An Intraoperative Guidance Platform for Radio Frequency Ablation
Phase: NA
Conditions: Hepatocellular Carcinoma
Sponsor: Dartmouth-Hitchcock Medical Center

PROTOCOL TITLE: An Intraoperative Guidance Platform for Radio Frequency Ablation
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D-HH IRB OVERSIGHT:
One of the following must be true in order to submit to the D-HH IRB. Please check all that apply:
☒ The Principal Investigator is employed by D-H
☒ The study will utilize any D-H data or specimens
☒ The study will enroll D-H patients or recruit from D-H sites
☒ The study will utilize any D-H resources, e.g. study procedures will occur at 
     D-H locations and/or use of D-H equipment or shared resources
PROTOCOL TITLE:
An Intraoperative Guidance Platform for Radio Frequency Ablation
PRINCIPAL INVESTIGATOR:
Eric Hoffer, MD
Department of Radiology
Section of Interventional Radiology
Dartmouth-Hitchcock Medical Center
One Medical Center Drive
Lebanon, NH 03756
Tel: 603-650-7417
Email: Eric.K.Hoffer@hitchcock.org
VERSION NUMBER/DATE: Version 1.1_10102019
REVISION HISTORY
Revision #
Version Date
Summary of Changes
Consent Change?
NCT: 
NCT04152343

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Table of Contents
1.0
Study Summary.................................................................................................................................3
2.0
Objectives* .......................................................................................................................................4
3.0
Background*.....................................................................................................................................4
4.0
Study Endpoints*..............................................................................................................................4
5.0
Study Intervention/Investigational Agent.........................................................................................4
6.0
Procedures Involved*........................................................................................................................5
7.0
Data and Specimen Banking*...........................................................................................................5
8.0
Sharing of Results with Subjects* ....................................................................................................5
9.0
Study Timelines* ..............................................................................................................................5
10.0
Inclusion and Exclusion Criteria*.....................................................................................................6
11.0
Vulnerable Populations*...................................................................................................................6
12.0
Local Number of Subjects ................................................................................................................6
13.0
Recruitment Methods........................................................................................................................6
14.0
Withdrawal of Subjects*...................................................................................................................6
15.0
Risks to Subjects*.............................................................................................................................7
16.0
Potential Benefits to Subjects* .........................................................................................................9
17.0
Data Management* and Confidentiality...........................................................................................9
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*...................................................9
19.0
Provisions to Protect the Privacy Interests of Subjects.....................................................................9
20.0
Compensation for Research-Related Injury......................................................................................9
21.0
Economic Burden to Subjects.........................................................................................................10
22.0
Consent Process ..............................................................................................................................10
23.0
Process to Document Consent in Writing.......................................................................................10
24.0
Setting .............................................................................................................................................11
25.0
Resources Available........................................................................................................................11
26.0
Multi-Site Research* ......................................................................................................................11

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1
Study Summary
Study Title
An Intraoperative Guidance Platform for Radio Frequency Ablation
Study Design
Prospective, single center, single-arm clinical study
Primary Objective
To test the hypothesis that use of the research RFA Physics Library will 
result in more frequent technical success (complete necrotization of target 
tissues) compared to ablations conducted without computer guidance.
Secondary 
Objective(s)
To demonstrate that use of the RFA Physics Library will result in lower rates 
of local recurrence compared to ablations conducted without computer 
guidance.
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
The RFA Physics Library -- a Planning and Guidance Platform (PGP) (NE 
Scientific, LLC) -- will be used to support percutaneous liver RFA under CT-
guidance by assisting physicians in the identification of ablation targets, 
assessment of proper ablation probe placement, and projection of the created 
ablation zones on the CT image.
IND/IDE # 
TBD
Study Population
Adult patients with known hepatocellular carcinoma scheduled for 
percutaneous RFA.
Sample Size
52 patients
Study Duration for 
individual 
participants
One visit, during which the research PGP will be used to support physicians 
during the participant’s scheduled standard of care RFA procedure. Use of 
the research PGP will not increase the time of the RFA procedure. Post-RFA, 
an abdominal MRI will be obtained for research purposes only. Duration of 
this MRI is approximately 30 minutes (including set-up and imaging). 
Participants will be followed for 2 years post-RFA for associated clinical 
outcome (local recurrence) information. .
Study Specific 
Abbreviations/ 
Definitions 
Hepatocellular carcinoma (HCC)
Interventional Radiology (IR)
Operating Room (OR)
Planning and Guidance Platform (PGP)
Radio Frequency Ablation (RFA)

