A Post-market Multi-Center Retrospective-Prospective Study to Assess Long-term Clinical Outcomes of Non-melanoma Skin Cancer Patients Treated With eBx
Conditions: Non-melanoma Skin Cancer
Sponsor: Xoft, Inc.

 
 
 
Electronic Brachytherapy (eBx) Study 
 
A Post-market Multi-Center Retrospective-Prospective 
Study to Assess Long-term Clinical Outcomes of Non-
melanoma Skin Cancer Patients Treated with eBx  
   
Protocol Number:  CTPR-0019 
 
 
 
 
 
Principal Investigator 
Stephen Doggett, MD, FACR 
 
 
Sponsor: 
Xoft, Inc., a Subsidiary of iCAD, Inc. 
 
 
 
 

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Table of Contents 
2 
PROTOCOL SYNOPSIS .........................................................................................................3 
3 
STUDY CONTACTS ...............................................................................................................4 
4 
INTRODUCTION AND BACKGROUND .............................................................................5 
5 
STUDY RATIONALE .............................................................................................................7 
6 
STUDY PURPOSE ..................................................................................................................8 
7 
STUDY DESIGN, ENROLLMENT, AND DURATION .......................................................8 
7.1 Study Design ............................................................................................................... 8 
7.2 Sample Size ................................................................................................................. 8 
7.3 Study Objective ........................................................................................................... 8 
7.4 Primary Effectiveness Endpoint .................................................................................. 8 
7.5 Secondary Safety Endpoint ......................................................................................... 9 
7.6 Eligibility Criteria ........................................................................................................ 9 
7.6.1 
Inclusion Criteria .........................................................................................................9 
7.6.2 
Exclusion Criteria ........................................................................................................9 
8 
METHODOLOGY ...................................................................................................................9 
8.1 Identifying the Population............................................................................................. 9 
8.2 Long-term Follow-up Visits ....................................................................................... 10 
9 
ADVERSE EVENTS - SAFETY ...........................................................................................10 
10 RISKS .....................................................................................................................................11 
11 STUDY MANAGEMENT .....................................................................................................11 
11.1 Site Requirements and Selections ............................................................................. 11 
11.2 Principal Investigator ................................................................................................ 11 
11.3 Investigator Responsibilities ..................................................................................... 11 
11.4 Sponsor Responsibilities ........................................................................................... 12 
11.5 Monitor Responsibilities ........................................................................................... 12 
12 INFORMED CONSENT PROCESS:  ON-SITE VISITS AND REMOTE VISITS .............14 
12.1  On-site Visits Informed Consent .............................................................................. 14 
13  STATISTICAL CONSIDERATIONS ...................................................................................14 
13.1 Data Collection ......................................................................................................... 14 
Table 1.  Case Report Forms ...................................................................................................15 
13.2 Statistical Analyses ................................................................................................... 15 
14 PUBLICATIONS AND PRESENTATIONS ........................................................................15 
15 GLOSSARY .............................................................................................................................16 
16 REFERENCES .......................................................................................................................17 

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STUDY SITE PRINCIPAL INVESTIGATOR’S  
PROTOCOL SIGNATURE PAGE 
 
A Post-market Multi-Center Retrospective-Prospective Study to Assess 
Long-term Clinical Outcomes of Non-melanoma Skin Cancer Patients 
Treated with eBx  
 
 
 
The Study Site’s Principal Investigator’s Signature signifies acceptance of this Multi-
Center Retrospective-Prospective Follow-up Study of Patients Treated with Electronic 
Brachytherapy for the treatment of Non-melanoma Skin Cancer (NMSC) and agrees to 
participate in the study in accordance with the protocol and protocol requirements stated 
herein: 
 
1. Willingness to work with study project manager to facilitate study progress; 
2. Adherence to applicable IRB requirements and willingness to comply with all 
applicable regulations and applicable good clinical practice guidelines; 
3. Protocol compliance, including willingness to complete all relevant study 
documentation legibly; 
4. Maintenance of confidentiality at all times; 
5. Willingness to allow clinical research associates, at reasonable times agreed 
upon by the site and sponsor, to inspect all records pertaining to this trial; and 
6. Willingness to agree to and sign the Investigator Agreement Page in this protocol 
indicating the protocol will be followed. 
 
