Percutaneous Image Guided Video Assisted Thoracic Surgery (VATS) Resection of Lung Lesions
Phase: PHASE2
Conditions: Lung Cancer
Sponsor: Brigham and Women's Hospital

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Detailed Protocol 2012p 001915 
 
 
 
Title 
Percutaneous Image guided VATS resection of 
lung lesions 
Principal Investigator 
 
Raphael Bueno, MD rbueno@partners.org  
Study Coordinator 
Tamara Tilleman, MD/PhD ttilleman@partners.org 
221 Longwood Ave. Boston MA   1-617-505-5400
 
 
 
 
 
Coordinating Center 
BWH 
Protocol Version Date 
 01.29.14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Lung lesions nodules/GGO  
Longest diameter <= 30 mm  
Subject candidate for VATS procedure  
Subject was consented for VATS 
Lesion outer half lung/lobe  
Adults >=18 years  
After 12 Months-  
Removed 2012p 001915 
OR AMIGO Suite 
Fine Needle Biopsy under fluoroscopy 
Enroll 2012p 001915 

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TABLE OF CONTENTS 
To update the Table of Contents, put your cursor in the Table of Contents and 
press F9 to update it or ctrl-a F9 to update all fields.  When you update the Table 
of Contents, always choose to update the Entire Table. 
1. 
SPECIFIC AIMS ................................................................................................................................................. 1 
2. 
BACKGROUND .................................................................................................................................................. 1 
3. 
Participant SELECTION .................................................................................................................................... 4 
3.1 
Eligibility Criteria ..................................................................................................................................... 5 
4. 
SUBJECT ENROLLMENT ................................................................................................................................ 5 
5. 
STUDY PROCEDURE ........................................................................................................................................ 7 
5.1 
Device ............................................................................................................................................................ 9 
5.2 
Duration of Follow Up .................................................................................................................................... 9 
6. 
BIOSTATISTICIAN ANALYSIS ...................................................................................................................... 9 
6.1 
Data Collection ............................................................................................................................................. 10 
7. 
RISKS and DISCOMFORT .............................................................................................................................. 10 
8. 
POTENTIAL BENEFITS ................................................................................................................................. 11 
9. 
MONITORING and QUALITY ASSURANCE .............................................................................................. 11 
10. 
REFERENCES ................................................................................................................................................. 12 

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1 
1. SPECIFIC AIMS  
The purpose of this pilot clinical study is to test a methodology for using imaging by 
CT offered through the Advanced Multimodality Image Guided Operating (AMIGO) 
to guide an excisional biopsy of lung abnormalities identified by CT scans.  
 
Our hypothesis is that an effective marking strategy of 3cm or smaller lung lesions, 
using intra-operative imaging-guidance, will enable accurate and efficient lesion 
resection while preserving as much as possible of the normal lung parenchyma by 
limiting the resection to the lesion and its immediate surrounding.  
 
Our clinical initiative has 2 specific aims, one primary major and the other 
secondary taking advantage of this design: 
 
Aim 1: To determine the feasibility of image guided VATS (Video Assisted 
Thoracoscopic Surgery) resection using real-time anatomical imaging modality for 
lung lesions/nodules.  Specifically, we seek to establish the flow of the procedure 
and to determine the morbidity, success rate (as defined by complete resection), 
time from incision to closure of each procedure and radiation dose used in each 
procedure. 
 
Aim 2: to determine whether molecular analysis of the lesion/nodule in conjunction 
with cytological analysis using FNAs (Fine Needle Aspirations) just prior to resection 
can predict diagnosis and prognosis. 
 
2. BACKGROUND 
Approximately 1,000,000 lung nodule and other abnormal lesions such as GGO 
(ground glass opacities) are detected in people in the United States each year. Lung 
nodules are found on 1 in 500 chest x-rays, and 1 in 100 CT scans of the chest. In 
reported studies, up to 51% of smokers aged 50 years or older have pulmonary 
nodules/lesions on CT scans.  
 
