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Article ; Online: Evaluation of hyaluronic acid gel dissolution with hyaluronidase in an in-vitro prostate cancer model.

Vanneste, Ben G L / Lutgens, Ludy / Van Limbergen, Evert J

Clinical and translational radiation oncology

2022 Volume 33, Page(s) 53–56

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2022-01-05
Publishing country	Ireland
Document type	Journal Article
ISSN	2405-6308
ISSN (online)	2405-6308
DOI	10.1016/j.ctro.2021.12.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evaluation of hyaluronic acid gel dissolution with hyaluronidase in an in-vitro prostate cancer model

Ben G.L. Vanneste / Ludy Lutgens / Evert J. Van Limbergen

Clinical and Translational Radiation Oncology, Vol 33, Iss , Pp 53-

2022 Volume 56

Abstract: 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 ...

Abstract	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.
Keywords	Rectum spacer ; Hyaluronic acid ; Hyaluronidase ; In-vitro ; Prostate cancer radiotherapy ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	630
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Treatment verification in high dose rate brachytherapy using a realistic 3D printed head phantom and an imaging panel.

van Wagenberg, Teun / Fonseca, Gabriel Paiva / Voncken, Robert / van Beveren, Celine / van Limbergen, Evert / Lutgens, Ludy / Vanneste, Ben G L / Berbee, Maaike / Reniers, Brigitte / Verhaegen, Frank

Brachytherapy

2023 Volume 22, Issue 2, Page(s) 269–278

Abstract: Purpose: Even though High Dose Rate (HDR) brachytherapy has good treatment outcomes in different treatment sites, treatment verification is far from widely implemented because of a lack of easily available solutions. Previously it has been shown that an ...

Abstract	Purpose: Even though High Dose Rate (HDR) brachytherapy has good treatment outcomes in different treatment sites, treatment verification is far from widely implemented because of a lack of easily available solutions. Previously it has been shown that an imaging panel (IP) near the patient can be used to determine treatment parameters such as the dwell time and source positions in a single material pelvic phantom. In this study we will use a heterogeneous head phantom to test this IP approach, and simulate common treatment errors to assess the sensitivity and specificity of the error-detecting capabilities of the IP. Methods and materials: A heterogeneous head-phantom consisting of soft tissue and bone equivalent materials was 3D-printed to simulate a base of tongue treatment. An High Dose Rate treatment plan with 3 different catheters was used to simulate a treatment delivery, using dwell times ranging from 0.3 s to 4 s and inter-dwell distances of 2 mm. The IP was used to measure dwell times, positions and detect simulated errors. Measured dwell times and positions were used to calculate the delivered dose. Results: Dwell times could be determined within 0.1 s. Source positions were measured with submillimeter accuracy in the plane of the IP, and average distance accuracy of 1.7 mm in three dimensions. All simulated treatment errors (catheter swap, catheter shift, afterloader errors) were detected. Dose calculations show slightly different distributions with the measured dwell positions and dwell times (gamma pass rate for 1 mm/1% of 96.5%). Conclusions: Using an IP, it was possible to verify the treatment in a realistic heterogeneous phantom and detect certain treatment errors.
MeSH term(s)	Humans ; Radiotherapy Dosage ; Brachytherapy/methods ; Equipment Design ; Phantoms, Imaging ; Radiotherapy Planning, Computer-Assisted/methods ; Printing, Three-Dimensional
Language	English
Publishing date	2023-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2098608-7
ISSN	1873-1449 ; 1538-4721
ISSN (online)	1873-1449
ISSN	1538-4721
DOI	10.1016/j.brachy.2022.11.012
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Article ; Online: Is prostate cancer radiotherapy using implantable rectum spacers safe and effective in inflammatory bowel disease patients?

Vanneste, Ben G L / Van Limbergen, Evert J / Marcelissen, Tom / Reynders, Kobe / Melenhorst, Jarno / van Roermund, Joep G H / Lutgens, Ludy

Clinical and translational radiation oncology

2021 Volume 27, Page(s) 121–125

Abstract: Background: Prostate cancer radiotherapy (RT) in patients with (active) inflammatory bowel disease (IBD) remains controversial. We hypothesized that RT in combination with a biodegradable prostate-rectum spacer balloon implantation, might be a safe ... ...

