- Email: [email protected]
Stereotactic Body Radiation Therapy Followed by Sorafenib Improves Survival Without Increasing Toxicity
Poster Viewing Abstracts S369
Volume 90 Number 1S Supplement 2014 Conclusions: It is feasible to deliver SBRT to liver tumors utilizing modulated 60Co beams with the added advantages of MRI-guidance. For peripheral liver tumors, dosimetry was comparable to delivered plans. However, for central liver tumors, a trade-off between dosimetric compactness and MRI-guidance needs to be considered in order to optimize local control and reduce toxicity.
Scientific Abstract 2385; Table Average Dosimetry of VMAT vs Modulated Cobalt-60 For 4 Patients with Comparable Plans Institutional OAR Constraints
VMAT
Modulated Cobalt-60
Max cord dose/fx < 2.5 Gy Max R kidney dose/fx < 2.5 Gy Max L kidney dose/fx < 2.5 Gy Normal liver, keep 1000 cc < 15 Gy Small bowel V20Gy < 20 cc Stomach V20Gy < 20 cc
1.5 Gy 1.7 Gy 0.6 Gy 1614 cc 6.8 cc 1.2 cc
1.5 Gy 1.0Gy 0.8 Gy 1432 cc 12.6 cc 4.8 cc
Author Disclosure: A.U. Kishan: None. M. Cao: None. S. Tenn: None. K. Sheng: None. D.A. Low: K. Advisory Board; Scientific Advisory Board for ViewRay Inc. P.A. Kupelian: K. Advisory Board; Scientific Advisory Board for ViewRay Inc. M.L. Steinberg: None. P. Lee: K. Advisory Board; Clinical Advisory Board for ViewRay Inc.
2386 Risk Factors of Hepatic Failure After Re-irradiation for Recurrent Hepatocellular Carcinoma Y. Huang,1 S. Chen,2,3 C. Kuo,1 L. Ting,1 and J. Chiou1,3; 1Taipei Medical University Hospital, Taipei, Taiwan, 2China Medical University Hospital, Taichung, Taiwan, 3School of Medicine, Taipei Medical University, Taipei, Taiwan Purpose/Objective(s): Little is known about underlying hepatic tolerance after re-irradiation of liver. This study was to determine the risk factors in predicting hepatic toxicities after 2nd course of radiation therapy (RT) for recurrent hepatocellular carcinoma (HCC). Materials/Methods: Between July 2004 and March 2013, 30 patients who received 2 courses of radiation therapy (RT) to the liver were included for this analysis. The median cumulative dose to the hepatic tumor was 84 Gy (range, 61.2 to 111.6 Gy), whereas the median cumulative dose to the normal liver was 24.2 Gy (range, 12.3 to 38.7 Gy). The median interval between the two courses of RT was 14 months (range, 2 to 47 months). The Child-Pugh score before the 2nd RT was classified to be A in 25 patients and B in 5. The toxicities were graded according to the Common Terminology Criteria for adverse events Version 4. The data of liver function test and dosevolume histogram were retrieved for the analysis. Logistic regression test was performed to identify the predictors of S grade 3 and S grade 4 hepatotoxicities. Results: With a median follow-up duration of 12 months after reirradiation, 11 and 8 patients experienced S grade 3 and S grade 4 hepatotoxicities, respectively. Child-Turcotte-Pugh (CTP) score S 6 before the 2nd RT was associated with grade 3 or above hepatotoxicities (p Z 0.02, Odds ratio 10.53, 95% confidence interval 1.36 w 81.3), whereas existence of portal vein tumor thrombosis showed a marginal impact to the event (p Z 0.05, Odds ratio 8.35, 95% confidence interval 0.97 w 72.2). CTP score S 6 was the only predictor for S grade 4 liver toxicities (p < 0.0001). The cumulative tumor or normal liver doses were not associated with the development of grade 3 or above liver toxicities. Conclusions: For patients requiring re-irradiation for recurrent HCC, the risk of hepatic toxicities should be considered when CTP score S 6, or existence of portal vein tumor thrombosis. A study with large sample size is essential to verify the tolerance of liver to re-irradiation. Author Disclosure: Y. Huang: None. S. Chen: None. C. Kuo: None. L. Ting: None. J. Chiou: None.