A solitary pulmonary nodule is defined as a discrete, well-marginated, rounded 
opacity less than or equal to 3 cm in diameter that is completely surrounded by 
normal lung parenchyma, does not touch the hilum or mediastinum, and is without 
associated atelectasis or pleural effusion.  GGO (Glass Ground Opacity) refers to 
specific changes in the lung parenchyma on CT that may represent tumor, pre-
malignant lesion or other benign lung lesions. 
 
Whether detected serendipitously or during a routine investigation, solitary 
pulmonary nodules/lesions pose a challenge to both clinicians and subjects[1]. A 
nodule on a chest radiograph raises several questions: Is the nodule benign or 
malignant? Should it be investigated or observed? Should it be surgically resected?  
The clinical context is also important and includes age, history of immunodeficiency 
(inherent or due to disease, chemoradiation, diabetes), travel history in endemic 
area for specific pulmonary pathogens (Ohio River valley, San Joaquim Valley, TB 
endemic areas), current infectious symptoms etc.  In different clinical 

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2 
circumstances the lesions/nodules can represent specific infections, benign growth, 
cancers or intrinsic pulmonary abnormalities.   
 
Most solitary pulmonary nodules are benign. Seventy five percent of nodules less 
than 2 cm are benign [2] but they may represent an early stage of lung cancer. 
Lung cancer survival rates remain dismally low at 16% at 5 years [3,4]. If detected 
early enough, lung cancer can be treated and survival chances improved [5,6]. 
Early lung cancer, when the primary tumor is less than 3 cm in diameter (stage 1A 
or 1B), may lead to 5-year survival rates as high as 70-80%, yet only 15% of lung 
cancers are diagnosed at this early stage [3].  Likewise, a benign diagnosis can 
relieve patients from the radiation burden of follow up with CT scans and in some 
cases can provide a life saving treatment with steroids, antibiotics etc. 
 
Recently, a large prospective randomized trial demonstrated that screening 
subjects at risk for lung cancer based on age and smoking history with chest 
computed tomography (CT) reduces the mortality from lung cancer [7,8]. The 
National Lung Screening Trial (NLST) involving more than 53,000 heavy smokers 
resulted in 20 percent fewer lung cancer deaths among trial participants who met 
specific criteria and were screened with low-dose helical CT [9].   As a consequence 
of this positive study, it is expected that hundreds of thousands of subjects with 
lung nodules/lesions will come to surgical biopsy.  Statistically, the majority of 
these people will have benign diseases, but definitive diagnosis will be required in 
those with sufficiently large lesions or in radiographically suspicious lesions.  
Furthermore, subjects with very small lesions (<<1cm) that are suspicious for 
cancer will be discovered that are challenging to resection using current surgical 
techniques.  Thus new protocols are required to improve resection accuracy, 
preserve normal lung and reduce morbidity, mortality and costs to society. 
 
Based on clinical circumstances, lesions discovered on CT screening may be 
followed up radiographically or subjects may be referred for biopsy, radiological or 
surgical.  The decision tree is based on size, appearance and clinical scenario (true 
for lesions suspected of either malignant or non-malignant etiologies).  The protocol 
described herein, is designed for and limited to subjects who are referred for 
surgical biopsies. 
 
Screening with computed tomographic (CT) scans has to some degree changed the 
technologies available for surgery for both lung cancers and for benign diseases.  In 
the past and for most cases in the US currently (>75%), most lung cancers were 
relatively large and subjects required open thoracotomy for resection.  Now-a-day, 
many cancers are much smaller and can be accessed through minimally invasive 
approaches, Video Assisted Thoracic Surgery (VATS) [10].  This is particularly the 
case in specialized centers such as BWH where most Thoracic Surgeons will attempt 
VATS resection for the majority of pulmonary nodules for any etiology.  The same 
applies to non-cancerous nodules that need to be biopsied or resected for diagnosis 
and/or treatment.  This surgery is routinely performed through 3 small incisions 
(1cm or so each) whereby one incision is used for the placement of a rigid video 
telescope camera and the other incisions are used to grab and mobilize the lung, 
bring it closer to one incision which will allow palpation of the lung with a finger tip 

