Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes

Edward Michael Mannina, Higinia Rosa Cardenes, Foster D. Lasley, Benjamin Goodman, Jennifer Zook, Sandra Althouse, John Alvin Cox, Romil Saxena, Joseph Tector, Mary Maluccio

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)931-938
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume97
Issue number5
DOIs
StatePublished - Apr 1 2017

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transplantation
liver
Liver Transplantation
radiation therapy
Radiotherapy
tumors
evaluation
Neoplasms
Treatment Failure
Disease-Free Survival
Hepatocellular Carcinoma
Fetal Proteins
cancer
Kaplan-Meier Estimate
scoring
pathology
stratification
death
hazards
Pathology

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation : Retrospective Evaluation of Pathologic Response and Outcomes. / Mannina, Edward Michael; Cardenes, Higinia Rosa; Lasley, Foster D.; Goodman, Benjamin; Zook, Jennifer; Althouse, Sandra; Cox, John Alvin; Saxena, Romil; Tector, Joseph; Maluccio, Mary.

In: International Journal of Radiation Oncology Biology Physics, Vol. 97, No. 5, 01.04.2017, p. 931-938.

Research output: Contribution to journalArticle

Mannina, Edward Michael ; Cardenes, Higinia Rosa ; Lasley, Foster D. ; Goodman, Benjamin ; Zook, Jennifer ; Althouse, Sandra ; Cox, John Alvin ; Saxena, Romil ; Tector, Joseph ; Maluccio, Mary. / Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation : Retrospective Evaluation of Pathologic Response and Outcomes. In: International Journal of Radiation Oncology Biology Physics. 2017 ; Vol. 97, No. 5. pp. 931-938.
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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.",
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T2 - Retrospective Evaluation of Pathologic Response and Outcomes

AU - Mannina, Edward Michael

AU - Cardenes, Higinia Rosa

AU - Lasley, Foster D.

AU - Goodman, Benjamin

AU - Zook, Jennifer

AU - Althouse, Sandra

AU - Cox, John Alvin

AU - Saxena, Romil

AU - Tector, Joseph

AU - Maluccio, Mary

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N2 - 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.

AB - 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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