A Phase I Study of Low Dose Radiotherapy for Advanced Hidradenitis Suppurativa
Phase: NA
Conditions: Hidradenitis Suppurativa, Hidradenitis
Sponsor: Montefiore Medical Center

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TITLE: A Phase I Study of Low Dose Radiotherapy for Advanced Hidradenitis 
Suppurativa 
 
Contents 
1.0 OBJECTIVES ........................................................................................................... 2 
1.1 Primary Objective ............................................................................................................................................. 2 
1.2 Secondary Objectives ....................................................................................................................................... 2 
2.0 BACKGROUND ....................................................................................................... 2 
2.1 Hidradenitis Suppurativa ............................................................................................................................... 2 
2.2 Current Treatment Options .......................................................................................................................... 2 
2.3 Radiotherapy for HS ......................................................................................................................................... 3 
3.0 PATIENT ELIGIBILITY .............................................................................................. 4 
3.1 Inclusion Criteria ............................................................................................................................................... 4 
4.0 STUDY DESIGN ...................................................................................................... 4 
4.1 General Design.................................................................................................................................................... 4 
4.2 Study Calendar ................................................................................................................................................... 5 
4.3 Study Endpoints ................................................................................................................................................. 5 
4.4 Radiotherapy ....................................................................................................................................................... 6 
5.0 STATISTICAL CONSIDERATIONS .............................................................................. 7 
6.0 REGULATORY CONSIDERATIONS ............................................................................ 8 
6.1 Protection of Human Subjects ...................................................................................................................... 8 
6.2 Compliance with the Protocol and Protocol Revisions ...................................................................... 9 
7.0 DATA HANDLING AND RECORD KEEPING ............................................................... 9 
7.1 Confidentiality .................................................................................................................................................... 9 
7.2 Source Documents ......................................................................................................................................... 10 
7.3 Case Report Forms ......................................................................................................................................... 10 
8.0 Data Safety and Monitoring Boards ..................................................................... 10 
9.0 ADVERSE EVENTS ................................................................................................ 11 
9.1 Adverse Event Definitions .......................................................................................................................... 11 
9.2 Adverse Event Reporting ............................................................................................................................ 11 
10.0 RISKS/BENEFITS ................................................................................................. 11 
11.0 REFERENCES ...................................................................................................... 13 
12.0 APPENDICES ...................................................................................................... 14 
Appendix A: Photos ............................................................................................................................................... 14 
Appendix B: Relevant Skin and Subcutaneous Tissue CTCAE Items [6] ......................................... 15 
Appendix C: PROMIS – Pain Interference .................................................................................................... 17 
Appendix D: PROMIS - Physical Functioning ............................................................................................. 19 
Appendix E: DLQI ................................................................................................................................................... 21 
Appendix F: Ultrasound Criteria for Diagnosis & Staging Hidradenitis Suppurativa [10] ...... 22 

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1.0 OBJECTIVES 
1.1 Primary Objective 
• To establish the safety of radiotherapy in the treatment of advanced 
hidradenitis suppurativa 
1.2 Secondary Objectives 
• To examine the efficacy of radiotherapy in improving quality of life for 
patients with advanced hidradenitis suppurativa 
• To explore histologic changes following radiotherapy for advanced 
hidradenitis suppurativa 
• To explore changes in ultrasound findings following radiotherapy for 
advanced hidradenitis suppurativa 
• To determinepossible changes in assessment of cutaneous discharge 
from HS lesions  
2.0 BACKGROUND 
 