2387 Stereotactic Body Radiation Therapy Followed by Sorafenib Improves Survival Without Increasing Toxicity K.S. Keene, D. Dubay, B. McGuire, R. Desmond, R. Jacob, M.C. Dobelbower, D. Eckhoff, and J. Posey; University of Alabama at Birmingham, Birmingham, AL Purpose/Objective(s): Local control options for unresectable hepatocellular carcinoma (HCC) are limited due to vascular invasion, tumor location and size. Stereotactic body radiation therapy (SBRT) has ability to treat these tumors with favorable toxicity. Sorafenib is a tyrosine kinase inhibitor that has been shown to be efficacious in this disease. This retrospective analysis examines toxicity and survival in patients with HCC treated with SBRT with or without adjuvant sorafenib. Materials/Methods: Patients treated with SBRT for unresectable HCC between 2006 and 2012 were reviewed from a single institution and 49 patients met inclusion criteria and were treated with SBRT alone (n Z 13), SBRT/sorafenib (n Z 12), SBRT/TACE (n Z 17), SBRT/TACE/sorafenib (n Z 6). Patients with HCC were treated with SBRT (mean 45Gy in 3-6 fractions). Sorafenib dosing was typically 400mg daily 2 weeks after SBRT and then escalated as tolerated. Adverse events were summarized by frequencies and survival was estimated by Kaplan Meier. Baseline characteristic between the sorafenib and SRBT groups were compared by exact chi-square test for categorical variables and t-test for continuous variables. Cox proportional hazards models were used to examine covariates for association with survival. Results: Baseline characteristics included age (mean 63 years; range 2089); prior TACE(n Z 24, 49%); Child Pugh score (A Z 35, 71.4%, B Z 13, 26.5%, C Z 1, 2.1%), number of lesions (1 Z 33, 67.4%, 2 Z 12, 24.5%, 3 Z 2, 4.1%; vascular invasion (n Z 18, 36.7%). Baseline characteristics did not differ significantly between treated groups although those treated with sorafenib trended toward a higher proportion of portal vein involvement (55.6% vs 25.8%, p Z 0.06) and higher platelet toxicity (p Z 0.07). Toxicities evaluated included elevation in liver enzymes (AST, ALT, Alk Phos, total bilirubin); ascites; encephalopathy; hemoglobin and platelet counts, as well as prothrombin time. The grade of toxicity did not change with the addition of sorafenib at 3, 6 and 12 months after SBRT compared to those without sorafenib. There was a trend toward improvement in overall survival in patients receiving sorafenib post SBRT (p Z 0.22) although development of local and distant failure did not differ significantly between the two groups (p Z 0.42 and 0.68). There was improved survival with SBRT/sorafenib (p Z 0.023) and a trend with SBRT/TACE (p Z 0.062) compared with SBRT alone in univariate but not multivariate analysis. In multivariate analysis, significant predictors of poor survival included larger lesion size, higher Child Pugh score, and extrahepatic disease. Conclusions: The combination of sequential SBRT and sorafenib is safe without appreciable added toxicity. The addition of sorafenib may be useful in improving overall survival in patients with unresectable HCC. Author Disclosure: K.S. Keene: E. Research Grant; R21 Molecular predictors of breast cancer, Bayer Onyx-phase I study of SBRT and sorafenib for HCC. F. Honoraria; Halcyon pharma. D. Dubay: G. Consultant; Onyx. B. McGuire: None. R. Desmond: None. R. Jacob: None. M.C. Dobelbower: None. D. Eckhoff: None. J. Posey: None.
2388 Evaluation of Dose Distribution and Tracking Accuracy in Dynamic Tumor-Tracking Irradiation for Liver Tumors Using a Gimbaled Linac Y. Iizuka,1 N. Ueki,1 Y. Ishinara,1 M. Akimoto,1 H. Tanabe,2 K. Takayama,2 N. Mukumoto,1 M. Nakamura,1 Y. Miyabe,1 S. Kaneko,1 Y. Matsuo,1 T. Mizowaki,1 H. Monzen,1 A. Sawada,3 M. Kokubo,4 and M. Hiraoka1; 1Kyoto University, Kyoto, Japan, 2Institute of Biomedical Research and Innovation, Kobe, Japan, 3Kyoto College of Medical Science, Nantan, Japan, 4Kobe City Medical Center General Hospital, Kobe, Japan
Volume 90 Number 1S Supplement 2014 Conclusions: It is feasible to deliver SBRT to liver tumors utilizing modulated 60Co beams with the added advantages of MRI-guidance. For peripheral liver tumors, dosimetry was comparable to delivered plans. However, for central liver tumors, a trade-off between dosimetric compactness and MRI-guidance needs to be considered in order to optimize local control and reduce toxicity.