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to identify the nodule/lesion that will then be cut out using a stapling device.   
We recently reviewed (unpublished results submitted for publication) all subjects 
aged 21-85 years who had surgical resection for small (≤ 2cm) non-small cell lung 
cancer at BWH from 2004-2008. Of 347subjects , 10.1% experienced ≥1 major 
complication and 16.1% a hospital stay of ≥1 week. The complications included: 
Adult respiratory distress syndrome (1), Aspiration (1), Bronchoplueral fistula (1), 
Cerebro vascular accident (1), Empyema (1), Myocardial infarction (1), Pulmonary 
edema (1), Pulmonary embolism (1), Ventilator for more than 7 days (1), Wound 
infection (1), Chylous leak (2), Tracheostomy (2), Acute renal failure (3), Atrial 
fibrillation (4), Re-operation due to bleeding (4), Re-intubation (5), Pneumonia (7), 
Air leak for at least 7 days (20).  Of interest we also found that for a 30-minute 
increase in operative time, the odds of ≥ 1 major complication are estimated to 
increase by 103% (OR 2.03; 95% CI: 1.45-2.84), supporting the need to reduce 
operative time with a strategy such as proposed in this protocol.   Though these 
complications and rates are only representative of one specific subset of our 
subjects they provide a highly relevant snap shot of rates and types of 
complications expected in this protocol. 
 
The crux of the challenge and the reason for this protocol is that at 
surgery, many of these nodules/lesions are hard to palpate and to 
precisely define their location for resection.  This is particularly true for 
smaller nodules or GGOs, precisely the ones that require resection to provide early 
diagnosis and therapy since at least half may be benign.  Thus, using current 
technologies, which are non-image guided, result in three potential non-ideal 
outcomes: 1. A more extensive resection of normal lung parenchyma (such as 
lobectomy or segmentectomy) to make sure that the lesion is included even if it is 
non-palpable; 2. An enlargement of at least one incision to insert the hand into the 
chest for better physical definition-resulting in a more painful and complex recovery 
for the subject with resulting longer recovery, chronic pain and greater cost; 3. Too 
close a surgical margin to the cancer requiring re-operative surgery of increasing 
the chance of recurrence. 
 
The concept of intra-operative imaging-guidance is not new and has been used for 
breast biopsy (needle localized breast biopsy) for many decades and more recently 
for neurosurgery. There are also a few reports in the literature using similar 
marking as for breast biopsies for lung lesions (using either a dye or the same coil 
as breast biopsies).  The reports show that this is a safe and effective strategy [11-
17].  However, the difference between what was previously reported in a few 
publications from what we propose herein is that the previous markings have been 
done at some time pre-operatively in a CT scanner as opposed to on the operating 
table with fluoro CT capabilities as available in AMIGO.  The former approach limits 
the types of nodules that could be accessed because lack of general anesthesia and 
potential risk of pneumothorax which are eliminated in our protocol by having lung 
isolation already in place.  Our approach is perform the -CT-guided marking directly 
in the operating room allowing for both marking and intra-operative tracking as 
required to ensure complete resection without moving the subject .   
 

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The AMIGO suite at BWH is an innovative operating room that allows for concurrent 
radiological imaging.  It has a centralized, fully equipped and credentialed operating 
room with all the amenities as well as a fluoro-CT, movable MRI, Focused US and a 
PETCT area.  The AMIGO suite is unique NIH funded resource for developing and 
perfecting novel surgical procedures which require imaging support.  The intention 
is to develop these types of procedures in the AMIGO suite and then to modify 
them so that the successful procedures may be performed in the operating rooms.  
Parenthetically, an identical fluoro-CT is also available in one of the BWH operating 
rooms.     
 
Our goal in this protocol is to enroll subjects who require VATS for specified lung 
lesions, have the subject be operated in the AMIGO suite where they undergo the 
following process: intubated with a double lumen tube, positioned in the lateral 
decubitus position, undergo CT- to confirm the location of the nodule, perform 
image guided needle biopsies and mark the lesion by placing a needle guided 
hookwire and/or T-bar.  At this point, VAT surgery will be performed to resect the 
lung lesion utilizing the marking, which will remove the hookwire and/or T-bar with 
the specimen.  The specimen will then be removed in an Endo-bag and submitted 
for a quick CT picture (away from the subject) and sent for pathological analysis.  
Only the underlined elements are experimental, the operation itself and indications 
are standard of care.   The intentions are to define the methodology, risks, 
exposure etc. and then work in follow-up trials to potentially improve upon the 
marking device and the procedure to get them to the point where this approach is 
available for any subject undergoing lung resection.  We believe that this is a game 
changing approach that is long overdue for thoracic surgery.  
 
