A Multi-Center Retrospective-Prospective Matched Pairs Cohort Study to Assess Long-term Clinical Outcomes of Non-melanoma Skin Cancer Patients Treated With eBx Compared to Non-melanoma Skin Cancer Patients Treated With Mohs Surgery
Conditions: Nonmelanoma Skin Cancer
Sponsor: Xoft, Inc.

Electronic Brachytherapy (eBx)-Mohs 
Matched Pair - Cohort Study 
A Multi-Center Retrospective-Prospective Matched 
Pairs Cohort Study to Assess Long-term Clinical 
Outcomes of Non-melanoma Skin Cancer Patients 
Treated with eBx Compared to Non-melanoma Skin 
Cancer Patients Treated with Mohs Surgery 
  
Protocol Number:   
CTPR-0014 Revision F 
Co-Principal Investigators 
Rakesh Patel, MD and Robert Strimling, MD 
Scientific Advisor 
Ahjay Bhatnagar, MD 
Sponsor: 
Xoft, Inc. – a subsidiary of iCAD, Inc. 
NCT03024866

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Table of Contents 
1 
PROTOCOL SIGNATURE PAGE ................................................... 3 
2 
PROTOCOL SYNOPSIS ............................................................. 4 
3 
STUDY CONTACTS ................................................................. 6 
4 
INTRODUCTION AND BACKGROUND ............................................ 7 
5 
STUDY RATIONALE ................................................................ 9 
6 
STUDY PURPOSE ................................................................. 10 
7 
STUDY DESIGN, ENROLLMENT, AND DURATION ............................ 10 
7.1 Study Design ................................................................................................................................... 10 
7.2 Sample Size ..................................................................................................................................... 10 
7.3 Study Objectives ............................................................................................................................ 10 
7.4 Primary Endpoint ........................................................................................................................... 10 
7.5 Secondary Endpoints .................................................................................................................... 11 
7.6 Eligibility Criteria .......................................................................................................................... 11 
7.6.1 
Inclusion Criteria ...................................................................................................... 11 
7.6.2 
Exclusion Criteria ..................................................................................................... 11 
8 
METHODOLOGY ................................................................. 11 
8.1 Identifying the Population ............................................................................................................. 11 
8.1.1 Step by Step Instructions ............................................................................................... 12 
8.2 Long-term Follow-up Visits ......................................................................................................... 13 
8.3 Study Methodology Schema for Initial Follow-up Visits .................................................... 13 
9  SITE REQUIRMENTS AND SELECTIONS ....................................... 14 
10 CO-PRINCIPAL INVESTIGATORS AND SUB-INVESTIGATORS .............. 14 
SUB-INVESTIGATORS ................................................................ 14 
11 INVESTIGATOR RESPONSIBILITIES ........................................... 15 
12  STATISTICAL CONSIDERATIONS .............................................. 15 
12.1 Data Collection .............................................................................................................................. 15 
Table 1.  Case Report Forms .................................................................................................. 15 
12.2 Statistical Analyses ....................................................................................................................... 16 
13 GLOSSARY ......................................................................... 17 
14 REFERENCES ..................................................................... 18 

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15 APPENDICES ...................................................................... 20 
15.1 INFORMED CONSENT FORM .............................................................................................. 21 
15.2 CASE REPORT FORM ............................................................................................................... 22 
15.3 PATIENT REPORTED OUTCOMES (PRO) SURVEY ........................... 23 

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1 
PROTOCOL SIGNATURE PAGE 
 
INVESTIGATOR AND SUB-INVESTIGATOR AGREEMENT 
 
eBx-Mohs Matched Pair Cohort Study 
A Multi-Center Retrospective-Prospective Matched Pairs Cohort Study to Assess 
Long-term Clinical Outcomes of Non-melanoma Skin Cancer Patients Treated with 
eBx Compared to Non-melanoma Skin Cancer Patients Treated with Mohs Surgery 
 
PROTOCOL NUMBER: CTPR-0014 REV F 
 
Signature below signifies Xoft – a subsidiary of iCAD has approved this Protocol: 
 
 
______________________________________________________________ 
 
_______________________________________________________________ 
John DeLucia 
 
 
 