Scientific Abstract 2385; Table Average Dosimetry of VMAT vs Modulated Cobalt-60 For 4 Patients with Comparable Plans Institutional OAR Constraints
VMAT
Modulated Cobalt-60
Max cord dose/fx < 2.5 Gy Max R kidney dose/fx < 2.5 Gy Max L kidney dose/fx < 2.5 Gy Normal liver, keep 1000 cc < 15 Gy Small bowel V20Gy < 20 cc Stomach V20Gy < 20 cc
1.5 Gy 1.7 Gy 0.6 Gy 1614 cc 6.8 cc 1.2 cc
1.5 Gy 1.0Gy 0.8 Gy 1432 cc 12.6 cc 4.8 cc
Author Disclosure: A.U. Kishan: None. M. Cao: None. S. Tenn: None. K. Sheng: None. D.A. Low: K. Advisory Board; Scientific Advisory Board for ViewRay Inc. P.A. Kupelian: K. Advisory Board; Scientific Advisory Board for ViewRay Inc. M.L. Steinberg: None. P. Lee: K. Advisory Board; Clinical Advisory Board for ViewRay Inc.
2386 Risk Factors of Hepatic Failure After Re-irradiation for Recurrent Hepatocellular Carcinoma Y. Huang,1 S. Chen,2,3 C. Kuo,1 L. Ting,1 and J. Chiou1,3; 1Taipei Medical University Hospital, Taipei, Taiwan, 2China Medical University Hospital, Taichung, Taiwan, 3School of Medicine, Taipei Medical University, Taipei, Taiwan Purpose/Objective(s): Little is known about underlying hepatic tolerance after re-irradiation of liver. This study was to determine the risk factors in predicting hepatic toxicities after 2nd course of radiation therapy (RT) for recurrent hepatocellular carcinoma (HCC). Materials/Methods: Between July 2004 and March 2013, 30 patients who received 2 courses of radiation therapy (RT) to the liver were included for this analysis. The median cumulative dose to the hepatic tumor was 84 Gy (range, 61.2 to 111.6 Gy), whereas the median cumulative dose to the normal liver was 24.2 Gy (range, 12.3 to 38.7 Gy). The median interval between the two courses of RT was 14 months (range, 2 to 47 months). The Child-Pugh score before the 2nd RT was classified to be A in 25 patients and B in 5. The toxicities were graded according to the Common Terminology Criteria for adverse events Version 4. The data of liver function test and dosevolume histogram were retrieved for the analysis. Logistic regression test was performed to identify the predictors of S grade 3 and S grade 4 hepatotoxicities. Results: With a median follow-up duration of 12 months after reirradiation, 11 and 8 patients experienced S grade 3 and S grade 4 hepatotoxicities, respectively. Child-Turcotte-Pugh (CTP) score S 6 before the 2nd RT was associated with grade 3 or above hepatotoxicities (p Z 0.02, Odds ratio 10.53, 95% confidence interval 1.36 w 81.3), whereas existence of portal vein tumor thrombosis showed a marginal impact to the event (p Z 0.05, Odds ratio 8.35, 95% confidence interval 0.97 w 72.2). CTP score S 6 was the only predictor for S grade 4 liver toxicities (p < 0.0001). The cumulative tumor or normal liver doses were not associated with the development of grade 3 or above liver toxicities. Conclusions: For patients requiring re-irradiation for recurrent HCC, the risk of hepatic toxicities should be considered when CTP score S 6, or existence of portal vein tumor thrombosis. A study with large sample size is essential to verify the tolerance of liver to re-irradiation. Author Disclosure: Y. Huang: None. S. Chen: None. C. Kuo: None. L. Ting: None. J. Chiou: None.