The second aim of this proposal takes advantage of the design of the protocol.  In 
addition to placing an image guided marker, we propose to also obtain FNA from 
the lesion to be used for both cytological and molecular analysis.  The results 
supporting this proposed aim come from our laboratory where through NCI funded 
projects we developed molecular tests based on gene expression strategies to 
distinguish normal lung from lung cancer [18] and mesothelioma from other 
cancers. We currently have a separate open clinical trial (with IRB approval) to 
obtain FNA biopsies under image guidance with ultrasound in subjects with 
mesothelioma (DFCI IRB protocol number 04-349).  To-date about 115 subjects 
underwent this procedure with no complications [19].   
 
The genetic analysis for this protocol involves taking the specimens obtained during 
the FNA procedure and using the RNA from these specimens to make cDNA. This 
cDNA will be used for transcriptional profiling and RNA sequencing. This will be 
done both in the tumor specimen as well as the adjacent normal specimen.  
 
3. Participant SELECTION 
Subject Selection:  
This study will be initially limited to subjects with lung nodules or lesions 3cm or 
smaller in the outer half portion of the lung/lobe and who are candidate for VATS at 

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5 
DFCI or BWH and consent for the procedure.  The subjects will be formally 
consented at BWH only. The subjects may initially be told about the research 
procedure during a visit at DFCI with their thoracic surgeon, but if they choose to 
participate in the trial they will be consented at BWH. The CT will be reviewed by 
the study radiologist and thoracic surgeon prior to enrollment.  At least 25 subjects 
scheduled for lung resection surgery will be enrolled to the study. The goal is 25 
subjects who are enrolled into the trial..  All subjects will be chosen from the 
outpatient clinic of Thoracic Surgery, BWH. 
 
3.1 Eligibility Criteria 
Participants must meet the following criteria on screening examination to be eligible 
to participate in the study: 
•  Subjects Procedures – subjects who are candidate for VATS and were 
consented for the procedure will be eligible for enrolled to the study. 
•  Measurable Nodule – lesions that are nodules/GGO or other abnormal 
opacity that can be accurately measured in at least one dimension with longest 
diameter <= 30 mm using conventional techniques.  
•  Nodule Location - lesions that are located in the outer half portion of the 
lung/lobe.  
•  Enrolment Site – Subjects who are seen at BWH and or DFCI Thoracic 
Surgery outpatient clinics. However, the subjects will formally consented at 
BWH only.  
• Age – Enrollment at Partners will be limited to adults, 18 years and older. 
• Number of subjects = 25 subjects will be enrolled to this stage of the 
study. Adult subjects, non-pregnant, non breast feeding to avoid radiation 
exposure.  Urine and/or blood pregnancy test will be obtained based on clinical 
indications. 
   
4. SUBJECT ENROLLMENT 
We will use our clinical research standard operational procedures to recruit subjects 
ensuring that the confidentiality and privacy of potential subjects are protected.  
Potential subjects will be identified by their thoracic surgeon attending and other 
surgeon investigators during their visit to the outpatient clinic.  These thoracic 
attendings have firsthand knowledge of the subject’s medical history. The surgeon 
will evaluate and initially discuss the research with thesubject. If the subject agrees 
to participate in the research, the surgeon will obtain verbal consent from him/her 
to be contacted by the research staff. However, informed consent will be obtained 
by a licensed physician investigator. 
Consent will be obtained by a licensed physician investigator at least a day prior to 
the start of the study procedures.    
In addition: 
• 
The CRA will ensure that subject identification is on all pages of the CF. 
• 
There is documentation that the subject is given a copy of the consent 
form. 
• 
Clinic research note documenting informed consent process. 