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2
Objectives
Please reference SF19108 clinical protocol v29July2019, page 7, Section 2.0 Study Objectives
3
Background
Please reference SF19108 clinical protocol v29July2019, pages 4-7, Section 1.0 Introduction and 
Background
4
Study Endpoints
Please reference SF19108 clinical protocol v29July2019, pages 7-8, Section 3.1-3.2 Outcomes 
Assessments
5
Study Intervention/Investigational Device
5.1 Description of device
The investigational device used in this study is software called the RFA Physics Library--Planning 
and Guidance Platform (PGP), developed by NE Scientific LLC (Boston, MA) under the support of 
a SBIR Phase II grant (CA189515-03) awarded by the National Cancer Institute.
The investigational software is designed to support physicians during RFA treatment of HCC 
tumors (lesions), with the goal of improving the rate of complete ablation and thereby reducing the 
rate of local recurrence. Please reference SF19108 clinical protocol v29July2019, page 5, Section 
1.2 Investigational Technology, for a high-level description of the PGP and its operation.
5.2 Abbreviated IDE information
We are requesting a Nonsignificant risk determination from the D-HH IRB. 
The investigational device used in this study does not satisfy any of the criteria for a significant 
risk device:
a) It is not intended as an implant, 
b) It is not for use in supporting or maintaining human life, 
c) When used for supportive guidance in treating disease, it does not present a potential for 
serious risk to the health, safety, or welfare of a subject,
d) It does not otherwise present a potential for serious risk to the health, safety, or welfare of a 
subject.  
Use of the investigational device in the context of this protocol has no potential for harm to 
subjects that could a) be life threatening, b) result in permanent impairment of a body function, c) 
result in permanent damage to body structure, or d) necessitate medical or surgical intervention to 
preclude permanent impairment of body function or permanent damage to body structure.
Use of the investigational device takes place at the same time as the subject’s planned surgical 
procedure, which would occur independent of participation in this study. Use of the device during 
the procedure will not prolong or interfere with the planned surgical procedure.

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The investigational device will be labeled in accordance with FDA regulations (21 CFR 812.5). 
Specifically, the investigational device (software) is installed on a laptop which is the property of 
NE Scientific LLC. The laptop will be in use at DHMC by the PI in full compliance with all 
institutional requirements for computer security and in full cooperation with D-H IT. 

The laptop will be labeled with the name and place of the manufacturer and the following 
statement:  “CAUTION—Investigational device. Limited by Federal law to investigational 
use. Operation of this device is strictly limited to authorized personnel only.”

The operating system (Windows 10 Professional) on the laptop requires immediate log in 
(with password).  No one without an account specific to that computer can access the PGP. 
Accounts are limited to the PI (Eric K. Hoffer, MD), the sponsor (Andrea Borsic, NE 
Scientific LLC), and D-H IT (for administrative purposes). 

A message box will pop up when the PGP application is started, and it will require the user 
to acknowledge the investigational use before the PGP software can be used. 

The PI will remove the laptop from the procedural suite immediately after each use. 
Outside of use during procedures, the laptop will be kept in the PI’s locked office.   
The investigator will comply with prohibitions against promotion and other practices as set forth in 
FDA regulations (21 CFR 812.7). Specifically, the investigator will not:
a) Promote or test market the investigational device until after the FDA has approved the device 
for commercial distribution.
b) Commercialize the investigational device.
c) Unduly prolong the research investigation.
d) Represent that the investigational device is safe or effective for the purposes for which it is 
being investigated.
6
Procedures Involved
Please reference SF19108 clinical protocol v29July2019, pages 9-13, Section 5.0 Study Procedures; 
pages 13-18, Section 6.0 Statistical Plan 
7
Data and Specimen Banking
N/A
8
Sharing of Results with Subjects
Any new clinically significant findings from the study (post-RFA) abdominal MRI will be 
conveyed to the patient’s primary (referring) physician.
9
Study Timelines
9.1 Duration of the individual subject participation
Study procedures occur during a single visit, during which the research PGP will be used in the 
standard of care RFA procedure. Use of the research PGP will not increase the time of the RFA 
procedure. Post-RFA procedure, an abdominal MRI will be obtained for research purposes only. 
Duration of this MRI is approximately 30 minutes (including set-up and imaging). Duration of 
follow-up for associated clinical outcomes (i.e. local recurrence) is 2 years post-RFA procedure. 

