Anthony M Brade1, Sylvia Ng2, James Brierley2, John Kim2, Robert Dinniwell2, Jolie Ringash2, Rebecca R Wong2, Charles Cho3, Jennifer Knox4, Laura A Dawson2. 1. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: anthony.brade@rmp.uhn.on.ca. 2. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 3. Department of Radiation Oncology, Southlake Regional Cancer Centre, Newmarket, Ontario, Canada. 4. Division of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Abstract
PURPOSE: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC). METHODS AND MATERIALS: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned. RESULTS: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum. CONCLUSIONS: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial.
PURPOSE: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC). METHODS AND MATERIALS: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned. RESULTS: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum. CONCLUSIONS: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial.
Authors: S G C Kroeze; C Fritz; L Basler; E Gkika; T B Brunner; A L Grosu; M Guckenberger Journal: Strahlenther Onkol Date: 2019-02-08 Impact factor: 3.621
Authors: Dominik Bettinger; David J Pinato; Michael Schultheiss; Rohini Sharma; Lorenza Rimassa; Tiziana Pressiani; Michela E Burlone; Mario Pirisi; Masatoshi Kudo; Joong Won Park; Nico Buettner; Christoph Neumann-Haefelin; Tobias Boettler; Nasrin Abbasi-Senger; Horst Alheit; Wolfgang Baus; Oliver Blanck; Sabine Gerum; Mathias Guckenberger; Daniel Habermehl; Christian Ostheimer; Oliver Riesterer; Jörg Tamihardja; Anca-Ligia Grosu; Robert Thimme; Thomas Baptist Brunner; Eleni Gkika Journal: Liver Cancer Date: 2018-07-12 Impact factor: 11.740
Authors: Zhao-Chong Zeng; Jinsil Seong; Sang Min Yoon; Jason Chia-Hsien Cheng; Ka-On Lam; Ann-Shing Lee; Ada Law; Jian-Ying Zhang; Yong Hu Journal: Liver Cancer Date: 2017-08-30 Impact factor: 11.740