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• 
The subject and study representative signed and dated the consent 
form for him/herself.  
• 
The subject initialed and dated all appropriate pages on the informed 
consent form.  
• 
Note to file made for any informed consent deviations.   
• 
The CRAs will ensure that a valid (current version date) copy of the 
consent form was used. 
• 
Eligible participants will be registered in an enrollment log by the 
CRAs. 
• 
Following registration, participants should begin protocol as soon as 
their procedure is scheduled. If a participant does not receive 
protocol treatment/procedure, the participant’s protocol status will be 
changed (off-protocol)

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7 
 
5. STUDY PROCEDURE 
 
For Aim 1: To determine the feasibility of image guided VATS resection using 
AMIGO for lung lesions/nodules in subjects scheduled for lung resection surgery.   
 
In practice, the subject will be placed under general anesthesia in an operating 
room with CT capabilities. The Advanced Multimodality Image Guided Operating 
(AMIGO) Suite is an innovative surgical and interventional environment that is the 
clinical translational test bed of the National Center for Image-Guided Therapy 
(NCIGT) at the Brigham and Women’s Hospital (BWH) and Harvard Medical School. 
In AMIGO, real-time anatomical imaging modalities like x-ray and ultrasound are 
combined with cross sectional digital imaging systems like CT, MRI, and PET. There 
are two such rooms (with fluoro-CT) at the BWH currently, one in an AMIGO suite 
and the other being the hybrid operating room #1.   
 
After the subject is asleep and appropriately positioned in lateral decubitus with a 
double lumen endotracheal tube in place, a brief image of the region of interest in 
the chest and or lung will be generated with the fluoro-CT and be fused with the 
preoperative CT (in this way minimizing exposure to radiation). Based on each 
subject’s weight they will either receive their initial scan by Dyna-CT or by CT both 
of which are available in the AMIGO operating room suite. A needle will then be 
guided into the lesion under fluoroscopy, biopsies will be obtained and a hookwire 
and/or T-bar device  will be placed through the needle, several needle passes may 
be required which is standard for image guided biopsies and localizations.  The 
hookwire and/or T-bar are metallic objects that can be tracked with imaging and be 
used to precisely locate the lesion using imaging.  Since it is better visualized on 
imaging than the original lesion, it is easier to track even when the lung is collapsed 
as it is in preparation for surgery.  For the initial work in this protocol we proposed 
to use a hookwire and/or T-bar [Picture 1, 2, 3 and 4]. 
 Each device is connected by a suture to the outside of the chest wall to allow 
constant guidance.  Also, by visualizing the tract of the suture one can see where it 
enters the lung.  Depending on the extent and location of the lesion one or two 
such devices may be placed (if needed to encompass the borders of the lesion).  
Once the device is placed, standard video assisted lung surgery will commence 
using 3-4 incisions, rigid video telescope camera and fluoroscopy if needed will 
guide the localization of the nodule.  The lung around the nodule will then be 
grasped and resected with the hookwire and/or T-bar within it.  The specimen will 
be then removed, investigated with imaging (away from the subject to avoid 
unnecessary radiation) to confirm that the original lung nodule/lesion is within and 
then taken to pathology to confirm that an abnormal nodule was resected and that 
the margins are appropriate, following our standard of care.  The operation will 
then proceed and be concluded per standard of care. 
 
  
Picture 1, 2: Metallic Hookwire that can be tracked with imaging. In picture 1: 

 
 
 
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Human lung specimen (staples in the perimeter of the biopsy)- the tip of the 
Kopan’s wire is market with red arrow  
         
Picture 1 
 
In picture 2: Wire in a breast tissue. 
   
Picture 2 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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In picture 3 and 4: Metallic T-bar that can be tracked with imaging. 
 
  
 
 
 
For Aim 2: to determine whether molecular analysis of the nodule in conjunction 
with cytology using Fine Needle Aspirations FNAs can predict diagnosis and 
outcome. Aim 2 is based on preliminary work from our group showing that 
molecular analysis of FNA from thoracic lesions can provide accurate diagnosis. 
Since the subject will be in a position under general anesthesia to undergo needle 
placement of the hookwires and/or T-bar, we request permission for two more 
needle passes prior to it to obtain material for cytology and molecular testing to 
determine the diagnostic accuracy of combining the two.  This is based on an 
approved protocol (DFCI 04-349 FINE NEEDLE BIOPSIES IN MPM) for which over 
100 subject have been enrolled with no complications and diagnostic accuracy for 
mesothelioma of 93%.  We anticipate that in this setting there should not be added 
risk to the subject .  
 
