16 results on '"Niezink, Anne G. H."'
Search Results
2. Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities.
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de Boer, Janneke W., Keijzer, Kylie, Pennings, Elise R. A., van Doesum, Jaap A., Spanjaart, Anne M., Jak, Margot, Mutsaers, Pim G. N. J., van Dorp, Suzanne, Vermaat, Joost S. P., van der Poel, Marjolein W. M., van Dijk, Lisanne V., Kersten, Marie José, Niezink, Anne G. H., and van Meerten, Tom
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NEUROTOXICOLOGY ,C-reactive protein ,SYNDROMES ,CELLULAR therapy ,FERRITIN ,B cell lymphoma ,MANN Whitney U Test ,CYTOKINE release syndrome ,LACTATE dehydrogenase ,RESEARCH funding ,RECEIVER operating characteristic curves ,LONGITUDINAL method - Abstract
Simple Summary: CAR T-cell therapy became standard of care for patients with relapsed or refractory large B-cell lymphoma. However, their administration can be accompanied by toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. It is important to identify patients at risk for these toxicities in order to start an early intervention in high-risk patients and guide outpatient CAR T-cell treatment. As a consequence, several easy-to-use risk scores including the EASIX and its derivatives were developed. However, in the available studies, disparities existed among the used endpoints and cutoff values, hampering the utility of these tools in practice. This study aims to validate these EASIX scores in a population-based cohort. This can be used to select the best predictive model and to further guide optimization of the proposed risk scores. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (both p = 0.04), and the EASIX approached statistical significance at infusion (p = 0.05). However, the predictive performance was moderate, with area under the curves of 0.61–0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Inflammatory reactions mimic residual or recurrent lymphoma on [18F]FDG-PET/CT after CD19-directed CAR T-cell therapy
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de Boer, Janneke W., Pennings, Elise R. A., Kleinjan, Ankie, van Doesum, Jaap A., Spanjaart, Anne M., Mutsaers, Pim G. N. J., Jak, Margot, van der Poel, Marjolein W. M., Kuipers, Maria T., Adam, Judit A., Diepstra, Arjan, Koens, Lianne, van Dorp, Suzanne, Vermaat, Joost S. P., Niezink, Anne G. H., Kersten, Marie José, and van Meerten, Tom
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- 2023
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4. The Dutch CAR-T Tumorboard Experience: Population-Based Real-World Data on Patients with Relapsed or Refractory Large B-Cell Lymphoma Referred for CD19-Directed CAR T-Cell Therapy in The Netherlands.
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Spanjaart, Anne M., Pennings, Elise R. A., Mutsaers, Pim G. N. J., van Dorp, Suzanne, Jak, Margot, van Doesum, Jaap A., de Boer, Janneke W., Niezink, Anne G. H., Kos, Milan, Vermaat, Joost S. P., Sijs-Szabo, Aniko, van der Poel, Marjolein W. M., Nijhof, Inger S., Kuipers, Maria T., Chamuleau, Martine E. D., Lugtenburg, Pieternella J., Doorduijn, Jeanette K., Serroukh, Yasmina I. M., Minnema, Monique C., and van Meerten, Tom
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RESEARCH ,DISEASE progression ,B cell lymphoma ,CANCER relapse ,TREATMENT effectiveness ,CANCER patients ,SURVIVAL rate ,QUALITY of life ,DESCRIPTIVE statistics ,SURVIVAL analysis (Biometry) ,KAPLAN-Meier estimator ,QUESTIONNAIRES ,RESEARCH funding ,T cells ,PROGRESSION-free survival ,DATA analysis software ,IMMUNOTHERAPY ,OVERALL survival ,PROPORTIONAL hazards models - Abstract
Simple Summary: CAR T-cell therapy has emerged as the new standard of care for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), but real-world outcomes differ across countries. Additionally, real-world data on health-related quality of life (HR-QoL) are scarce but important, as they reflect the direct experience of patients. In the Netherlands, patients can be referred to the CAR-T tumorboard, a national CAR-T expert panel, who decide whether CAR-T is a feasible treatment option. This multicenter study reports on the favorable outcomes, including the HR-QoL, of axicabtagene ciloleucel (axi-cel) for patients with R/R LBCL after ≥2 lines of systemic therapy in the Netherlands. On the other hand, we show that a substantial proportion of patients are still in need of alternative treatments, including improved CAR-T strategies, as they are unfit for or do not respond to axi-cel. Comparing real-world outcomes between cohorts could help to select best practices and further optimize CAR-T treatment. The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020–May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Off-Label Use of Drugs in Pain Medicine and Palliative Care: An Algorithm for the Assessment of its Safe and Legal Prescription
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Verhagen, Constans C. A. H. H. V. M., Niezink, Anne G. H., Engels, Yvonne Y, Hekster, Yechiel Y. A., Doornebal, Joan J., and Vissers, Kris C. P.