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9.2 Enrollment Duration
We expect to enroll 52 participants over 12 months. 
9.3 Study Duration
Total study duration, from study initiation through patient enrollment and follow-up, is expected to 
be less than 4 years. 
10 Inclusion and Exclusion Criteria
Please reference SF19108 clinical protocol v29July2019, page 9, Section 4.0 Subject Selection.
Patient eligibility for enrollment shall be based on known information at the time of the clinical 
RFA procedure. Information obtained at a later date may contradict these criteria, but this will not 
be considered a violation of the clinical protocol. 
11 Vulnerable Populations
This study will not enroll members of vulnerable populations.
12 Local Number of Subjects
The study will enroll 52 participants.
13 Recruitment Methods 
Participants will be recruited from the interventional radiology clinical practice. Patients scheduled 
for CT-guided RFA ablation of HCC lesions will be informed of the study and asked if they would 
like to participate. There will be no advertisements or other promotional material. There will be no 
finder’s fees or incentives.
14 Withdrawal of Subjects
A participant may decide to withdraw from the study at any time without prejudice or loss of care. 
The investigator may also decide to withdraw a participant from the study at any time based on 
medical judgement. A participant may be withdrawn from the research if:
a) Conditions change between consent and procedure such that the participant no longer 
meets the eligibility criteria, e.g. if the participant’s HCC lesion is not identifiable on the 
procedural CT scan.
b) There are technical malfunctions during the study such that the data would not be 
analyzable, e.g., power loss, dysfunction of PGP software during the clinical RFA 
procedure.
c) The post-RFA abdominal MRI is not completed.
If a participant is withdrawn due to not completing the MRI portion of the study, or if the participant 
withdraws during the 2 year follow-up or is lost to follow-up, they will be included in the analysis of 
outcomes to the extent their data was been collected (e.g., if an MRI is missing, the imaging data may 
not be included in the technical success analysis, yet the participant may still be included in the 
clinical follow-up recurrence rate analysis.)

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In the event that a participant revokes authorization to collect or use PHI, the investigator will retain 
the ability to use all information collected prior to the revocation of participant authorization. For 
participants who revoke authorization to collect or use PHI, the investigator will consult public 
records to establish survival status.
15 Risks to Subjects
Risks to participants as part of their involvement in this research protocol are minimal. A detailed 
statement of risks is described here:
Risks associated with use of the PGP
The following chart summarizes the differences between the standard clinical procedure (i.e. 
estimation of ablated tissues based on printed kill charts) and the PGP. Please reference Attachment 
A, “Risks and Safety Measures Associated with Use of the Research Software” for in-depth 
explanations.
Standard of care
Research PGP 
Co-registration of Images
Assessment of electrode position is based on 
intraoperative CT images capturing the deployed 
electrode. There is no co-registration to the contrast 
CT images highlighting the tumor. 
Co-registration of Images
The PGP software implements a rigid co-
registration of the intraoperative CT images 
capturing the electrode to the contrast CT images 
highlighting the tumor.
Multiple Overlapping Ablations
The interventionalist must build a mental map of 
which tissues have been treated and which still require 
ablation.
Multiple Overlapping Ablations
The PGP software displays on the CT image 
which tissues have been treated by accumulating 
the volumes of each single ablation. Treated 
tissues and target tissues are shown in 2D and 
3D.
Adequacy Assessment
Ablation volume is estimated by mentally 
superimposing kill chart information to CT images. 
This requires mentally scaling, rotating and adjusting, 
and forming a 3D model of treated tissues and target 
tissues.
Adequacy Assessment
The ablation volume is displayed superimposed 
on CT images in 2D and 3D, together with the 
tumor and margins. The overlap between treated 
and target tissues is evaluated visually in 2D and 
3D views.  
The physician can easily compare the visualizations of the manufacturer’s kill chart and the PGP 
model by pressing the TAB key on the keyboard. (The PGP display clearly indicates which source 
of information is being used at the time.) The physician will assess the discrepancies (if any) 
between the kill chart and the PGP model predictions, and in all cases will perform the ablation 
procedure as is deemed to be safe and optimal for the patient. 

If the standard of care kill chart indicates specific tissues need to be treated and the PGP 
model indicates a smaller volume, the physician will defer to the standard of care kill chart 
tissue in order to minimize the risk of undertreatment. This is expected to be a rare 
occurrence.

