Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) HCC

NCT05433701 | Active Not Recruiting

• 1 other identifier: STR_1
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality and the sixth most prevalent cancer in the world. Standard treatments for early-stage HCCs include resection, liver transplantation, and percutaneous ablation, with 5-year survival rates of over 50 percent. Less than one-third of patients, however, are candidates for hepatic resection, and the use of radiofrequency ablation (RFA) may be significantly limited in cases with unfavorable tumor location and poor visibility on images, which increase the risk of technical failures and complications after RFA. Recent advancements in radiotherapy and imaging have made it possible to deliver optimal radiation doses on the tumor site while minimizing exposure to normal organs. Stereotactic body radiation therapy (SBRT) is a method of high-precision radiation therapy that concentrates high-dose radiation to HCC in a short period of time to maximize the therapeutic effect on the tumor and minimize the side effects on normal tissues. Prospective and retrospective studies on SBRT for HCC have demonstrated its efficacy for local tumor control in small HCC. On the basis of these promising clinical results, a number of studies have compared the efficacy of RFA and SBRT. However, there is no strong evidence from randomized controlled trials comparing SBRT and RFA. In order to evaluate and compare the local efficacy and clinical outcomes of SBRT and RFA in patients with recurrent HCC, we conduct this non-inferiority trial.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Local progression-free survival rate, per-protocol (PP)

  Local progression-free survival rate, PP

  At year 2

Secondary Outcomes (14)

• Progression-free survival rate, intention-to-treat (ITT)

  At year 2

• Overall survival rate, ITT

  At year 2

• Intrahepatic progression-free survival rate, PP

  At year 2

• Intrahepatic progression-free survival rate, ITT

  At year 2

• Progression-free survival rate, PP

  At year 2

Study Arms (2)

RFA group

ACTIVE COMPARATOR

* RFA are performed under local anesthesia or monitored anesthesia care with either a 15-gause or 17-gause internally cooled electrode, depending on the size of the tumor. * RFA procedures are continued by modifying the output power based on the location and size of the tumor until the entire tumor and border area sizes of greater than 0.5 cm are included in the detected target lesion on ultrasound or CT.

Procedure: Radiofrequency Ablation

SBRT group

EXPERIMENTAL

A total dose of 45 Gy is presecribed using 15 Gy per fraction over 3 consecutive days.

Radiation: Stereotactic Body Radiotherapy

Interventions

Stereotactic Body Radiotherapy RADIATION

* Verify the setup position and respiration of patients as in the simulation CT image. * To precisely align the tumor prior to each treatment, cone-beam CT and gated fluoroscopy using the On-board Imager mounted on the linear accelerator are performed. * The Real-time Position Management system is used to monitor the accuracy of breathing phase during treatment.

SBRT group

Radiofrequency Ablation PROCEDURE

\- RFA are performed under local anesthesia or monitored anesthesia care with either a 15-gause or 17-gause internally cooled electrode, depending on the size of the tumor.

RFA group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patient over the age of 18
• primary or recurrent HCC that is not suitable for surgery
• HCCs with a longest diameter of ≤3cm and ≤2 lesions
• no evidence of intrahepatic or extrahepatic residual disease except for target lesions
• Child-Pugh class A or B hepatic function
• no macroscopic vascular invasion or extrahepatic metastasis
• written informed consent

You may not qualify if:

• Eastern Cooperative Oncology Group performance status score 3 or 4
• uncontrolled ascites, variceal bleeding, or hepatic encephalopathy
• previous history of liver transplantation
• an active gastric or duodenal ulcer within 3 months before screening
• pregnant woman
• uncontrolled other malignancies except for HCC within 2 years before screening
• platelet count \<50,000/µl
• Patients who are judged by the researcher to be difficult to conduct clinical research

Sponsors & Collaborators

• Jonggi Choi: lead

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

Location

Related Publications (22)

• Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2020 Jul;70(4):313. doi: 10.3322/caac.21609. Epub 2020 Apr 6. No abstract available.