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- 2008
6. Development of an instrument to analyze organizational characteristics in multidisciplinary care pathways; the case of colorectal cancer.
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Pluimers, Dorine J., van Vliet, Ellen J., Niezink, Anne G. H., van Mourik, Martijn S., Eddes, Eric H., Wouters, Michel W., Tollenaar, Rob A. E. M., and van Harten, Wim H
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COLON cancer treatment ,TREATMENT of cataracts ,HEALTH outcome assessment ,PHYSICIAN services utilization - Abstract
Background: To analyze the organization of multidisciplinary care pathways such as colorectal cancer care, an instrument was developed based on a recently published framework that was earlier used in analyzing (monodisciplinary) specialist cataract care from a lean perspective. Methods: The instrument was constructed using semi-structured interviews and direct observation of the colorectal care process based on a Rapid Plant Assessment. Six lean aspects that were earlier established that highly impact process design, were investigated: operational focus, autonomous work cell, physical lay-out of resources, multi-skilled team, pull planning and non-value adding activities. To test reliability, clarity and face validity of the instrument, a pilot study was performed in eight Dutch hospitals. Results: In the pilot it proved feasible to apply the instrument and generate the intended information. The instrument consisted of 83 quantitative and 24 qualitative items. Examples of results show differences in operational focus, number of patient visits needed for diagnosis, numbers of staff involved with treatment, the implementation of protocols and utilization of one-stop-shops. Identification of waste and non-value adding activities may need further attention. Based on feedback from involved clinicians the face validity was acceptable and the results provided useful feedback- and benchmark data. The instrument proved to be reliable and valid for broader implementation in Dutch health care. The limited number of cases made statistical analysis not possible and further validation studies may shed better light on variation. Conclusions: This paper demonstrates the use of an instrument to analyze organizational characteristics in colorectal cancer care from a lean perspective. Wider use might help to identify best organizational practices for colorectal surgery. In larger series the instrument might be used for in-depth research into the relation between organization and patient outcomes. Although we found no reason to adapt the underlying framework, recommendations were made for further development to enable use in different tumor- and treatment modalities and in larger (international) samples that allow for more advanced statistical analysis. Waste from defective care or from wasted human potential will need further elaboration of the instrument. [ABSTRACT FROM AUTHOR]
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- 2015
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7. Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy.
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Cortiula F, Hendriks LEL, Wijsman R, Houben R, Steens M, Debakker S, Canters R, Trovò M, Sijtsema NM, Niezink AGH, Unipan M, Urban S, Michelotti A, Dursun S, Bootsma G, Hattu D, Nuyttens JJ, Moretti E, Taasti VT, and De Ruysscher D
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- Humans, Male, Aged, Female, Protons, Positron Emission Tomography Computed Tomography, Retrospective Studies, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Carcinoma, Non-Small-Cell Lung therapy, Proton Therapy adverse effects, Proton Therapy methods, Lung Neoplasms therapy, Lung Neoplasms etiology, Lymphopenia etiology, Anemia etiology, Radiotherapy, Intensity-Modulated adverse effects, Radiotherapy, Intensity-Modulated methods
- Abstract
Background and Purpose: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment., Materials and Methods: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients., Results: 271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0-4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9-12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16-0.79, P = 0.01)., Conclusion: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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8. External validation of NTCP-models for radiation pneumonitis in lung cancer patients treated with chemoradiotherapy.
