• 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
  • 2 Chang Gung Memorial Hospital - Linkou, Taoyuan, Taiwan
  • 3 Third Central Hospital of Tianjin, Tianjin, China
  • 4 Beijing You'an Hospital, Capital Medical University, Beijing, China
  • 5 National Cancer Institute of Naples, Naples, Italy
  • 6 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
  • 7 Peking University Cancer Hospital, Department of Ultrasound, Beijing, China
  • 8 Chinese General Hospital, Manila, Philippines
  • 9 Hunan Cancer Hospital, Department of Hepatobiliary and Pancreatic Internal Medicine, Changsha, China
  • 10 China Medical University Hospital, Taichung, Taiwan
  • 11 Taipei Veterans General Hospital, Taipei, Taiwan
  • 12 National Taiwan University Hospital, Taipei, Taiwan
  • 13 Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China
  • 14 University Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 15 Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
  • 16 Seoul National University Hospital, Seoul, Republic of Korea
  • 17 Catholic University of Korea, Seoul, Republic of Korea
  • 18 St. Luke's Medical Center, Quezon City, Philippines
  • 19 Toronto General Hospital, Toronto, Ontario, Canada
  • 20 Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, California
  • 21 Yamanashi Prefectural Central Hospital, Yamanashi, Japan
  • 22 BioClinica Inc., Princeton, New Jersey
  • 23 Stathmi, New Hope, Pennsylvania
  • 24 Celsion Corporation, Lawrenceville, New Jersey
  • 25 Queen Mary Hospital, University of Hong Kong, Hong Kong, China
  • 26 University of Miami Miller School of Medicine, Section of Vascular and Interventional Radiology, Sylvester Comprehensive Cancer Center, Miami, Florida
Clin. Cancer Res., 2018 01 01;24(1):73-83.
PMID: 29018051 DOI: 10.1158/1078-0432.CCR-16-2433


Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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