  PMID: 32767693 BACKGROUND

• Reig M, Forner A, Rimola J, Ferrer-Fabrega J, Burrel M, Garcia-Criado A, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022 Mar;76(3):681-693. doi: 10.1016/j.jhep.2021.11.018. Epub 2021 Nov 19.

  PMID: 34801630 BACKGROUND

• Lau WY, Lai EC. Salvage surgery following downstaging of unresectable hepatocellular carcinoma--a strategy to increase resectability. Ann Surg Oncol. 2007 Dec;14(12):3301-9. doi: 10.1245/s10434-007-9549-7. Epub 2007 Sep 22.

  PMID: 17891443 BACKGROUND

• Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ, Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 2006 Mar;243(3):321-8. doi: 10.1097/01.sla.0000201480.65519.b8.

  PMID: 16495695 BACKGROUND

• Feng K, Yan J, Li X, Xia F, Ma K, Wang S, Bie P, Dong J. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012 Oct;57(4):794-802. doi: 10.1016/j.jhep.2012.05.007. Epub 2012 May 23.

  PMID: 22634125 BACKGROUND

• Huang J, Yan L, Cheng Z, Wu H, Du L, Wang J, Xu Y, Zeng Y. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg. 2010 Dec;252(6):903-12. doi: 10.1097/SLA.0b013e3181efc656.

  PMID: 21107100 BACKGROUND

• Liu PH, Hsu CY, Hsia CY, Lee YH, Huang YH, Chiou YY, Lin HC, Huo TI. Surgical Resection Versus Radiofrequency Ablation for Single Hepatocellular Carcinoma </= 2 cm in a Propensity Score Model. Ann Surg. 2016 Mar;263(3):538-45. doi: 10.1097/SLA.0000000000001178.

  PMID: 25775062 BACKGROUND

• Taguchi H, Sakuhara Y, Hige S, Kitamura K, Osaka Y, Abo D, Uchida D, Sawada A, Kamiyama T, Shimizu T, Shirato H, Miyasaka K. Intercepting radiotherapy using a real-time tumor-tracking radiotherapy system for highly selected patients with hepatocellular carcinoma unresectable with other modalities. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):376-80. doi: 10.1016/j.ijrobp.2007.03.042.

  PMID: 17869660 BACKGROUND

• Krishnan S, Dawson LA, Seong J, Akine Y, Beddar S, Briere TM, Crane CH, Mornex F. Radiotherapy for hepatocellular carcinoma: an overview. Ann Surg Oncol. 2008 Apr;15(4):1015-24. doi: 10.1245/s10434-007-9729-5. Epub 2008 Jan 31. No abstract available.

  PMID: 18236114 BACKGROUND

• Tse RV, Guha C, Dawson LA. Conformal radiotherapy for hepatocellular carcinoma. Crit Rev Oncol Hematol. 2008 Aug;67(2):113-23. doi: 10.1016/j.critrevonc.2008.01.005. Epub 2008 Mar 4.

  PMID: 18308583 BACKGROUND

• Jeong Y, Jung J, Cho B, Kwak J, Jeong C, Kim JH, Park JH, Kim SY, Shim JH, Kim KM, Lim YS, Lee HC, Yoon SM. Stereotactic body radiation therapy using a respiratory-gated volumetric-modulated arc therapy technique for small hepatocellular carcinoma. BMC Cancer. 2018 Apr 13;18(1):416. doi: 10.1186/s12885-018-4340-7.

  PMID: 29653562 BACKGROUND

• Takeda A, Sanuki N, Tsurugai Y, Iwabuchi S, Matsunaga K, Ebinuma H, Imajo K, Aoki Y, Saito H, Kunieda E. Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer. 2016 Jul 1;122(13):2041-9. doi: 10.1002/cncr.30008. Epub 2016 Apr 8.

