The patient data set acquired in the study is used to validate the software prediction and to improve its quality and accuracy. The existing RFA model has to be adapted to the real-time requirements of the clinical environment and to be integrated into the clinical workflow.
The developed and validated software model has to be fully integrated into the interventional work flow to allow IRs for real-time and patient specific planning and support of the RFA intervention.
Primary objective of the clinical trial is to compare the size and shape of the real ablation zone directly (1 month) after RFA treatment of liver tumours with the simulation results of the ClinicIMPPACT software.
Secondary objectives of the study are to evaluate the workflow steps and feasibility of the ClinicIMPPACT procedure and to analyse patient outcome (tumour recurrence, tissue damage, survival) related to the results from the ablation comparison (real ablation after RFA vs. simulated RFA).
A total of 60 patients (15 patients per participating clinical site) will be enrolled in this clinical study over the course of one year. Patients will be selected through interdisciplinary assignment via local tumour conferences at each clinical site.
A diagnostic CT scan for up to date anatomical information and a perfusion CT scan, which will provide insights into the patient specific liver – vascularization, will be performed prior to the scheduled RFA - intervention.
Follow – up abdominal CT imaging will be scheduled for 1, 3, 6 and 12 months after the RFA to evaluate primary and secondary endpoints as stipulated above.
Finalization of the study protocol and development of a fully functional prototype of the RFA guardian application were the main focus during the first 12 months of the project.
The second year of the trial was dedicated to final implementation of the RFA guardian application, thorough clinical testing of the guardian, including establishment of core trial - teams comprised of two interventional radiologists and one technical assistant, at each of the four clinical sites, as well as standardization of soft- and hardware, and workflows at each site.
Since the official start of the clinical trial in February 2016 each site recruited and successfully included patients into the study.
The clinical study is carried out by four university hospitals in Turku (Finland), Graz (Austria), Nijmegen (Netherlands), and Leipzig (Germany). The local study center of the University of Leipzig (ZKS, Centre for Clinical Studies) is responsible for monitoring patient safety and adherence to good clinical practice.
Each medical unit consists of a project leader (experienced interventional radiologist) and one or two assistants (e.g. resident radiologists). Technical partners, who provide software development and data implementation, are located at Graz (Austria), Helsinki (Finland), and Dublin (Ireland).
Approvals were granted by the institutional ethics committees and the German Federal Office for Radiation Protection (Bundesamt für Strahlenschutz, BfS, only necessary for Leipzig, Germany).
All participating subjects are patients (both men and women) with primary (hepatocellular carcinoma, HCC) or secondary (e.g. colorectal metastasis) malignant liver tumors who are referred for RFA treatment after interdisciplinary consent of the local tumor board (consisting of radiologists, oncologists and hepatobiliary surgeons) according to AASDL guidelines for HCC (http://www.aasdl.org) and interdisciplinary agreement for secondary liver tumors regarding operability, patient safety and compliance.
Patients must fulfill standard eligibility criteria for undergoing pre-interventional diagnostic such as contrast enhanced multiphase CT of the abdomen and perfusion CT of the liver.
Trial Design and Enrolment
Each trial participant (15 per clinical site, 60 patients in total) requires a pre-diagnosed suspicious primary or secondary tumor of the liver, preferably shown in two independent imaging modalities, alternatively histologically proven. Decisions on optimal therapies will be conducted through each local tumor board, which will evaluate options such as surgical resection, liver transplantation, adjuvant or neoadjuvant chemotherapy or image-guided procedures such as RFA.
Each clinical centre follows the same pre- per- and post-interventional imaging protocol, CT perfusion protocol as well the RFA treatment protocol (Protocol details are to appear in a publication).
Follow up imaging are acquired at months 1, 3, 6, and 12 after RFA via multiphase CT (non-enhanced, arterial, portal venous, venous) for HCC lesions or by mono-phase CT (portal venous) for, e.g., (colorectal) metastases in expiration. All CT images, whether pre-, peri- or post-interventional (i.e. follow-up) are evaluated by radiologists with more than 10 years of experience in abdominal imaging.
For the primary objective, we compare lesions, on a level of volume- and surface deviation, visualized by routine CT one month after ablation with their simulated counterparts to define the accuracy of the method itself. The coinciding volumes of the real RFA lesion and the simulated one are determined by counting the number of matching voxels, i.e. voxels of simulation and recorded data, sharing the space coordinates, and dividing by the sum of the voxels of simulated and real lesions.
Accuracy of the simulation is estimated based on the ratio of segmented to simulated lesion volume the results as follows using the categorization metrics:
If the simulated lesion is comparable with the real lesion based on a), we further investigate the accuracy based on the following two metrics namely, sensitivity (SN), relative volume difference (RVD). We introduce the rating level between 1 and 5 for the simulated lesion based on two metrics as explained below. Simulation rating (based on average absolute error:
Simulation rating (based on volume deviation):
We take average of the rating level obtained from a) and b). If the average rating level is:
For the secondary objective we validate the following questionnaire: