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Other Publications (71)
- International Journal of Radiation Oncology, Biology, Physics
- European Journal of Internal Medicine
- International Journal of Radiation Oncology, Biology, Physics
- Haematologica
- Acta Neurologica Belgica
- International Journal of Radiation Oncology, Biology, Physics
- BMC Cancer
- Nature Reviews. Cancer
- International Journal of Radiation Oncology, Biology, Physics
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Bulletin Du Cancer
- Nitric Oxide : Biology and Chemistry / Official Journal of the Nitric Oxide Society
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- Anticancer Research
- Surgical Neurology
- International Journal of Radiation Oncology, Biology, Physics
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Cancer
- International Journal of Radiation Oncology, Biology, Physics
- Physics in Medicine and Biology
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- International Journal of Radiation Oncology, Biology, Physics
- The Lancet. Oncology
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- International Journal of Radiation Oncology, Biology, Physics
- Radiation Oncology (London, England)
- Physics in Medicine and Biology
- World Journal of Surgical Oncology
- Frontiers in Oncology
- Radiation Oncology (London, England)
- European Journal of Cancer (Oxford, England : 1990)
- European Journal of Nuclear Medicine and Molecular Imaging
- International Journal of Radiation Oncology, Biology, Physics
- Radiation Oncology (London, England)
- Breast Cancer : Basic and Clinical Research
- Breast Cancer Research and Treatment
- BMC Cancer
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- International Journal of Radiation Oncology, Biology, Physics
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiation Oncology (London, England)
- PloS One
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- World Journal of Gastroenterology : WJG
- Journal of Applied Clinical Medical Physics / American College of Medical Physics
- Radiation Oncology (London, England)
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- BioMed Research International
- Medical Physics
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Oncoimmunology
- Technology in Cancer Research & Treatment
- Expert Review of Gastroenterology & Hepatology
- Nature Genetics
- Oncotarget
- International Journal of Radiation Oncology, Biology, Physics
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
- Acta Oncologica (Stockholm, Sweden)
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Articles by Mark De Ridder in JoVE
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Dinámica de seguimiento del tumor de pulmón para estereotáctica ablativa Radioterapia Corporal
Charles A. Kunos1, Jeffrey M. Fabien1, John P. Shanahan1, Christine Collen2, Thierry Gevaert2, Kenneth Poels2, Robbe Van den Begin2, Benedikt Engels2, Mark De Ridder2
1Department of Radiation Oncology, Summa Cancer Institute, 2Department of Radiation Oncology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel
Other articles by Mark De Ridder on PubMed
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Hypoxic Tumor Cell Radiosensitization: Role of the INOS/NO Pathway
Bulletin Du Cancer.
Mar, 2008 |
Pubmed ID: 18390408 Hypoxia is a common feature of the tumor microenvironment and a major cause of clinical radioresistance. During the last decades, several strategies to improve tumor oxygenation were developed such as breathing high oxygen content gas under hyperbaric conditions (3 atmosphere) and improving tumor perfusion by nicotinamide, in combination with carbogen breathing and accelerated radiotherapy to counteract tumor repopulation (ARCON). Other strategies to overcome hypoxia induced radioresistance are the use of hypoxic cell radiosensitizers, which mimic oxygen and enhance thereby radiation damage (e.g. the nitroimidazoles) and bioreductive drugs, which undergo intracellular reduction to form active cytotoxic species under low oxygen tension (e.g. mitomycin C and tirapazamine). A meta-analysis of all randomized trials in which some form of hypoxic modification was performed, showed an improved local control and survival, especially in cervix and head-and-neck cancer. Nevertheless, none of the discussed strategies are used in clinical routine because of feasibility and toxicity issues. We developed an alternative strategy that takes advantage of the microenvironment of solid tumors for tumor specific radiosensitization. The inducible isoform of nitric oxide synthase (iNOS) may be induced by bacterial LPS or its derivate lipid A, is expressed by a variety of solid tumors and generates NO at high rates inside tumor cells. This local production of NO results in efficient hypoxic tumor cell radiosensitization, at non-toxic extracellular concentrations of NO. In addition, iNOS is transcriptionally upregulated by hypoxia and proinflammatory cytokines such as interferon-gamma. Hence, we proposed the pro-inflammatory tumor infiltrate as a new target for radiosensitizing strategies and identified two mechanisms: First, tumor associated immune cells (macrophages, T/NK-cells) are a source of mediators that may induce the iNOS/NO pathway inside tumor cells. Second, tumor associated macrophages can produce high levels of NO that may radiosensitize bystander tumor cells. Our ongoing research is focused on combining immunostimulatory and radiosensitizing strategies.
