Philipp Hoegen-Saßmannshausen , Patrick Naumann , Paula Hoffmeister-Wittmann , Semi Ben Harrabi , Katharina Seidensaal , Fabian Weykamp , Thomas Mielke , Malte Ellerbrock , Daniel Habermehl , Christoph Springfeld , Michael T. Dill , Thomas Longerich , Peter Schirmacher , Arianeb Mehrabi , De-Hua Chang , Juliane Hörner-Rieber , Oliver Jäkel , Thomas Haberer , Stephanie E. Combs , Jürgen Debus , Jakob Liermann
{"title":"肝细胞癌的碳离子放射治疗可提供出色的局部控制：前瞻性 I 期 PROMETHEUS 试验","authors":"Philipp Hoegen-Saßmannshausen , Patrick Naumann , Paula Hoffmeister-Wittmann , Semi Ben Harrabi , Katharina Seidensaal , Fabian Weykamp , Thomas Mielke , Malte Ellerbrock , Daniel Habermehl , Christoph Springfeld , Michael T. Dill , Thomas Longerich , Peter Schirmacher , Arianeb Mehrabi , De-Hua Chang , Juliane Hörner-Rieber , Oliver Jäkel , Thomas Haberer , Stephanie E. Combs , Jürgen Debus , Jakob Liermann","doi":"10.1016/j.jhepr.2024.101063","DOIUrl":null,"url":null,"abstract":"<div><h3>Background & Aims</h3><p>Inoperable hepatocellular carcinoma (HCC) can be treated by stereotactic body radiotherapy. However, carbon ion radiotherapy (CIRT) is more effective for sparing non-tumorous liver. High linear energy transfer could promote therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Because of different radiobiological models and the different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I.</p></div><div><h3>Methods</h3><p>CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1–10.5 Gy (total doses 32.4–42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks.</p></div><div><h3>Results</h3><p>Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression.</p></div><div><h3>Conclusions</h3><p>CIRT of HCC yields excellent local control without dose-limiting toxicity.</p></div><div><h3>Impact and implications</h3><p>To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. The results are of particular interest for European and American particle therapy centers, but also of relevance for all specialists involved in the treatment and care of patients with hepatocellular carcinoma, as we present the first prospective data on carbon ion radiotherapy in hepatocellular carcinoma outside of Asia. The excellent local control should encourage further use of carbon ion radiotherapy for hepatocellular carcinoma and design of randomized controlled trials.</p></div><div><h3>Clinical Trials Registration</h3><p>The study is registered at <span>ClinicalTrials.gov</span><svg><path></path></svg> (<span>NCT01167374</span><svg><path></path></svg>).</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5000,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000648/pdfft?md5=27680ac00f1b796875d6093a99a12f03&pid=1-s2.0-S2589555924000648-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Carbon ion radiotherapy of hepatocellular carcinoma provides excellent local control: The prospective phase I PROMETHEUS trial\",\"authors\":\"Philipp Hoegen-Saßmannshausen , Patrick Naumann , Paula Hoffmeister-Wittmann , Semi Ben Harrabi , Katharina Seidensaal , Fabian Weykamp , Thomas Mielke , Malte Ellerbrock , Daniel Habermehl , Christoph Springfeld , Michael T. 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The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I.</p></div><div><h3>Methods</h3><p>CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1–10.5 Gy (total doses 32.4–42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks.</p></div><div><h3>Results</h3><p>Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression.</p></div><div><h3>Conclusions</h3><p>CIRT of HCC yields excellent local control without dose-limiting toxicity.</p></div><div><h3>Impact and implications</h3><p>To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. 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Carbon ion radiotherapy of hepatocellular carcinoma provides excellent local control: The prospective phase I PROMETHEUS trial
Background & Aims
Inoperable hepatocellular carcinoma (HCC) can be treated by stereotactic body radiotherapy. However, carbon ion radiotherapy (CIRT) is more effective for sparing non-tumorous liver. High linear energy transfer could promote therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Because of different radiobiological models and the different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I.
Methods
CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1–10.5 Gy (total doses 32.4–42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks.
Results
Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression.
Conclusions
CIRT of HCC yields excellent local control without dose-limiting toxicity.
Impact and implications
To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. The results are of particular interest for European and American particle therapy centers, but also of relevance for all specialists involved in the treatment and care of patients with hepatocellular carcinoma, as we present the first prospective data on carbon ion radiotherapy in hepatocellular carcinoma outside of Asia. The excellent local control should encourage further use of carbon ion radiotherapy for hepatocellular carcinoma and design of randomized controlled trials.
Clinical Trials Registration
The study is registered at ClinicalTrials.gov (NCT01167374).
期刊介绍：
JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology.
The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies.
In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.
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