Software-Aided Imaging (Morfeus) for Confirming Tumor Coverage With Ablation in Patients With Liver Tumors, the COVER-ALL Study

Phase 2Active Not RecruitingNCT04083378

M.D. Anderson Cancer Center107 enrolled

Overview

This phase II trial studies how well software-aided imaging works in confirming tumor coverage with ablation (the removal or destruction of a body part or tissue or its function) on patients with liver tumors. The current standard for targeting tumor cells and evaluating the outcome of a liver ablation procedure is a visual inspection of the pre- and post-procedure computed tomography (CT) scans. Software-aided imaging systems, such as Morfeus, may help to improve the accuracy and effectiveness of liver ablation.

PRIMARY OBJECTIVE: I. To evaluate if the intra-procedure feedback of a biomechanical deformable registration volumetric image method during percutaneous ablation will increase the minimal ablation margins on a three-dimensional computed tomography-generated analysis. SECONDARY OBJECTIVES: I. To assess whether applying the proposed method during percutaneous ablation improves local tumor progression-free survival (LTPFS) rates. II. Evaluate impact of software use on procedure workflow. III. Impact of software use on complication rates, quality of life, liver function. IV. Evaluate oncological outcomes (intra-hepatic and overall progression-free survivals, and overall survival). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo standard of care ablation. ARM II: Patients undergo standard of care ablation with software-aided imaging (Morfeus). After completion of study, patients are followed up at 1, 3, and 6 months, and then at 1 and 2 years.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

107

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients presenting with ≤ 3 liver tumors (biopsy-proven or documented by imaging) measuring 1 to 5 cm planned to undergo percutaneous thermal ablation with either microwave or radiofrequency ablation. Patients with more than 3 tumors might also be eligible in case other tumors can be treated with another curative-intended loco-regional therapy (i.e. surgical resection, radiation therapy). 2. Ability to completely cover the target tumor with at least a 5 mm ablation margin. 3. Written informed consent to voluntarily participate in the study and follow-up CT scan schedule 4. Age \> 18 years-old 5. Performance status 0-2 (Eastern Cooperative Oncology Group Classification \[ECOG\]) 6. Target tumor should be visualized on contrast-enhanced CT 7. Adequate glomerular filtration rate Exclusion Criteria 1. Active bacterial infection or fungal infection on the day of the ablation that, in the opinion of the investigator, would interfere with safe delivery of the study procedure or with the interpretation of study results. 2. Platelet \< 50,000/mm3. 3. INR \> 1.5 4. Patients with uncorrectable coagulopathy. 5. Currently breastfeeding or pregnant (latter confirmed by serum pregnancy test). 6. Physical or psychological condition which would impair study participation. 7. ASA (American Society of Anesthesiologists) score of \> 4. 8. Any other loco-regional therapies at the target lesion(s) within 30 days of the ablation procedure.

Outcomes

Primary Outcomes

Minimal Ablative Margin Assessment on Post-ablation Intraprocedural CT.

For control group, MAM was assessed by rigid co-registration with side-by-side juxtaposition to verify applicator placement and by visual landmark-based CT measurements on CT workstation (Siemens Healthineers; Forchheim, Germany). For experimental group, CT images were processed with a software-based method on a radiation treatment planning system (Raystation, RaySearch Laboratories; Stockholm, Sweden) with biomechanical deformable imaging registration coupled with AI-based autosegmentation. For experimental group, interventional radiologist (IR) was informed of ablation applicator position relative to tumor on non-contrast CT before thermal ablation energy delivery and of MAM results (including spatial location of suboptimal margins) generated by software-based assessment, with this information not disclosed to IR in control group. Software-based assessment was used to compare MAMs results between both study groups with a two-sample t-test.

Time frame: Visit 2 (baseline/ablation day)

Secondary Outcomes

Cumulative Incidence of 2-year Local Tumor Progression

A competing risk analysis was conducted to estimate the 2-year cumulative incidence of local tumor progression. Progression followed ablation reporting standards and RECIST v1.1 (mRECIST for HCC).

Time frame: Time to local tumor progression (LTP) was measured from ablation to earliest LTP or death (competing event). Follow-up imaging continued up to 24 months.

Overall Survival

The Kaplan-Meier method was used to estimate overall survival

Time frame: Overall survival was measured from the date of ablation to the date of death from any cause. Patients still alive were censored at the date of last clinic visit, with follow-up up to 24 months after ablation.

Intrahepatic Progression-free Survival (for the Randomized Group)

Competing risk analysis was conducted to estimate the 2-year intrahepatic (progression outside of ablation zone), considering the progression of the ablated tumor and treating death as a competing event.

Time frame: Up to 2 years

Extrahepatic Progression-free Survival

Competing risk analysis was conducted to estimate the 2-year extrahepatic cumulative incidence of progression, considering the progression of the ablated tumor and treating death as a competing event.