 
 
Study Site Name 
  
 
Study Site Principal Investigator Signature  
 
 
Site Principal Investigator’s Printed / Typed Name 
 
 
City, State, Zip 
 
 

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2 
PROTOCOL SYNOPSIS 
STUDY NAME 
A Post-market Multi-Center Retrospective-Prospective Study to 
Assess Long-term Clinical Outcomes of Non-melanoma Skin Cancer 
Patients Treated with eBx  
PRINCIPAL 
INVESTIGATOR 
Stephen W. Doggett, MD, FACR 
SITES 
Up to 5 sites will participate 
STUDY DESIGN 
This 
is 
a 
retrospective-prospective 
post-market, 
on-label, 
observational study. Patients who completed eBx treatment ≥ 5 years 
ago since final treatment will be identified and any existing data in the 
patient’s record will be collected in addition to conducting follow-up 
visits for long-term follow-up.  The study will include 2 parts: 
1. Retrospective Chart Review: Collect data from patient records who 
completed eBx treatment a minimum of five years prior to study 
onset. The history and demographic data will be retrospectively 
collected from up to 300 subjects previously treated with eBx for 
the treatment of NMSC. 
2. Prospective Follow-up:  Patients will either return for a minimum 
of five-year long-term follow-up visits or telehealth (video) for the 
investigators to assess the lesion site, document absence/presence 
of local recurrence and long-term skin toxicities after treatment.  
SAMPLE SIZE  
Up to 300 patients will return for follow-up a minimum of five years 
post eBx treatment. 
STUDY 
OBJECTIVES 
1. To evaluate local recurrence of eBx treated lesions in subjects with 
a minimum of five-year follow-up. 
2. Assess long-term skin toxicities. 
PRIMARY  
EFECTIVENESS 
ENDPOINT 
Absence of local recurrence at ≥ 5-year follow-up at treatment site(s). 
SECONDARY  
SAFETY 
ENDPOINT 
Occurrence of long-term skin toxicities. 
ESTIMATED 
STUDY PERIOD 
Follow-up Visits: Estimated to occur over 6 months. 
SPONSOR & 
FUNDING PARTY 
Xoft, Inc., a Subsidiary of iCAD, Inc. 
98 Spit Brook Road, Suite 100 
Nashua, NH 03062 
STATISTICAL 
ANALYSES, STUDY 
MANAGEMENT, 
EDC, MEDICAL 
WRITING 
Eminence Clinical Research, Inc. 
13521 Northgate Estates Drive 
Suite 150 
Colorado Springs, CO 80921 

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3 
STUDY CONTACTS 
 
PRINCIPAL INVESTIGATOR 
Stephen Doggett, MD, FACR 
DrDoggett@nocancer.com 
 
STUDY SPONSOR 
Xoft, Inc., a Subsidiary of iCAD, Inc. 
98 Spit Brook Road, Suite 100 
Nashua, NH 03062 
 
 
CLINICAL STUDY CONTACTS 
 
 
SPONSOR CONTACT 
 
Crystal Leonard, CCRP 
Xoft, Inc., a Subsidiary of iCAD, Inc. 
Phone: (937) 503-8588 
cleonard@icadmed.com 
 
Patricia Rohne-McCarthy, RN, RCES 
Eminence Clinical Research, Inc. 
Sr. Clinical Research Associate 
Phone : 719-400-7463 
Email: pmccarthy@ecr-inc.com 
Grace Millholland, PhD 
Eminence Clinical Research, Inc. 
Clinical Trial Assistant 
Phone : 719-400-7463 
Email: gmillholland@ecr-inc.com 
 
 

