Treatment of Field Cancerization for Reduction in Tumor Burden - A Prospective Study
Phase: NA
Conditions: Extensive Photodamage, Actinic Keratosis, History of Numerous Skin Cancers
Sponsor: Massachusetts General Hospital

PARTNERS HUMAN RESEARCH COMMITTEE 
PROTOCOL SUMMARY 
Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
1 
 
Answer all questions accurately and completely in order to provide the PHRC with the relevant 
information to assess the risk-benefit ratio for the study.  Do not leave sections blank. 
 
PRINCIPAL/OVERALL INVESTIGATOR 
R. Rox Anderson, MD 
 
PROTOCOL TITLE 
Treatment of Field Cancerization for Reduction in Tumor Burden – A Prospective Study 
 
NCT NUMBER 
NCT02150863 
 
FUNDING 
Wellman Center for Photomedicine 
 
VERSION DATE 
December 28, 2016 
 
 
SPECIFIC AIMS 
Concisely state the objectives of the study and the hypothesis being tested. 
This project aims to treat field cancerization in a manner that will reduce the tumor burden in 
patients with significant photodamage 
 
1. 
To demonstrate that we can reduce the non melanoma skin tumor burden over 
time by treating the entire field of actinic keratoses and atypical keratinocytes. 
2. 
To compare the efficacy and side effects of ablative CO2 laser resurfacing vs. 
ablative CO2 laser resurfacing plus post treatment suction blister epidermal grafts vs. 
control (no intervention). 
3. 
To demonstrate a reduction in the number of actinic keratosis over time 
4. 
To demonstrate an improvement in clinical appearance of the treatment area 
5. 
To demonstrate a reduction in the degree of P53 mutations seen with 
histopathology 
6. 
To demonstrate that subjects tolerate the treatment with few side effects 
7. 
To demonstrate increased telomere length in treated areas 
 
BACKGROUND AND SIGNIFICANCE 
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures. 
 
Field cancerization is a risk for any individual with excessive and prolonged sun exposure, 
immunosuppression, or exposure to radiation or carcinogens. We are very good at treating the 
skin cancer but if we leave behind the atypical field of keratinocytes it is only a matter of time 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
2 
until the next skin cancer needs to be excised. The current treatment regimensfor treating AKs 
and SCCs involve frequent office visits with extensive cryotherapy, numerous biopsies and 
excisions.We often use topical medications to treat field cancerization, such a 5-fluorouracil or 
imiquimod. These treatments are often ineffective and need to be repeated frequently. The need 
for multiple treatments may be related to compliance. Often people cannot tolerate these 
treatment regimens. Thus there is the need for an optimized treatment regimen to improve 
clearing the field of atypia and precancerous lesions. This would cut down on cost, risks of 
surgical procedures, and patient discomfort. 
 
We want to evaluate of effectiveness of ablative carbon dioxide (CO2) laser used to precisely 
remove the epidermis of an entire field, thus removing all the typical keratinocytes and basal 
stem cells that have been mutated. After the CO2 treatment a portion of the area treated would 
then be covered with autologous epidermal skin grafts from a non-exposed area (buttocks or 
thigh). We hypothesize that the epidermal skin grafts would not only improve/hasten the wound 
healing process after CO2 but it would also provide the field with stem cells that have yet to 
receive damaging radiation.  
 
Ablative CO2 laser was first used by surgeons to cut and vaporize tissue. It then became a 
popular device with both surgeons and dermatologists for treatment of deep facial rhytides. More 
recently these lasers have been used to treat significantly photodamaged skin and actinic 
keratoses. The studies showing varying rates of reduced AK counts over short periods of time. 
The longest follow up being 2 years. 
 
Suction blister autologous epidermal grafting is a simple procedure being used most commonly 
for vitiligo, but also wound healing and scarring.  There are several IRB approved protocols at 
MGH already using this technique (PI: Alexandra Boer Kimball, MD, MPH).  
 
RESEARCH DESIGN AND METHODS 
Briefly describe study design and anticipated enrollment, i.e., number of subjects to be enrolled 
by researchers study-wide and by Partners researchers.  Provide a brief summary of the 
eligibility criteria (for example, age range, gender, medical condition).  Include any local site 
restrictions, for example, “Enrollment at Partners will be limited to adults although the sponsor’s 
protocol is open to both children and adults.”
 
The proposed pilot study is a 3 year prospective, randomized, controlled comparison of a single 
treatment with carbon dioxide laser resurfacing vs. carbon dioxide resurfacing plus autologous 
epidermal skin graft from a non sun exposed site vs. control. Thirty subjects will receive 
treatment with each of the modalities on randomly-assigned portions of the treatment area.  The 
primary measures of efficacy are (a) count of the number of actinic keratosis and non melanoma 
skin cancers, (b) blinded evaluation of severity from standard digital photographs taken before 
and after the treatments, and (c) change in histology before and after treatment: seen by grading 
and change of p53 immunostaining.  Other study endpoints include time point to the next skin 
cancer is found in the treatment area, overall clinical appearance, change in mutant P53 of skin 
samples, and telomere length variability. 
Safety measures include (a) pain, (b) scarring, (c) wound healing, (d) and infection 
 
Subjects will be recruited through advertisements posted within the hospital(s), outpatient 
dermatology clinics and partners electronic mail.   