 
Date 
Vice President, RA, CA, QA 
iCAD Inc. and Xoft Inc., a subsidiary of iCAD 
98 Spit Brook Road, Suite 100 
Nashua, NH   03062 
 
 
The Study Principal Investigator’s Signature or the study site’s sub-investigator’s signature 
signifies acceptance of this Multi-Center Retrospective-Prospective Follow-up Study of 
Patients Treated with Electronic Brachytherapy or Mohs Surgery 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: 
 
  
Principal Investigator or Sub-Investigator Signature 
 
Printed Name 
 
City, State Zip 
 
 

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2 
PROTOCOL SYNOPSIS 
STUDY NAME 
CTPR-0014 Rev F March 7, 2017: A Multi-Center Retrospective-
prospective Matched Pairs Cohort Study to Assess Clinical Outcomes 
of Lesions Treated with eBx Compared to Lesions Treated with Mohs 
Surgery 
CO-PRINCIPAL 
INVESTIGATORS Rakesh Patel, MD and Robert Strimling, MD  
SITES 
Up to 5 sites will participate 
STUDY DESIGN 
This is a retrospective-prospective study design.  Patients who 
completed treatment approximately 3 years (range of 2-4 years) at time 
of initial IRB approval of this study will be identified and any existing 
data in the patient’s record will be collected in addition to conducting 
office visits for long-term follow-up.  The study will include 2 parts: 
1. Retrospective chart review: Collect data from patient records who 
completed treatment a minimum of 2 years prior to study onset and 
determine the feasibility of doing a matched pair cohort study 
comparison of eBx versus Mohs surgery. The history, demographic 
and treatment data will be retrospectively collected from up to 320 
subjects previously treated with eBx for the treatment of NMSC and 
up to 320 subjects previously treated with Mohs surgery for the 
treatment of NMSC. 
2. Prospective Follow-up:  Patients will return for long-term follow-up 
visits for the investigators to assess the lesion site, document absence 
of recurrence/ absence of recurrence, toxicities, and collect patient 
reported outcomes. 
SAMPLE SIZE  
Up to 640 patients who will return for follow-up approximately 2 to 5 
years post treatment so that at least 586 lesions have long term follow-
up data collected. Follow-up may range from approximately 2 to 5 
years post treatment. Up to 2 visits may be completed by each subject, 
one in 2016, and one in 2017-2018. 
STUDY 
OBJECTIVES 
1. To evaluate local recurrence of eBx and Mohs treated lesions. 
2. To evaluate toxicities related to eBx and Mohs treatments. 
3. To evaluate cosmetic outcomes for lesions treated with eBx and 
Mohs. 
4. To assess the ability to deliver therapy with eBx and Mohs 
treatment modalities. 
PRIMARY 
ENDPOINT 
Absence of local recurrence at approximately 3 to 5 year follow-up 
(range is approximately two to five years) at treatment site(s). 
 
 
 
 
 

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SECONDARY 
ENDPOINTS 
1. Comparison of long-term toxicities related to eBx vs. Mohs 
treatment; 
2. Comparison of long-term cosmetic outcomes for lesions treated for 
NMSC with eBx vs. Mohs;  
3. Comparison of Chronic toxicities; 
4. Comparison of Patient Reported Outcomes (PRO) using a patient 
survey. 
ESTIMATED 
STUDY PERIOD 
Follow-up Visits #1: August 29, 2016 – August 31, 2017 
Data Collection & Data Entry:  August 29, 2016 – September 31, 2017 
Prospective Follow-up Visit #2: August 31, 2017- January 31, 2018 
Data Entry: August 1, 2017 – February 28, 2018 
SPONSOR & 
FUNDING 
PARTY 
Xoft – a subsidiary of iCAD, Inc. 
San Jose, CA 
STATISTICAL 
ANALYSES 
Xoft – a subsidiary of iCAD, Inc. 
San Jose, CA 
STUDY 
MANAGEMENT 
Eminence Clinical Research, Inc. 
Colorado Springs, CO 
ELECTRONIC 
DATA CAPTURE 
Eminence Clinical Research, Inc. 
Colorado Springs, CO 
MEDICAL 
WRITING 
ASSISTANCE 
Eminence Clinical Research, Inc. 
Colorado Springs, CO 