2387 Stereotactic Body Radiation Therapy Followed by Sorafenib Improves Survival Without Increasing Toxicity K.S. Keene, D. Dubay, B. McGuire, R. Desmond, R. Jacob, M.C. Dobelbower, D. Eckhoff, and J. Posey; University of Alabama at Birmingham, Birmingham, AL Purpose/Objective(s): Local control options for unresectable hepatocellular carcinoma (HCC) are limited due to vascular invasion, tumor location and size. Stereotactic body radiation therapy (SBRT) has ability to treat these tumors with favorable toxicity. Sorafenib is a tyrosine kinase inhibitor that has been shown to be efficacious in this disease. This retrospective analysis examines toxicity and survival in patients with HCC treated with SBRT with or without adjuvant sorafenib. Materials/Methods: Patients treated with SBRT for unresectable HCC between 2006 and 2012 were reviewed from a single institution and 49 patients met inclusion criteria and were treated with SBRT alone (n Z 13), SBRT/sorafenib (n Z 12), SBRT/TACE (n Z 17), SBRT/TACE/sorafenib (n Z 6). Patients with HCC were treated with SBRT (mean 45Gy in 3-6 fractions). Sorafenib dosing was typically 400mg daily 2 weeks after SBRT and then escalated as tolerated. Adverse events were summarized by frequencies and survival was estimated by Kaplan Meier. Baseline characteristic between the sorafenib and SRBT groups were compared by exact chi-square test for categorical variables and t-test for continuous variables. Cox proportional hazards models were used to examine covariates for association with survival. Results: Baseline characteristics included age (mean 63 years; range 2089); prior TACE(n Z 24, 49%); Child Pugh score (A Z 35, 71.4%, B Z 13, 26.5%, C Z 1, 2.1%), number of lesions (1 Z 33, 67.4%, 2 Z 12, 24.5%, 3 Z 2, 4.1%; vascular invasion (n Z 18, 36.7%). Baseline characteristics did not differ significantly between treated groups although those treated with sorafenib trended toward a higher proportion of portal vein involvement (55.6% vs 25.8%, p Z 0.06) and higher platelet toxicity (p Z 0.07). Toxicities evaluated included elevation in liver enzymes (AST, ALT, Alk Phos, total bilirubin); ascites; encephalopathy; hemoglobin and platelet counts, as well as prothrombin time. The grade of toxicity did not change with the addition of sorafenib at 3, 6 and 12 months after SBRT compared to those without sorafenib. There was a trend toward improvement in overall survival in patients receiving sorafenib post SBRT (p Z 0.22) although development of local and distant failure did not differ significantly between the two groups (p Z 0.42 and 0.68). There was improved survival with SBRT/sorafenib (p Z 0.023) and a trend with SBRT/TACE (p Z 0.062) compared with SBRT alone in univariate but not multivariate analysis. In multivariate analysis, significant predictors of poor survival included larger lesion size, higher Child Pugh score, and extrahepatic disease. Conclusions: The combination of sequential SBRT and sorafenib is safe without appreciable added toxicity. The addition of sorafenib may be useful in improving overall survival in patients with unresectable HCC. Author Disclosure: K.S. Keene: E. Research Grant; R21 Molecular predictors of breast cancer, Bayer Onyx-phase I study of SBRT and sorafenib for HCC. F. Honoraria; Halcyon pharma. D. Dubay: G. Consultant; Onyx. B. McGuire: None. R. Desmond: None. R. Jacob: None. M.C. Dobelbower: None. D. Eckhoff: None. J. Posey: None.
2388 Evaluation of Dose Distribution and Tracking Accuracy in Dynamic Tumor-Tracking Irradiation for Liver Tumors Using a Gimbaled Linac Y. Iizuka,1 N. Ueki,1 Y. Ishinara,1 M. Akimoto,1 H. Tanabe,2 K. Takayama,2 N. Mukumoto,1 M. Nakamura,1 Y. Miyabe,1 S. Kaneko,1 Y. Matsuo,1 T. Mizowaki,1 H. Monzen,1 A. Sawada,3 M. Kokubo,4 and M. Hiraoka1; 1Kyoto University, Kyoto, Japan, 2Institute of Biomedical Research and Innovation, Kobe, Japan, 3Kyoto College of Medical Science, Nantan, Japan, 4Kobe City Medical Center General Hospital, Kobe, Japan