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Niezink AGH, van der Schaaf A, Wijsman R, Chouvalova O, van der Wekken AJ, Rutgers SR, Pieterman RM, van Putten JWG, de Hosson SM, van der Leest AHD, Ubbels JF, Woltman-van Iersel M, Widder J, Langendijk JA, and Muijs CT
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- Humans, Prospective Studies, Probability, Chemoradiotherapy adverse effects, Radiotherapy Dosage, Radiation Pneumonitis diagnosis, Radiation Pneumonitis epidemiology, Radiation Pneumonitis etiology, Lung Neoplasms radiotherapy
- Abstract
Purpose: Normal tissue complication probability (NTCP) models can be used to estimate the risk of radiation pneumonitis (RP). The aim of this study was to externally validate the most frequently used prediction models for RP, i.e., the QUANTEC and APPELT models, in a large cohort of lung cancer patients treated with IMRT or VMAT. [1-2] METHODS AND MATERIALS: This prospective cohort study, included lung cancer patients treated between 2013 and 2018. A closed testing procedure was performed to test the need for model updating. To improve model performance, modification or removal of variables was considered. Performance measures included tests for goodness of fit, discrimination, and calibration., Results: In this cohort of 612 patients, the incidence of RP ≥ grade 2 was 14.5%. For the QUANTEC-model, recalibration was recommended which resulted in a revised intercept and adjusted regression coefficient (from 0.126 to 0.224) of the mean lung dose (MLD),. The APPELT-model needed revision including model updating with modification and elimination of variables. After revision, the New RP-model included the following predictors (and regression coefficients): MLD (B = 0.250), age (B = 0.049, and smoking status (B = 0.902). The discrimination of the updated APPELT-model was higher compared to the recalibrated QUANTEC-model (AUC: 0.79 vs. 0.73)., Conclusions: This study demonstrated that both the QUANTEC- and APPELT-model needed revision. Next to changes of the intercept and regression coefficients, the APPELT model improved further by model updating and performed better than the recalibrated QUANTEC model. This New RP-model is widely applicable containing non-tumour site specific variables, which can easily be collected., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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9. Semi-automated 18 F-FDG PET segmentation methods for tumor volume determination in Non-Hodgkin lymphoma patients: a literature review, implementation and multi-threshold evaluation.
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Keijzer K, Niezink AGH, de Boer JW, van Doesum JA, Noordzij W, van Meerten T, and van Dijk LV
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In the treatment of Non-Hodgkin lymphoma (NHL), multiple therapeutic options are available. Improving outcome predictions are essential to optimize treatment. The metabolic active tumor volume (MATV) has shown to be a prognostic factor in NHL. It is usually retrieved using semi-automated thresholding methods based on standardized uptake values (SUV), calculated from
18 F-Fluorodeoxyglucose Positron Emission Tomography (18 F-FDG PET) images. However, there is currently no consensus method for NHL. The aim of this study was to review literature on different segmentation methods used, and to evaluate selected methods by using an in house created software tool. A software tool, MU ltiple S UV T hreshold (MUST)-segmenter was developed where tumor locations are identified by placing seed-points on the PET images, followed by subsequent region growing. Based on a literature review, 9 SUV thresholding methods were selected and MATVs were extracted. The MUST-segmenter was utilized in a cohort of 68 patients with NHL. Differences in MATVs were assessed with paired t-tests, and correlations and distributions figures. High variability and significant differences between the MATVs based on different segmentation methods ( p < 0.05) were observed in the NHL patients. Median MATVs ranged from 35 to 211 cc. No consensus for determining MATV is available based on the literature. Using the MUST-segmenter with 9 selected SUV thresholding methods, we demonstrated a large and significant variation in MATVs. Identifying the most optimal segmentation method for patients with NHL is essential to further improve predictions of toxicity, response, and treatment outcomes, which can be facilitated by the MUST-segmenter., Competing Interests: The Department of Radiation Oncology has research collaborations with Elekta, IBA, RaySearch, Siemens, Mirada, Bergoz Instrumentation and Medical Data Works, Genentech. Dr. van Meerten reported research grants from Genentech, Celgene/BMS; personal fees from Kite/Gilead and Janssen (advisory boards); and honoraria from Kite/Gilead and Celgene/BMS (speaker fees) outside the submitted work., (© 2023 The Authors.)- Published
- 2023
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10. Robustness assessment of clinical adaptive proton and photon radiotherapy for oesophageal cancer in the model-based approach.