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IFN-gamma+ CD8+ T Lymphocytes: Possible Link Between Immune and Radiation Responses in Tumor-relevant Hypoxia
International Journal of Radiation Oncology, Biology, Physics.
Jul, 2008 |
Pubmed ID: 18514774 Activated T lymphocytes are known to kill tumor cells by triggering cytolytic mechanisms; however, their ability to enhance radiation responses remains unclear. This study examined the radiosensitizing potential of mouse CD8+ T cells, obtained by T-cell-tailored expansion and immunomagnetic purification. Activated CD8+ T cells displayed an interferon (IFN)-gamma+ phenotype and enhanced by 1.8-fold the radiosensitivity of EMT-6 tumor cells in 1% oxygen, which modeled tumor-relevant hypoxia. Radiosensitization was counteracted by neutralizing IFN-gamma or by blocking the inducible isoform of nitric oxide synthase, thus delineating the immune-tumor cell interaction through the IFN-gamma secretion pathway. Reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and fluorescence-activated cell sorter data in agreement detected downregulation of the IFN-gamma gene by hypoxia, which caused IFN-gamma deficiency next to radioresistance. Therefore, immune and radiation responses are likely to be allied in the hypoxic tumor microenvironment, and CD8+ T cells may bridge immunostimulatory and radiosensitizing strategies.
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Delivering Affordable Cancer Care in High-income Countries
The Lancet. Oncology.
Sep, 2011 |
Pubmed ID: 21958503 The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
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Computer-aided Analysis of Star Shot Films for High-accuracy Radiation Therapy Treatment Units
Physics in Medicine and Biology.
May, 2012 |
Pubmed ID: 22538289 As mechanical stability of radiation therapy treatment devices has gone beyond sub-millimeter levels, there is a rising demand for simple yet highly accurate measurement techniques to support the routine quality control of these devices. A combination of using high-resolution radiosensitive film and computer-aided analysis could provide an answer. One generally known technique is the acquisition of star shot films to determine the mechanical stability of rotations of gantries and the therapeutic beam. With computer-aided analysis, mechanical performance can be quantified as a radiation isocenter radius size. In this work, computer-aided analysis of star shot film is further refined by applying an analytical solution for the smallest intersecting circle problem, in contrast to the gradient optimization approaches used until today. An algorithm is presented and subjected to a performance test using two different types of radiosensitive film, the Kodak EDR2 radiographic film and the ISP EBT2 radiochromic film. Artificial star shots with a priori known radiation isocenter size are used to determine the systematic errors introduced by the digitization of the film and the computer analysis. The estimated uncertainty on the isocenter size measurement with the presented technique was 0.04 mm (2σ) and 0.06 mm (2σ) for radiographic and radiochromic films, respectively. As an application of the technique, a study was conducted to compare the mechanical stability of O-ring gantry systems with C-arm-based gantries. In total ten systems of five different institutions were included in this study and star shots were acquired for gantry, collimator, ring, couch rotations and gantry wobble. It was not possible to draw general conclusions about differences in mechanical performance between O-ring and C-arm gantry systems, mainly due to differences in the beam-MLC alignment procedure accuracy. Nevertheless, the best performing O-ring system in this study, a BrainLab/MHI Vero system, and the best performing C-arm system, a Varian Truebeam system, showed comparable mechanical performance: gantry isocenter radius of 0.12 and 0.09 mm, respectively, ring/couch rotation of below 0.10 mm for both systems and a wobble of 0.06 and 0.18 mm, respectively. The methodology described in this work can be used to monitor mechanical performance constancy of high-accuracy treatment devices, with means available in a clinical radiation therapy environment.
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Small Airways Function in Breast Cancer Patients Before and After Radiotherapy
Breast Cancer Research and Treatment.
Oct, 2012 |
Pubmed ID: 22910929 Radiotherapy treatments for early stage breast cancer patients potentially affect the lung in its most distal air spaces, and previous studies have indicated consistently low baseline values for diffusing capacity in breast cancer patients. We aimed to quantitatively assess baseline small airway function and the acute effects of radiotherapy in breast cancer patients with no confounding effects from respiratory disease or considerable smoking history. In 60 breast cancer patients selected from an ongoing randomized controlled trial, the small airways function was assessed at baseline and 3 months later, after having received either conventional radiotherapy (CR; n = 26) or hypofractionated tomotherapy (TT; n = 34). All indices of small airway function in breast cancer patients were found to be indistinguishable from healthy controls. The total lung capacity was significantly decreased and ventilation heterogeneity was significantly increased 3 months after baseline in the CR arm, but not in the TT arm. When corrected for hemoglobin and lung volume, pulmonary diffusing capacity was not affected by radiotherapy in either treatment arm. Alternatively, discarding patients receiving chemotherapy or loco-regional treatment did not affect these results. We conclude that middle-aged women with breast cancer, but no history of respiratory disease, have normal baseline small airways function. Conventional radiotherapy induces a restrictive pattern and increases heterogeneity of ventilation, the latter most likely resulting from differential expansion between locally irradiated peripheral lung zones and the remainder of the lung. The TT modality did not lead to any such changes.
