14 results on '"Raaijmakers, Cornelis P. J."'
Search Results
2. Target Definition in MR-Guided Adaptive Radiotherapy for Head and Neck Cancer
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Ridder, Mischa de, primary, Raaijmakers, Cornelis P. J., additional, Pameijer, Frank A., additional, Bree, Remco de, additional, Reinders, Floris C. J., additional, Doornaert, Patricia A. H., additional, Terhaard, Chris H. J., additional, and Philippens, Marielle E. P., additional
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- 2022
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3. MUC5B levels in submandibular gland saliva of patients treated with radiotherapy for head-and-neck cancer: A pilot study
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Dijkema Tim, Terhaard Chris H J, Roesink Judith M, Raaijmakers Cornelis P J, van den Keijbus Petra A M, Brand Henk S, and Veerman Enno C I
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Xerostomia ,Head-and-neck cancer ,Radiotherapy ,MUC5B ,Mucin ,Submandibular gland ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The salivary mucin MUC5B, present in (sero)mucous secretions including submandibular gland (SMG) saliva, plays an important role in the lubrication of the oral mucosa and is thought to be related to the feeling of dry mouth. We investigated if MUC5B levels in SMG saliva could distinguish between the presence or absence of severe dry mouth complaints 12 months after radiotherapy (RT) for head-and-neck cancer (HNC). Findings Twenty-nine HNC patients with a residual stimulated SMG secretion rate of ≥0.2 ml/10 min at 12 months after RT were analyzed. MUC5B (in U; normalized to 1) and total protein levels (mg/ml) were measured in SMG saliva at baseline and 12 months after RT using ELISA and BCA protein assay, respectively. Overall, median MUC5B levels decreased after RT from 0.12 to 0.03 U (p = 0.47). Patients were dichotomized into none/mild xerostomia (n = 12) and severe xerostomia (n = 17) based on a questionnaire completed at 12 months. SMG and whole saliva flow rates decreased after RT but were comparable in both groups. The median MUC5B level was higher in patients with no or mild xerostomia compared to patients with severe xerostomia (0.14 vs 0.01 U, p = 0.22). Half of the patients with severe xerostomia had no detectable MUC5B at 12 months after RT. No differences in total protein levels were observed. Conclusions Qualitative saliva parameters like MUC5B need further investigation in RT-induced xerostomia. This pilot study showed a trend towards lower MUC5B levels in the SMG saliva of patients with severe xerostomia 12 months after RT for HNC.
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- 2012
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4. Brain and Head-and-Neck MRI in Immobilization Mask: A Practical Solution for MR-Only Radiotherapy
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Mandija, Stefano, primary, D'Agata, Federico, additional, Navest, Robin J. M., additional, Sbrizzi, Alessandro, additional, Tijssen, Rob H. N., additional, Philippens, Marielle E. P., additional, Raaijmakers, Cornelis P. J., additional, Seravalli, Enrica, additional, Verhoeff, Joost J. C., additional, Lagendijk, Jan J. W., additional, and van den Berg, Cornelis A. T., additional
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- 2019
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5. Target Volume Delineation Using Diffusion-weighted Imaging for MR-guided Radiotherapy: A Case Series of Laryngeal Cancer Validated by Pathology
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Ligtenberg, Hans, primary, Schakel, Tim, additional, Dankbaar, Jan Willem, additional, Ruiter, Lilian N, additional, Peltenburg, Boris, additional, Willems, Stefan M, additional, Kasperts, Nicolien, additional, Terhaard, Chris H J, additional, Raaijmakers, Cornelis P J, additional, and Philippens, Marielle E P, additional
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- 2018
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6. Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma
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van den Bosch, Sven, primary, Dijkema, Tim, additional, Kunze-Busch, Martina C., additional, Terhaard, Chris H. J., additional, Raaijmakers, Cornelis P. J., additional, Doornaert, Patricia A. H., additional, Hoebers, Frank J. P., additional, Vergeer, Marije R., additional, Kreike, Bas, additional, Wijers, Oda B., additional, Oyen, Wim J. G., additional, and Kaanders, Johannes H. A. M., additional
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- 2017
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7. GTV delineation in supraglottic laryngeal carcinoma: interobserver agreement of CT versus CT-MR delineation.
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Jager, Elise Anne, Kasperts, Nicolien, Caldas-Magalhaes, Joana, Philippens, Mariëlle E. P., Pameijer, Frank A., Terhaard, Chris H. J., and Raaijmakers, Cornelis P. J.
