Beom Kyung Kim1, Do Young Kim1, Hwa Kyung Byun2, Hye Jin Choi3, Seung-Hoon Beom3, Hye Won Lee1, Seung Up Kim1, Jun Yong Park1, Sang Hoon Ahn1, Jinsil Seong4, Kwang-Hyub Han5. 1. Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea. 2. Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: jsseong@yuhs.ac. 5. Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea. Electronic address: gihankhys@yuhs.ac.
Abstract
PURPOSE: Although sorafenib as a standard of care for advanced hepatocellular carcinoma (HCC) prolongs overall survival (OS), its efficacy is limited owing to its unsatisfactory objective response and marginal survival benefit. To counter these limitations, we designed a single-arm, phase II trial with liver-directed concurrent chemoradiotherapy (LD-CCRT) and sequential sorafenib treatment in patients with advanced HCC. METHODS AND MATERIALS: We enrolled advanced HCC patients diagnosed between 2014 and 2017 who were ineligible for curative treatment. During the first and last 5 days of 5-week radiation therapy, concurrent hepatic arterial infusion with 5-fluorouracil (500 mg/d) and leucovorin (50 mg/d) through an implanted port was administered 4 weeks after initiation of LD-CCRT and sequential sorafenib treatment (400 mg, twice daily). The primary endpoint was OS. This trial has been registered at clinicaltrials.gov. RESULTS: Among the enrolled patients (n = 47), objective response rates 4 weeks after LD-CCRT and during/up to sorafenib maintenance were 44.7% and 53.2%, respectively. Overall, 9 patients (19.1%) underwent curative resection or transplantation after down staging. The median radiation dose was 60 Gy. The median OS was 24.6 months for the entire cohort and 13.0 months for the subgroup with tumor invasion into the main portal trunk or its first branch, whereas the median progression-free survival for the cohort and subgroup was 6.8 and 5.6 months, respectively. The most frequent treatment-related adverse events were diarrhea (36.2%) and hand-foot skin reaction (34%), which were manageable with conservative treatment. CONCLUSIONS: LD-CCRT and sequential sorafenib treatment provided favorable OS and progression-free survival with good tolerability. Tumor reduction using an initial LD-CCRT enabled down staging, subsequent curative treatment, and long-term survival in about 20% of the patients with advanced HCC. However, further randomized trials are required to confirm these results.
PURPOSE: Although sorafenib as a standard of care for advanced hepatocellular carcinoma (HCC) prolongs overall survival (OS), its efficacy is limited owing to its unsatisfactory objective response and marginal survival benefit. To counter these limitations, we designed a single-arm, phase II trial with liver-directed concurrent chemoradiotherapy (LD-CCRT) and sequential sorafenib treatment in patients with advanced HCC. METHODS AND MATERIALS: We enrolled advanced HCCpatients diagnosed between 2014 and 2017 who were ineligible for curative treatment. During the first and last 5 days of 5-week radiation therapy, concurrent hepatic arterial infusion with 5-fluorouracil (500 mg/d) and leucovorin (50 mg/d) through an implanted port was administered 4 weeks after initiation of LD-CCRT and sequential sorafenib treatment (400 mg, twice daily). The primary endpoint was OS. This trial has been registered at clinicaltrials.gov. RESULTS: Among the enrolled patients (n = 47), objective response rates 4 weeks after LD-CCRT and during/up to sorafenib maintenance were 44.7% and 53.2%, respectively. Overall, 9 patients (19.1%) underwent curative resection or transplantation after down staging. The median radiation dose was 60 Gy. The median OS was 24.6 months for the entire cohort and 13.0 months for the subgroup with tumor invasion into the main portal trunk or its first branch, whereas the median progression-free survival for the cohort and subgroup was 6.8 and 5.6 months, respectively. The most frequent treatment-related adverse events were diarrhea (36.2%) and hand-foot skin reaction (34%), which were manageable with conservative treatment. CONCLUSIONS:LD-CCRT and sequential sorafenib treatment provided favorable OS and progression-free survival with good tolerability. Tumor reduction using an initial LD-CCRT enabled down staging, subsequent curative treatment, and long-term survival in about 20% of the patients with advanced HCC. However, further randomized trials are required to confirm these results.
Authors: Sojung Han; Hye Jin Choi; Seung-Hoon Beom; Hye Rim Kim; Hyein Lee; Jae Seung Lee; Hye Won Lee; Jun Yong Park; Seung Up Kim; Do Young Kim; Sang Hoon Ahn; Kwang-Hyub Han; Jinsil Seong; Jong Yun Won; Beom Kyung Kim Journal: J Cancer Res Clin Oncol Date: 2021-04-23 Impact factor: 4.553
Authors: Jina Kim; Hwa Kyung Byun; Tae Hyung Kim; Sun Il Kim; Beom Kyung Kim; Seung Up Kim; Jun Yong Park; Do Young Kim; Jinsil Seong Journal: Cancers (Basel) Date: 2022-05-12 Impact factor: 6.575
Authors: Dai Hoon Han; Beom Kyung Kim; Sojung Han; Hye Won Lee; Jun Yong Park; Seung Up Kim; Do Young Kim; Sang Hoon Ahn; Kwang-Hyub Han; Jinsil Seong; Jong Yun Won Journal: J Hepatocell Carcinoma Date: 2020-12-17