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      Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas.

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          Abstract

          Proton minibeam radiation therapy (pMBRT) is a novel strategy which has already shown a remarkable reduction in neurotoxicity as to compared with standard proton therapy. Here we report on the first evaluation of tumor control effectiveness in glioma bearing rats with highly spatially modulated proton beams. Whole brains (excluding the olfactory bulb) of Fischer 344 rats were irradiated. Four groups of animals were considered: a control group (RG2 tumor bearing rats), a second group of RG2 tumor-bearing rats and a third group of normal rats that received pMBRT (70 Gy peak dose in one fraction) with very heterogeneous dose distributions, and a control group of normal rats. The tumor-bearing and normal animals were followed-up for 6 months and one year, respectively. pMBRT leads to a significant tumor control and tumor eradication in 22% of the cases. No substantial brain damage which confirms the widening of the therapeutic window for high-grade gliomas offered by pMBRT. Additionally, the fact that large areas of the brain can be irradiated with pMBRT without significant side effects, would allow facing the infiltrative nature of gliomas.

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          Most cited references43

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          Understanding survival analysis: Kaplan-Meier estimate

          Kaplan-Meier estimate is one of the best options to be used to measure the fraction of subjects living for a certain amount of time after treatment. In clinical trials or community trials, the effect of an intervention is assessed by measuring the number of subjects survived or saved after that intervention over a period of time. The time starting from a defined point to the occurrence of a given event, for example death is called as survival time and the analysis of group data as survival analysis. This can be affected by subjects under study that are uncooperative and refused to be remained in the study or when some of the subjects may not experience the event or death before the end of the study, although they would have experienced or died if observation continued, or we lose touch with them midway in the study. We label these situations as censored observations. The Kaplan-Meier estimate is the simplest way of computing the survival over time in spite of all these difficulties associated with subjects or situations. The survival curve can be created assuming various situations. It involves computing of probabilities of occurrence of event at a certain point of time and multiplying these successive probabilities by any earlier computed probabilities to get the final estimate. This can be calculated for two groups of subjects and also their statistical difference in the survivals. This can be used in Ayurveda research when they are comparing two drugs and looking for survival of subjects.
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            Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS).

            We have reviewed the studies on radiation-induced vascular changes in human and experimental tumors reported in the last several decades. Although the reported results are inconsistent, they can be generalized as follows. In the human tumors treated with conventional fractionated radiotherapy, the morphological and functional status of the vasculature is preserved, if not improved, during the early part of a treatment course and then decreases toward the end of treatment. Irradiation of human tumor xenografts or rodent tumors with 5-10 Gy in a single dose causes relatively mild vascular damages, but increasing the radiation dose to higher than 10 Gy/fraction induces severe vascular damage resulting in reduced blood perfusion. Little is known about the vascular changes in human tumors treated with high-dose hypofractionated radiation such as stereotactic body radiotherapy (SBRT) or stereotactic radiosurgery (SRS). However, the results for experimental tumors strongly indicate that SBRT or SRS of human tumors with doses higher than about 10 Gy/fraction is likely to induce considerable vascular damages and thereby damages the intratumor microenvironment, leading to indirect tumor cell death. Vascular damage may play an important role in the response of human tumors to high-dose hypofractionated SBRT or SRS.
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              Systemic effects of local radiotherapy.

              Radiotherapy is generally used to treat a localised target that includes cancer. Increasingly, evidence indicates that radiotherapy recruits biological effectors outside the treatment field and has systemic effects. We discuss the implications of such effects and the role of the immune system in standard cytotoxic treatments. Because the effects of chemotherapy and radiotherapy are sensed by the immune system, their combination with immunotherapy presents a new therapeutic opportunity. Radiotherapy directly interferes with the primary tumour and possibly reverses some immunosuppressive barriers within the tumour microenvironment-ideally, recovering the role of the primary tumour as an immunogenic hub. Local radiation also triggers systemic effects that can be used in combination with immunotherapy to induce responses outside the radiation field.
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                Author and article information

                Journal
                Sci Rep
                Scientific reports
                Springer Science and Business Media LLC
                2045-2322
                2045-2322
                November 07 2018
                : 8
                : 1
                Affiliations
                [1 ] Laboratoire d'Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), Centre National de la Recherche Scientifique (CNRS), Universités Paris 11 and Paris 7, Campus d'Orsay, 91405, Orsay, France. prezado@imnc.in2p3.fr.
                [2 ] Institut Pasteur, Neuropathologie Expérimentale, Institut Pasteur, 28 Rue du Docteur Roux, 75015, Paris, France.
                [3 ] Institut Curie, PSL Research University, Radiation Oncology Department, Centre de Protonthérapie d'Orsay, 101, F-91898, Orsay, France.
                [4 ] Laboratoire d'Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), Centre National de la Recherche Scientifique (CNRS), Universités Paris 11 and Paris 7, Campus d'Orsay, 91405, Orsay, France.
                [5 ] Institut Curie, PSL Research University, Translational Research Department, Experimental Radiotherapy Platform, Orsay, France.
                [6 ] Paris Sud University, Paris -Saclay University, 91405, Orsay, France.
                [7 ] IR4M, UMR8081, Université Paris Sud, CNRS, Université Paris-Saclay, 91405, Orsay, France.
                Article
                10.1038/s41598-018-34796-8
                10.1038/s41598-018-34796-8
                6220274
                30405188
                66b376a6-5a08-4706-a389-f74fa552cd76
                History

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