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3 
STUDY CONTACTS 
 
CO-PRINCIPAL INVESTIGATORS 
Rakesh Patel, MD 
Good Samaritan Radiation Oncology 
15400 National Ave. 
Suite 201 
Los Gatos, CA 95032 
Robert Strimling, MD 
Strimling Dermatology Laser and Vein 
Institute 
10105 Banburry Cross Dr. 
Las Vegas, NV 89144 
 
SCIENTIFIC ADVISOR 
Ajay Bhatnagar, MD, MBA 
Cancer Treatment Services 
1876 East Sabin Dr – Suite 10 
Casa Grande, AZ 85222 
 
STUDY SPONSOR 
Xoft, Inc. − a subsidiary of iCAD, Inc. 
98 Spit Brook Road, Suite 100 
Nashua, NH 03062 
 
SPONSOR CONTACT 
John A. DeLucia 
VP, Regulatory Affairs, Clinical Affairs, and Quality Assurance 
iCAD Inc. and Xoft Inc., a subsidiary of iCAD, Inc. 
98 Spit Brook Road, Suite 100 
Nashua, NH 03062 
T: 603-546-7430 
C: 603-566-0146 
F: 603-880-3843 
 
CLINICAL STUDY OVERSIGHT 
Pamela Dicamillo, LVN, CCRC 
Eminence Clinical Research, Inc. 
Clinical Research Specialist 
Phone : 903-352-2714 
Email: pdicamillo@ecr-inc.com 
Kelly W. Elliott RN, MS 
Eminence Clinical Research, Inc. 
President and CEO 
Phone : 720-425-0528 
Email : Kelliott@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.  
Electron beam ranged from 70 to 75% local control.  Patients were stratified into groups by the 

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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 Cosmesis may be adversely affected and the process of 
care can be lengthy.  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.   
 
It is important to understand the recurrence rates and cosmesis for this treatment option.   The 
rationale for this retrospective data collection study is to understand longer-term outcomes in 

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patients treated with eBx for the treatment of both BCC and SCC NMSC and how the outcomes 
compare to Mohs surgery outcomes.   
6 
STUDY PURPOSE 
The purpose of this retrospective-prospective study is to compare data after treatment for BCC or 
SCC NMSC with eBx to data after treatment with Mohs surgery in order to gain a better 
understanding of the clinical outcomes, cosmesis and durability, for this patient population.    
7 
STUDY DESIGN, ENROLLMENT, AND DURATION 
7.1 Study Design 
This is a retrospective-prospective study design.  Patients who completed treatment 
approximately 3 years (range of 2-4 years) at time of IRB approval of this study 
will be identified and any existing data in the patient’s record will be collected in 
addition to conducting office visits for long-term follow-up.     
The study will include:   
Identifying patients, retrospectively, who completed treatment a minimum of 2 
years prior to study onset. The history, demographic and treatment data will be 
collected from up to 320 subjects previously treated with eBx for the treatment of 
NMSC and up to 320 subjects previously treated with Mohs surgery for the 
treatment of NMSC. Data will be collected from enough patients to achieve the 
required sample size of 293 lesions in each treatment group. Patients will then 
return for long-term follow-up visit for the investigators to assess the lesion site, 
document absence of recurrence, chronic toxicities, and collect patient reported 
outcomes.  
7.2 Sample Size 
Up to 320 subjects treated with eBx and up to 320 subjects treated with Mohs 
surgery 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.   
7.3 Study Objectives 
i. To evaluate long-term local recurrence of eBx and Mohs treated lesions. 
ii. To evaluate long-term toxicities related to eBx and Mohs treatments. 
iii. To evaluate long-term cosmetic outcomes for lesions treated with eBx and Mohs. 
7.4 Primary Endpoint 
i. 
Freedom from local recurrence at the prospective follow-up visit in this study.   

