Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of
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TOPIC REVIEW
Radiation therapy combined with intracerebral convection‑enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma Hélène Elleaume1,3 · Rolf F. Barth2 · Julia Rousseau1,3 · Laure Bobyk1,3 · Jacques Balosso1,4,5 · Weilian Yang2,6 · Tianyao Huo2,7 · Robin Nakkula2,8 Received: 8 June 2020 / Accepted: 8 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords F98 glioma · Cis/Carboplatin · Convection-enhanced delivery · Radiation therapy · Brain tumors · Synchrotron radiation
Hélène Elleaume and Rolf F. Barth have contributed equally to this work.
Abbreviations AZQ Aziridinyl-benzoquinone BBB Blood–brain barrier BBB-D Blood–brain barrier disruption
* Hélène Elleaume [email protected]
4
Service de Radiothérapie, Centre Hospitalier Universitaire Grenoble-Alpes, 38700 La Tronche, France
* Rolf F. Barth [email protected]
5
Present Address: Centre de lutte contre le Cancer F. Baclesse, 3 avenue du général Harris, 14000 Caen, France
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Present Address: Department of Neurosurgery, Suzhou Medical College, Suzhou, China
7
Present Address: Department of Health Outcomes and Poli
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