Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy

Background: Current treatments of unresectable hepatocellular carcinoma (HCC) are trans-arterial chemo-embolization (TACE), stereotactic body radiotherapy (SBRT), and targeted therapy. However, these treatments are limited in efficacy and safety for patients with large tumor sizes. Here, we report a...

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Main Authors: Chi-Leung Chiang, Albert C. Y. Chan, Keith W. H. Chiu, Feng-Ming (Spring) Kong
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2019.01157/full
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author Chi-Leung Chiang
Albert C. Y. Chan
Keith W. H. Chiu
Feng-Ming (Spring) Kong
Feng-Ming (Spring) Kong
author_facet Chi-Leung Chiang
Albert C. Y. Chan
Keith W. H. Chiu
Feng-Ming (Spring) Kong
Feng-Ming (Spring) Kong
author_sort Chi-Leung Chiang
collection DOAJ
description Background: Current treatments of unresectable hepatocellular carcinoma (HCC) are trans-arterial chemo-embolization (TACE), stereotactic body radiotherapy (SBRT), and targeted therapy. However, these treatments are limited in efficacy and safety for patients with large tumor sizes. Here, we report a case series of combined SBRT and anti-PD-1 therapy in patients with unresectable HCC of large tumors.Methods: This is a retrospective case series of five patients with unresectable hepatocellular carcinoma who were treated with SBRT followed by anti-PD1 antibodies. Four patients (80%) received a single dose of TACE prior to SBRT. All patients had advanced HCC ineligible of curative intervention. In this study, we report their treatment responses according to modified RECIST (response evaluation criteria in solid tumor) criteria, 1-year local control (LC), progression-free survival (PFS), 1-year overall survival (OS) rate, and toxicities.Results: Among the five evaluated patients, three patients had underlying diseases of hepatitis B and four patients had Barcelona clinic liver cancer stage C. The median size of their tumors was 9.8 cm (range: 9–16.1 cm). In addition, two patients had tumor vascular thrombosis and one had extra-hepatic disease. Five out of five patients (100%) responded to treatment, with two complete responses (CR) and three partial responses (PR). Among the partial responders, one had a down-staged tumor that became amenable for radiofrequency ablation for tumor clearance. No patient developed tumor progression at the time of analysis during the median follow-up of 14.9 months (range 8.6–19 months). The median PFS was 14.9 months (range: 8.6–19 months); 1-year LC and OS rate were both 100%. One patient had grade ≥ 3 toxicities (pneumonitis and skin reaction). There was no classical radiation-induced liver disease.Conclusions: The results obtained from these 5 cases demonstrate impressive tumor control from the combination of SBRT and checkpoint inhibitors in patients with large tumors of advanced HCC. Further prospective trials are warranted.
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spelling doaj.art-b391c93337ac493686b5b7a93c3da0692022-12-21T19:13:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-11-01910.3389/fonc.2019.01157482954Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment StrategyChi-Leung Chiang0Albert C. Y. Chan1Keith W. H. Chiu2Feng-Ming (Spring) Kong3Feng-Ming (Spring) Kong4Department of Clinical Oncology, University of Hong Kong, Hong Kong, Hong KongDepartment of Surgery, University of Hong Kong, Hong Kong, Hong KongDepartment of Diagnostic Radiology, University of Hong Kong, Hong Kong, Hong KongDepartment of Clinical Oncology, University of Hong Kong, Hong Kong, Hong KongDepartment of Radiation Oncology, University Hospitals Cleveland Medical Center, Case Western Reserve University Medical School, Case Comprehensive Cancer Center, Cleveland, OH, United StatesBackground: Current treatments of unresectable hepatocellular carcinoma (HCC) are trans-arterial chemo-embolization (TACE), stereotactic body radiotherapy (SBRT), and targeted therapy. However, these treatments are limited in efficacy and safety for patients with large tumor sizes. Here, we report a case series of combined SBRT and anti-PD-1 therapy in patients with unresectable HCC of large tumors.Methods: This is a retrospective case series of five patients with unresectable hepatocellular carcinoma who were treated with SBRT followed by anti-PD1 antibodies. Four patients (80%) received a single dose of TACE prior to SBRT. All patients had advanced HCC ineligible of curative intervention. In this study, we report their treatment responses according to modified RECIST (response evaluation criteria in solid tumor) criteria, 1-year local control (LC), progression-free survival (PFS), 1-year overall survival (OS) rate, and toxicities.Results: Among the five evaluated patients, three patients had underlying diseases of hepatitis B and four patients had Barcelona clinic liver cancer stage C. The median size of their tumors was 9.8 cm (range: 9–16.1 cm). In addition, two patients had tumor vascular thrombosis and one had extra-hepatic disease. Five out of five patients (100%) responded to treatment, with two complete responses (CR) and three partial responses (PR). Among the partial responders, one had a down-staged tumor that became amenable for radiofrequency ablation for tumor clearance. No patient developed tumor progression at the time of analysis during the median follow-up of 14.9 months (range 8.6–19 months). The median PFS was 14.9 months (range: 8.6–19 months); 1-year LC and OS rate were both 100%. One patient had grade ≥ 3 toxicities (pneumonitis and skin reaction). There was no classical radiation-induced liver disease.Conclusions: The results obtained from these 5 cases demonstrate impressive tumor control from the combination of SBRT and checkpoint inhibitors in patients with large tumors of advanced HCC. Further prospective trials are warranted.https://www.frontiersin.org/article/10.3389/fonc.2019.01157/fullstereotactic radiation therapystereotactic ablative radiation therapycheckpoint inhibitorimmunotherapyhepatocellular carcinomaHCC
spellingShingle Chi-Leung Chiang
Albert C. Y. Chan
Keith W. H. Chiu
Feng-Ming (Spring) Kong
Feng-Ming (Spring) Kong
Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy
Frontiers in Oncology
stereotactic radiation therapy
stereotactic ablative radiation therapy
checkpoint inhibitor
immunotherapy
hepatocellular carcinoma
HCC
title Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy
title_full Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy
title_fullStr Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy
title_full_unstemmed Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy
title_short Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy
title_sort combined stereotactic body radiotherapy and checkpoint inhibition in unresectable hepatocellular carcinoma a potential synergistic treatment strategy
topic stereotactic radiation therapy
stereotactic ablative radiation therapy
checkpoint inhibitor
immunotherapy
hepatocellular carcinoma
HCC
url https://www.frontiersin.org/article/10.3389/fonc.2019.01157/full
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