Phase I/II trial of helical IMRT-based stereotactic body radiotherapy for hepatocellular carcinoma

e14683 Background: Stereotactic body radiotherapy (SBRT) is a promising therapeutic modality in hepatocelular carcinoma (HCC). A Phase I trial was conducted at Indiana University (IU) in patients with Child Pugh Class (CPC) A and B. Based on our results, patients with CPC-B patients with score <=7 continued enrollment in the phase II. We now present an interim analysis for this patient population. Methods: 14 patients with HCC with liver cirrhosis, CPC-B, were treated with SBRT in a Phase I-II trial at IU. All patients were scheduled to receive five fractions, 800 cGy per fraction (total dose 4000 cGy), 1-2 fractions per week. Dose was prescribed to the 80-90% isodose line covering the planning target volume (PTV). A modified RECIST criterion was used to determine local failure. Demographics, clinical variables, treatment –related toxicities within 90 days of end of treatment, and local control (LC) at 6 and 12 months were tabulated. Progression Free Survival (PFS), Time to Progression (TTP), and Overall Survival (OS) estimates were calculated using Kaplan-Meier methodology. This was an unplanned interim analysis. A formal interim analysis will take place later. Results: There were 13 males and 1 female; median age of 56.5 years (range 49-69). All patients had 1 treated lesion. Median (range) for gross tumor volume (GTV) (cc) was 40.1 (8.0-74.6); PTV volume (cc) was 120.1 (34.7-210.0); and uninvolved liver volume (cc) was 2137.9 (973.0-2796.0). There were 3 grade 4 toxicities, 1 each of hyperbilirubinemia, hypokalemia, and thrombycytopenia. Four patients underwent orthotopic liver transplant. Local control at 6 and 12 months were 90% [95% C.I. (55.5%, 99.8%)] and 87.5% [95% C.I. (47.4%, 99.7%)], respectively. Median PFS is 11.0 months (95% CI: 3.9 months, 17.4 months). Ten patients died or progressed including 4 patients who died without progressing. Median TTP is 17.4 months (95% CI: 5.3 months, upper limit not estimable). Median OS is 19.8 months (95% CI: 4.0 months, upper limit not estimable). Conclusions: in carefully selected patients with hepatocellular carcinoma in the context of CPC B liver cirrhosis, score less or equal than 7, SBRT is an effective therapy with a good toxicity profile. Phase II is ongoing.

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Phase I Study of Individualized Stereotactic Body Radiotherapy for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.3529 ◽

2008 ◽

Vol 26 (4) ◽

pp. 657-664 ◽

Cited By ~ 373

Author(s):

Regina V. Tse ◽

Maria Hawkins ◽

Gina Lockwood ◽

John J. Kim ◽

Bernard Cummings ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase I ◽

Intrahepatic Cholangiocarcinoma ◽

Stereotactic Body Radiotherapy ◽

Phase I Study ◽

Liver Enzymes ◽

Liver Toxicity ◽

Liver Volume ◽

Estimated Risk ◽

Grade 3

Purpose To report outcomes of a phase I study of individualized stereotactic body radiotherapy treatment (SBRT) for unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). Patients and Methods Patients with unresectable HCC or IHC, and who are not suitable for standard therapies, were eligible for six-fraction SBRT during 2 weeks. Radiation dose was dependent on the volume of liver irradiated and the estimated risk of liver toxicity based on a normal tissue complication model. Toxicity risk was escalated from 5% to 10% and 20%, within three liver volume–irradiated strata, provided at least three patients were without toxicity at 3 months after SBRT. Results Forty-one patients with unresectable Child-Pugh A HCC (n = 31) or IHC (n = 10) completed six-fraction SBRT. Five patients (12%) had grade 3 liver enzymes at baseline. The median tumor size was 173 mL (9 to 1,913 mL). The median dose was 36.0 Gy (24.0 to 54.0 Gy). No radiation-induced liver disease or treatment-related grade 4/5 toxicity was seen within 3 months after SBRT. Grade 3 liver enzymes were seen in five patients (12%). Two patients (5%) with IHC developed transient biliary obstruction after the first few fractions. Seven patients (five HCC, two IHC) had decline in liver function from Child-Pugh class A to B within 3 months after SBRT. Median survival of HCC and IHC patients was 11.7 months (95% CI, 9.2 to 21.6 months) and 15.0 months (95% CI, 6.5 to 29.0 months), respectively. Conclusion Individualized six-fraction SBRT is a safe treatment for unresectable HCC and IHC.

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Preliminary Toxicity Analysis of a Phase I/II Trial Evaluating Stereotactic Body Radiotherapy for the Treatment of Hepatocellular Carcinoma

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2007.07.1343 ◽

2007 ◽

Vol 69 (3) ◽

pp. S297 ◽

Cited By ~ 2

Author(s):

M.A. Henderson ◽

F. Azzouz ◽

T. Breen ◽

J. DeLuca ◽

K. Tudor ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase I ◽

Stereotactic Body Radiotherapy ◽

Toxicity Analysis

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Faculty Opinions recommendation of Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725979903.793512329 ◽

2015 ◽

Author(s):

Eugene Koay

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Stereotactic Body Radiotherapy

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Axitinib in combination with radiotherapy for advanced hepatocellular carcinoma: a phase I clinical trial

Radiation Oncology ◽

10.1186/s13014-020-01742-w ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Kai-Lin Yang ◽

Mau-Shin Chi ◽

Hui-Ling Ko ◽

Yi-Ying Huang ◽

Su-Chen Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase I ◽

Response Rate ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Normal Liver ◽

Maximum Tolerated Dose ◽

Outcome Analysis ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc

Abstract Background To investigate maximum tolerated dose (MTD) of axitinib, a selective vascular endothelial growth factor receptor 1–3 inhibitor, in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC). Methods This phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) patients with advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization, or who failed after prior local–regional treatment; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT. The secondary endpoints included overall response rate (ORR), RT in-field response rate, acute and late toxicities, overall survival (OS) and progression free survival (PFS). Results Total nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months. Conclusions Axitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort. Trial registration ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461

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