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4 
INTRODUCTION AND BACKGROUND 
More than one million skin cancer cases occur annually.1 Most of these forms of skin cancers are 
curable.  Carcinoma is a medical word for a cancer that starts in a lining layer of cells such as the 
skin or the lining cells of the digestive system. There are many types of keratinocyte cancer, but 
two types of epithelial skin cancers are most common, basal cell carcinoma (BCC) and 
squamous cell carcinoma (SCC).    
Epithelial skin cancer is a common neoplasm that affects more than a half of a million people 
each year.  The most serious of skin cancers is melanoma, which was diagnosed in 
approximately 60,000 people in 2007.  However, the majority of these lesions, estimated to be 
eighty to ninety percent, are basal cell cancers and the remainder is categorized as squamous cell.   
Both types of malignancies are related to ultraviolet light exposure from the sun.1-3 Basal cell 
cancer begins in the lowest layer of the epidermis, the basal cell layer. About eight out of ten 
skin cancers are BCCs. They usually begin on areas exposed to the sun, such as the head and 
neck. BCC was once found mostly in middle-aged or older people, in the fourth decade of life 
and beyond. But now it is also being seen in younger people. This may be because people are 
spending more time in the sun without protecting their skin.  BCC tends to grow slowly. It is 
very rare for a basal cell cancer to metastasize. But if left untreated, it can grow into nearby areas 
and spread into the bone or other tissues beneath the skin.  
SCCs are more likely to spread into fatty tissues just beneath the skin. They are also more likely 
to spread to lymph nodes or to distant parts of the body than are BCCs, but this is not common.   
With thorough screening these neoplasms can be identified at an early stage.  With the selection 
of the appropriate treatment option, these cancers can result in excellent local control with 
excellent cosmesis results.1, 2 
There has been a diverse variety of modalities developed for the treatment of basal cell and SCC 
over the years, from surgical excision to Mohs micrographic surgery, to radiation therapy.   The 
location of the cancer and the extent of the disease effect the treatment options available to 
patients.3 The following section provides an overview of the different treatment modalities 
published in the literature. 
Lovett et al reported on 339 patients who were consecutively treated for histologically confirmed 
basal cell (71%) and squamous cell (29%) carcinoma.5 A retrospective study was performed to 
assess local recurrence.   The majority of the basal cell lesions (93%) and 97% of the SCCs were 
on the head.  Radiation therapy was the initial treatment modality in 212 patients, and 127 
patients were treated with radiation therapy after the initial surgical excision failed.  Tumor 
control was analyzed by the type of external beam radiation therapy administered.  The local 
control for superficial x-ray ranged from 91 to 100% reported categorically by tumor size.  

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Electron beam ranged from 70 to 75% local control.  Patients were stratified into groups by the 
type of radiation beam used on the treatment.  Excellent to good cosmesis was seen in 97% of 
the patients treated with superficial X-rays and in 78% of the patients treated with electrons, 78% 
of the patients treated with mixed beams, and in 80% of the patients treated with megavoltage 
photons.  The overall complication rate (complications were defined as grade 4 toxicities4) for the 
310 patients whose data was available was 5.5%.  Of the 217 previously untreated patients, the 
complication rate was 3.2%.,5 
Silva et al report on a retrospective review of radiation therapy treatment for basal cell, 
squamous cell, and basal-SCC from 313 patients with 334 lesions treated.  The objective of this 
study was to assess local control and late toxicities in patients treated with radiation therapy for 
the treatment of cancer of the pinna of the ear.  For 270 patients, radiation therapy was the 
primary treatment, 50 patients received radiation therapy for recurrent cancer that had not 
previously undergone resection, and 12 patients received radiation therapy as an adjuvant 
treatment.6 
 
Orthovoltage X-ray radiation therapy (100-250 kV) was used in 83% of the patients, and electron 
radiation therapy was used in approximately 12%.  The rest were treated with megavoltage X-
rays (primarily 60Cobalt).  The prescriptions were as follows: 17.5 Gy-20 Gy in one fraction, 35 
Gy in five fractions with 7 Gy per fraction, 42-45 Gy in ten fractions with 4.2 to 4.5 Gy per 
fraction, and 50 to 60 Gy divided among 20 to 30 fractions with less than 3 Gy per fraction.  
Thirty-five (35) Gy was prescribed for 124 of the 313 patients.  The follow-up ranged from 0.12 
to 13.37 years.  The primary endpoint was time to local failure, and the secondary endpoint was 
significant grade 4 late toxicities.  Local control rate was reported to be 9% for patients who 
present with early-stage cancer with tumor size 2cm or less in diameter.  Orthovoltage X-ray 
radiation therapy has been shown to be efficacious primary treatment for squamous cell and 
BCC.6 
 