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7.5 Secondary Endpoints 
i. 
Comparison of long-term toxicities related to eBx vs. Mohs treatment; 
ii. 
Comparison of long-term cosmetic outcomes for lesions treated for NMSC 
with eBx vs. Mohs;  
iii. 
Chronic toxicities; 
iv. 
Patient Survey for reporting Patient Reported Outcomes (PRO) 
7.6 Eligibility Criteria 
7.6.1 Inclusion Criteria 
All 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 or Mohs surgery; 
2. 
Provides informed Consent; 
3. 
Greater than 40 years of age; 
4. 
Pathological diagnosis confirmed to be squamous cell or basal cell 
carcinoma prior to treatment; 
5. 
Cancer Staging included in this study: 
• Stage 0: Tis, N0, M0 
• Stage 1: T1, N0, M0 
• Stage 2: T2, N0, M0 and ≤ 4cm in diameter 
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 
8 
METHODOLOGY 
8.1 Identifying the Population 
The first phase of this study will be to identify patients who completed treatment with 
eBx or Mohs treatment approximately 3 years ago or more prior to study onset and 
collect history and demographic data, and eligibility and treatment planning and 
treatment data retrospectively from the patient records and on source worksheets to 
complete a matched pair cohort study comparison.  

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This phase will include a review of the site’s patient 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.  These variables include: 
• Patient Age (within ≤ 15 year brackets) 
• Pathology report for evidence of: 
o Lesion size (cm) 
o Lesion diagnosis (BCC, SCC) 
• Last treatment date for each location 
• Lesion location (e.g. face, extremities, neck, nose, scalp, torso) 
• Toxicities at time of prospective follow-up visit 
Matching will be performed according to: 
• Calendar year of treatment for equivalent follow-up 
• Patient age bracket [15-year brackets or less] 
• Lesion diagnosis (BCC, SCC) 
• Lesion size range (< 1 cm, ≥1 and <2 cm, ≥2 and <3 cm, ≥3 and ≤4 cm) 
• Location according to the methodology below: 
o Scalp 
o Face (includes neck) 
o Nose 
o Ear 
o Torso  
o Upper extremities (Arms, hands, fingers) 
o Legs (Thighs, lower leg, feet, toes) 
Data Collected Prospectively: 
• Cosmesis rating by physician  
• Cosmesis rating by the patient 
• Recurrence of cancer  
• Chronic toxicities 
• Patient reported outcomes (PRO) survey 
Patients who return for long-term follow-up will be required to provide informed consent 
for both the retrospective data and the prospective data that are collected at the time of 
the visit. 
8.1.1 Step by Step Instructions 
1. The eBx patients will be determined first.  They are called consecutively based 
on the length of follow-up required by this protocol. 

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2. As patients are called back for consenting and follow-up visits begin, the 
patients treated with Mohs are called consecutively and asked to come back who 
match those treated with eBx.    
8.2 Long-term Follow-up Visits 
Each patient agreeable to participating in this study will be asked to return for an office 
visit for prospective data collection.   There may be up to two (2) visits over the next 
years. 
Since the subjects have already received treatment, the study cannot include a 
randomization design. Each lesion from the eBx treatment group will be matched to a 
lesion treated with Mohs surgery.  The variables used for matching will be: 
• Calendar year of treatment for equivalent follow-up   
• Patient age bracket [Attempt to ensure 15-year brackets or less] 
• Lesion diagnosis (BCC or SCC) 
• Lesion size range (< 1 cm, ≥1 and <2 cm, ≥2 cm and <3 cm, ≥3 and ≤4 cm) 
• Lesion Location 
It is not expected that there will be an equal number of patients treated with eBx and Mohs at 
each site, as some practices may not use both types of treatment modalities.  To ensure that a 
minimum of 293 lesions are matched, the participating sites will be asked for a list of all patients 
treated approximately 2 to 4 years prior to study onset including the variables being used for 
matching. The study sponsor will then compare all the available data from the participating sites 
and notify each site which patient and lesion data will be included in the study.   
8.3 Study Methodology Schema for Initial Follow-up Visits 
 
Please see Figure 1 on page 14. 
 
