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Title: Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy

Abstract

Purpose: Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumors followed by stereotactic irradiation with X-rays from a synchrotron source. The purpose of this study was to determine whether the efficacy of iodine-enhanced SSR could be further improved in the F98 rodent glioma model, by using a concomitant injection of an iodinated contrast agent and a transient blood-brain barrier opener (mannitol) during irradiation. Methods and Materials: Fourteen days after intracerebral inoculations of F98 cells, the rats were irradiated with 50-keV X-rays while receiving an infusion of hyperosmotic mannitol with iodine, either intravenously or via the carotid (9 to 15 rats per group, 117 rats total). Results: For doses {<=}15 Gy, the intracarotid infusion of mannitol and iodine improved the rats' survival compared with intravenous injection or irradiation alone. The percentage-increased life spans (ILS) were 91%, 116%, and 169% without iodine, after infusion of iodine and mannitol intravenously, and intracarotid, respectively (15 Gy). At 25 Gy, the rats irradiated without iodine had the longest survival (ILS = 607%), but no additional benefit was obtained with iodine and mannitol. Conclusions: Iodine-enhanced SSR is significantly improved with concomitant intracarotid infusion of iodine and mannitol formore » radiation doses {<=}15 Gy.« less

Authors:
 [1];  [2];  [2];  [1];  [2];  [2];  [1];  [2];  [2];  [1];  [2];  [2];  [3];  [1];  [2];  [2];  [1];  [2];  [2];  [1] more »;  [2];  [2];  [2];  [4] « less
  1. INSERM U647, Grenoble (France)
  2. (France)
  3. Centre Hospitalier Bellevue, Departement de pathologie, Saint Etienne (France)
  4. INSERM U647, Grenoble (France) and Universite Joseph Fourier, Grenoble (France) and European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble (France). E-mail: h.elleaume@esrf.fr
Publication Date:
OSTI Identifier:
20793322
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2005.09.004; PII: S0360-3016(05)02595-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BLOOD-BRAIN BARRIER; BRAIN; CONTRAST MEDIA; GLIOMAS; INFUSION; INTRAVENOUS INJECTION; IODINE; IRRADIATION; LIFE SPAN; RADIATION DOSES; RADIOTHERAPY; RATS; SYNCHROTRON RADIATION; SYNCHROTRON RADIATION SOURCES; SYNCHROTRONS; X RADIATION