2.1 Hidradenitis Suppurativa 
 
Hidradenitits Suppurative (HS) is a chronic inflammatory skin disease 
characterized by recurrent, painful abscesses, sinus tracts, and scarring. The 
majority of HS lesions are found in apocrine bearing skin, which includes the 
axilla, groin, and inframammary regions. The etiology of HS is still unclear, but it 
is hypothesized that the lesions develop due to follicular occlusion where the 
aprocine gland meets the hair follicle. This follicular blockage leads to cyst 
formation. The colonization of the cyst by skin flora leads to an exuberant 
immune reaction to cyst contents that results in painful inflammation and abscess 
formation. The abscesses may heal over the following 1-2 weeks, leaving a scar. 
Even with treatment, inflammation can continue and lead to the formation of skin 
tracts that burrow in the dermis. Over time, the HS inflammation persists, and 
painful suppurating and connecting dermal tracts are found in the whole region, 
such as the axilla and groin. The impact of HS on quality of life can be 
devastating. Patients often report extreme embarrassment from the disfiguring 
lesions and their associated foul, odiferous discharge. 
2.2 Current Treatment Options 
There are only a few options for effective treatment of HS, and no 
definitive cure exists. Treatment depends on severity and clinical staging. The 
mainstay of treatment of mild disease involves antibacterial washes and topical 
antibiotics, and acute flares may be managed by intralesional corticosteroids 
and/or minor surgical procedures.  Oral therapies include 3-6 months of broad-
spectrum antibiotics, oral anti-androgens may be helpful in women, and systemic 
retinoids (isotretinoin or acitretin) may be beneficial in a subset of patients. Laser 
hair removal with 1064nm Nd:Yag laser has shown promise, but many patients 

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cannot afford this treatment. The only FDA approved treatment for HS is 
adalimumab (Humira), an antibody against tumor necrosis factor α (TNF-α)[1]. 
Patients who fail medical management or who are ineligible for TNF-α 
inhibitors are left with few options for salvage treatment. In this situation, patients 
will often resort to extensive surgical resection of the affected area with or without 
graft placement. Unfortunately, the recurrence rate of HS lesions in this area is 
high, with recurrence rates up to 50% of patients who have surgery. The use of a 
more “conservative” surgical approach, such as the CO2 laser to excise all 
apocrine bearing tissue, has shown potential for improved surgical results, but it’s 
not widely available.  In addition, recurrence of HS lesions still occurs in a 
number of patients who have undergone this laser procedure 
2.3 Radiotherapy for HS 
Given the current understanding of the etiology of HS and the mixed success 
rates of existing treatments, it is imperative to continue the search for more 
effective treatments. Radiotherapy is a good option on which to focus our efforts. 
Low to intermediate dose radiotherapy has been used to provide effective control 
for a number of benign cutaneous conditions, including inflammatory and 
proliferative disorders, as well as benign and malignant tumors [2]. The rationale 
for using radiotherapy to treat inflammatory disorders stems from the ability to 
directly target infiltrating and localized white blood cells. The proposed 
mechanisms of action of radiotherapy include apoptosis of infiltrating leukocytes, 
prevention of diapedesis of leukocytes into tissues, and prevention of 
macrophage production of toxic mediators [3]. Overall, this leads to normalization 
of the inflammatory cytokine milieu, which helps to dampen the inflammation 
leading to resolution of associated debilitating physical symptoms.  
Only a few reports using radiotherapy for HS treatment have been published. 
In one case report, radiotherapy was given to a 53 year-old female with a history 
of HS for 5-6 years, who had failed previous medical management and surgery. 
External beam radiotherapy was directed to HS sites utilizing 6 MeV electrons 
prescribed to the 90 percent focus of the electron curve. A 5 mm tissue 
equivalent bolus was added to the skin surface and 1.0 cm margins around the 
visible disease was added to the Planning Treatment Volume. Over the course of 
five months she received multiple courses of radiotherapy with multiple dosing 
and fractionation schedules (1.5 – 2.5Gy per fraction with total doses of 4.5Gy to 
7.5Gy). She tolerated the procedures well without any acute side effects. Over 
the course of treatment, the patient presented with two episodes of recurrent 
lesions (at 3 weeks and again at 3 months following initial treatment) and one 
new foci of disease (at 3 months after initial treatment). Recurrent and new foci of 
disease were treated with higher fracture schedules of higher fraction size. The 
patient remained lesion free for the following 1.5 years, until the time of 
publication [4]. 
As reviewed in above case report, a center in Germany treated 231 HS 
patients over 20 years who failed other treatment options. These patients 
received multiple fraction schedules with multiple fraction sizes (0.5 Gy – 1.5 Gy 
per fraction up to a total dose of 3.0 Gy to 8.0 Gy in one series). Chronic 