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
3 
 
Inclusion criteria 
1. Subjects with ages between 18 and 85 years, male or female. 
2. Subjects with at least 4 clinically diagnosed AKs per treatment site ( up to 200 sq cm), 
excluding the face. 
3. Subjects with history of at least 1 skin cancer within the past year 
4. Willingness to participate in the study 
5. Informed consent agreement signed by the subject 
6. Willingness to follow the treatment schedule and post treatment care requirements 
7. Willingness to not use topical or systemic (oral) TREATMENT medications including 
imiquimod, 5 Fluorouracil, photodynamic therapy, during the treatment period. 
8. Has not had treatment for AKs in the treatment area for 4 weeks prior to enrollment 
 
Exclusion criteria 
1. Subjects with active skin cancer in the treatment area. Once the non-melanoma skin 
cancer has been treated, the subject can be immediately enrolled. 
2. Infection of the area to be treated 
3. An open wound in the area to be treated 
4. Presence of suntan in the area to be treated, or active tanning during the study 
5. Subjects who have taken medication known to induce photosensitivity in the previous 
3 months  
6. The patient has any contraindication to use of the CO2 laser 
7. Subject is unable to comply with treatment, home care or follow-up visits 
8. Subject is pregnant or breast feeding  
9. Prior use of topical retinoids, 5 fluorouracil, or imiquimod in treated areas within one 
month of initial treatment  
10. Prior skin treatment with laser or other devices in the treated area within two months 
of initial treatment or during the course of the study; 
11. Adverse reactions to compounds of any external agent (e.g., gels, lotions or anesthetic 
creams) required for use in the study, if no alternative to the said agent exists;  
12. Concurrent inflammatory skin conditions, including, but not limited to, eczema, 
contact dermatitis of any severity; 
13. Active Herpes Simplex at the time of treatment; 
14. Multiple dysplastic nevi in area to be treated; 
15. Having a bleeding disorder or taking anticoagulation medications, including heavy use 
of aspirin, in a manner which does not allow for a minimum 10 day washout period prior 
to each treatment (as per the patient’s physician discretion); 
16. Significant concurrent illness, such as uncontrolled diabetes, (i.e., any disease state 
that in the opinion of the Investigator would interfere with the anesthesia, treatment, or 
healing process); 
17. Mentally incompetent, prisoner or evidence of active substance or alcohol abuse; 
18. Any condition which, in the Investigator’s opinion, would make it unsafe (for the 
subject or study personnel) to treat the subject as part of this research study. 
Briefly describe study procedures.  Include any local site restrictions, for example, “Subjects 
enrolled at Partners will not participate in the pharmacokinetic portion of the study.”  Describe 
study endpoints.
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
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This study will be conducted at the Wellman Center for Photomedicine human studies facility at 
MGH.  The first contact will be made in by the subject in response to the study advertisement.  
During this first study contact subjects will be informed regarding the goals of the study, 
inclusion/exclusion criteria, study procedure, potential benefits, risks and duration of the study.   
Subjects will be asked if they would like a copy of the consent form to read, either through the 
mail or email.  Subjects who meet the inclusion and exclusion criteria and remain interested in 
the study will be in invited for a screening visit.   
The study involves 1 screening visit, 1 baseline/ treatment visit, and 10 study visits over a period 
of 3 years. Objective and safety assessments will be done at all treatment visits.   
 
Baseline/Treatment  Visit 1(Day 0) 
• 
Baseline and treatment can occur on separate days if necessary. These visits 
will occur within 2 weeks of each other if done separately 
Part I– Baseline Evaluations (lasting 1 hour).   
Part II- Treatment (lasting 2.5 hours) 
 
Part I– Baseline Evaluations (lasting 1 hour).   
The investigator will determine the treatment area  
I. AK count within the treatment area 
II. Confirm no clinically evident NMSC within the treatment area 
III. Obtain history of number of skin cancers and locations. History will be taken 
orally from patient but will also review the medical records. 
IV. Tracings of the treatment area and control site as needed to document 
Visit 
Informed 
consent 
Urine 
preg 
test 
TX 
Photo 
# 
NMSC 
prior 
AK/NMSC 
count 
Biopsy 
Overall 
Appeara
nce 
scale 
AE 
Pain 
scale 
(VAS) 
 
Patient  
side effect 
report 
Inv 
wound 
assess 
Screen 
X 
 
 
 
 
 
 
 
 
 
 
 
Baseline/TX 
(Day 0) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Day 3 
 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
Day 7 
 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
Week 4 
 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
3 month 
 
 
 
