Dynamic Contrast Enhanced HCC SABR Liver Study

Carcinoma, Hepatocellular Clinical Trial

Official title: Dynamic Contrast Enhanced Imaging of Patients Receiving SABR for Unresectable or Medically Inoperable Hepatocellular Carcinoma in BC

Status Not yet recruiting

Clinical Trial Summary

The high dose per fraction (>10Gy/fraction) used in Stereotactic Ablative Body Radiotherapy (SABR) has been shown to be more effective at local tumor control than treatments employing more conventional dose fractions. The mechanisms for this are currently under debate. One possible mechanism for this increased effectiveness is that high dose/fraction causes significant vascular damage to the tumor. This study hopes to measure vascular integrity pre and post SABR treatment using kinetic models obtained from dynamic contrast enhanced CT.

Clinical Trial Description

Purpose:

The purpose of this study is to determine if high dose per fraction SABR has an impact on the vasculature of both the tumor and of healthy liver tissue.

Hypothesis:

High dose / fraction in HCC patients with tumours < 5 cm will result in detectable changes to kinetic model parameters derived from dynamic contrast enhanced images.

Objectives:

Primary objective:

To quantify changes in tumor vascular support for patients receiving SABR.

Secondary objectives:

To investigate the correlation between PK derived model liver perfusion parameters and QoL metrics as measured by EORTC QLQ-C30 and FACT-Hep QoL assessments.

Research Methods:

Target population are patients receiving liver SABR for no more than 2 discrete liver tumors with a maximum dimension <5cm.

Perfusion CT Image Data Post Processing and Analysis. Patient motion will be corrected using deformable registration, fiducial tracking, and RPM breathing traces. Organ ROIs will be added to the perfusion image series by manually translating anatomical planning CT ROIs to the motion-corrected perfusion image series, or by algorithmically deforming planning ROIs. Portal vein and abdominal aorta ROIs will be demarcated.

Analysis will proceed via custom software we have built during related projects. Contrast enhancement time courses will be generated for key structures (i.e., abdominal aorta, portal vein, and gross liver tissues) and used to derive a variety of perfusion map images, such as liver perfusion, mean transit time, arterial fraction, and distribution volume. A distributed parameter model will be preferred for kinetic modeling. Supplementary non-parametric techniques will be used for other parameters of interest (e.g., IAUC, maximum slope).

Images acquired before and after treatment will be registered so that parameter maps can be compared on a per-patient basis. Changes in perfusion parameters will be characterized with special emphasis placed on regional structure and clustering effects. Pre and post parameter maps will be computed near individual-voxel level. Regions of interest (1) within or near tumour and (2) at a low-dose portion of liver will be defined. A distribution of parameters within each ROI will be used to generate estimates of the mean parameters and uncertainty. Estimates of mean parameters and whole distributions will be compared using standard statistical comparisons (t-test and Whitney respectively).

Quality of Life We will evaluate quality of life (QOL) in HCC patients treated with SBRT using EORTC QLQ-C30 and FACT-Hep QOL assessments at baseline, 3, 6, 9 and 12 months. Correlation between perfusion parameter changes and patient outcomes or QOL (second-order analysis) will be applied if statistically significant first-order parameter changes can be detected. Standard correlative measures such as the Pearson product-moment correlation measure will be used to assess statistical significance. As there is currently no data relating liver perfusion to toxicity or quality of life, this study will examine whether a change in liver perfusion is correlated with enhanced or reduced QOL. ;

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

• NCT number: NCT02847767
• Study type: Interventional
• Source: British Columbia Cancer Agency
• Contact: Steven Thomas
• Phone: 604-877-6000
• Email: sthomas-02@bccancer.bc.ca
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2016
• Completion date: October 2018