Hélène Elleaume1,2, Rolf F Barth3, Julia Rousseau4,5, Laure Bobyk4,5, Jacques Balosso4,6,7, Weilian Yang8,9, Tianyao Huo8,10, Robin Nakkula8,11. 1. INSERM UA07 Team STROBE, ESRF, 71 Avenue des Martyrs, 38000, Grenoble, France. Helene.Elleaume@inserm.fr. 2. European Synchrotron Radiation Facility, ID17 Medical Beamline, 71 Avenue Martyrs, 38000, Grenoble, France. Helene.Elleaume@inserm.fr. 3. Department of Pathology, The Ohio State University, 4132 Graves Hall - 333 W. 10th Avenue, Columbus, OH, 43210, USA. rolf.barth@osumc.edu. 4. INSERM UA07 Team STROBE, ESRF, 71 Avenue des Martyrs, 38000, Grenoble, France. 5. European Synchrotron Radiation Facility, ID17 Medical Beamline, 71 Avenue Martyrs, 38000, Grenoble, France. 6. Service de Radiothérapie, Centre Hospitalier Universitaire Grenoble-Alpes, 38700, La Tronche, France. 7. Centre de lutte contre le Cancer F. Baclesse, 3 avenue du général Harris, 14000, Caen, France. 8. Department of Pathology, The Ohio State University, 4132 Graves Hall - 333 W. 10th Avenue, Columbus, OH, 43210, USA. 9. Department of Neurosurgery, Suzhou Medical College, Suzhou, China. 10. Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. 11. Research Institute, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
Abstract
BACKGROUND: The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.) by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation. METHODS: F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Approximately 14 days later, either CDDP or carboplatin was administered i.c. by CED, followed 24 h later by radiotherapy using either a synchrotron or, subsequently, megavoltage linear accelerators (LINAC). RESULTS: CDDP was administered at a dose of 3 µg in 5 µL, followed 24 h later with an irradiation dose of 15 Gy or carboplatin at a dose of 20 µg in 10 µL, followed 24 h later with 3 fractions of 8 Gy each, at the source at the European Synchrotron Radiation Facility (ESRF). This resulted in a median survival time (MeST) > 180 days with 33% long term survivors (LTS) for CDDP and a MeST > 60 days with 8 to 22% LTS, for carboplatin. Subsequently it became apparent that comparable survival data could be obtained with megavoltage X-irradiation using a LINAC source. The best survival data were obtained with a dose of 72 µg of carboplatin administered by means of Alzet® osmotic pumps over 7 days. This resulted in a MeST of > 180 days, with 55% LTS. Histopathologic examination of all the brains of the surviving rats revealed no residual tumor cells or evidence of significant radiation related effects. CONCLUSIONS: The results obtained using this combination therapy has, to the best of our knowledge, yielded the most promising survival data ever reported using the F98 glioma model.
BACKGROUND: The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 ratglioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.) by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation. METHODS: F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Approximately 14 days later, either CDDP or carboplatin was administered i.c. by CED, followed 24 h later by radiotherapy using either a synchrotron or, subsequently, megavoltage linear accelerators (LINAC). RESULTS:CDDP was administered at a dose of 3 µg in 5 µL, followed 24 h later with an irradiation dose of 15 Gy or carboplatin at a dose of 20 µg in 10 µL, followed 24 h later with 3 fractions of 8 Gy each, at the source at the European Synchrotron Radiation Facility (ESRF). This resulted in a median survival time (MeST) > 180 days with 33% long term survivors (LTS) for CDDP and a MeST > 60 days with 8 to 22% LTS, for carboplatin. Subsequently it became apparent that comparable survival data could be obtained with megavoltage X-irradiation using a LINAC source. The best survival data were obtained with a dose of 72 µg of carboplatin administered by means of Alzet® osmotic pumps over 7 days. This resulted in a MeST of > 180 days, with 55% LTS. Histopathologic examination of all the brains of the surviving rats revealed no residual tumor cells or evidence of significant radiation related effects. CONCLUSIONS: The results obtained using this combination therapy has, to the best of our knowledge, yielded the most promising survival data ever reported using the F98 glioma model.
Authors: Joshua L Wang; Rolf F Barth; Robert Cavaliere; Vinay K Puduvalli; Pierre Giglio; Russell R Lonser; J Bradley Elder Journal: PLoS One Date: 2020-12-29 Impact factor: 3.240