X 
 
X 
X 
X 
X 
 
 
X 
6 month 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
1 year 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
1.5 – 2.5 year 
visits 
 
 
 
X 
 
X 
 
 
X 
 
 
 
3 year 
 
 
 
X 
 
X 
X 
X 
X 
 
 
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
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V. Shave biopsy technique will be used to harvest epidermal biopsies for histologic 
assessment. 6 scouting biopsies will be done in the treatment area for histologic 
evaluation and immunostaining 
VI. Baseline pre-treatment Photography of treatment area and control site 
Shave biopsy for histology 
 
Area will be prepped with alcohol swab, injected with Lidocaine 1% with or without 
epinephrine. Shave biopsy will be performed with a dermablade. Tissue samples will be taken to 
the lab and processed for immunostaining of p53 and PCR to determine telomere length. A 
portion will be frozen and backed for PCR analysis at the end of the study. 
 
Part II- Treatment (lasting 2.5 hours) 
I) 
  Urine pregnancy test for female not yet in menopause 
II) 
Subject will receive laser treatment to the treatment area. Topical anesthesia will be 
applied for 1 hour prior to the laser treatment.  
III) 
Epidermal suction blister graft harvest from donor site and application on 
randomized treatment area 
IV) 
Adverse event evaluation 
V) 
Patient assessments: pain 
 
Procedures in more detail 
 
Laser treatment 
The laser used is the Ultrapulse CO2 Laser (Lumenis). Patients will be treated according to the 
standard of care.  The settings used for the CO2 laser will be commonly used settings that will 
ablate down to the bottom layer of the epidermis (8 – 20 J/cm2). Any remaining epidermis will 
be removed with saline soaked gauze. The papillary dermis has a characteristic glistening 
appearance and this will also be used as a treatment endpoint. If the papillary dermis is seen, the 
treatment in that area will be considered completed. 
Participants or caregivers will be instructed to do saline soaked gauze soaks three times daily and 
apply Vaseline™ or Aquaphor™ onto the treated areas for up to 7 days post op as needed. 
Wound care instructions will be given to the patient, and a Day 3 follow-up visit will be 
scheduled.    
 
Epidermal Blistering and Micrograft Preparation  
 
A suction device will be applied to area of skin approximately 5.0 cm in diameter. This will be 
left in place approximately 30-40 minutes and may cause mild discomfort because of the suction. 
After the microblisters have been raised, the blister roofs (a superficial epidermal sample) with 
an average thickness of 200 microns and size of 1.75 mm in diameter will be removed and 
transferred to a sterile Tegaderm wound dressing that will be applied to the recipient site. The 
superficial donor wound will then covered with sterile Tegaderm or Duoderm.  
 
Post- Procedure follow up Visits (Day 3, Day 7)  (lasting 30 minutes) 
I) 
Photography  

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
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II) 
 Exam of the treatment area: wound check; evidence of scarring, evidence of 
infection; evidence of healing  
III) 
Adverse event evaluation 
IV) 
Investigator assessments: wound assessment, overall clinical appearance 
V) 
Patient assessments: pain scale and side effects 
 
Follow-up Visits(Week 4) (lasting 30 minutes) 
I) 
Photography 
II) 
 Exam of the treatment area: AK count, evaluate for clinically appearing NMSC 
present; evidence of scarring, evidence of infection; evidence of healing. Also will 
get history from patient: visits to dermatologist? and treatments rendered?. 
III) 
Adverse event evaluation 
IV) Investigator assessments: wound assessment, overall clinical appearance 
V) 
Patient assessments: Pain scale and side effects 
 
Follow-up Visits 
(Month 3) (lasting 1.5 hours) 
I) 
Photography  
II) 
 Exam of the treatment area: AK count, evaluate for clinically appearing NMSC 
present; evidence of scarring, evidence of infection; evidence of healing . Also 
will get history from patient: visits to dermatologist? and treatments rendered? 
Will also review medical records to confirm the history. 
III) 
6 scouting epidermal biopsies, using shave biopsy technique (from the treatment 
area) for histology and immunostaining. Will also bank a portion for PCR at the 
end of the study.  
IV) Adverse event evaluation 
V) 
Investigator assessments: wound assessment, overall clinical appearance 
Follow-up Visits(6 months, 1 year, 1.5 year, 2 year, 2.5 year) (lasting 30 minutes 
each) 
I) 
Photography  
II) 
 Exam of the treatment area: AK count, evaluate for clinically appearing NMSC 
present; evidence of scarring, evidence of infection; evidence of healing . Also 
will get history from patient: visits to dermatologist? and treatments rendered? 
Will also review medical records to confirm the history. 
III) 
Adverse event evaluation 
IV) 
Investigator assessments: overall clinical appearance 
 
 
End of Study visit (3 year) (lasting 1.5 hours) 
Patients will exit the study after 3 years 
II) 
Photography  
III) 
Exam of the treatment area: AK count, evaluate for clinically appearing NMSC 
present; evidence of scarring, evidence of infection; evidence of healing . Also 
will get history from patient: visits to dermatologist? and treatments rendered? 
Will also review medical records to confirm the history 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
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IV) 
**6 scouting epidermal biopsies, using shave biopsy technique (from the treatment 
area) for histology and immunostaining. Will also bank a portion for PCR at the 
end of the study. 
V) 
Adverse event evaluation 
VI) Investigator assessments: overall clinical appearance 
 
** During the course of the study, the subjects will have a total of 18 scouting epidermal 
biopsies using the shave biopsy technique 
 
Evaluation of Safety and Efficacy 
Assessed by investigators (non-blinded) and by blinded evaluators (clinical photographs), 
periodically for 3 years after a single treatment session. 
 