Abstract	Background: Prostate cancer radiotherapy (RT) in patients with (active) inflammatory bowel disease (IBD) remains controversial. We hypothesized that RT in combination with a biodegradable prostate-rectum spacer balloon implantation, might be a safe treatment approach with acceptable toxicities for these high risk for rectal toxicity patients. Materials and methods: We report on a small prospective mono-centric series of 8 patients with all-risk prostate cancer with the comorbidity of an IBD. Four patients had Crohn's disease and 4 patients had ulcerative colitis. One out of four had an active status of IBD. All patients were intended to be treated with curative high-dose RT: 5 patients were treated with external beam RT (70 Gray (Gy) in 28 fractions), and 3 patients were treated with Results: Median follow-up was 13 months (range: 3-42 months). Only one acute grade 2 gastro-intestinal (GI) toxicity was observed: an increased diarrhea (4-6 above baseline) during RT, which resolved completely 6 weeks after treatment. No late grade 3 or more GI toxicity was reported, and no acute and late grade ≥2 genitourinary toxicity events were observed. Conclusion: Prostate cancer patients with IBD are a challenge to treat with RT. Our results suggest that RT in combination with a balloon implant in selective patients with (active) IBD may be promising, however additional validation is needed.
Language	English
Publishing date	2021-01-25
Publishing country	Ireland
Document type	Case Reports
ISSN	2405-6308
ISSN (online)	2405-6308
DOI	10.1016/j.ctro.2021.01.007
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Article ; Online: Molecular and Clinicopathologic Characterization of Mismatch Repair-Deficient Endometrial Carcinoma Not Related to MLH1 Promoter Hypermethylation.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2024 Volume 37, Issue 3, Page(s) 100423

Abstract: Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed ... ...

Abstract	Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed through the identification of germline MMR pathogenic variants (PV). In cases where these are not detected, emerging evidence highlights the significance of double-somatic MMR gene alterations as a sporadic cause of MMRd, alongside POLE/POLD1 exonuclease domain (EDM) PV leading to secondary MMR PV. Our understanding of the incidence of different MMRd EC origins not related to MLH1-PHM, their associations with clinicopathologic characteristics, and the prognostic implications remains limited. In a combined analysis of the PORTEC-1, -2, and -3 trials (n = 1254), 84 MMRd EC not related to MLH1-PHM were identified that successfully underwent paired tumor-normal tissue next-generation sequencing of the MMR and POLE/POLD1 genes. Among these, 37% were LS associated (LS-MMRd EC), 38% were due to double-somatic hits (DS-MMRd EC), and 25% remained unexplained. LS-MMRd EC exhibited higher rates of MSH6 (52% vs 19%) or PMS2 loss (29% vs 3%) than DS-MMRd EC, and exclusively showed MMR-deficient gland foci. DS-MMRd EC had higher rates of combined MSH2/MSH6 loss (47% vs 16%), loss of >2 MMR proteins (16% vs 3%), and somatic POLE-EDM PV (25% vs 3%) than LS-MMRd EC. Clinicopathologic characteristics, including age at tumor onset and prognosis, did not differ among the various groups. Our study validates the use of paired tumor-normal next-generation sequencing to identify definitive sporadic causes in MMRd EC unrelated to MLH1-PHM. MMR immunohistochemistry and POLE-EDM mutation status can aid in the differentiation between LS-MMRd EC and DS-MMRd EC. These findings emphasize the need for integrating tumor sequencing into LS diagnostics, along with clear interpretation guidelines, to improve clinical management. Although not impacting prognosis, confirmation of DS-MMRd EC may release patients and relatives from burdensome LS surveillance.
MeSH term(s)	Female ; Humans ; DNA Mismatch Repair/genetics ; MutL Protein Homolog 1/genetics ; MutL Protein Homolog 1/metabolism ; Endometrial Neoplasms/pathology ; Germ-Line Mutation ; Mismatch Repair Endonuclease PMS2/genetics ; Microsatellite Instability ; DNA Methylation
Chemical Substances	MutL Protein Homolog 1 (EC 3.6.1.3) ; Mismatch Repair Endonuclease PMS2 (EC 3.6.1.3) ; MLH1 protein, human
Language	English
Publishing date	2024-01-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2024.100423
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Zs.A 2450: Show issues

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Article ; Online: QPOLE

JCO global oncology

2023 Volume 9, Page(s) e2200384

Abstract: Purpose: Detection of 11 pathogenic variants in the : Materials and methods: Primer and fluorescence-labeled 5'-nuclease probe sequences of the 11 established pathogenic : Results: Cutoffs for : Conclusion: ... ...

Abstract	Purpose: Detection of 11 pathogenic variants in the Materials and methods: Primer and fluorescence-labeled 5'-nuclease probe sequences of the 11 established pathogenic Results: Cutoffs for Conclusion: QPOLE
MeSH term(s)	Female ; Humans ; Genotype ; Poly-ADP-Ribose Binding Proteins/genetics ; Disease-Free Survival ; Endometrial Neoplasms/diagnosis ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Polymerase Chain Reaction
Chemical Substances	Poly-ADP-Ribose Binding Proteins
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2687-8941
ISSN (online)	2687-8941
DOI	10.1200/GO.22.00384
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Article ; Online: Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer.