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Visser S, O Ribeiro C, Dieters M, Mul VE, Niezink AGH, van der Schaaf A, Knopf AC, Langendijk JA, Korevaar EW, Both S, and Muijs CT
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- Humans, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy Dosage, Protons, Organs at Risk, Radiotherapy, Intensity-Modulated methods, Proton Therapy methods, Esophageal Neoplasms radiotherapy
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Purpose: In the Netherlands, oesophageal cancer (EC) patients are selected for intensity modulated proton therapy (IMPT) using the expected normal tissue complication probability reduction (ΔNTCP) when treating with IMPT compared to volumetric modulated arc therapy (VMAT). In this study, we evaluate the robustness of the first EC patients treated with IMPT in our clinic in terms of target and organs-at-risk (OAR) dose with corresponding NTCP, as compared to VMAT., Materials and Methods: For 20 consecutive EC patients, clinical IMPT and VMAT plans were created on the average planning 4DCT. Both plans were robustly evaluated on weekly repeated 4DCTs and if target coverage degraded, replanning was performed. Target coverage was evaluated for complete treatment trajectories with and without replanning. The planned and accumulated mean lung dose (MLD) and mean heart dose (MHD) were additionally evaluated and translated into NTCP., Results: Replanning in the clinic was performed more often for IMPT (15x) than would have been needed for VMAT (8x) (p = 0.11). Both adaptive treatments would have resulted in adequate accumulated target dose coverage. Replanning in the first week of treatment had most clinical impact, as anatomical changes resulting in insufficient accumulated target coverage were already observed at this stage. No differences were found in MLD between the planned dose and the accumulated dose. Accumulated MHD differed from the planned dose (p < 0.001), but since these differences were similar for VMAT and IMPT (1.0 and 1.5 Gy, respectively), the ΔNTCP remained unchanged., Conclusion: Following an adaptive clinical workflow, adequate target dose coverage and stable OAR doses with corresponding NTCPs was assured for both IMPT and VMAT., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2022
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11. [New treatment for patients with therapy-resistant lymphoma: CD19-targeted chimeric antigen receptor (CAR) T-cell therapy].
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van Doesum JA, Niezink AGH, and van Meerten T
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- Antigens, CD19, Cell- and Tissue-Based Therapy, Humans, Immunotherapy, Adoptive, Lymphoma, Large B-Cell, Diffuse, Receptors, Chimeric Antigen
- Abstract
The prognosis of patients with diffuse large B-cell lymphoma a primary refractory disease or relapsed within 12 months after autologous hematopoietic cell transplantation is poor with a median survival of only 6 months. With the new CD19-directed CAR T-cell therapy, 40% of the patients still achieve a long-term remission. However, this new treatment does bring new challenges such as bridging the time during the CAR T-cell product time, and recognition of treatment-related side effects such as cytokine release syndrome or neurotoxicity. Therefore, treatment by a dedicated, multidisciplinary team is necessary. Future research will focus on extending CAR T-cell therapy to other diseases and improve treatment in non-responsiveness or resistance to CAR-T cell therapy.
- Published
- 2021
12. Extranodal Natural Killer/T-cell Lymphoma, Nasal Type: Diagnosis and Treatment.
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van Doesum JA, Niezink AGH, Huls GA, Beijert M, Diepstra A, and van Meerten T
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The aggressive lymphoma, extranodal natural killer/T-cell lymphoma-nasal type, is strongly associated with Epstein-Barr virus (EBV) and is most common in Asia and in South and Central America. By contrast, incidence is low in the United States and Europe, where extranodal natural killer/T-cell lymphoma represents only 0.2%-0.4% of all newly diagnosed non-Hodgkin lymphomas. At diagnosis, it is important to test for EBV DNA in plasma by polymerase chain reaction and to carry out positron emission tomography/computer tomography and magnetic resonance imaging of the nasopharynx. In stage I/II disease, radiotherapy is the most important treatment modality, but in high-risk stage I/II disease (stage II, age > 60 y, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group performance score ≥2, primary tumor invasion), it should be combined with chemotherapy. The most optimal responses are reached with nonmultidrug resistance-based therapy (eg, asparaginase- or platinum-based therapy). Therapeutic approaches consist of either platinum-based concurrent chemoradiotherapy or sequential chemoradiotherapy. The minimum dose of radiotherapy should be 50-56 Gy. Treatment of stage III/IV disease consists of 3 cycles of chemotherapy followed by autologous hematopoietic cell transplantation. Allogeneic hematopoietic cell transplantation should only be considered in case of relapsed disease or after difficulty reaching complete remission. During treatment and follow-up, plasma EBV levels should be monitored as a marker of tumor load., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)
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- 2021
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13. Updating Photon-Based Normal Tissue Complication Probability Models for Pneumonitis in Patients With Lung Cancer Treated With Proton Beam Therapy.