Study endpoint: morbidity rate, 25subject . 
 
5.1 Device 
Metal wire, FDA approved like: Kopans Lesion Localization Hookwire. 
http://fdazilla.com/fda/devices/search?q=hookwire 
 
Metal T-bar, FDA approved like: Gastrointestinal Anchor Set with SaF-T-
Pexy T-Fasteners by Kimberly-Clark Franklin, MA 02038 1-508-520-1328  
 
 
5.2 Duration of Follow Up  
 
Participants will be followed after removal from study for 12 months. 
 
  
6. BIOSTATISTICIAN ANALYSIS  

 
 
 
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Percutaneous image-guided VATS resection of lung lesions will be considered 
to have acceptable morbidity if major complications were observed among 3 
or fewer of the 25 subject total. The decision rule achieves 76% power to 
detect a 10% morbidity rate and accept the alternative hypothesis of non-
inferiority of the protocol procedure. In contrast, the decision rule is 
associated with only 10% probability if the morbidity rate were truly 25% 
and thus unacceptably higher than the expected rate of 5-20%. 
 In order to protect the privacy and confidentiality of subjects, data retained 
in our research laboratories or sent to collaborators will be labeled with an 
alphanumeric code rather than with the subject’s name, initials, medical 
record number, date of birth, or Social Security number. 
 
 
6.1 
Data Collection 
Coded encounter data (diagnoses, procedures, dates) 
Demographic data (age, gender, vital status) 
Personal data (name, address, PCP) 
Discharge Summary 
History / Physical 
History / Physical 
Office / Clinic Notes 
Medication List 
Health / Medical Reports / Results including: 
 Blood Bank, Laboratory, Pathology, radiology 
 
7. RISKS and DISCOMFORT  
The risk to subject is considered relatively low.  The major difference compared to 
standard care of either a percutaneous image guided biopsy or VAT surgery is the 
placement of the hookwire and/or T-bar and some added radiation anticipated but it 
is quite low.  In addition, the entire needles track used to place the hookwires 
and/or T-bar will be removed during the resection of the lung nodule(s). The 
hookwires and/or T-bars will be tagged with a suture so that they are unlikely to 
disappear into thesubject . 
The added amount of radiation you will be exposed to is from the additional x-ray 
exams, including fluoroscopy and CT scans. The amount of radiation you will 
receive will depend upon your body size rather than being a fixed amount. 
Depending on the number of image scans taken, the amount of radiation exposure 
you will receive is estimated to range between 5 to 30 millisieverts (mSv). A mSv is 
a unit of radiation dose. For comparison, everyone receives radiation exposure from 
natural background sources from the earth and the sky. The dose that you could 
receive from participation in this research study is about the same as you would 
normally receive in 1.5 to 10 years from these natural sources. Scientists disagree 
on whether radiation doses at these levels are harmful. A possible effect that could 
occur at doses associated with this study is a slight increase in the risk of 
developing cancer later in life. 
  

 
 
 
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8. POTENTIAL BENEFITS  
Expected benefits to the individual subjects participating in the research: unlike 
many research protocols that do not provide clear subject benefit, we expect that 
this one will do so by allowing for: 
1. Precise removal of the lesion with the minimum of lung parenchyma, 
preserving lung function. 
2. Shorter operative time. 
3. More likely to stay VATS resulting in smaller incisions as well as less pain and 
faster recovery. 
 
9.  MONITORING and QUALITY ASSURANCE  
The Research Coordinators (CRAs) are responsible for compiling and 
submitting data collection for all participants and for providing the data to the 
Principal Investigator for review. The Research Coordinators will meet weekly 
and/or more often if required to review side effects and accrual data.  Information 
to be reviewed:  up-to-date participant accrual; all grade 2 or higher unexpected 
adverse events; summary of all deaths occurring within 7 days; summary of all 
deaths while being treated and during active follow-up; any audit results, and a 
summary provided by the study team.  
 