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
It is expected that the PGP model will frequently highlight additional tissue to be treated 
versus what is indicated by the manufacturer’s kill charts alone. These will usually be small 
tissue volumes, e.g. an additional 2 - 3mm margin beyond kill chart estimates. In most 
cases, extending the ablation to this additional tissue is the very mechanism by which the 
treating physician can reduce the risk of recurrence. However, the physician will only 
proceed with ablation of these additional tissues (based on the research PGP estimates) if it 
does not pose a significant risk, i.e., the additional tissue is of negligible quantity with 
regard to liver function and the additional tissue is at least 1 cm from any critical structure. 

If the PGP model is within 1cm of vital structures, the physician will defer to standard 
clinical practice and proceed using the manufacturer’s kill chart and standard clinical 
procedures. 

Overestimation, i.e. ablation of tissue in excess of what is needed to achieve adequate 
margins, is common in standard clinical procedures—because any given kill chart ablation 
zone rarely fits exactly to the desired target (tumor + margin), and so the surgeon routinely 
errs in favor of taking additional normal tissue rather than risk leaving tumor. We do not 
expect overestimation with PGP to happen with any greater frequency than in standard 
clinical procedures. It should also be noted that the alternative to RFA treatment of tumors, 
a surgical resection, routinely takes twice as much normal surrounding liver tissue—and this 
is a commonly accepted clinical practice.
Risks associated with the post-RFA abdominal MRI:
MRIs are part of the standard clinical work-up for HCC; approximately 90% of participants will 
have experienced an MRI exam prior to enrollment in this study. Some individuals may feel 
claustrophobic inside the MR unit. Potential participants are alerted to this possibility and will not 
be enrolled if known to be claustrophobic. Metal implants, such as surgical clips, and electronic 
devices, such as pacemakers, can be contraindications for MR exams. Participants are questioned 
about these conditions and enrolled accordingly. The post-RFA MRI will be performed using 
standard of care imaging units, and participants will be actively monitored, per clinical protocol, 
during the imaging session and following the completion of imaging.
Psychological risks:
Psychological risks are limited to possible transient distress related to discussion of the patient's 
cancer.  The PI will be consenting patients and thus will be available to answer and attend to 
questions and anxieties concerning diagnosis. The Norris Cotton Cancer Center has clinical social 
workers on call if additional support is required.
Risk associated with loss of confidentiality:
Because clinical records (i.e. imaging exams) are viewed, the risk exists that the participant's 
medical records could be viewed by individuals who are not responsible for the participant's 
medical care or part of this research project. Individuals who are permitted to view participants’ 
medical records may abuse the privilege and expose the patient to loss of confidentiality. 

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All participant data will be handled in a HIPAA-compliant manner which minimizes confidentiality 
exposure. Participants enrolled into this research study will be assigned study ID numbers and all 
data will be coded accordingly, with personal identifiers redacted or removed. Decoding 
information will be secured and accessible by a limited number of research personnel. All 
Dartmouth-Hitchcock research staff involved with this research project have completed the required 
IRB training regarding the protection of human subjects, and understand the importance of 
maintaining and protecting participant confidentiality.
16 Potential Benefits to Subjects*
Although the PGP model prediction is currently equivalent in accuracy to the manufacturer’s kill 
charts, the PGP software provides the immediate advantage of clear visualization of either predicted 
ablation zone. Even experienced interventional physicians cannot accurately superimpose 
overlapping volumes when a larger tumor is treated with multiple ablations — and this is an 
essential function of the software.  Participants should benefit from this advantage through better 
assurance of complete coverage of target tissues and minimization of non-target tissue damage. In 
turn, this should manifest as a decrease in local recurrence rates, possibly shorter procedure times, 
and fewer complications.
17 Data Management and Confidentiality
Please reference SF19108 clinical protocol v29July2019, pages 13-18, Section 6.0 Statistical Plan; 
pages 22-23, Section 8.0 Data Handling and Record Keeping
18 Provisions to Monitor the Data to Ensure the Safety of Subjects
Please reference SF19108 clinical protocol v29July2019, pages 18-22, Section 7.0 Safety and 
Adverse Events; pages 23-24 Section 9.0 Study Monitoring, Auditing, and Inspecting 
19 Provisions to Protect the Privacy Interests of Subjects
All efforts will be made to protect the privacy interests of participants in this study and the personal 
health information collected as part of this study. Eligible participants will be at DHMC for a 
scheduled clinical procedure, and all DHMC staff are required to maintain and respect patient 
privacy in adherence to HIPAA and institutional regulations. Discussions about personal health 
matters and other personal information will be conducted in private areas, with patient access 
limited to required clinical staff.
20 Compensation for Research-Related Injury
This research is funded by NE Scientific, LLC through an SBIR Phase II grant (CA189515-03) 
awarded by the National Cancer Institute and compensation for a research-related injury or illness is 
not provided by federal law.
If participants are injured or become ill as a result of research procedures, they will be provided 
with medical treatment but the following organizations do not plan to pay for this treatment:
Mary Hitchcock Memorial Hospital
Dartmouth-Hitchcock Clinic