Chan et al report on a single center experience for the treatment of basal cell and SCCs.  They 
studied 1005 lesions treated with single fraction radiotherapy.  This retrospective chart review 
took place ten years later to allow for follow-up.  All patients were treated with 45-100 kV X-
ray.  The radiation doses administered were 22.5 Gy, 20 Gy and 18 Gy.  The 18 Gy prescription 
was reserved for patients who were considered frail or had very small tumors.  The study 
endpoints were recurrence and late necrosis over a ten-year period.  There was no difference in 
the recurrence rate for the group treated with 20 Gy versus 22 Gy, but there was a significant 
increase in late skin necrosis rate (p=0.002).  Most tumors were in the head and neck regions.  
One subgroup in this study, patients who received radiation therapy for the treatment of cancer of 
the inner canthus of the ear, showed a higher recurrence rate because of the concavity, or 
standoff, of the treatment area.  Chan concluded that a standoff of 0.5 cm-1.5 cm would cause 
the radiation dose to decrease by six to 23%.2  
 

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Guix et al. published their series of 136 patients with basal cell or SCC of the skin of the face 
treated with surface molds and Ir-192 HDR brachytherapy with 98% 5-year local control rate 
with no severe early or late complications detected.7  
Other treatment options for patients with basal cell or SCCs include curettage, Mohs surgery and 
conventional surgery.  Curettage has been said to be quick, requires minimal equipment, and is 
associated with a cure rate of 90% or better for select low-risk skin cancers. With this strategy, 
however, there is no margin control, and healing and cosmesis can be variable; moreover, it is 
not a very effective treatment for high-risk tumors and tumors in certain locations.3, 5, 6 
A common treatment for non-melanoma skin cancer (NMSC) has been Mohs surgery, which 
uniquely orients, maps, and processes removed tissue, permitting the microscopic evaluation of 
virtually 100% of the specimen margins. The completeness of this margin control permits the 
accurate identification and removal of all tumor extensions under the microscope. Tissues in 
Mohs surgery are processed as modified frozen sections which allow the accurate and rapid 
interpretation of most skin cancers.6,9 For those patients where surgical resection is not an option, 
primary treatment with radiation therapy was selected for patients whose data will be collected in 
this study.  The treatment approach was individualized based on specific risk factors, and patient 
characteristics for the most acceptable cosmetic and functional outcome.10, 11 
5 
STUDY RATIONALE 
Non-melanoma skin cancers, BCC and SCC, are the most prevalent of all skin cancers.  Multiple 
publications have shown that radiation therapy using kilovoltage X-rays is a viable option for the 
treatment of BCC and SCC but treatment must be individualized to determine if radiation 
therapy should be an adjuvant therapy following surgical resection or if the radiation therapy is 
the primary treatment for skin cancer.  Local recurrence rate varies depending on the histology, 
BCC versus SCC. SCC has a higher recurrence rate than BCC; deaths have been attributed to the 
recurrence of SCC.2, 5, 6, 11-14 
 
Brachytherapy has the advantage of delivering a high dose to the tumor while sparing the 
surrounding normal tissues. With proper case selection and delivery technique, high-dose rate 
(HDR) brachytherapy has great promise, allows short treatment times, and can be performed on 
an outpatient basis.15 The Xoft Axxent Electronic Brachytherapy (eBx) System allows for the 
administration of high dose rate brachytherapy treatments using an electronic source.  The Xoft 
Axxent System Controller and Source are cleared by the United States Food and Drug 
Administration to deliver high dose rate X-ray radiation for brachytherapy.   
 
A matched pairs study was completed previously comparing eBx treatment outcomes to Mohs 
surgery outcomes. The median follow-up was three years.  Local recurrence, toxicities, and 
cosmesis were the endpoints.16 Because of the excellent cosmetic outcomes evident in this study 
at three years, the physicians rated cosmesis as “excellent” or “good” in 97.6% of EBx-treated 