 Reported by the Patients  
Specific form is attached. 
 
I. Side effects reported by the patient: 
To assess major and minor side-effects, patients will be asked for each treatment site to fill in the 
following sentence for each test site: “The side effects I experienced after the treatment 
were:” E.G. 
Table I. N/A: Did not have this side effect / 1: Mild /  2: Moderate / 3: Severe 
A. Blistering 
B. Scarring 
------------------------------------------------------- 
1. Swelling  
2. Redness 
3. Scabs (crusting) 
4. Weeping skin (pustulation) 
5. Scaling or flaking skin (exfoliation) 
6. Itchy skin 
7. Erosion (ulceration) 
8. Tanning  
9. Lightening of the skin 
11. Wheals  
12. Bleeding  
13. Folliculitis/ Acne 
14. Oozing 
15. Change in sensitivity/numbness 
N/A          1             2              3 
N/A          1             2              3 
----------------------------------------------------- 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
 
 
 
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
8 
I. 
 Pain assessment - Visual Analog Scale (VAS).  
 
The VAS will be completed by study subjectimmediately after the treatment, and at each 
procedure follow up visit (Day 3, Day 7, week 4) 
Pain is any of the following: sensation of tingling, stinging, prickling, or burning 
feeling, heat under the skin, tenderness, mild, moderate or severe pain). 
Specific VAS form is attached  
 
Patients will be asked to circle the number below that most closely corresponds 
to pain associated with their DISEASE. 
□     □ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
 0        1     2    
 3        4    
 5 
 6        7 
 8     
 9      10 
(NO PAIN  
 
 
                                         WORST PAIN) 
 
Reported by the Investigators and Blinded-evaluators  
 
Reported by the Investigator 
Specific form is attached. 
Investigator’s Wound Assessment 
 
Table 2. N/A: Did not have this side effect / 1: Mild /  2: Moderate / 3: Severe 
A. Blistering 
B. Scarring 
------------------------------------------------------- 
1. Swelling  
2. Redness 
3.Crusting 
4.Pustulation 
5. Scaling or flaking skin (exfoliation) 
6. Erosion (ulceration) 
7.Hyperpigmentation 
9.Hypopigmentation 
10.Urticaria 
11.Infection 
12. Folliculitis/ Acne 
14. Oozing 
N/A          1             2              3 
N/A          1             2              3 
----------------------------------------------------- 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 
N/A          1             2              3 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
9 
 
 
 
 
 
Overall Appearance Scale (blinded MD to complete with photos) 
- 
Physicians will consider both cosmetic appearance but also the degree of 
photodamage and clinical atypia. 
 
 
Co2 
treatment 
site 
Co2 + 
epidermal 
graft 
Treatment site 
Control 
site 
Excellent 
□ 5 
□ 5  
 
□  
Good 
□ 4 
□ 4  
 
□  
Satisfactory 
□ 3 
□ 3  
 
□  
Poor 
□ 2 
□ 2  
 
□  
Unacceptable 
□ 1 
□ 1  
 
□  
 
End points: 
- AK count 
- NMSC count 
- change in overall clinical appearance 
- time to healing  
- change in p53mutations 
-change in telomere length 
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
10 
For studies involving treatment or diagnosis, provide information about standard of care at 
Partners (e.g., BWH, MGH) and indicate how the study procedures differ from standard care.  
Provide information on available alternative treatments, procedures, or methods of diagnosis.
 
Field cancerization and pre-skin cancers are currently treated through a number of ways 
including: spot treatment with cryotherapy, biopsy, excision; photodynamic therapy; or topical 
therapies, such a 5-fluorouracil, imiquimod, or ingenolmebutate. These treatments are often 
ineffective and need to be repeated frequently. The CO2 laser is another method for destruction 
of the epidermis. The hope is that this in office treatment would be effective as a single 
treatment. In addition, in office CO2 would be better controlled than at home treatments with 
topical creams or the spot treatment approach with cryotherapy, biopsy, or excision. 
 