Citation Formats

Adam, Jean-Francois, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Joubert, Aurelie, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Biston, Marie-Claude, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Charvet, Anne-Marie, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Peoc'h, Michel, Le Bas, Jean-Francois, Universite Joseph Fourier, Grenoble, CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble, Balosso, Jacques, Universite Joseph Fourier, Grenoble, CHRU Grenoble, Hopital Michallon, Departement de Cancerologie et d'Hematologie, Grenoble, Esteve, Francois, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble, and Elleaume, Helene. Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Adam, Jean-Francois, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Joubert, Aurelie, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Biston, Marie-Claude, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Charvet, Anne-Marie, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Peoc'h, Michel, Le Bas, Jean-Francois, Universite Joseph Fourier, Grenoble, CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble, Balosso, Jacques, Universite Joseph Fourier, Grenoble, CHRU Grenoble, Hopital Michallon, Departement de Cancerologie et d'Hematologie, Grenoble, Esteve, Francois, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble, & Elleaume, Helene. Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy. United States. doi:10.1016/J.IJROBP.2005.0.
Adam, Jean-Francois, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Joubert, Aurelie, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Biston, Marie-Claude, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Charvet, Anne-Marie, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, Peoc'h, Michel, Le Bas, Jean-Francois, Universite Joseph Fourier, Grenoble, CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble, Balosso, Jacques, Universite Joseph Fourier, Grenoble, CHRU Grenoble, Hopital Michallon, Departement de Cancerologie et d'Hematologie, Grenoble, Esteve, Francois, Universite Joseph Fourier, Grenoble, European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble, CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble, and Elleaume, Helene. Wed . "Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20793322,
title = {Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy},
author = {Adam, Jean-Francois and Universite Joseph Fourier, Grenoble and European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble and Joubert, Aurelie and Universite Joseph Fourier, Grenoble and European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble and Biston, Marie-Claude and Universite Joseph Fourier, Grenoble and European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble and Charvet, Anne-Marie and Universite Joseph Fourier, Grenoble and European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble and Peoc'h, Michel and Le Bas, Jean-Francois and Universite Joseph Fourier, Grenoble and CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble and Balosso, Jacques and Universite Joseph Fourier, Grenoble and CHRU Grenoble, Hopital Michallon, Departement de Cancerologie et d'Hematologie, Grenoble and Esteve, Francois and Universite Joseph Fourier, Grenoble and European Synchrotron Radiation Facility, Medical Beamline ID17, Grenoble and CHRU Grenoble, Hopital Michallon, Unite IRM, Grenoble and Elleaume, Helene},
abstractNote = {Purpose: Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumors followed by stereotactic irradiation with X-rays from a synchrotron source. The purpose of this study was to determine whether the efficacy of iodine-enhanced SSR could be further improved in the F98 rodent glioma model, by using a concomitant injection of an iodinated contrast agent and a transient blood-brain barrier opener (mannitol) during irradiation. Methods and Materials: Fourteen days after intracerebral inoculations of F98 cells, the rats were irradiated with 50-keV X-rays while receiving an infusion of hyperosmotic mannitol with iodine, either intravenously or via the carotid (9 to 15 rats per group, 117 rats total). Results: For doses {<=}15 Gy, the intracarotid infusion of mannitol and iodine improved the rats' survival compared with intravenous injection or irradiation alone. The percentage-increased life spans (ILS) were 91%, 116%, and 169% without iodine, after infusion of iodine and mannitol intravenously, and intracarotid, respectively (15 Gy). At 25 Gy, the rats irradiated without iodine had the longest survival (ILS = 607%), but no additional benefit was obtained with iodine and mannitol. Conclusions: Iodine-enhanced SSR is significantly improved with concomitant intracarotid infusion of iodine and mannitol for radiation doses {<=}15 Gy.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 64,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2006},
month = {Wed Feb 01 00:00:00 EST 2006}
}
  • Purpose: To evaluate direct intracerebral and intratumoral iodine delivery as means to improve iodine distribution for synchrotron stereotactic radiotherapy (SSR) and to evaluate the corresponding X-ray dose distribution. Methods and Materials: Healthy rats and F98 glioma-bearing rats received an iodinated contrast agent (iopamidol) intracerebrally either by bolus injection (5 {mu}L over approximately 1 min) or by convection-enhanced delivery (infusion volumes of 5, 10, and 20 {mu}L at a rate of 0.5 {mu}L/min). We used synchrotron computed tomography (CT) to determine the iodine distribution after completion of infusion and a Monte Carlo code to compute the resulting radiation dose in SSR.more » Results: Post-infusion CT imaging revealed high iodine concentrations in the perfused area with both injection methods. The iodine concentration remained elevated, with an exponential decay time constant of approximately 50 min, well suited for SSR treatment. Convection-enhanced delivery was shown to provide more uniform and controlled volumes of distribution than bolus injection and was chosen to evaluate the corresponding X-ray dose distribution. Sharp dose gradients around the target and excellent sparing of the contralateral brain were achievable with low iodine concentrations in the surrounding healthy brain tissues and blood vessels. Conclusions: Convection-enhanced delivery is an effective method to deliver high iodine concentrations and could improve the outcome of iodine-enhanced SSR.« less
  • Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability mapsmore » were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.« less
  • Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyomore » Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R{sup 2}) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R{sup 2} between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R{sup 2} was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by the JSPS Core-to-Core Program(No. 23003) and Grant-in-aid from the JSPS Fellows.« less
  • Purpose: To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. Methods and Materials: Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gymore » (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. Results: Median tumor height and volume decreased from 4.8 mm and 270.7 mm{sup 3} at baseline to 2.6 mm and 86.6 mm{sup 3} at the last individual follow-up, respectively (p < 0.001, p < 0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p < 0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. Conclusion: Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the total dose below 60 Gy seems to be possible.« less
  • Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Coremore » Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.« less