Edward Michael Mannina1, Higinia Rosa Cardenes2, Foster D Lasley3, Benjamin Goodman4, Jennifer Zook5, Sandra Althouse6, John Alvin Cox7, Romil Saxena8, Joseph Tector9, Mary Maluccio10. 1. Department of Radiation Oncology, Slidell Memorial Hospital Regional Cancer Center, Slidell, Louisiana. Electronic address: emmannina@gmail.com. 2. Department of Radiation Oncology, Schneck Medical Center, Seymour, Indiana. 3. Department of Radiation Oncology, Mercy Hospital, Oklahoma City, Oklahoma. 4. Department of Radiation Oncology, St. Francis Healthcare, Cape Girardeau, Missouri. 5. Department of Radiation Oncology, Community Hospital Anderson, Anderson, Indiana. 6. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana. 7. Department of Radiation Oncology, Columbus Regional, Columbus, Indiana. 8. Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana. 9. Department of Surgery, University of Alabama-Birmingham, Birmingham, Alabama. 10. Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
Abstract
PURPOSE: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). METHODS AND MATERIALS: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. RESULTS: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survival are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non-statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (-25 IU/mL vs -162 IU/mL). CONCLUSIONS: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.
PURPOSE: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). METHODS AND MATERIALS: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. RESULTS: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survival are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non-statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (-25 IU/mL vs -162 IU/mL). CONCLUSIONS: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.
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