Describe how risks to subjects are minimized, for example, by using procedures which are 
consistent with sound research design and which do not unnecessarily expose subjects to risk or 
by using procedures already being performed on the subject for diagnostic or treatment purposes.
The CO2 laser has been used for many years and the standard of care for use is well established. 
All standard of care laser safety procedures will be followed (i.e. wearing appropriate eye 
protection) and all standard of care measures for prepping for a clean field will be taken 
minimize risk of infection. Will also review wound care instruction with patients and give them 
written instructions to take home.  
Describe explicitly the methods for ensuring the safety of subjects.  Provide objective criteria for 
removing a subject from the study, for example, objective criteria for worsening disease/lack of 
improvement and/or unacceptable adverse events.  The inclusion of objective drop criteria is 
especially important in studies designed with placebo control groups.
There is only one treatment for this procotol. Safety data will be collected at each visit of the 
study. We will ensure that the patients continue to have regular dermatologic care. This study 
will not interfere with treatment of future skin conditions.  
 
FORESEEABLE RISKS AND DISCOMFORTS 
Provide a brief description of any foreseeable risks and discomforts to subjects.  Include those 
related to drugs/devices/procedures being studied and/or administered/performed solely for 
research purposes.  In addition, include psychosocial risks, and risks related to privacy and 
confidentiality.  When applicable, describe risks to a developing fetus or nursing infant.
 
 
Foreseeable Risks and Discomforts of Ablative CO2 laser 
 
 
 
Common 
Uncommon 
Major: 
1. Severe Pain (Pain 8/10 or higher on VAS scale) 
 
x 
2. Blistering (with potential for secondary infection) 
 
x 
3. Ulceration (deep erosion, deep wound) with scarring  
 
x 
4.Blindess (There is a risk of blindness from the CO2 
 
X 

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laser.  Everyone in the room will wear protective goggles 
or corneal shields at all times during the treatment to 
prevent eye injury.) 
Minor: 
1. Mild to Moderate Pain (Pain 1-7/10 on VAS scale) 
(tenderness) (tingling, stinging, prickling, or 
burning feeling, tenderness) 
Topical anesthesia plus cooling air (Zimmer) will decrease 
pain during treatment.   
 
During the treatment we will be asking the patient to rate 
their level of pain according to the visual analog pain 
scale that will be provided and explained to them. If at any 
time during the procedure the patient indicates a pain 
level of 7 or above based on the visual analog pain scale 
laser treatments will stop and use intralesional 1% 
lidocaine for anesthesia in the treatment area 
 
x 
 
2. Swelling  (edema) 
x 
 
3. Redness  (erythema) 
x 
 
4. Crusting (scabbing) 
x 
 
5. Pustulation (weeping skin) 
x 
 
6. Exfoliation (scaling or flaking skin) 
x 
 
7. Itchy Skin 
x 
 
8. Ulceration (erosion)  
x 
 
9. Tanning (pigmentation)< 3 months 
x 
 
10. DISEASE flare  
 
X 
11. Hypopigmentation (lightening of the skin) 
X 
 
12. Minor Blistering (vesiculation) 
 
x 
13. Wheals  
 
x 
14. Bleeding  
X 
 
15. Folliculitis/ acne 
 
x 
16. Oozing 
X 
 
17. Dysesthesia (change in sensitivity, numbness) 
 
x 
18. Infection: The area may become infected; however, 
keeping the site clean and using the petroleum ointment 
should prevent this.  If the site does become infected, the 
patient may need to take oral antibiotics.  Signs of 
infection include redness or swelling lasting longer than 3 
days, oozing, or fever.  If the patients experience any of 
 
X 

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these symptoms, they will be instructed to contact the 
study doctor for immediate evaluation.  Oral valacyclovir 
and dicloxacillin will be given to the patients to prevent the 
risk of herpes virus related complications.   
 
19. Milia 
 
X 
 
CO2 ablative laser – Complications: All are uncommon and include pain lasting greater 
than 7 days, scarring, bleeding, hyper/hypopigmenation, secondary infection 
There are rare reports blindness from complication/malfunction of the UltraPulse Co2 
device when used without proper eye wear. The patient and all those in the room will 
wear appropriate eyewear for the entire visit.  
 
Foreseeable Risks and Discomforts of Skin Biopsy 
Skin Biopsy – Risks and discomforts 
 
Common 
Uncommon 
Pain 
X 
 
Edema (swelling) 
X 
 
Erythema (redness) 
X 
 
Crusting (scabbing) 
X 
 
Tenderness 
X 
 
Itching 
X 
 
Small scar 
X 
 
Bruising 
X 
 
Bleeding 
X 
 
Skin discoloration (hyperpigmentation 
or hypopigmentation)  
X 
 
 
Biopsy complications: All very rare: prolonged pain > 7 days, ulceration, oozing, 
infection, dysesthesia, bleeding 
 
Suction blister epidermal skin grafts– Risks and discomforts 
 
Common 
Uncommon 
Pain 
 
X 
Edema (swelling) 
 
