Malignant Liver Neoplasm
Conditions
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREAblation Therapy
Undergo standard of care ablation
PROCEDUREImage-Guided Therapy
Undergo software-aided imaging (Morfeus)
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Ablative Margin Assessment on Post-ablation Intraprocedural CT. | Visit 2 (baseline/ablation day) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of 2-year Local Tumor Progression | 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. | 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). |
| Overall Survival | 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. | The Kaplan-Meier method was used to estimate overall survival |
| Intrahepatic Progression-free Survival (for the Randomized Group) | Up to 2 years | 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. |
| Extrahepatic Progression-free Survival | Up to 2 years | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBRUNO C ODISIO
M.D. Anderson Cancer Center
Participant flow
Recruitment details
MD Anderson Cancer Center
Pre-assignment details
Randomized and non-randomized experimental groups were combined as both received the same ablation confirmation (AC) software. Per DSMB recommendation, an interim stopping rule for control enrollment, which was triggered, halting further accrual. Thus, analyses comparing experimental versus control are presented in this simplified structure to ensure consistency in evaluating the novel AC software for liver tumor ablation.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Clinical impact of Morfeus software usage on patients undergoing percutaneous ablation of hepatic mets | 74 |
| Control Morfeus software was not used during percutaneous ablation of hepatic mets | 26 |
| Total | 100 |
Baseline characteristics
| Characteristic | Experimental | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 8 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 18 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 20 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 57 Participants | 18 Participants | 75 Participants |
| Region of Enrollment United States | 74 participants | 26 participants | 100 participants |
| Sex: Female, Male Female | 31 Participants | 8 Participants | 39 Participants |
| Sex: Female, Male Male | 43 Participants | 18 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 26 / 74 | 6 / 26 |
| other Total, other adverse events | 18 / 74 | 3 / 26 |
| serious Total, serious adverse events | 39 / 74 | 12 / 26 |
Outcome results
Primary
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)
Population: The primary endpoint included all enrolled patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Minimal Ablative Margin Assessment on Post-ablation Intraprocedural CT. | 6.8 mm | Standard Deviation 2.9 |
| Control | Minimal Ablative Margin Assessment on Post-ablation Intraprocedural CT. | 2.2 mm | Standard Deviation 2.8 |
Secondary
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.
Population: The 2-year secondary endpoints were evaluated for the randomized group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Cumulative Incidence of 2-year Local Tumor Progression | 6 percentage of participants |
| Control | Cumulative Incidence of 2-year Local Tumor Progression | 17.9 percentage of participants |
Secondary
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.
Time frame: Up to 2 years
Population: The 2-year secondary endpoints are provided in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Extrahepatic Progression-free Survival | 34.5 percentage of participants |
| Control | Extrahepatic Progression-free Survival | 41.4 percentage of participants |
Secondary
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
Population: The 2-year secondary endpoints are provided in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Intrahepatic Progression-free Survival (for the Randomized Group) | 34.5 percentage of participants |
| Control | Intrahepatic Progression-free Survival (for the Randomized Group) | 41.4 percentage of participants |
Secondary
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.
Population: The 2-year secondary endpoints were evaluated for the randomized group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Overall Survival | 73.9 percentage of participants |
| Control | Overall Survival | 83.6 percentage of participants |