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

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2023 Volume 41, Issue 27, Page(s) 4369–4380

Abstract: Purpose: The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and ... ...

Abstract	Purpose: The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC). Methods: Data of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used. Locoregional (including vaginal and pelvic) recurrence-free survival was compared between treatment groups across the four molecular classes using Kaplan-Meier's methodology and log-rank tests. Results: A total of 880 molecularly classified ECs, 484 from PORTEC-1 and 396 from PORTEC-2, were included. The majority were FIGO-2009 stage I EEC (97.2%). The median follow-up was 11.3 years. No locoregional recurrences were observed in EC with a pathogenic mutation of DNA polymerase-ε ( Conclusion: The molecular classification of EC predicts response to radiotherapy in stage I EEC and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in
MeSH term(s)	Female ; Humans ; Radiation Oncology ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/radiotherapy ; Brachytherapy ; Combined Modality Therapy
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.23.00062
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas.

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 23, Page(s) 4949–4957

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 ... ...

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.
MeSH term(s)	Humans ; Female ; Endometrial Neoplasms/pathology ; Carcinoma, Endometrioid/pathology ; Tumor Suppressor Protein p53/genetics ; Retrospective Studies ; Neoplasm Recurrence, Local ; Canada
Chemical Substances	Tumor Suppressor Protein p53
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-1397
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Zs.A 4223: Show issues

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Article ; Online: Development of a Management Algorithm for Acute and Chronic Radiation Urethritis and Cystitis.

Vanneste, Ben G L / Van Limbergen, Evert J / Marcelissen, Tom A / van Roermund, Joep G H / Lutgens, Ludy C / Arnoldussen, Carsten W K P / Lambin, Philippe / Oelke, Matthias

Urologia internationalis

2021 Volume 106, Issue 1, Page(s) 63–74

Abstract: Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm.: Material and methods: The PubMed/ ...

Abstract	Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm. Material and methods: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021. Results: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae. Conclusions: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.
MeSH term(s)	Acute Disease ; Algorithms ; Chronic Disease ; Cystitis/diagnosis ; Cystitis/therapy ; Humans ; Radiation Injuries/diagnosis ; Radiation Injuries/therapy ; Urethritis/diagnosis ; Urethritis/therapy
Language	English
Publishing date	2021-06-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	204045-1
ISSN	1423-0399 ; 0042-1138
ISSN (online)	1423-0399
ISSN	0042-1138
DOI	10.1159/000515716
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Ui VI Zs.180: Show issues

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Article ; Online: Implantation of a biodegradable rectum balloon implant: tips, Tricks and Pitfalls.

Vanneste, Ben G L / van De Beek, Kees / Lutgens, Ludy / Lambin, Philippe

International braz j urol : official journal of the Brazilian Society of Urology

2017 Volume 43

Abstract: Introduction: A rectum balloon implant (RBI) is a new device to spare rectal structures during prostate cancer radiotherapy. The theoretical advantages of a RBI are to reduce the high radiation dose to the anterior rectum wall, the possibility of a post- ...

Abstract	Introduction: A rectum balloon implant (RBI) is a new device to spare rectal structures during prostate cancer radiotherapy. The theoretical advantages of a RBI are to reduce the high radiation dose to the anterior rectum wall, the possibility of a post-implant correction, and their predetermined shape with consequent predictable position. Objective: To describe, step-by-step, our mini-invasive technique for hands-free transperineal implantation of a RBI before start of radiotherapy treatment. Materials and methods: We provide step-by-step instructions for optimization of the transperineal implantation procedure performed by urologists and/or radiation oncologists experienced with prostate brachytherapy and the use of the real-time bi-plane transrectal ultrasonography (TRUS) probe. A RBI was performed in 15 patients with localised prostate cancer. Perioperative side-effects were reported. Results: We provide 'tips and tricks' for optimizing the procedure and proper positioning of the RBI. Please watch the animation, see video in https://vimeo.com/205852376/789df4fae4. The side-effects included mild discomfort to slight pain at the perineal region in 8 out of 15 patients. Seven patients (47%) had no complaints at all. Two patients developed redness of the skin, where prompt antibiotic regimen was started with no further sequelae. One patient revealed a temporary urine retention, which resolved in a few hours following conservative treatment. Further no perioperative complications occurred. Conclusion: This paper describes in detail the implantation procedure for an RBI. It is a feasible, safe and very well-tolerated procedure.
Language	English
Publishing date	2017-03-24
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2206649-4
ISSN	1677-6119 ; 1677-5538
ISSN (online)	1677-6119
ISSN	1677-5538
DOI	10.1590/S1677-5538.IBJU.2016.0494
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