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recurrences were treated with 2 or more series with a total dose of greater than 
10.0 Gy. No acute side effects were observed in this study. Complete 
symptomatic relief was documented in 38% (89/231) patients by the end of 
therapy and 40% (92 / 231) of patients reported an overall improvement in 
symptomatology. Only two patients had no response.  
3.0 PATIENT ELIGIBILITY 
 
Each of the criteria in the checklist that follows must be met in order for a patient 
to be considered eligible for this study.  
3.1 Inclusion Criteria 
• The subject must be diagnosed with HS at Montefiore HS Treatment 
Center, with Hurley Stage 2-3 (Recurrent abscesses or boils with diffuse 
or broad involvement, multiple interconnected sinus tracts in the whole 
area) [5].See Appendix A for photos.  
• Subject must have failed maximal medical therapy for HS or be ineligible 
for “standard” medical therapy or surgery  
• Age > 20 years old 
• Women of childbearing potential must: 
o Have a negative serum or urine pregnancy test within 72 hours 
prior to the start of study therapy 
o Agree to utilize an adequate method of contraception throughout 
treatment and for at least 4 weeks after study therapy is completed. 
Adequate methods of contraception include hormonal methods (i.e. 
birth control pills, patches, injections, vaginal ring, or implants), 
barrier methods (i.e. condom or diaphragm), intrauterine device, or 
abstinence. 
o Be advised of the importance of avoiding pregnancy during trial 
participation and the potential risks of an unintentional pregnancy 
• All patients must sign study specific informed consent prior to study entry. 
4.0 STUDY DESIGN 
 
4.1 General Design 
• This phase I clinical trial will use a Simon two-stage design. In the first 
stage, 6 patients will be enrolled, if the patients in the study do not meet 
the termination criteria then the study will extend to a second stage and 
we will enroll a maximum of 20 patients. Patients will be treated with skin-
directed radiotherapy, using a total prescription dose of 7.5 Gy in five 
fractions of 1.5 Gy over one week. Neither patient nor insurance will be 
billed for the radiotherapy procedures. If any subject experiences Grade > 
3 toxicities, the study will be stopped and the IRB will be informed 
immediately so the study can be reevaluated. 

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• Interim Analysis. 
Once the first 6 patients are recruited, the study recruitment will be 
temporarily suspended and the patients will be followed for 3 months to 
monitor any toxicity issues. At the end of 3 months follow-up of the 6 
patients, the results will be sent to the DSMB for further evaluation. The 
trial will be terminated if grade 3 or more toxicity is observed in more than 
2 patients or at least one showing grade 4 level toxicity. Otherwise, upon 
approval from the DSMB, the second phase of recruiting will be initiated. 
 
 
 
 
4.2 Study Calendar 
 
  
Pre-treatment 
Week 1 
Week 5* 
Week 9* 
Week 13* 
Week 25 & 49# 
History and Physical 
Examination 
X 
X 
X 
X 
X 
X 
Adverse Event 
Assessment 
X 
X 
X 
X 
X 
X 
Questionnaires: DLQI, 
PROMIS 
X 
X 
X 
X 
X 
X 
Photos 
X 
X 
X 
X 
X 
X 
Ultrasound 
X 
 