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RADIOTHERAPY ,MAGNETIC resonance imaging ,BIOPSY ,GADOLINIUM ,LARYNGEAL cancer ,THERAPEUTICS - Abstract
Background: GTV delineation is the first crucial step in radiotherapy and requires high accuracy, especially with the growing use of highly conformal and adaptive radiotherapy techniques. If GTV delineations of observers concord, they are considered to be of high accuracy. The aim of the study is to determine the interobserver agreement for GTV delineations of supraglottic laryngeal carcinoma on CT and on CT combined with MR-images and to determine the effect of adding MR images to CT-based delineation on the delineated volume and the interobserver agreement. Methods: Twenty patients with biopsy proven T1-T4 supraglottic laryngeal cancer, treated with curative intent were included. For all patients a contrast enhanced planning CT and a 1.5-T MRI with gadolinium were acquired in the same head-and-shoulder mask for fixation as used during treatment. For MRI, a two element surface coil was used as a receiver coil. Three dedicated observers independently delineated the GTV on CT. After an interval of 2 weeks, a set of co-registered CT and MR-images was provided to delineate the GTV on CT. Common volumes (C) and encompassing volumes (E) were calculated and C/E ratios were determined for each pair of observers. The conformity index general (CIgen) was used to quantify the interobserver agreement. Results: In general, a large variation in interobserver agreement was found for CT (range: 0.29-0.77) as well as for CT-MR delineations (range: 0.17-0.80). The mean CIgen for CT (0.61) was larger compared to CT-MR (0.57) (p = 0.032). Mean GTV volume delineated on CT-MR (6.6 cm³) was larger compared to CT (5.6 cm³) (p = 0.002). Conclusion: Delineation on CT with co-registered MR-images resulted in a larger mean GTV volume and in a decrease in interobserver agreement compared to CT only delineation for supraglottic laryngeal carcinoma. [ABSTRACT FROM AUTHOR]
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- 2015
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8. Consequences of tumor planning target volume reduction in treatment of T2-T4 laryngeal cancer.
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Vugts, Cornelia A. J. M., Terhaard, Chris H. J., Philippens, Marielle E. P., Pameijer, Frank A., Kasperts, Nicolien, and Raaijmakers, Cornelis P. J.
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Background and purpose: Since lymph nodes volumes are generally four times the volume of the primary PTV, the advantage of using tight margins around the primary PTV is not clear. Therefore treatment margins of T2-T4 laryngeal carcinoma for IMRT are generally chosen in such a way that the PTV is comparable to that in conventional radiotherapy. The aim of this study is to quantify the effect of volume reduction of the primary PTV of T2-T4 laryngeal carcinoma with regard to late toxicity despite elective irradiation of lymph node levels II to IV. Methods: Two treatment plans based on conservative (GTV-PTV = 15 mm and 20 mm cranial), and on evidence-based tight margins (GTV-PTV = 8 mm) were calculated for 16 patients. Toxicity effects were estimated based on the dose distributions. Results: Compared to conservative margins, using tight margins resulted in: 1) significant reduction of the normal tissue complication probability (NTCP) for swallowing muscles and submandibular glands, 2) significant reduction of the mean dose in all organs at risk (OAR), 3) a mean dose smaller than 60 Gy for all OARs except for the laryngeal cartilages. When the lymph node levels II to IV were prescribed with an elective dose, an NTCP reduction of 53% for the swallowing muscles and of 23% for the submandibular glands was found by using tight instead of conservative margins. When positive nodes were present, NTCP reduction amounted to 29% and 15%, respectively. Conclusions: There is a potential benefit in realizing evidence-based tight margins for laryngeal cancer patients despite elective irradiation of lymph node levels II to IV. [ABSTRACT FROM AUTHOR]
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- 2014
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9. Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy.
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Braam, Pètra M., Roesink, Judith M., Raaijmakers, Cornelis P. J., Busschers, Wim B., and Terhaard, Chris H. J.
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QUALITY of life ,PATIENTS ,HEAD & neck cancer ,RADIOTHERAPY ,MEDICAL radiology - Abstract
Background: To describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy. Methods: Forty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQH& N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured. Results: There was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years followup. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01). Conclusion: Most of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio. [ABSTRACT FROM AUTHOR]
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- 2007
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10. Detectability and intra-fraction motion of individual elective lymph nodes in head and neck cancer patients on the Magnetic Resonance Image guided linear accelerator.