X 

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Erythema (redness) 
X 
 
Crusting (scabbing) 
X 
 
Tenderness, Burning sensation 
 
X 
Itching 
X 
 
Small scar 
 
X 
Bruising 
 
X 
Bleeding 
 
X 
Skin discoloration (hyperpigmentation 
or hypopigmentation)  
X 
 
Infection 
 
X 
 
Psychosocial (non-medical) risks 
Side-effects related to the treatment may affect patient’s social life, especially within those 
concerned with physical appearance. Covering the treated areas or missing work/school 
for 1-7 days after the treatment is be advised to subjects 
 
EXPECTED BENEFITS 
Describe both the expected benefits to individual subjects participating in the research and the 
importance of the knowledge that may reasonably be expected to result from the study.  Provide 
a brief, realistic summary of potential benefits to subjects, for example, “It is hoped that the 
treatment will result in a partial reduction in tumor size in at least 25% of the enrolled subjects.”  
Indicate how the results of the study will benefit future patients with the disease/condition being 
studied and/or society, e.g., through increased knowledge of human physiology or behavior, 
improved safety, or technological advances. 
 
Participating patients may have a decrease in the number of future actinic keratosis and 
non melanoma skin cancers within the treatment area. Potentially they will need less 
future treatment with cryotherapy, surgical excisions, topical chemotherapy, etc. 
 
Potential benefits to society 
If this treatment regimen does decrease the number of future actinic keratosis and non 
melanoma skin cancers within the treatment areait will provide physicians with another 
treatment option. A single treatment with a CO2 laser would be much more cost effective 
than recurrent cryotherapy, biopsies, excisions, etc. The treatment would not only be cost 
effective but time efficient. 
 
EQUITABLE SELECTION OF SUBJECTS 
The risks and benefits of the research must be fairly distributed among the populations that stand 
to benefit from it.  No group of persons, for example, men, women, pregnant women, children, 
and minorities, should be categorically excluded from the research without a good scientific or 
ethical reason to do so.  Please provide the basis for concluding that the study population is 
representative of the population that stands to potentially benefit from this research.

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
14 
 
The risks and benefits of the research are fairly distributed among the populations that stand to 
benefit from it. Pregnant or breast feeding women will be excluded because the use of 
epinephrine in the anesthesia is considered class C by the FDA. In addition, lasers are typically 
not used in a pregnancy patient. Children will be excluded but it is very unlikely that children 
develop field cancerization, pre skin cancers, or full blown non melanoma skin cancers. No 
other group of persons will be categorically excluded from the research.  
 
When people who do not speak English are excluded from participation in the research, provide 
the scientific rationale for doing so.  Individuals who do not speak English should not be denied 
participation in research simply because it is inconvenient to translate the consent form in 
different languages and to have an interpreter present.
 
Individuals who do not speak English will not be denied participation in this research. 
Translation will be provided if need, with appropriate consent form. 
For guidance, refer to the following Partners policy: 
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English
 
 
 
RECRUITMENT PROCEDURES 
Explain in detail the specific methodology that will be used to recruit subjects.  Specifically 
address how, when, where and by whom subjects will be identified and approached about 
participation.  Include any specific recruitment methods used to enhance recruitment of women 
and minorities.
 
Subjects will be recruited through advertisements posted within the hospital(s), outpatient 
dermatology clinics and partners electronic mail.  We feel that recruitment may be augmented if 
we target private dermatology practices where physicians are currently treating many patients 
with skin cancers.  In this way we hope to tap into a pool of eligible and willing subjects.  We 
also intend to make calls to private practices and meet with the clinicians to explain the study 
and post study advertisements. The first contact will be made in by the subject in response to 
the study advertisement.  During this first study contact subjects will be informed regarding the 
goals of the study, inclusion/exclusion criteria, study procedure, potential benefits, risks and 
duration of the study.   Subjects will be asked if they would like a copy of the consent form to 
read, either through the mail or email.  Subjects who meet the inclusion and exclusion criteria 
and remain interested in the study will be in invited for a screening visit.  During the screening 
visit, an investigator will ask the subject a few questions to ensure that inclusion and exclusion 
criteria are met, and to visually examine the area to be treated.  
 
 
 
Provide details of remuneration, when applicable.  Even when subjects may derive medical 
benefit from participation, it is often the case that extra hospital visits, meals at the hospital, 
parking fees or other inconveniences will result in additional out-of-pocket expenses related to 
study participation.  Investigators may wish to consider providing reimbursement for such 
expenses when funding is available

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
15 
The topical anesthesia and study supplies will be purchased the Wellman Center for 
Photomedicine to be used in this study with departmental discretionary funds.  We will 
reimburse subjects according to the grid below for each visit that they complete.  If subjects do 
not complete all visits, they will be compensated for the visits that they do complete. The 
compensation for taking part of this study will be paid at the last follow-up visit (#3).  Parking 
vouchers for the hospital garage for all study visits will be given immediately after each study 
visit or follow-up visit. Clinically, all patients who finish this research may have some benefit of 
the treatments. 
 