 
 
 
 
 
 
 
 
THIS SPACE INTENTIONALLY LEFT BLANK 
 
 
 
 
 
 
 

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Figure 1. Study Schema 
 
 
 
 
 
 
 
 
 
 
 
9  SITE REQUIRMENTS AND SELECTIONS 
The sites will conduct the study following approval by an Institutional Review Board (IRB) and 
in accordance with 45 CFR 160 and 164 [Human Subjects Protection].   
Sites selected have expressed an interest in the conduct of a controlled study to collect and report 
long-term outcomes and compare clinical outcomes of eBx versus Mohs surgery for the 
treatment of non-melanoma skin cancer. 
Source worksheets will be used to collect data not found in the patients’ records.  The data from 
the source worksheets and the patient records will be entered into the EDC.  ECR will have a 
unique user name and password, and the EDC system is 21 CFR 11 compliant. 
10 
CO-PRINCIPAL INVESTIGATORS AND SUB-INVESTIGATORS 
CO-PRINCIPAL INVESTIGATORS 
Rakesh Patel, MD and Robert Strimling, MD  
SUB-INVESTIGATORS 
Stephen Doggett, MD - Tustin Medical Plaza, Tustin CA 
Mark Willoughby, MD - San Diego Dermatology and Laser Institute, San Diego CA 
Kenneth A. Miller, MD - Kenneth A. Miller, MD PC, Los Gatos CA 
Select eBx Patients with Longest Follow-up 
Search Records for Mohs Patients with Similar Patient and Lesion Characteristics and Follow-up 
concurrently 
Call eBx Patients and Schedule Follow-up 
Call Mohs Patients and Schedule Follow-up 
Conduct Follow-up Visits and Complete by 
date stated in contract 
Complete Data Entry  

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Erick A. Mafong, MD - San Diego Dermatology and Laser Institute, San Diego CA 
Amy Ellsworth PA-C - San Diego Dermatology and Laser Institute, San Diego CA 
Erica Ventrella PA-C - San Diego Dermatology and Laser Institute, San Diego CA 
11 
INVESTIGATOR RESPONSIBILITIES 
The following responsibilities are required for investigators participating in this study: 
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 monitors, 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. 
12  STATISTICAL CONSIDERATIONS  
12.1 Data Collection 
Data will be collected at the study site on case report forms and will be entered into 
the online database by ECR personnel.  The following data collection requirements 
are listed below: 
  Table 1.  Case Report Forms 
Form # and Name  
Retrospective 
Chart Review 
Prospective 
Follow-up and 
Data Collection 
Demographics and History 
X 
 
Eligibility 
X 
 
Treatment Planning and Treatment 
X 
 
Follow-up Including Cosmesis, Chronic 
Toxicities, Recurrence 
 
X 
Patient Reported Outcomes (PRO) Survey 
 
X 

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12.2 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 compared to a Mohs micrographic surgery. The 
lesion data will be matched on 4 categories as outlined in Section 8 and the results will 
be compared between the two treatment groups. 
 
A sample size calculation comparing treatment of NMSC with eBx to treatment with 
Mohs micrographic surgery was done using a 1.5% historical 3-year recurrence rate for 
NMSC treated with Mohs, and a 2.5% non-inferiority margin.  A total of 293 lesions for 
each treatment group will provide 80% power with a 0.05 alpha level of significance.  
Data from up to three hundred-twenty (320) subjects with each type of treatment will be 
collected to ensure a sufficient number of lesions to adequately power the study. There 
may be more than one lesion per patient that is matched to another lesion in the other 
treatment group.  The total lesions will be compared in this study and the lesion count 
determines the number of patients that are ultimately enrolled. 
 
The primary endpoint of freedom from recurrence and the secondary endpoints will be 
summarized for each treatment group and Chi-square tests performed as applicable.  All 
tests will be 2-sided, with significance level set at 0.05, and performed using SAS 
(version 9.4 SAS Institute, Inc., Cary, NC). 
 