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lesions, and 95.7% of MMS-treated lesions, cosmetic outcomes in this study will not be 
collected.16 It is most important to understand the long-term recurrence rates for this treatment 
option. The rationale for this retrospective data collection study is to understand longer-term 
outcomes in patients treated with eBx for the treatment of both BCC and SCC NMSC.   
6 
STUDY PURPOSE 
The purpose of this retrospective-prospective study is to evaluate lesions after treatment for BCC 
or SCC NMSC in order to gain a better understanding of the durability of the treatment, and risk 
of late toxicities for this patient population.    
7 
STUDY DESIGN, ENROLLMENT, AND DURATION 
7.1 Study Design 
This is a retrospective-prospective study design. The study is post-market, on-label 
observational study for the treatment of NMSC.  Patients who completed treatment 
at least five years from the last treatment will be identified and existing data as 
required by this protocol in the patient’s record will be collected in addition to 
conducting office visits or telehealth visits (video) for long-term follow-up.     
 
The study will include:   
Identifying patients, retrospectively, who completed treatment a minimum of five 
years from the last treatment. The history and demographic data will be collected 
from up to 300 subjects previously treated with eBx for the treatment of NMSC. 
Patients will have an office visit or telehealth visit in order for the investigators to 
assess the lesion site, document absence of recurrence, treatment for recurrence (if 
applicable), and long-term toxicities at the time of the prospective visit.   
7.2 Sample Size 
Up to 300 subjects treated with eBx will have data collected retrospectively from the 
patient’s medical records, and prospectively at the time of the follow-up visit for 
those who agree to participate in this study.  Up to three lesions per subject may be 
included in this study. The sample size will include those who were treated 
previously with eBx per the standard of care treatment as published in Patel et al and 
Doggett et al.16-17 
7.3 Study Objective 
Evaluate long-term local recurrence (≥ 5 years post-treatment) of eBx treated lesions 
at follow-up.  
7.4  Primary Effectiveness Endpoint 
Absence of local recurrence at ≥ 5-year follow-up at treatment site(s). 

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7.5  Secondary Safety Endpoint 
Occurrence of long-term skin toxicities at the prospective follow-up visit. 
7.6 Eligibility Criteria 
7.6.1 Inclusion CriteriaAll answers must be YES to have lesions included in 
this study. 
1. 
Previously completed treatment for non-melanoma skin cancer using Xoft 
eBx Electronic Brachytherapy System according to standard of care;16 
2. 
Provides informed consent; 
3. 
Greater than 40 years of age; 
4. 
Pathological diagnosis confirmed to be squamous cell carcinoma, or 
squamous cell carcinoma-in-situ,  or basal cell carcinoma prior to treatment; 
5. 
Cancer Staging included in this study: 
 Stage 0: Tis, N0, M0 
 Stage 1: T1a, b, c, N0, M0 
 Stage 2: T2a, N0, M0 
7.6.2 Exclusion Criteria 
All answers must be NO to have lesions included in this study. 
1. 
Target area is adjacent to a burn scar; 
2. 
Any prior definitive surgical resection of the cancer, prior to Radiation 
Treatment;  
3. 
Known perineural invasion; 
4. 
Actinic Keratosis; 
5. 
Known spread to regional lymph nodes; 
6. 
Known metastatic disease; 
7. 
Lesion treated with Mohs surgery. 
8 
METHODOLOGY 
8.1 Identifying the Population 
The first phase of this study will be to identify patients who completed treatment with 
eBx at least five years ago prior to study onset and collect history and demographic data, 
and eligibility data retrospectively from the patient records and on source worksheets.  
This phase will include a review of the site’s medical records to determine if the source 
documentation contains the variables that are needed to determine eligibility, and which 
will be used in the endpoint analyses.   
 
 

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These variables include: 
Patient Age 
Pathology report for evidence of: 
o Lesion size (cm) / TNM stage 
o Lesion diagnosis (BCC, SCC) 
Last treatment date for each location 
Lesion location (e.g. face, extremities, neck, nose, scalp, torso) 
 