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Reinders FCJ, de Ridder M, Stijnman PRS, Doornaert PAH, Raaijmakers CPJ, and Philippens MEP
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Background and Purpose: Individual elective lymph node irradiation instead of elective neck irradiation is a new concept for head-and-neck cancer (HNC) patients developed for the Magnetic Resonance Image guided linear accelerator (MR-linac). To prepare this, the detectability, volume changes and intra-fraction motion of elective lymph nodes on the MR-linac was assessed., Materials and Methods: A total of 15 HNC patients underwent diagnostic pre-treatment MRI. Additionally, two MR-linac scans were obtained with a 10-minute time difference in the first week of radiation treatment. Elective lymph node contours inside lymph node levels (Ib-V) were segmented on the pre-treatment MRI and the MR-linac scans and compared on number and maximal transversal diameter. Intra-fraction motion of elective lymph nodes on the MR-linac was estimated using Center of Mass (COM) distances and incremental isotropic expansion of lymph node segmentations., Results: Of all 679 detected lymph nodes on the pre-treatment MRI, eight lymph nodes were not detectable on the first MR-linac scan and 16 new lymph nodes were detected. Lymph node diameters between the pre-treatment MRI scan and the MR-linac scan varied from -0.19 to + 0.13 mm. COM distances varied from 1.2 to 1.7 mm and lymph node contours had to be expanded with 3 mm., Conclusions: Nearly all elective lymph nodes were detectable on the 1.5T MR-linac scan with no major changes in target volumes compared to the pre-treatment MRI. Simulated intra-fraction motion during the MR-linac scans was smaller than the 5-mm margin that will be used in the first elective lymph node radiation treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)
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- 2024
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11. Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification.
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Millen R, De Kort WWB, Koomen M, van Son GJF, Gobits R, Penning de Vries B, Begthel H, Zandvliet M, Doornaert P, Raaijmakers CPJ, Geurts MH, Elias SG, van Es RJJ, de Bree R, Devriese LA, Willems SM, Kranenburg O, Driehuis E, and Clevers H
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- Humans, Biomarkers metabolism, Organoids metabolism, Organoids pathology, Protein-Arginine N-Methyltransferases metabolism, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms genetics, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Antineoplastic Agents metabolism, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology
- Abstract
Background: Organoids are in vitro three-dimensional structures that can be grown from patient tissue. Head and neck cancer (HNC) is a collective term used for multiple tumor types including squamous cell carcinomas and salivary gland adenocarcinomas., Methods: Organoids were established from HNC patient tumor tissue and characterized using immunohistochemistry and DNA sequencing. Organoids were exposed to chemo- and radiotherapy and a panel of targeted agents. Organoid response was correlated with patient clinical response. CRISPR-Cas9-based gene editing of organoids was applied for biomarker validation., Findings: A HNC biobank consisting of 110 models, including 65 tumor models, was generated. Organoids retained DNA alterations found in HNC. Comparison of organoid and patient response to radiotherapy (primary [n = 6] and adjuvant [n = 15]) indicated potential for guiding treatment options in the adjuvant setting. In organoids, the radio-sensitizing potential of cisplatin and carboplatin could be validated. However, cetuximab conveyed radioprotection in most models. HNC-targeted treatments were tested on 31 models, indicating possible novel treatment options with the potential for treatment stratification in the future. Activating PIK3CA mutations did not predict alpelisib response in organoids. Protein arginine methyltransferase 5 (PRMT5) inhibitors were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC., Conclusions: Organoids hold potential as a diagnostic tool in personalized medicine for HNC. In vitro organoid response to radiotherapy (RT) showed a trend that mimics clinical response, indicating the predictive potential of patient-derived organoids. Moreover, organoids could be used for biomarker discovery and validation., Funding: This work was funded by Oncode PoC 2018-P0003., Competing Interests: Declaration of interests H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/. H.C. is inventor of several patents related to organoid technology, is a co-founder of Xilis, Inc., and is currently an employee of Roche, Basel. E.D. is inventor on a patent related to head and neck organoid technology. R.M. is currently an employee of Roche Products, Welwyn. S.M.W. holds unrestricted research grants from Bayer, Pfizer, Roche, MSD, Amgen, and AstraZeneca, all paid to the UMCG., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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12. Magnetic resonance guided elective neck irradiation targeting individual lymph nodes: A new concept.