  PMID: 27062278 BACKGROUND

• Su TS, Liang P, Lu HZ, Liang J, Gao YC, Zhou Y, Huang Y, Tang MY, Liang JN. Stereotactic body radiation therapy for small primary or recurrent hepatocellular carcinoma in 132 Chinese patients. J Surg Oncol. 2016 Feb;113(2):181-7. doi: 10.1002/jso.24128. Epub 2015 Dec 14.

  PMID: 26799260 BACKGROUND

• Kimura T, Aikata H, Takahashi S, Takahashi I, Nishibuchi I, Doi Y, Kenjo M, Murakami Y, Honda Y, Kakizawa H, Awai K, Chayama K, Nagata Y. Stereotactic body radiotherapy for patients with small hepatocellular carcinoma ineligible for resection or ablation therapies. Hepatol Res. 2015 Apr;45(4):378-86. doi: 10.1111/hepr.12359. Epub 2014 Jun 16.

  PMID: 24849379 BACKGROUND

• Takeda A, Sanuki N, Eriguchi T, Kobayashi T, Iwabutchi S, Matsunaga K, Mizuno T, Yashiro K, Nisimura S, Kunieda E. Stereotactic ablative body radiotherapy for previously untreated solitary hepatocellular carcinoma. J Gastroenterol Hepatol. 2014 Feb;29(2):372-9. doi: 10.1111/jgh.12350.

  PMID: 23927053 BACKGROUND

• Jung J, Yoon SM, Kim SY, Cho B, Park JH, Kim SS, Song SY, Lee SW, Ahn SD, Choi EK, Kim JH. Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters. Radiat Oncol. 2013 Oct 27;8:249. doi: 10.1186/1748-717X-8-249.

  PMID: 24160910 BACKGROUND

• Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ, Zook J, Johnstone PA, Cardenes HR. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e447-53. doi: 10.1016/j.ijrobp.2011.04.011. Epub 2011 Jun 7.

  PMID: 21645977 BACKGROUND

• Wahl DR, Stenmark MH, Tao Y, Pollom EL, Caoili EM, Lawrence TS, Schipper MJ, Feng M. Outcomes After Stereotactic Body Radiotherapy or Radiofrequency Ablation for Hepatocellular Carcinoma. J Clin Oncol. 2016 Feb 10;34(5):452-9. doi: 10.1200/JCO.2015.61.4925. Epub 2015 Nov 30.

  PMID: 26628466 BACKGROUND

• Kim TH, Koh YH, Kim BH, Kim MJ, Lee JH, Park B, Park JW. Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: A randomized phase III trial. J Hepatol. 2021 Mar;74(3):603-612. doi: 10.1016/j.jhep.2020.09.026. Epub 2020 Oct 5.

  PMID: 33031846 BACKGROUND

• Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, Roberts LR, Heimbach JK. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018 Aug;68(2):723-750. doi: 10.1002/hep.29913. No abstract available.

  PMID: 29624699 BACKGROUND

• Rhim H, Yoon KH, Lee JM, Cho Y, Cho JS, Kim SH, Lee WJ, Lim HK, Nam GJ, Han SS, Kim YH, Park CM, Kim PN, Byun JY. Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings. Radiographics. 2003 Jan-Feb;23(1):123-34; discussion 134-6. doi: 10.1148/rg.231025054.

  PMID: 12533647 BACKGROUND

• Takaki H, Yamakado K, Nakatsuka A, Yamada T, Shiraki K, Takei Y, Takeda K. Frequency of and risk factors for complications after liver radiofrequency ablation under CT fluoroscopic guidance in 1500 sessions: single-center experience. AJR Am J Roentgenol. 2013 Mar;200(3):658-64. doi: 10.2214/AJR.12.8691.

  PMID: 23436859 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiosurgery; Radiofrequency Ablation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Radiofrequency Therapy; Ablation Techniques

Study Officials

• Jonggi Choi, M.D, Ph D

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: June 27, 2022
• Study Start: August 29, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 18, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)