The Principal Investigator (PI) will report to the IRB any of the following 
unanticipated problems and adverse events that occur: 1) during the conduct of the 
study, 2) after study completion, or 3) after subject withdrawal or completion.  
Any adverse events and unanticipated problems involving risks to subjects or other 
will be reported to the IRB per PHRC reporting guidelines. 
http://healthcare.partners.org/phsirb/Guidance/Reporting_Unanticipated_Problems_including_A
dverse_Events.1.11.pdf 
 
1. Internal adverse events that are unexpected, and related or possibly related 
to the research and that indicate there are new or increased risks to 
subjects; 
2. External adverse events that are serious, unexpected, and related or possibly 
related to the research and that indicate there are new or increased risks to 
subjects that require some action (e.g., modification of the protocol, consent 
process, or informing subjects); 
3. Unanticipated adverse device effects that are serious and caused by, or 
associated with, the device; 
4. Deviation from the approved research protocol or plan without IRB approval 
in order to eliminate apparent immediate hazard to subjects or harm to 
others; 
5. Deviation from the approved research protocol or plan that placed subjects or 
others at an increased risk of harm regardless of whether there was actual 
harm to subjects or others; 
6. Any event that requires prompt reporting according to the research protocol 
or investigational plan or the sponsor; 
7. Breach of confidentiality or violation of HIPAA (e.g., lost or stolen laptop); 

 
 
 
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8. Procedural or laboratory error (e.g., errors in surgical or other procedure, or 
testing of samples or test results) regardless of whether subjects experienced 
any harm; 
9. Interim analysis, safety monitoring report, publication in a peer-reviewed 
journal, or other finding that indicates that there are new or increased risks 
to subject or others or that subjects are less likely to receive any direct 
benefits from the research. 
 
As part of monitoring plan: 
• 
CVs for all study staff are on file and updated every 2 years 
• 
Medical licenses for the Co-Investigators are on file and updated prior to 
expiration 
• 
Delegation Log is updated as new staff are added or removed from the 
study or new procedures are added 
• 
Financial disclosures for PIs and those listed on the 1572 are on file 
• 
All other essential documents have been prepared and completed as 
appropriate 
 
10. REFERENCES  
 
1. CT of the pulmonary nodule: a cooperative study. Zerhouni EA, Stitik FP, et al. Radiology. 
1986 Aug;160(2):319-27. 
2. CT Screening for Lung Cancer: Five-year Prospective Experience  Stephen J. Swensen et al  Radiology 2005;235:259-
265. 
3. Cancer Facts and Figures 2012: 
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entered 8.6.2012) 
4. United States Cancer Statistics (USCS), Cancer Death Rates (Table 4.1.M2). 
http://apps.nccd.cdc.gov/uscs/toptencancers.aspx  (last entered 8.6.2012) 
5. Lung cancer risk prediction to select smokers for screening CT- a model based on the Italian 
COSMOS trial. Maisonneuve P, Bagnardi V, Bellomi M, et al. Cancer Prev Res (Phila). 2011 
Nov;4(11):1778-89. Epub 2011 Aug 2. 
6. Lung cancer screening update. Bellomi M, Rampinelli C, De Fiori E, Preda L, Veronesi G. 
Cancer Imaging. 2009 Oct 2;9 Spec No A:S122-5. Diagnostic Radiology, European Institute of 
Oncology 
7. The Danish randomized lung cancer CT screening trial--overall design and results of the 
prevalence round. Pedersen JH, Ashraf H, Dirksen A, et al.  AJ Thorac Oncol. 2009 
May;4(5):608-14. 
8. Lung cancer screening with low-dose helical CT: results from the National Lung Screening Trial 
(NLST). Kramer BS, Berg CD, Aberle DR, Prorok PC. J Med Screen. 2011;18(3):109-11. 
9. The National Lung Screening Trial: overview and study design.National Lung Screening Trial 
Research Team, Aberle DR, Berg CD, Black WC, et al. Radiology. 2011 Jan;258(1):243-53 
10. Video-assisted thoracic surgery lobectomy: report of CALGB 39802--a prospective, multi-
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