Data Collected Prospectively: 
Recurrence of cancer at prospective follow-up visit  
Recurrence occurred prior to prospective follow-up visit 
Long term skin toxicity (graded according to CTCAE v.5) 
8.2 Long-term Follow-up Visits 
Patient Selection: Patients who are due for their annual skin assessment with a minimum 
of five years since their last eBx treatment will be selected to call for an appointment.  
The patients who were in prior studies will be called from a list kept at the study sites.  
Additional patients who were not in the previous studies will be contacted if they meet 
eligibility criteria.  The patient will be told about the study and asked if they would be 
willing to participate in the Xoft study through an on-site or remote telehealth 
appointment.   
On-site Visits:  Patients agreeable to participating that return for an office visit for 
prospective data collection will be offered $100.00 compensation for his/her time and 
effort required to participate in this study.  Written informed consent will be required for 
participation in the study. 
Remote Visits:  Patients agreeable to participating that choose a remote visit by video, 
such as Zoom or Web-Ex or another video conference platform will be offered $100.00 
compensation  for his/her time and effort to participate in this study. Verbal informed 
consent documented by the study staff will be required for participation in the study.  
Signed informed consent will be waived. 
9 ADVERSE EVENTS - SAFETY 
The late skin toxicities that potentially occur in these subjects are primarily mild and typically 
hypopigmentation and telangiectasia. All late skin toxicities at the time of the visit will be 
documented and graded according to CTCAE  current version. 

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10 RISKS 
Given the nature of this trial there are no risks related to the eBx treatment in this trial, as the 
treatment occurred previously, five or more years ago. The only risk is to confidentiality of 
information. The study sites will maintain confidentiality at all times. No subject identifiers will 
be published or presented from this study. The sponsor and sponsor representatives shall 
maintain confidentiality at all times. 
11 STUDY MANAGEMENT 
11.1 
Site Requirements and Selections 
Study sites will be those that previously participated in the matched pair study with a 
retrospective-prospective study design.  Sites will be associated with and under the approval of 
an Institutional Review Board (IRB) [45 CFR 46.10(b)]      
Sites selected have expressed an interest in the conduct of a controlled study to collect and report 
long-term outcomes of eBx for the treatment of non-melanoma skin cancer. Each site will 
execute a clinical trial agreement with the sponsor. The contract will be executed prior to first 
subject enrollment at the site.   
Case report forms will be used to collect data for the prospective visits.  These will also be 
considered source documentation for data not in the patient medical record. 
11.2 
Principal Investigator 
Stephen W. Doggett, MD, FACR – San Diego Dermatology and Laser Institute, San Diego, CA. 
11.3 
Investigator Responsibilities 
The following responsibilities are required for investigators participating in this study: 
1. Have adequate experience in skin cancer treatment and therapies as documented on the 
physician’s Curriculum Vitae (CV). 
2. Be familiar with all regulatory requirements associated with the conduct of a clinical 
investigation and have the desire and time to comply with the requirements of this study. 
3. Have access to an appropriate medical facility, staff, training, and equipment necessary 
for the conduct of this study. 
4. Always observe confidentiality throughout this study. 
5. Conduct research under an IRB that oversees the conduct of research studies. 
6. Have primary responsibility and oversight of this study for the accuracy, legibility and 
security of all subject data. 
7. Have an adequate patient population to meet study requirements.   
8. Follow the protocol procedures and provide the clinical monitor with accurate data in a 
timely manner. 

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9. Provide direct access to complete patient medical records for the purposes of conducting 
source document verification by monitoring, audits, IRB review and regulatory 
inspections(s) throughout the duration of the study. 
10. Provide current (signed and dated) CV to the Sponsor at time of site qualification.  
11. Provide current medical license to the Study Management at time of site qualification. 
12. Sign and date the Protocol Signature Page to signify agreement to participate in this study 
and comply with all protocol requirements. 
13. Attend the Site Initiation Visit as provided by CRO (web-based presentation or on-site) to 
ensure understanding of the study requirements, case report forms, and data collection. 
14. Identify a study coordinator for this study. Working with and under the authority of the 
Principal Investigator, the study coordinator assures that all study requirements are 
fulfilled and is the contact person at the site for all aspects of study administration. 
15. Maintain a list of appropriately qualified persons to whom the investigator has delegated 
significant trial-related duties. 
11.4 
Sponsor Responsibilities 
Xoft is the manufacturer of the Axxent® eBx System and the Sponsor of this study.  Xoft 
has overall responsibility for the study and shall delegate study management to the CRO: 
1. Select qualified Principal Investigators and study sites. 
2. Select qualified monitors. 
3. Provide the Protocol and any subsequent amendments to the centers. 
4. Provide appropriate information and training to Investigators and study staff. 
5. Ensure that all variations from the protocol are reviewed with the appropriate 
investigator(s), where appropriate, are reported to the relevant authorities and IRBs. 
6. Ensure uniform data collection and protocol compliance. 
7. Provide site initiation training (remote or on-site) that will include review of the protocol, 
Case Report Form (CRFs), CRF completion guidelines,  
8. Retain ownership of all clinical data generated in this study and control the use of the 
data. 
9. Protect patient confidentiality. 
10. Collect, store and keep secure the following documents: 
a. A current, signed, and dated Curriculum Vitae for each site PI 
b. Current medical license for each site PI 
c. The IRB opinions and/or approvals, in writing, and relevant correspondence 
d. IRB approved informed consent form 
e. Protocol signature page signed by the PI at each site 
11.5 
Monitor Responsibilities 
Study site monitoring (remote or on-site) will be performed by the CRO. Each site will be 
monitored on-site or remotely on a regular schedule to ensure that the study is conducted in 

