Clinical Application of Image-Guided Liver Surgery

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00878215
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 4
• Actual Duration (Months): 103
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Image-guided surgery is a new technology, which is used to create 3-D pictures that generate a map of the liver. This map will allow surgeons to know the exact anatomical location of their instruments, including instances when direct visualization is not possible. This study is designed to determine the safety and feasibility of using image-guided techniques for treatment of liver tumors. The overall goal of this study is to use image-guided surgery for the improvement of the surgeon's ability to remove liver tumors.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Cancer	Device: Explorer Liver Image Guided System; Device: Explorer Liver Passive Tracking; Procedure: Liver surgery; Procedure: Liver abalation	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Application of Image-Guided Liver Surgery
• Actual Study Start Date: Oct 24, 2002
• Actual Primary Completion Date: May 25, 2011
• Actual Study Completion Date: May 25, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1:Localize Anatomical Points on Liver Surface -The surgeon will use image-guided surgery equipment to create the mapping with 3-D pictures of the participants liver. Laser range scanning will also be used to take 3-D pictures of the liver surface. The participant will then have planned standard surgery.	Device: Explorer Liver Image Guided System; Device: Explorer Liver Passive Tracking; Procedure: Liver surgery; -Standard of care
Experimental: Phase 2: Ceramic bead -The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. During the surgery, a ceramic bead will be placed in a pre-operatively determined target location within the tumor using image-guided surgery. Standard surgical procedures will then be used to remove the tumors. Magnetic resonance (MR) images of the resected liver will confirm targeting accuracy.	Device: Explorer Liver Image Guided System; Device: Explorer Liver Passive Tracking; Procedure: Liver surgery; -Standard of care
Experimental: Phase 3: Ablative therapy -The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. The liver tumors will be ablated using image-guided surgery. Standard surgical procedures will then be used to remove the portion of the liver that has the ablated tumors. The accuracy of the ablation will be confirmed via pathology sectioning.	Device: Explorer Liver Image Guided System; Device: Explorer Liver Passive Tracking; Procedure: Liver surgery; -Standard of care; Procedure: Liver abalation; -Standard of care
Experimental: Phase 4: Ablative therapy (not liver resection candidates) -This phase is for patients who otherwise do not qualify to have a portion of their liver to be surgically removed. The surgeon will use image-guidance to create the mapping with 3-D pictures of the liver. The tumors will be ablated using image-guided therapy.	Device: Explorer Liver Image Guided System; Device: Explorer Liver Passive Tracking; Procedure: Liver abalation; -Standard of care

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Have a Successful Intraoperative Registrations (Phase 1 Portion of Study) [Completion of surgery]

   10 successful intraoperative registrations with no more than 30% failure rate over all the cases will be considered a successful endpoint A successful registration is defined as one which yields an RMS surface residual of ≤ 10 mm and is determined to be success after qualitative evaluation.

2. Accuracy With Which Image-guided Surgery (IGS) Can be Used to Implant a Ceramic Bead Inside a Tumor as Measured by Successful Deliveries of the Bead to Within 8mm of the Pre-operatively Planned Target Point (Phase 2 Portion of Study) [Completion of surgery]

   Calculation of bead delivery accuracy using the IGS system involves the acquisition of images of the resected specimen and then the co-registration of the post-resection images to the pre-operative image set. Given that the target location is marked in the pre-operative image set and the registration calculation allows an overlay of the two image sets a Euclidean distance error can be calculated between the true bead location and the pre-operatively determined target. Given that the error involved in computing the registration between the two image sets is included within the bead delivery target error calculation it is imperative that the impact of registration error is minimized. Numbers represented are the distance between the planned target site and the true bead location

3. Target Accuracy of an Ablation Probe Using Image-guided Surgery Technology as Measured by the Number of Participants Who Had Ablation Burns Within a 5mm Radius of the Tumor Centroid (Phase 3 Portion of Study) [Completion of surgery]

   -A measurement of the ablation probe placement via the burn zone will be performed by pathology via specimen sectioning.

4. The Number of Participants Who Have Complete Ablation According to Early Post-ablative Imaging Studies as Well as no Recurrence of the Tumor Within 6 Months (Phase 4 Portion of the Study) [6 months post-ablation]

   -A successful endpoint will be a 90% success rate of complete ablation according to early post-ablative imaging studies as well as no recurrence of the tumor within 6 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent must be obtained.