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Reinders FCJ, Heijst TCFV, Mases J, Terhaard CHJ, Doornaert PAH, Philippens MEP, and Raaijmakers CPJ
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Background and Purpose: Conventional elective neck irradiation (ENI) in head and neck cancer consists of radiotherapy (RT) to the regional lymph node (LN) levels contoured on computed tomography. Hybrid Magnetic Resonance (MR) - RT modalities, such as combined magnetic resonance imaging - linear accelerators (MRLs), might enable new ENI strategies in which individual non-suspect lymph nodes (i-LNs) are targeted. In this treatment planning study, new MR-based strategies targeting i-LNs (i-ENI) were compared to conventional treatment., Materials and Methods: All i-LNs were delineated on MR images of ten retrospectively selected patients with T2-4aN0M0 laryngeal cancer. Three strategies were considered. Strategy A: Conventional ENI delivered with a conventional linear accelerator (35x 1.55 Gy). Strategy B: MRL-based i-ENI (35x 1.55 Gy) to the individual lymph nodes including a background dose to the conventional elective neck volumes (35x 1.03 Gy). Strategy C: Same as Strategy B, but without background dose. In all plans the dose prescription to the primary tumor was 35x 2 Gy. Mean dose ( D
mean ) reductions in the organs at risk (OAR) were compared using the Wilcoxon signed rank test., Results: Compared to conventional ENI (strategy A), significant Dmean reductions of 6.0 Gy and 8.0 Gy were observed in the submandibular glands, of 9.4 Gy and 13 Gy in the carotid arteries and of 9.9 Gy and 19.4 Gy in the thyroid for strategy B and C, respectively. Large inter-patient variations of Dmean reductions were observed in all OARs., Conclusion: MRL-based i-ENI is a new promising concept that could reduce the mean dose to OARs in the neck significantly for patients with laryngeal cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)- Published
- 2021
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13. Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.
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Bahig H, Yuan Y, Mohamed ASR, Brock KK, Ng SP, Wang J, Ding Y, Hutcheson K, McCulloch M, Balter PA, Lai SY, Al-Mamgani A, Sonke JJ, van der Heide UA, Nutting C, Li XA, Robbins J, Awan M, Karam I, Newbold K, Harrington K, Oelfke U, Bhide S, Philippens MEP, Terhaard CHJ, McPartlin AJ, Blanchard P, Garden AS, Rosenthal DI, Gunn GB, Phan J, Cazoulat G, Aristophanous M, McSpadden KK, Garcia JA, van den Berg CAT, Raaijmakers CPJ, Kerkmeijer L, Doornaert P, Blinde S, Frank SJ, and Fuller CD
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Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC)., Methods: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT., Discussion: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC., Trial Registration: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.
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- 2018
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14. Verification of HE-based CTV in laryngeal and hypopharyngeal cancer using pan-cytokeratin.
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Ligtenberg H, Willems SM, Ruiter LN, Jager EA, Terhaard CHJ, Raaijmakers CPJ, and Philippens MEP
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Background: For accurate target definition, we determined margins for the clinical target volume (CTV) for laryngeal and hypopharyngeal cancer in computed tomography (CT, 4.3 mm), magnetic resonance imaging (MR, 6.1 mm) and fluorodeoxyglucose (FDG)-positron emission tomography (PET, 5.2 mm). Previously, we used Hematoxylin-eosin (HE) stained whole-mount sections of total laryngectomy specimens as gold standard to define CTV margins. In the present study, we verified the HE-based tumor delineation with staining for pan-cytokeratin, specific for squamous cell carcinoma., Methods: Twenty-seven patients with a T3/T4 laryngeal hypopharyngeal tumor were included. From each patient, a total laryngectomy specimen was obtained. Four subsequent 3-mm thick slices containing tumor were selected of which 4-µm thick whole-mount sections were obtained and stained with HE and for pan-cytokeratin CK-AE1/3. Tumors were microscopically delineated on both sections by an experienced head-and-neck pathologist. Tumor delineations were compared using the conformity index (CI) and the distance between both contours., Results: The CI between HE-based and CK-AE1/3-based tumor delineations was 0.87. The maximum and 95th percentile (p95) extent of the HE-based tumor delineations from the CK-AE1/3-based tumor delineations were 1.7 mm and 0.7 mm, respectively. The maximum and p95 extent of the CK-AE1/3-based tumor delineations from the HE-based tumor delineations was 1.9 mm and 0.8 mm, respectively., Conclusions: Histopathological assessment of tumor outline on standard HE-stained sections is comparable to microscopic tumor extent based on squamous cell specific pan-cytokeratin staining. Therefore, CTV margins based on HE based tumor contour will be adequate.
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- 2018
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