Ultrasound (US) is a well known widely used diagnostic technique for qualitative imaging of soft tissues such as the prostate. Nowadays a quantitative intramodality 3D US system for radiotherapy image guidance is available (Clarity system, Elekta, Stockholm, Sweden). In this work a comparison was performed between 3D US image guidance and the currently used prostate localization procedure.

Published
2012

49. Synopsis of partial-body radiation diagnostic biomarkers and medical management of radiation injury workshop.

Author

Prasanna, Pataje G S, Blakely, William F, Bertho, Jean-Marc, Chute, John P, Cohen, Eric P, Goans, Ronald E, Grace, Marcy B, Lillis-Hearne, Patricia K, Lloyd, David C, Lutgens, Ludy C H W, Meineke, Viktor, Ossetrova, Natalia I, Romanyukha, Alexander, Saba, Julie D, Weisdorf, Daniel J, Wojcik, Andrzej, Yukihara, Eduardo G, Pellmar, Terry C, Prasanna, Pataje G S, Blakely, William F, Bertho, Jean-Marc, Chute, John P, Cohen, Eric P, Goans, Ronald E, Grace, Marcy B, Lillis-Hearne, Patricia K, Lloyd, David C, Lutgens, Ludy C H W, Meineke, Viktor, Ossetrova, Natalia I, Romanyukha, Alexander, Saba, Julie D, Weisdorf, Daniel J, Wojcik, Andrzej, Yukihara, Eduardo G, and Pellmar, Terry C

Abstract

Radiation exposures from accidents, nuclear detonations or terrorist incidents are unlikely to be homogeneous; however, current biodosimetric approaches are developed and validated primarily in whole-body irradiation models. A workshop was held at the Armed Forces Radiobiology Research Institute in May 2008 to draw attention to the need for partial-body biodosimetry, to discuss current knowledge, and to identify the gaps to be filled. A panel of international experts and the workshop attendees discussed the requirements and concepts for a path forward. This report addresses eight key areas identified by the Workshop Program Committee for future focus: (1) improved cytogenetics, (2) clinical signs and symptoms, (3) cutaneous bioindicators, (4) organ-specific biomarkers, (5) biophysical markers of dose, (6) integrated diagnostic approaches, (7) confounding factors, and (8) requirements for post-event medical follow-up. For each area, the status, advantages and limitations of existing approaches and suggestions for new directions are presented.

Published
2010
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50. The Use of FDG-PET to Target Tumors by Radiotherapy

Author

Lammering, Guido, Lammering, Guido, De Ruysscher, Dirk, van Baardwijk, Angela, Baumert, Brigitta G., Borger, Jacques, Lutgens, Ludy, van den Ende, Piet, Ollers, Michel, Lambin, Philippe, Lammering, Guido, Lammering, Guido, De Ruysscher, Dirk, van Baardwijk, Angela, Baumert, Brigitta G., Borger, Jacques, Lutgens, Ludy, van den Ende, Piet, Ollers, Michel, and Lambin, Philippe

Abstract

Fluorodeoxyglucose positron emission tomography (FDG-PET) plays an increasingly important role in radiotherapy, beyond staging and selection of patients. Especially for non-small cell lung cancer, FDG-PET has, in the majority of the patients, led to the safe decrease of radiotherapy volumes, enabling radiation dose escalation and, experimentally, redistribution of radiation doses within the tumor. In limited-disease small cell lung cancer, the role of FDG-PET is emerging. For primary brain tumors, PET based on amino acid tracers is currently the best choice, including high-grade glioma. This is especially true for low-grade gliomas, where most data are available for the use of (11)C-MET (methionine) in radiation treatment planning. For esophageal cancer, the main advantage of FDG-PET is the detection of otherwise unrecognized lymph node metastases. In Hodgkin's disease, FDG-PET is essential for involved-node irradiation and leads to decreased irradiation volumes while also decreasing geographic miss. FDG-PET's major role in the treatment of cervical cancer with radiation lies in the detection of para-aortic nodes that can be encompassed in radiation fields. Besides for staging purposes, FDG-PET is not recommended for routine radiotherapy delineation purposes. It should be emphasized that using PET is only safe when adhering to strictly standardized protocols.

Published
2010

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