• Patient must be 18 years or older.

• Are male or non-pregnant, non-lactating females. Liver resection or ablation could be harmful to an unborn child therefore, is not recommended during pregnancy. After informed consent is obtained, women of childbearing potential will be required to have a blood or urine pregnancy test. All consented patients of childbearing potential will be advised to use adequate birth control (oral, implanted, or barrier methods) along with their sexual partners while being considered for liver tumor resection or ablation and at least up to a month following surgery.

• Patients enrolled in Phase I must be candidates for surgical liver resection per a treating surgeon's discretion. Patients enrolled in Phase 2-3 must be candidates for surgical liver resection of liver mass. Patients enrolled in Phase 4 must be candidates for surgical ablation, but not candidates for surgical resection.

• Patients are scheduled clinically for use of the Pathfinder Explorer Liver Image Guided System which is indicated for open liver surgical procedures where image-guidance may be appropriate and where the patient can tolerate long apneic periods under general anesthesia.

Exclusion Criteria:

• Any condition which, in the judgment of the investigator, might increase the risk to the subject or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.

• Mental condition rendering the subject or his/her legal representative unable to understand informed consent to the nature, scope, and possible consequences of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: William C Chapman, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

• Arun KS, Huang TS, Blostein SD. Least-squares fitting of two 3-d point sets. IEEE Trans Pattern Anal Mach Intell. 1987 May;9(5):698-700.
• Besl PM,McKay ND.A method for registraion of 3-D shapes.IEEE Transaactions on Pattern Analysis and Machine Intelligence 14:239-256,1992
• Cash DM,Siha Tk,Chapman,WC.Fast, accurate surface acquistion using a laser range scanner for image-guided surgical system.SPIE Medical Imaging,2002
• Dick EA, Taylor-Robinson SD, Thomas HC, Gedroyc WM. Ablative therapy for liver tumours. Gut. 2002 May;50(5):733-9. Review.
• Herline AJ, Herring JL, Stefansic JD, Chapman WC, Galloway RL Jr, Dawant BM. Surface registration for use in interactive, image-guided liver surgery. Comput Aided Surg. 2000;5(1):11-7.
• Herline AJ, Stefansic JD, Debelak JP, Hartmann SL, Pinson CW, Galloway RL, Chapman WC. Image-guided surgery: preliminary feasibility studies of frameless stereotactic liver surgery. Arch Surg. 1999 Jun;134(6):644-9; discussion 649-50.
• Horn BKP.closed-form solution of absolute orientation using unit quaternions 4:629-642,1987
• Pan S,Dawant BM.Automatic 3-D segmentation of the liver from abdominal CT images: a level-set approach. Proceedings of SPIE 4322:128-138,2001.
• Parikh AA, Curley SA, Fornage BD, Ellis LM. Radiofrequency ablation of hepatic metastases. Semin Oncol. 2002 Apr;29(2):168-82. Review.
• Rosen CB. Management of Hepatic Metastases. Cancer Control. 1998 May;5(3 Suppl 1):30-31.
• Sardi A, Akbarov A, Conaway G. Management of primary and metastatic tumors to the liver. Oncology (Williston Park). 1996 Jun;10(6):911-25; discussion 926, 929-30. Review.
• Stefansic JD, Bass WA, Hartmann SL, Beasley RA, Sinha TK, Cash DM, Herline AJ, Galloway RL Jr. Design and implementation of a PC-based image-guided surgical system. Comput Methods Programs Biomed. 2002 Nov;69(3):211-24.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00878215
• Other Study ID Numbers: 201104308
• First Posted: Apr 8, 2009
• Last Update Posted: Feb 13, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Washington University School of Medicine: Image Guided Liver Surgery
• Additional relevant MeSH terms: Liver Neoplasms; Carcinoma, Hepatocellular; Liver Extracts

Study Results

Participant Flow

Recruitment Details	The study opened to participant enrollment on 10/24/2002 with the first participant enrolled on 12/27/2002 and the final participant was enrolled on 05/25/2011.