Payment Schedule per visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lunch vouchers (coupons) of $10 to pay for your meal in the hospital cafeteria for the 
Baseline/treatment visit 
 
 
 
 
For guidance, refer to the following Partners policies: 
          Recruitment of Research Subjects 
http://healthcare.partners.org/phsirb/recruit.htm
 
          Guidelines for Advertisements for Recruiting Subjects
http://healthcare.partners.org/phsirb/advert.htm
 
          Remuneration for Research Subjects
http://healthcare.partners.org/phsirb/remun.htm
 
 
Study Events 
All patients 
         Payment 
Visit  Baseline Evaluations/Treatment (Day 0) 
$35 
Visit   Wound follow up Visits ( Day 3, 7 and 
week 4) 
$20/visit 
($60) 
Visit  Follow-Up Visit month 3 
$20 
 
Visit Follow-Up Visits (6 months – 2.5 years) 
$20/visit 
($100) 
Visit End of study ( Year 3) 
$20 
 
Total 
$235 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
16 
CONSENT PROCEDURES 
Explain in detail how, when, where, and by whom consent is obtained, and the timing of consent 
(i.e., how long subjects will be given to consider participation).  For most studies involving more 
than minimal risk and all studies involving investigational drugs/devices, a licensed physician 
investigator must obtain informed consent.  When subjects are to be enrolled from among the 
investigators’ own patients, describe how the potential for coercion will be avoided.
 
Following the investigator’s determination, the Informed Consent document will be reviewed, by 
the investigator, with the subject and signed if the subject understands and accepts the 
document. With this, the subject will be enrolled in the study.   
Subjects will have as much time as necessary to consult with family members or their physician 
before enrolling in the study.  If the subject understands and accepts the document, it will be 
signed.  The estimated time for the review and the explanation of the consent form is about 30 
minutes.  No treatment or other data collection will be obtained before a subject is consented.  If 
a potential subject if found in the investigators’ own clinic the patient will be notified that 
participation is voluntary and choosing not to participate will no have impact on his treatment in 
the clinic. 
 
NOTE: When subjects are unable to give consent due to age (minors) or impaired decision-
making capacity, complete the forms for Research Involving Children as Subjects of Research 
and/or Research Involving Individuals with Impaired Decision-making Capacity, available on 
the New Submissions page on the PHRC website: 
http://healthcare.partners.org/phsirb/newapp.htm#Newapp
 
For guidance, refer to the following Partners policy: 
          Informed Consent of Research Subjects
http://healthcare.partners.org/phsirb/infcons.htm
 
 
 
DATA AND SAFETY MONITORING 
Describe the plan for monitoring the data to ensure the safety of subjects.  The plan should 
include a brief description of (1) the safety and/or efficacy data that will be reviewed; (2) the 
planned frequency of review; and (3) who will be responsible for this review and for determining 
whether the research should be altered or stopped.  Include a brief description of any stopping 
rules for the study, when appropriate.  Depending upon the risk, size and complexity of the 
study, the investigator, an expert group, an independent Data and Safety Monitoring Board 
(DSMB) or others might be assigned primary responsibility for this monitoring activity.        
 
NOTE: Regardless of data and safety monitoring plans by the sponsor or others, the principal 
investigator is ultimately responsible for protecting the rights, safety, and welfare of subjects 
under his/her care. 
The principal investigator and sub investigator will be responsible for the safety monitoring. 
Safety data will be collected at each visit of the study: adverse events, serious adverse events, 
side effects from treatment. The safety data will be reviewed every 3 months. SAE’s will be dealt 
with immediately. It will be up to the investigator the develops the SAE to take immediate 
action. Efficacy data will be collected at each study visit. Blinded investigators will perform 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
17 
overall efficacy assessments of this study.  The Principal Investigator will be reviewing data on 
an ongoing and consistent basis throughout the duration of the study. The Principal Investigator 
is responsible for protecting the rights, safety, and welfare of subjects under his/her care. 
Principal investigator will be responsible for this review and for determining whether the 
research should be altered or stopped. If any severe adverse effect or death directly related to the 
treatment proposed occurs, Principal Investigator will report to the IRB and an expert group or 
an independent Data and Safety Monitoring Board (DSMB) or others might be assigned primary 
responsibility for this monitoring activity. 
 
Describe the plan to be followed by the Principal Investigator/study staff for review of adverse 
events experienced by subjects under his/her care, and when applicable, for review of sponsor 
safety reports and DSMB reports.  Describe the plan for reporting adverse events to the sponsor 
and the Partners’ IRB and, when applicable, for submitting sponsor safety reports and DSMB 
reports to the Partners’ IRBs.  When the investigator is also the sponsor of the IND/IDE, include 
the plan for reporting of adverse events to the FDA and, when applicable, to investigators at 
other sites.   
 
