4:03 PM Abstract No. 178 Tumor size and geometry in patients treated with radiofrequency ablation plus lyso thermosensitive liposomal doxorubicin (LTLD)

Lyso-thermosensitive liposomal doxorubicin (LTLD) releases cytotoxic doxorubicin locally in the region of mild hyperthermia (40–42 °C). LTLD had been shown to be effective drug delivery method for hepatocellular carcinoma in animal models mouse tumor models compared with conventional free drug or non-thermally sensitive liposome therapies. A recent phase III clinical trial (HEAT) compared survival of (a) radiofrequency ablation (RFA)-only and (b) LTLD administration together with RFA treatment patients (RFA+LTLD) but did not meet defined endpoints. This post hoc sub-analysis aims to provide ranges of tumor properties, where RFA+LTLD patient survival is better than RFA-only patient survival using Cox proportional hazard model. HEAT study is a double-blind and randomized controlled phase III trial of RFA-only vs. RFA+LTLD in patients with 3-7 cm diameter hepatocellular carcinoma (HCC). Although the trial included single as well as multiple tumor patients, we evaluated only patients with single tumors to normalize and simplify the study group and hypotheses (RFA only n = 210 vs. RFA+LTLD n = 227 patients). Tumor volume, longest diameter, area, ellipticity, one-month post ablation lesion volume, burn time, and burn time per tumor volume were investigated to find useful ranges for RFA+LTLD patients. We found the ranges of different geometrical sizes, where LTLD was significantly different (useful) to the patients compared with RFA-only group (Table). LTLD may improve overall survival as RFA duration per unit tumor volume increases. This is a post hoc study in search of favorable ranges, therefore the results are not definitive and need to be confirmed with further studies. Finally, for any drug-device combination studies, investigators need to consider the drug-device interactions and novel methodologies for response criteria to define potential benefits and standardize and optimize the combination treatments.Tabled 1Tumor Size vs. StatisticsMin-MaxUseful RangeP ValueHazard RatioDiameter (mm)20-8539.5-520.0411.72Volume (ml)5.2-246.830-105.50.0441.651Area (cm2)2.75-42.7310.3-16.50.0361.738Ellipticity (a.u.)0-0.830.475-0.730.0411.54 Open table in a new tab