Arm/Group Title	Phase 1:Localize Anatomical Points on Liver Surface	Phase 2: Ceramic Bead	Phase 3: Ablative Therapy	Phase 4: Ablative Therapy (Not Liver Resection Candidates)
Arm/Group Description	-The surgeon will use image-guided surgery equipment to create the mapping with 3-D pictures of the participants liver. Laser range scanning will also be used to take 3-D pictures of the liver surface. The participant will then have planned standard surgery.	-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. During the surgery, a ceramic bead will be placed in a pre-operatively determined target location within the tumor using image-guided surgery. Standard surgical procedures will then be used to remove the tumors. Magnetic resonance (MR) images of the resected liver will confirm targeting accuracy.	-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. The liver tumors will be ablated using image-guided surgery. Standard surgical procedures will then be used to remove the portion of the liver that has the ablated tumors. The accuracy of the ablation will be confirmed via pathology sectioning.	-This phase is for patients who otherwise do not qualify to have a portion of their liver to be surgically removed. The surgeon will use image-guidance to create the mapping with 3-D pictures of the liver. The tumors will be ablated using image-guided therapy.
Period Title: Overall Study
STARTED	21	19	0	0
COMPLETED	21	9	0	0
NOT COMPLETED	0	10	0	0

Baseline Characteristics

Arm/Group Title	Phase 1:Localize Anatomical Points on Liver Surface	Phase 2: Ceramic Bead	Phase 3: Ablative Therapy	Phase 4: Ablative Therapy (Not Liver Resection Candidates)	Total
Arm/Group Description	-The surgeon will use image-guided surgery equipment to create the mapping with 3-D pictures of the participants liver. Laser range scanning will also be used to take 3-D pictures of the liver surface. The participant will then have planned standard surgery.	-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. During the surgery, a ceramic bead will be placed in a pre-operatively determined target location within the tumor using image-guided surgery. Standard surgical procedures will then be used to remove the tumors. Magnetic resonance (MR) images of the resected liver will confirm targeting accuracy.	-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. The liver tumors will be ablated using image-guided surgery. Standard surgical procedures will then be used to remove the portion of the liver that has the ablated tumors. The accuracy of the ablation will be confirmed via pathology sectioning.	-This phase is for patients who otherwise do not qualify to have a portion of their liver to be surgically removed. The surgeon will use image-guidance to create the mapping with 3-D pictures of the liver. The tumors will be ablated using image-guided therapy.	Total of all reporting groups
Overall Participants	21	19	0	0	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	58	59
Sex: Female, Male (Count of Participants)
Female	6 28.6%	14 73.7%	20 Infinity
Male	15 71.4%	5 26.3%	20 Infinity
Region of Enrollment (participants) [Number]
United States	21 100%	19 100%	40 Infinity

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Have a Successful Intraoperative Registrations (Phase 1 Portion of Study)
Description	10 successful intraoperative registrations with no more than 30% failure rate over all the cases will be considered a successful endpoint A successful registration is defined as one which yields an RMS surface residual of ≤ 10 mm and is determined to be success after qualitative evaluation.
Time Frame	Completion of surgery

Outcome Measure Data

Analysis Population Description

2 patients were excluded due to the fact that liver surface data was not acquired for these cases due to equipment malfunctions and not due to a failure in the guidance method in general.

Arm/Group Title	Phase 1:Localize Anatomical Points on Liver Surface
Arm/Group Description	-The surgeon will use image-guided surgery equipment to create the mapping with 3-D pictures of the participants liver. Laser range scanning will also be used to take 3-D pictures of the liver surface. The participant will then have planned standard surgery.
Measure Participants	19
Number [participants]	18 85.7%

2. Primary Outcome

Title	Accuracy With Which Image-guided Surgery (IGS) Can be Used to Implant a Ceramic Bead Inside a Tumor as Measured by Successful Deliveries of the Bead to Within 8mm of the Pre-operatively Planned Target Point (Phase 2 Portion of Study)
Description	Calculation of bead delivery accuracy using the IGS system involves the acquisition of images of the resected specimen and then the co-registration of the post-resection images to the pre-operative image set. Given that the target location is marked in the pre-operative image set and the registration calculation allows an overlay of the two image sets a Euclidean distance error can be calculated between the true bead location and the pre-operatively determined target. Given that the error involved in computing the registration between the two image sets is included within the bead delivery target error calculation it is imperative that the impact of registration error is minimized. Numbers represented are the distance between the planned target site and the true bead location
Time Frame	Completion of surgery

Outcome Measure Data

Analysis Population Description

10 patients were excluded as they were determined to be ineligible after enrollment but prior to surgery.

