Papers by Yaacov Lawrence
International Journal of Radiation Oncology Biology Physics, 2013
Despite recent advances in the management of high-grade and recurrent gliomas, survival remains p... more Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m(2)) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide.
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Future Oncology, 2014
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European Journal of Cancer, 2014
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British Journal of Cancer, 2011
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Prostate Cancer and Prostatic Diseases, 2013
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The Lancet Oncology, 2008
Hypoxia in prostate cancer: observation to intervention. By - Yaacov Richard Lawrence, Adam P Dic... more Hypoxia in prostate cancer: observation to intervention. By - Yaacov Richard Lawrence, Adam P Dicker.
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Journal of Neuro-Oncology, 2014
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Journal of Neuro-Oncology, 2012
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Journal of Medical Imaging and Radiation Oncology, 2013
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International Journal of Radiation Oncology*Biology*Physics, 2012
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International Journal of Radiation Oncology*Biology*Physics, 2012
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International Journal of Radiation Oncology*Biology*Physics, 2010
We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation n... more We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation necrosis appears a median of 1-2 years after RT; however, cognitive decline develops over many years. The incidence and severity is dose and volume dependent and can also be increased by chemotherapy, age, diabetes, and spatial factors. For fractionated RT with a fraction size of <2.5 Gy, an incidence of radiation necrosis of 5% and 10% is predicted to occur at a biologically effective dose of 120 Gy (range, 100-140) and 150 Gy (range, 140-170), respectively. For twice-daily fractionation, a steep increase in toxicity appears to occur when the biologically effective dose is >80 Gy. For large fraction sizes (>or=2.5 Gy), the incidence and severity of toxicity is unpredictable. For single fraction radiosurgery, a clear correlation has been demonstrated between the target size and the risk of adverse events. Substantial variation among different centers' reported outcomes have prevented us from making toxicity-risk predictions. Cognitive dysfunction in children is largely seen for whole brain doses of >or=18 Gy. No substantial evidence has shown that RT induces irreversible cognitive decline in adults within 4 years of RT.
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International Journal of Radiation Oncology*Biology*Physics, 2011
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Future Oncology, 2008
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Cancer, 2013
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Background: Treatment of high-grade glioma consists of fractionated radiation therapy (RT) ± chem... more Background: Treatment of high-grade glioma consists of fractionated radiation therapy (RT) ± chemotherapy. The incidence/significance of neurological toxicity (NT) in this disease is not known. We evaluated the relationship between acute and chronic NT, and ultimate outcome, as well as risk factors for NT from the RTOG database.American Society of Clinical Oncology (ASCO) 46th Annual Meeting June 4-8, Chicago, IL.
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Therapy, 2008
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Papers by Yaacov Lawrence