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Jain V, Niezink AGH, Frick M, Doucette A, Mendes A, Simone CB 2nd, Langendijk JA, Wijsman R, Feigenberg SJ, Levin W, Cengel KA, van der Schaaf A, and Berman AT
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- Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung radiotherapy, Humans, Photons, Probability, Retrospective Studies, Lung Neoplasms radiotherapy, Pneumonia, Proton Therapy adverse effects, Radiation Pneumonitis etiology
- Abstract
Purpose: No validated models for predicting the risk of radiation pneumonitis (RP) with proton beam therapy (PBT) currently exist. Our goal was to externally validate and recalibrate multiple established photon-based normal tissue complication probability models for RP in a cohort with locally advanced nonsmall cell lung cancer treated with contemporary doses of chemoradiation using PBT., Methods and Materials: The external validation cohort consisted of 99 consecutive patients with locally advanced nonsmall cell lung cancer treated with chemoradiation using PBT. RP was retrospectively scored at 3 and 6 months posttreatment. We evaluated the performance of the photon Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) pneumonitis model, the QUANTEC model adjusted for clinical risk factors, and the newer Netherlands updated QUANTEC model. A closed testing procedure was performed to test the need for model updating, either by recalibration-in-the-large (re-estimation of intercept), recalibration (re-estimation of intercept/slope), or model revision (re-estimation of all coefficients)., Results: There were 21 events (21%) of ≥grade 2 RP. The closed testing procedure on the PBT data set did not detect major deviations between the models and the data and recommended adjustment of the intercept only for the photon-based Netherlands updated QUANTEC model (intercept update: -1.2). However, an update of the slope and revision of the model coefficients were not recommended by the closed testing procedure, as the deviations were not significant within the power of the data., Conclusions: The similarity between the dose-response relationship for PBT and photons for normal tissue complications has been an assumption until now. We demonstrate that the preexisting, widely used photon based models fit our PBT data well with minor modifications. These now-validated and updated normal tissue complication probability models can aid in individualizing selection of the most optimal treatment technique for a particular patient., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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14. Evaluation of interplay and organ motion effects by means of 4D dose reconstruction and accumulation.
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Meijers A, Knopf AC, Crijns APG, Ubbels JF, Niezink AGH, Langendijk JA, Wijsman R, and Both S
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- Four-Dimensional Computed Tomography, Humans, Movement, Organ Motion, Radiotherapy Planning, Computer-Assisted, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung radiotherapy, Lung Neoplasms radiotherapy, Proton Therapy
- Abstract
Purpose: Pencil beam scanned proton therapy (PBS-PT) treatment quality might be compromised by interplay and motion effects. Via fraction-wise reconstruction of 4D dose distributions and dose accumulation, we assess the clinical relevance of motion related target dose degradation in thoracic cancer patients., Methods and Materials: For the ten thoracic patients (Hodgkin lymphoma and non-small cell lung cancer) treated at our proton therapy facility, daily breathing pattern records, treatment delivery log-files and weekly repeated 4DCTs were collected. Patients exhibited point-max target motion of up to 20 mm. They received robustly optimized treatment plans, delivered with five-times rescanning in fractionated regimen. Treatment delivery records were used to reconstruct 4D dose distributions and the accumulated treatment course dose per patient. Fraction-wise target dose degradations were analyzed and the accumulated treatment course dose, representing an estimation of the delivered dose, was compared with the prescribed dose., Results: No clinically relevant loss of target dose homogeneity was found in the fraction-wise reconstructed 4D dose distributions. Overall, in 97% of all reconstructed fraction doses, D98 remained within 5% from the prescription dose. The V95 of accumulated treatment course doses was higher than 99.7% for all ten patients., Conclusions: 4D dose reconstruction and accumulation enables the clinical estimation of actual exhibited interplay and motion effects. In the patients considered here, the loss of homogeneity caused by interplay and organ motion did not show systematic pattern and smeared out throughout the course of fractionated PBS-PT treatment. Dose degradation due to anatomical changes showed to be more severe and triggered treatment adaptations for five patients., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2020
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15. Pulmonary Function Changes After Radiotherapy for Lung or Esophageal Cancer: A Systematic Review Focusing on Dose-Volume Parameters.