Arm/Group Title	Phase 2: Ceramic Bead
Arm/Group Description	-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. During the surgery, a ceramic bead will be placed in a pre-operatively determined target location within the tumor using image-guided surgery. Standard surgical procedures will then be used to remove the tumors. Magnetic resonance (MR) images of the resected liver will confirm targeting accuracy.
Measure Participants	9
Case 1	17.3
Case 2	16.6
Case 3	4.6
Case 4	15.9
Case 5	8.8
Case 6	10.9
Case 7	4.7
Case 8	13.0
Case 9	25.6

3. Primary Outcome

Title	Target Accuracy of an Ablation Probe Using Image-guided Surgery Technology as Measured by the Number of Participants Who Had Ablation Burns Within a 5mm Radius of the Tumor Centroid (Phase 3 Portion of Study)
Description	-A measurement of the ablation probe placement via the burn zone will be performed by pathology via specimen sectioning.
Time Frame	Completion of surgery

Outcome Measure Data

Analysis Population Description

The study closed early as the imaging-guidance system became commercially available as the Explorer Liver Image Guided System and the Explorer Liver Passive Tracking device.

Arm/Group Title	Phase 3: Ablative Therapy
Arm/Group Description	-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. The liver tumors will be ablated using image-guided surgery. Standard surgical procedures will then be used to remove the portion of the liver that has the ablated tumors. The accuracy of the ablation will be confirmed via pathology sectioning.
Measure Participants	0

4. Primary Outcome

Title	The Number of Participants Who Have Complete Ablation According to Early Post-ablative Imaging Studies as Well as no Recurrence of the Tumor Within 6 Months (Phase 4 Portion of the Study)
Description	-A successful endpoint will be a 90% success rate of complete ablation according to early post-ablative imaging studies as well as no recurrence of the tumor within 6 months.
Time Frame	6 months post-ablation

Outcome Measure Data

Analysis Population Description

The study closed early as the imaging-guidance system became commercially available as the Explorer Liver Image Guided System and the Explorer Liver Passive Tracking device.

Arm/Group Title	Phase 4: Ablative Therapy (Not Liver Resection Candidates)
Arm/Group Description	-This phase is for patients who otherwise do not qualify to have a portion of their liver to be surgically removed. The surgeon will use image-guidance to create the mapping with 3-D pictures of the liver. The tumors will be ablated using image-guided therapy.
Measure Participants	0

Adverse Events

Arm/Group Title	Phase 1:Localize Anatomical Points on Liver Surface		Phase 2: Ceramic Bead		Phase 3: Ablative Therapy		Phase 4: Ablative Therapy (Not Liver Resection Candidates)
Arm/Group Description	-The surgeon will use image-guided surgery equipment to create the mapping with 3-D pictures of the participants liver. Laser range scanning will also be used to take 3-D pictures of the liver surface. The participant will then have planned standard surgery.		-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. During the surgery, a ceramic bead will be placed in a pre-operatively determined target location within the tumor using image-guided surgery. Standard surgical procedures will then be used to remove the tumors. Magnetic resonance (MR) images of the resected liver will confirm targeting accuracy.		-The surgeon will use image-guided surgery to create the mapping with 3-D pictures of the liver. The liver tumors will be ablated using image-guided surgery. Standard surgical procedures will then be used to remove the portion of the liver that has the ablated tumors. The accuracy of the ablation will be confirmed via pathology sectioning.		-This phase is for patients who otherwise do not qualify to have a portion of their liver to be surgically removed. The surgeon will use image-guidance to create the mapping with 3-D pictures of the liver. The tumors will be ablated using image-guided therapy.
All Cause Mortality
	Phase 1:Localize Anatomical Points on Liver Surface		Phase 2: Ceramic Bead		Phase 3: Ablative Therapy		Phase 4: Ablative Therapy (Not Liver Resection Candidates)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Phase 1:Localize Anatomical Points on Liver Surface		Phase 2: Ceramic Bead		Phase 3: Ablative Therapy		Phase 4: Ablative Therapy (Not Liver Resection Candidates)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/19 (0%)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Phase 1:Localize Anatomical Points on Liver Surface		Phase 2: Ceramic Bead		Phase 3: Ablative Therapy		Phase 4: Ablative Therapy (Not Liver Resection Candidates)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/19 (0%)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.