X 
X 
X 
X 
Blood Tests: CBC, CRP, 
ESR 
X 
- 
- 
- 
X 
X 
Serum or Urine 
Pregnancy Test 
X 
- 
- 
- 
- 
- 
Skin Biopsy, Discharge 
Measurement 
X 
- 
- 
- 
X 
X 
Radiotherapy 
- 
XXXXX 
- 
- 
- 
- 
 
*+/- 1 week 
# Optional 
 
4.3 Study Endpoints 
 
The primary endpoint of this study is safety, defined as the absence of any 
treatment-related Grade ≥3 adverse events during radiotherapy or within 3 
months of radiotherapy completion, scored using CTCAE version 4.0.[6] 
Secondary study endpoints include: 

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• Quality of Life 
o Improvement in NIH Patient-Reported Outcomes Measurement 
Information System (PROMIS) measures, including pain interference 
and physical functioning at 3 months (and optionally at 6 months and 
12 months) after treatment[7, 8] 
o A one point change, either positive (improvement) or negative 
(decline), will be considered to be clinically meaningful[9] 
 
 
• Inflammation as measured by ultrasound. 
o Noninvasive imaging, such as ultrasound (US), allows for an 
objective assessment of subclinical disease activity.  
o Anechoic area will be measured in the dermis before and after 
treatment, as well as other sonographic criteria of HS [10](See 
Appendix for Sonographic Scoring and Diagnosis of HS) 
o As there are no validated ultrasound criteria to measure clinical 
improvement, reduction in anechoic areas and sonographic criteria 
will be calculated. It is estimated that the treatment will induce a 
50% reduction in the anechoic area.  
o Anechoic areas and other sonographic criteria will be correlated 
with PROMIS scores and Hurley Staging. 
 
• Evaluation of cutaneous discharge 
o Swabs will be collected from discharge and sent for fluid count, 
which will include evaluation of infiltrating leukocytes from the 
discharge.  
 
• 
Immunohistochemical Evaluation of HS Tissue Biopsies 
o Tissue biopsies will be collected before and after treatment. Tissue 
sections will be evaluated by H&E as well as immunohistochemistry 
for infiltrating leukocytes and other cells, such as T cells, B cells, 
plasma cells, dendritic cells, macrophages, and keratin. Image J 
will be used to quantify cells in a standard manner for comparison 
before and after treatment. 
 
4.4 Radiotherapy 
 
4.4.1Immobilization, Simulation, and Localization 
 
Patients will be positioned in a stable position capable of allowing accurate 
reproducibility of the target position from treatment to treatment. Positions 
uncomfortable for the patient will be avoided to prevent uncontrolled movement 
during treatments. A variety of immobilization systems may be used, including 
stereotactic frames that surround the patient on three sides and large rigid 
pillows (conforming to patients’ external contours) referenced to the stereotactic 
coordinate system.  Patient immobilization will be reliable enough to ensure that 

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the gross target volume (GTV) does not deviate beyond the confines of the 
planning treatment volume (PTV) with any significant probability (i.e., < 5%). 
 
4.4.2 Target Volumes and Treatment Planning 
 
While patients with hidradenitis suppurativa may have multiple sites of 
symptomatic disease, subjects on this protocol will only receive radiotherapy 
directed at one region.  This will generally be the region that is most bothersome 
to the patient. 
 
Computed tomography will be the primary image platform for targeting and 
treatment planning.  Radio-opaque markers may be placed on the patient at the 
time of simulation to aid with target delineation.  Target volumes will be drawn on 
simulation CT imaging, using appropriate window levels.  The general intent will 
be to include any grossly abnormal areas, based on clinical examination and CT 
findings, in the GTV.  In selected cases of extensive disease, the GTV may be 
limited to the most problematic area of disease. 
 
The GTV will be expanded to form a PTV.  PTV expansions will generally 
be 10 mm in all directions but may be between 5 and 15 mm depending on the 
perceived setup uncertainty in each individual case.  Nonuniform expansions are 
permitted, at the discretion of the treating physicians. 
 