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Niezink AGH, de Jong RA, Muijs CT, Langendijk JA, and Widder J
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- Female, Humans, Male, Risk Factors, Dose-Response Relationship, Radiation, Esophageal Neoplasms radiotherapy, Lung Neoplasms radiotherapy, Respiratory Function Tests methods
- Abstract
Background: Despite technical developments in treatment delivery, radiation-induced lung toxicity (RILT) remains a crucial problem in thoracic radiotherapy. Clinically based RILT scores have their limitations, and more objective measures such as pulmonary functions tests (PFTs) might help to improve treatment strategies., Purpose: To summarize the available evidence about the effect of dose to the lung in thoracic radiotherapy on forced expiratory volume in one second (FEV1) and diffusion capacity (DLCO) in patients with lung and esophageal cancer treated with curative intent., Material and Methods: A systematic review following the PRISMA guidelines was performed, using MEDLINE and including clinical studies using (chemo)radiotherapy (CRT) or stereotactic ablative radiotherapy (SABR) for lung or CRT for esophageal cancer that reported both lung dose-volume histogram (DVH) parameters and changes in PFT results. Search terms included lung and esophageal neoplasms, respiratory function tests, and radiotherapy., Results: Fifteen studies met the inclusion criteria. Seven out of 13 studies on lung cancer reported significant declines (defined as a p value < .05) in PFT results. Both esophageal studies reported significant DLCO declines. One SABR study found a correlation between low lung-dose parameters and FEV1 decline. Relations between decline of FEV1 (three studies) or decline of DLCO (five studies), respectively, and DVH parameters were found in eight studies analyzing CRT. Furthermore, a heterogeneous range of clinical risk factors for pulmonary function changes were reported in the selected studies., Conclusions: There is evidence that pulmonary function declines after RT in a dose-dependent manner, but solid data about lung DVH parameters predicting changes in PFT results are scarce. A major disadvantage was the wide variety of methods used, frequently lacking multivariable analyses. Studies using prospective high-quality data, analyzed with appropriate statistical methods, are needed. The Oncologist 2017;22:1257-1264 IMPLICATIONS FOR PRACTICE: Radiation-induced lung toxicity remains crucial in thoracic radiotherapy. To prevent this toxicity in the future and individualize patient treatment, objective measures of pulmonary toxicity are needed. Pulmonary function tests may provide such objective measures. This systematic review, included all available clinical studies using external beam radiotherapy for lung or esophageal cancer reporting pulmonary function combined with dose-volume histogram parameters. There is preliminary evidence that pulmonary function declines post radiotherapy in a dose-dependent manner. Data quality and analyses were generally limited. Analyses of high-quality data are therefore urgently needed to improve individualization of advanced radiation therapy., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)
- Published
- 2017
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16. An instrument dedicated for modelling of pulmonary radiotherapy.
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Niezink AG, Dollekamp NJ, Elzinga HJ, Borger D, Boer EJ, Ubbels JF, Woltman-van Iersel M, van der Leest AH, Beijert M, Groen HJ, Kraan J, Hiltermann TJ, van der Wekken AJ, van Putten JW, Rutgers SR, Pieterman RM, de Hosson SM, Roenhorst AW, Langendijk JA, and Widder J
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- Aged, Aged, 80 and over, Female, Humans, Imaging, Three-Dimensional, Lung pathology, Male, Middle Aged, Prospective Studies, Quality of Life, Radiotherapy adverse effects, Radiotherapy methods, Lung Neoplasms radiotherapy, Radiotherapy instrumentation
- Abstract
Background and Purpose: Radiotherapy plays a pivotal role in lung cancer treatment. Selection of patients for new (radio)therapeutic options aiming at improving outcomes requires reliable and validated prediction models. We present the implementation of a prospective platform for evaluation and development of lung radiotherapy (proPED-LUNG) as an instrument enabling multidimensional predictive modelling., Materials and Methods: ProPED-LUNG was designed to comprise relevant baseline and follow up data of patients receiving pulmonary radiotherapy with curative intent. Patient characteristics, diagnostic and staging information, treatment parameters including full dose-volume-histograms, tumour control, survival, and toxicity are scored. Besides physician-rated data, a range of patient-rated data regarding symptoms and health-related quality-of-life are collected., Results: After 18 months of accrual, 315 patients have been included (accrual rate, 18 per month). Of the first hundred patients included, 70 received conformal (chemo)radiotherapy and 30 underwent stereotactic radiotherapy. Compliance at 3 and 6 months follow-up was 96-100% for patient-rated, and 81-94% for physician-rated assessments. For data collection, 0.4 FTE were allocated in a 183 FTE department (0.2%)., Conclusions: ProPED-LUNG is feasible with high compliance rates and yields a large amount of high quality prospective disease-related, treatment-related, patient- and physician-rated data which can be used to evaluate new developments in pulmonary radiotherapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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