 
 
 
 
 
 
 
 
 
 
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13 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.cfm?
CFRPart=11 
CRF 
Case Report Form 
eBx 
Electronic brachytherapy treatment with Xoft 
EDC 
Electronic Data Capture-internet based secure electronic CRF 
N0 
No lymph node involvement 
M0 
No metastases 
PRO 
Patient Reported Outcomes 
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. 
T1 
Lesions ≤ 2cm 
T2 
Lesions > 2 and ≤ 5cm 
 

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14 
REFERENCES 
1. www.cancer.org.  2007 Statistics from the American Cancer Society.  Website last accessed 
February 9, 2009. 
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3. Barlow JO, Zalla MJ, Kyle A, DiCaudao DJ, Lim KK, Yiannias JA. Journal of the American 
Academy of Dermatology 2006; 54; 1034-1039. 
4. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, 
Version 3.0, DCTD, NCI, NIH, DHHS.  March 31, 2003 (http://ctep.cancer.gov), Publish 
Date:  August 9, 2006. 
5. Lovett RD, Perez CA, Shapiro SJ, Garcia DM.  External radiation of epithelial skin cancer.  
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6. Silva JJ, Tsang RW, Panzarella P, Levin W, Wells W.  Results of radiotherapy for epithelial 
skin cancer of the pinna: the Princess Margaret Hospital experience, 1982–1993.  
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Carcinomas of the Face by High Dose Rate Brachytherapy and Custom Made Surface Molds.  
International Journal of Radiation Oncology, Biology, and Physics 2000; 47(1); 95-102. 
8. Drake LA, Dinehart SM, Goltz RW, Graham GF, Hordinsky MK, Lewis CW, Pariser DM, 
Salasche SJ, Skouge JW, Chanco Turner ML, Webster SB, Whitaker DC, Butler B, Lowery 
BJ.  Guidelines of care for Mohs micrographic surgery.  Journal of the American Academy 
of Dermatology 1995; 33(2); 271-278. 
9. Swanson NA. Mohs surgery:  Technique, indications, applications, and the future.  Archives 
of Dermatology 1983. 119; 761-773. 
10. Ma CM, Coffey CW, DeWerd LA, Liu C, Nath R, Seltzer SM, Seuntjens JP.  AAPM 
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Physics 2001.  28(6); 868-893. 
11. Halperin EC, Perez CA, Brady LW.  Principals and Practice of Radiation Oncology 2008.  
Fifth edition.  Lippincott, Williams, and Wilkins, Philadelphia, PA. 
12. Kwan W, Wilson D, Moravan V.  Radiotherapy for locally advanced basal cell and 
squamous cell carcinomas of the skin; Journal of Radiation, Oncology, Biology, and Physics 
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13. Locke J, Karimpour S, Young G, Lockett MA, Perez CA.  Radiotherapy for epithelial skin 
cancer.  Journal of Radiation, Oncology, Biology, and Physics 2001; 51(3); 748-755.  

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14. Caccialanza M, Piccinno R, Kolesnikova L, and Gnecchi L.  Radiotherapy of skin 
carcinomas of the pinna: a study of 115 lesions in 108 patients.  International Journal of 
Dermatology 2005; 44; 513-517. 
15. Nag S.  High dose rate brachytherapy:  Its clinical applications and treatment guidelines.  
Technology in Cancer Research and Treatment 2004; 3(3); 269-287. 
16. Cox JD, Stetz J, Pajak TF.  Toxicity criteria of the radiation therapy oncology group (RTOG) 
and the European organization for research and treatment of cancer.  International Journal of 
Radiation Oncology, Biology, and Physics, (31)5; 1995, 1341-1346. 
17. Miller, K.  Electronic Brachytherapy: Understanding the Technology, Identifying 
Appropriate Use.  Practical Dermatology 2015;47-8. 
18. http://www.cancer.gov/types/skin/patient/skin-treatment-pdq#section/_29 
  

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15 
APPENDICES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15.1 INFORMED CONSENT FORM 
 
Attached separately in Microsoft® Word® format for edits by IRB and sites. 
 
 

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15.2 
CASE REPORT FORM 
 
Provided as a separate document in the form of a worksheet to use as a source document. The 
final case report form will be electronic data capture. 

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15.3 PATIENT REPORTED OUTCOMES (PRO) SURVEY 
 
Provided as a separate document to be used as a source document with this protocol. The PRO 
survey results shall be entered into the EDC.