NOTE: In addition to the adverse event reporting requirements of the sponsor, the principal 
investigator must follow the Partners Human Research Committee guidelines for Adverse Event 
Reporting
 
Any adverse events will be reviewed and analyzed by the Principal Investigator as soon as the 
event occurs and will be documented on Redcap. Any unanticipated problems involving risks to 
subjects or others including adverse events will be reported to the PHRC in accordance with 
PHRC unanticipated problems including adverse event reporting guidelines. 
 
Patients will receive only one study treatment (visit 0). After that, no test site will receive study 
treatment (follow-ups). The patients will continue to have routine dermatologic care. If a pre-
skin cancer, skin cancer, or other dermatologic disease develops within the treatment area or the 
control it will be treated with the standard of care by either the patient’s dermatologist or the 
investigators of this study. Our study documents will note all treatments that are needed in the 
treatment area and the control. We expect that the control sites will not improve as much as 
treated sites, and they will serve also as a comparative endpoint.  
 
 
MONITORING AND QUALITY ASSURANCE 
Describe the plan to be followed by the principal investigator/study staff to monitor and assure 
the validity and integrity of the data and adherence to the IRB-approved protocol.  Specify who 
will be responsible for monitoring, and the planned frequency of monitoring.  For example, 
specify who will review the accuracy and completeness of case report form entries, source 
documents, and informed consent.   
 
NOTE: Regardless of monitoring plans by the sponsor or others, the principal investigator is 
ultimately responsible for ensuring that the study is conducted at his/her investigative site in 
accordance with the IRB-approved protocol, and applicable regulations and requirements of the 
IRB.
 

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Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
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The Principal Investigator will be reviewing data on an ongoing and consistent basis throughout 
the duration of the study. Principal investigator will be responsible for this review and for 
determining whether the research should be altered or stopped. If any severe adverse effect or 
death directly related to the treatment proposed occurs, Principal Investigator will report to the 
IRB and an expert group or an independent Data and Safety Monitoring Board (DSMB) or others 
might be assigned primary responsibility for this monitoring activity. 
 
 
For guidance, refer to the following Partners policies: 
          Data and Safety Monitoring Plans and Quality Assurance
http://healthcare.partners.org/phsirb/guidance.htm#13
 
Reporting Unanticipated Problems (including Adverse Events)
http://healthcare.partners.org/phsirb/guidance.htm#7
 
 
 
PRIVACY AND CONFIDENTIALITY 
Describe methods used to protect the privacy of subjects and maintain confidentiality of data 
collected.  This typically includes such practices as substituting codes for names and/or medical 
record numbers; removing face sheets or other identifiers from completed 
surveys/questionnaires; proper disposal of printed computer data; limited access to study data; 
use of password-protected computer databases; training for research staff on the importance of 
confidentiality of data, and storing research records in a secure location.   
 
NOTE: Additional measures, such as obtaining a Certificate of Confidentiality, should be 
considered and are strongly encouraged when the research involves the collection of sensitive 
data, such as sexual, criminal or illegal behaviors.
 
All source data will be organized and entered onto RedCap (www.redcap.partners.org).  Any 
pertinent notes to file regarding the subject and their study visit will be documented by the 
study coordinator and kept in the applicable subject file on RecCAP. All subjects will be 
assigned a study identification numberWe will pre-test/pilot test the source documents on 
RedCap prior to enrolling any subjects to ensure confidentiality and effectiveness. The 
source documents on RedCap will only be accessible to study staff by a special 
login/password. The surveys will be accessible by invitation only with a special 
login/password. RedCap documents will not be accessible to the public. There will be no bias 
to conducting research using RedCap because all surveys will be completed by the patient 
while he or she is at the study visit. We will use computers and internet at Wellman Center 
for Photomedicine for the completion of these documents.   
 
This study will be performed in accordance with the Declaration of the World Assembly, 
1975, Tokyo (Fed. Reg. 40, 16056, April 9, 1975) and the “Guiding Principles for Human 
Studies” of the Massachusetts General Hospital.  These guidelines will be followed 
specifically with regard to the privacy and confidentiality of patient care and study records. 
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
 
19 
 
SENDING SPECIMENS/DATA TO RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
Specimens or data collected by Partners investigators will be sent to research collaborators 
outside Partners, indicate to whom specimens/data will be sent, what information will be sent, 
and whether the specimens/data will contain identifiers that could be used by the outside 
collaborators to link the specimens/data to individual subjects.
N/A 
 
 
Specifically address whether specimens/data will be stored at collaborating sites outside 
Partners for future use not described in the protocol.  Include whether subjects can withdraw 
their specimens/data, and how they would do so.  When appropriate, submit documentation of 
IRB approval from the recipient institution.
N/A 
 
 
RECEIVING SPECIMENS/DATA FROM RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
When specimens or data collected by research collaborators outside Partners will be sent to 
Partners investigators, indicate from where the specimens/data will be obtained and whether the 
specimens/data will contain identifiers that could be used by Partners investigators to link the 
specimens/data to individual subjects.  When appropriate, submit documentation of IRB 
approval and a copy of the IRB-approved consent form from the institution where the 
specimens/data were collected.
 
 
N/A