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Dartmouth-Hitchcock Medical Center
Norris Cotton Cancer Center
Trustees of Dartmouth College
NE Scientific, LLC
National Cancer Institute
These organizations will not offer any payments for study-related illness or injury such as lost 
wages, expenses other than medical care, or pain and suffering.
If participants have any questions or concerns about the legal responsibilities of these organizations, 
they will be advised to call the Mary Hitchcock Memorial Hospital Office of Risk Management at 
(603) 650-1250 during normal business hours.
21 Economic Burden to Subjects
All procedures performed for research purposes will be paid for by the study. Participants and their 
insurance companies are responsible for all costs associated with standard clinical procedures. 
22 Consent Process
The consent process will take place in the interventional radiology clinic office or in an 
interventional radiology pre-procedure area and will follow the D-HH IRB “SOP: Informed 
Consent Process for Research (HRP-090)”. 
Patients who meet the inclusion criteria and none of the exclusion criteria will be invited to 
participate in this study. During the patient’s preoperative clinical visit (taking place 1-30 days 
before their ablation procedure), the PI will discuss the research protocol with eligible patients and 
will provide them with a copy of the IRB-approved consent form for their review. The PI is 
responsible for explaining the study (including risks), answering questions, and obtaining informed 
consent.
On the day of the scheduled procedure, the PI will again explain the study in detail and provide the 
patient with a new copy of the IRB-approved consent form to sign. The patient will then have the 
choice to enroll or not to enroll in this study. The patient will be provided with as much time as 
necessary to decide, and will have the option of speaking to family members or other associates if 
so desired. 
Once informed consent has been obtained, the signed consent form will be scanned into the 
participant’s medical record and a copy of the signed informed consent form will be given to the 
patient. The PI will document the patient’s consent in the procedural note, located in the patient’s 
electronic medical record. 
23 Process to Document Consent in Writing

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Each patient who agrees to participate will be required to sign an informed consent document prior 
to undergoing the clinical RFA procedure. We will follow the D-HH IRB “SOP: Written 
documentation of Consent (HRP-091)”. 
 
24 Setting
Research will be conducted in the Radiology areas of Dartmouth-Hitchcock Medical Center. 
Research procedures will be performed in the DHMC Interventional CT suites and MRI suites.
25 Resources Available
Approximately 100 cases of new or recurrent HCC are seen annually in the DHMC Liver Tumor 
Clinic. Based on recruitment efforts in the prior phase of this study (W17179), enrollment of >80% 
of those to whom it is offered may be expected.  We believe it is reasonable to expect enrollment of 
1-2 patients per week and to reach our target of 52 participants in 12 months. 
The PI will initially devote 1 hour/week to conducting the research (i.e. enrolling patients and 
research procedures); this time will increase after the first few months to 2-3 hours/week to provide 
additional time for follow-up.
The available facilities include dedicated interventional radiology clinic space, two Philips 
interventional CT scanners, the Boston Scientific RFA Generator, and 4 permanent MRI scanners.
This research will be conducted in full cooperation with the DHMC Liver Tumor Clinic. If a 
participant requires counseling or support services, they will be referred to the clinical social 
workers program (in place at DHMC) for assistance. 
The RFA procedure utilizes experienced, trained staff at all levels, as this procedure is standard of 
care. The data collection for the PGP software was tested in the protocol (W17179/CPHS#30520) 
for Aim 2 of the SBIR grant, thus the investigator and technologist staff are familiar with its use.  
All study procedures will be reviewed with the entire team during the ‘time-out’ that occurs before 
each case. 
26 Multi-Site Research*
N/A