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compliance with sponsor requirements, the protocol, GCP, and the applicable regulations. The 
monitor will also ensure that the data reported is consistent with the information found in the 
subject’s medical records (source data verification) and in source documents. Monitoring will 
include the assessment of the site’s overall progress, including but not limited to the site’s ability 
to keep accurate records and to report study-related data to the sponsor in a timely fashion. 
Monitoring of each site will be performed according to the CRO’s Interim Monitoring Visits 
Standard Operating Procedure (SOP) and the monitoring plan.  In order to appropriately monitor 
the progress of the study, the site will provide the sponsors and/or its designees access to all 
source documents and other information necessary to ensure investigator compliance with the 
protocol and applicable rules and regulations, and to assess the progress of this study. 
 
The sponsors designees will maintain contact with the investigator and staff throughout 
the duration of the study by phone, e-mail, and remote or on-site visits.  The monitor will 
compile and file a monitoring report for each visit.  Monitoring will ensure continued protocol 
compliance, adequate patient enrollment, and accurate data reporting.   
The monitor will verify: 
1. Informed Consent Forms (ICF)s for on-site visits will be obtained from each subject prior to 
the participation in this study, and the ICF process is clearly and contemporaneously 
documented in the medical record. 
2. For remote visits, informed consent will be provided verbally by the participant prior to 
commencing with the prospective data collection at the time of the visit.  The signature on 
the informed consent will be waived for remote visits.   
3. The data in the CRF are completed and recorded and provided to the study management 
team (CRO), in a timely manner. 
4. Findings of non-compliance are reviewed with the Investigator(s) and disclosed in a written 
monitoring report 
5. Source Data Verification – Risked based monitoring will be implemented, and source data 
verification will be performed according to the monitoring plan for the Xoft Study.  
6. Site Close-Out: At the time of the site close-out visit, the site monitor will collect all 
outstanding study documents, ensure that the investigator’s files are accurate and complete, 
review record retention requirements with the investigator, and ensure that all applicable 
requirements are met for the study.   
7. Study Materials: Each Site will receive all the necessary materials needed to initiate and 
participate in this clinical study.  The materials include, but are not limited to: 
 Regulatory Binder and Contents 
1. 
Protocol 
2. 
Delegation of Authority Log  
3. 
Subject Screening Log 
4. 
Training Log 
 Subject Binder 
1. CRFs 
2. Tab for ICF 

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12 INFORMED CONSENT PROCESS:  ON-SITE VISITS AND REMOTE VISITS 
 
12.1 On-site Visits Informed Consent 
 
Potential study subjects will be called to determine interest in participation in the Xoft 
follow-up study. Should the person be interested, the patient will be scheduled for a follow-
up appointment that is in line with the next clinic visit required by insurance or Medicare. 
Once the patient arrives at the office, the study will be explained, and the consent will be 
reviewed and any questions the patient may have will be answered.  Should the patient agree 
to be a participating study subject, the informed consent will be signed and dated by the 
patient and the person providing informed consent. The subject will receive a copy of the 
consent and proceed with the visit. The investigator (MD or other healthcare professional) 
who is qualified to participate as an investigator shall assess the treatment locations and 
document if there is a local recurrence or late toxicity and grade the late toxicity according to 
CTCAE criteria. Once this is complete the subject has completed study participation. 
 