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Feasibility of Using the Vero SBRT System for Intracranial SRS
Journal of Applied Clinical Medical Physics / American College of Medical Physics.
2014 |
Pubmed ID: 24423838 The Vero SBRT system was benchmarked in a planning study against the Novalis SRS system for quality of delivered dose distributions to intracranial lesions and assessing the Vero system's capacity for SRS. A total of 27 patients with one brain lesion treated on the Novalis system, with 3 mm leaf width MLC and C-arm gantry, were replanned for Vero, with a 5 mm leaf width MLC mounted on an O-ring gantry allowing rotations around both the horizontal and vertical axis. The Novalis dynamic conformal arc (DCA) planning included vertex arcs, using 90° couch rotation. These vertex arcs cannot be reproduced with Vero due to the mechanical limitations of the O-ring gantry. Alternative class solutions were investigated for the Vero. Additionally, to distinguish between the effect of MLC leaf width and different beam arrangements on dose distributions, the Vero class solutions were also applied for Novalis. In addition, the added value of noncoplanar IMRT was investigated in this study. Quality of the achieved dose distributions was expressed in the conformity index (CI) and gradient index (GI), and compared using a paired Student's t-test with statistical significance for p-values ≤ 0.05. For lesions larger than 5 cm3, no statistical significant difference in conformity was observed between Vero and Novalis, but for smaller lesions, the dose distributions showed a significantly better conformity for the Novalis (ΔCI = 13.74%, p = 0.0002) mainly due to the smaller MLC leaf width. Using IMRT on Vero reduces this conformity difference to nonsignificant levels. The cutoff for achieving a GI around 3, characterizing a sharp dose falloff outside the target volume was 4 cm3 for Novalis and 7 cm3 for Vero using DCA technique. Using noncoplanar IMRT, this threshold was reduced to 3 cm3 for the Vero system. The smaller MLC and the presence of the vertex fields allow the Novalis system to better conform the dose around the lesion and to obtain steeper dose falloff outside the lesion. Comparable dosimetric characteristics can be achieved with Vero for lesions larger than 3 cm3 and using IMRT.
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Anti-melanoma Vaccines Engineered to Simultaneously Modulate Cytokine Priming and Silence PD-L1 Characterized Using Ex Vivo Myeloid-derived Suppressor Cells As a Readout of Therapeutic Efficacy
Oncoimmunology.
2014 |
Pubmed ID: 25954597 Efficacious antitumor vaccines strongly stimulate cancer-specific effector T cells and counteract the activity of tumor-infiltrating immunosuppressive cells. We hypothesised that combining cytokine expression with silencing programmed cell death ligand 1 (PD-L1) could potentiate anticancer immune responses of lentivector vaccines. Thus, we engineered a collection of lentivectors that simultaneously co-expressed an antigen, a PD-L1-silencing shRNA, and various T cell-polarising cytokines, including interferon γ (IFNγ), transforming growth factor β (TGFβ) or interleukins (IL12, IL15, IL23, IL17A, IL6, IL10, IL4). In a syngeneic B16F0 melanoma model and using tyrosinase related protein 1 (TRP1) as a vaccine antigen, we found that simultaneous delivery of IL12 and a PD-L1-silencing shRNA was the only combination that exhibited therapeutically relevant anti-melanoma activities. Mechanistically, we found that delivery of the PD-L1 silencing construct boosted T cell numbers, inhibited in vivo tumor growth and strongly cooperated with IL12 cytokine priming and antitumor activities. Finally, we tested the capacities of our vaccines to counteract tumor-infiltrating myeloid-derived suppressor cell (MDSC) activities ex vivo. Interestingly, the lentivector co-expressing IL12 and the PD-L1 silencing shRNA was the only one that counteracted MDSC suppressive activities, potentially underlying the observed anti-melanoma therapeutic benefit. We conclude that (1) evaluation of vaccines in healthy mice has no significant predictive value for the selection of anticancer treatments; (2) B16 cells expressing xenoantigens as a tumor model are of limited value; and (3) vaccines which inhibit the suppressive effect of MDSC on T cells in our ex vivo assay show promising and relevant antitumor activities.
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