12.2 Remote Visits Informed Consent  
 
Potential study subjects who choose to participate remotely by a video conference will be 
scheduled for a call that meets the regulatory requirements of a visit.  The video will start 
with the delegated site personnel reviewing the elements of the informed consent for this 
study.  Once the consent has been provided verbally, the visit may begin.  In this scenario, 
the waiver of informed consent documentation applies.  The study site personnel will 
document that they provided informed consent and that the patient provided verbal approval 
and consent to participate, with a written informed consent form being waived for these 
subjects.  All California sites will be required to obtain subject acknowledgement/signature 
in agreement with the California Bill of Rights.  The investigator (MD or healthcare 
provider) who is qualified to participate as an investigator shall remotely assess the treatment 
locations and document if there is a local recurrence or late toxicity and grade the late 
toxicity if applicable. Once this is complete, the subject has completed study participation. 
 
Should there be a situation where the lesion on a remote participant is suspect for a 
recurrence development, the site will proceed with standard of care. 
13  STATISTICAL CONSIDERATIONS  
13.1 Data Collection 
Data will be collected at the study site on case report form and will be entered into the 
online database by site and/or ECR personnel. The EDC system for the on-line database 
will be HIPAA compliant and 21 CFR compliant. The data entry personnel will be 

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separate from the monitoring personnel. Double data entry will take place to ensure 
accuracy.  The following data collection requirements are listed below: 
  Table 1.  Case Report Forms 
Form Name 
Retrospective 
Chart Review 
Prospective 
Follow-up and 
Data Collection 
Demographics and History 
X 
 
Eligibility 
X 
 
Assessment of Local Recurrence  
 
X 
Assessment of Late Skin Toxicities 
 
X 
Grading of Late Skin Toxicities 
 
X 
13.2 Statistical Analyses 
This is a multi-center, retrospective-prospective study comparing non-melanoma skin cancer 
treatment (basal cell carcinoma and squamous cell carcinoma) using Xoft electronic 
brachytherapy (eBx) results. The primary endpoint is freedom from recurrence at five-year 
follow-up or longer. The secondary safety endpoint is late skin toxicities as assessed at the 
time of the prospective follow-up visit.  This study is not powered, as it is for the purpose of 
reporting the number and percent of subjects who had a recurrence and the number and 
percent of subjects who showed a late skin toxicity at the follow-up visit.  The data will be 
analyzed and reported by subject and by lesion. The final analysis from the study will be 
reported as descriptive statistics, both categorical and continuous variables, as appropriate.  
14 PUBLICATIONS AND PRESENTATIONS 
The analyses from this study shall be published and presented by the sponsor.  Should an 
investigator from a study site wish to publish or present the data, this must be pre-approved by 
the study sponsor. The sponsor has the right to present the data first prior to sites presenting site 
data and multi-center data. 
 
 
 
 
 
 
 
 
 

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15 GLOSSARY 
TERM OR 
ABBREVIATION 
DEFINITION 
BCC 
Basal Cell Carcinoma 
21 CFR Part 11 
Title 21, Code of Federal Regulations Part 11: Electronic Records, 
Electronic Signatures 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cf
m?CFRPart=11 
CRF 
Case Report Form 
CRO  
Contract Research Organization 
CTCAE 
Common Terminology Criteria Adverse Events 
eBx 
Electronic brachytherapy treatment with Xoft 
EDC 
Electronic Data Capture 
N0 
No lymph node involvement 
M0 
No metastases 
SCC 
Squamous Cell Carcinoma 
Tis 
Tumor in stage 0; abnormal cells are found in the squamous 
cell or basal cell layer of the epidermis; also called carcinoma in situ. 
Tumor Stages 
8th Edition 
7th Edition18 
T1a 
Lesions ≤ 1cm 
Lesions ≤ 2cm 
T1b 
Lesions >1 and ≤ 2cm 
Lesions >2 and ≤ 3cm 
T1c 
Lesions >2 and ≤ 3cm 
N/A 
T2a 
Lesions > 3 and ≤ 4cm 
Lesions > 3cm, lesions must be ≤ 4cm  
 

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16 
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