Treatment planning will be performed using standard software packages 
utilized in the Department of Radiation Oncology.  Treatment may be delivered 
using external beam radiotherapy (EBRT) with either photons or electrons, or 
with high dose rate (HDR) brachytherapy, at the discretion of the treating 
physicians.  The modality that is expected to provide the most complete 
coverage of the target volumes while minimizing irradiation of uninvolved tissues 
will generally be selected.  The prescription isodose surface should encompass 
at least 95% of the PTV, and the minimum PTV dose must not fall below 90% of 
the prescription dose.  
 
Patients in this study will receive a total radiotherapy dose of 7.5 Gy in 
five daily fractions of 1.5 Gy.   
 
4.4.3  Critical Structures 
 
The radiotherapy dose used in this protocol is so low that standard dose 
limits for internal organs will not be exceeded.  Nevertheless, careful planning will 
be utilized to minimize the exposure of all internal organs to radiotherapy.  The 
“as low as reasonably achievable” (ALARA) principle will be employed.  
5.0 STATISTICAL CONSIDERATIONS 
 
A maximum of 20 patients will be enrolled into the study. The accrual rate is 
expected to be 1-2 patients per month based on the volume of patients with 
stage 2-3 HS treated within the Montefiore Hidradenitis Suppurativa Treatment 
Center. An early stopping rule for safety will be implemented as follows based on 
Simon’s optimal two-stage design. After the first 6 patients have been enrolled, 
accrual will be temporarily suspended while these patients are monitored for 
occurrence of treatment-related grade ≥ 3 toxicity for 3 months.  At the end of 3 

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months, results will be sent to the DSMB for further evaluation. The trial will be 
terminated early if more than 1 patient experiences grade ≥ 3 treatment related 
toxicity or any patient experiences grade 4 toxicity. Otherwise, upon approval 
from the DSMB, the second phase of recruiting will be initiated. If 1 or fewer 
grade ≥ 3 toxicities and 0 grade 4 toxicities are observed, the trial will continue 
until a total of 20 patients have been evaluated. At the end of the trial, the 
treatment will be considered safe and worthy of further study if no more than 3 
patients experience grade ≥ 3 treatment related toxicity and none experience 
grade 4 treatment related toxicity.  
The target Grade ≥ 3 toxicity rates is no more than 10%, and a toxicity rate 
greater than 30% is considered clinically unacceptable. The design specified 
above has the following operating characteristics. The probability of accepting 
the treatment for further study if the toxicity rate is unacceptably high (> 30%) is 
at most 10%. In contrast, there is an 80% probability of accepting the treatment 
for further study if the toxicity rate is less than 10%. In addition, if 0 out of 20 
patients experience Grade 4 toxicity at the end of the study, we will be able to 
conclude with 95% confidence that the true Grade 4 toxicity rate is not greater 
than 17%.  
The proportion of patients who have treatment-related toxicity will be 
computed, along with exact 95% confidence intervals. Since the study is a phase 
I trial, we will NOT do any hypothesis testing or models, The study will present 
the descriptive summary statistics for each outcomes.Biomarker levels measured 
at different time points and other continuous variables will be summarized by 
computing means, medians, standard deviations and ranges.  
PROMIS scores will be calculated using “PROMIS scoring manuals” found at 
http://www.healthmeasures.net/promis-scoring-manuals. The formula for scoring 
is: (Raw Sum of all questions answered X number of items on the short form) / 
Number of items that were actually answered. Using the provided score 
conversion table, the pro-rated raw score will be converted into a T-score for 
each participant. 
Interpretation of PROMIS scores will be completed as explained at 
http://www.healthmeasures.net/score-and-interpret/interpret-scores/promis. T 
scores for each participant will be compared to calibrated scores of a validated 
reference population, where a score of 50 is the average for the United States 
general population with a standard deviation of 10.  
 
6.0 REGULATORY CONSIDERATIONS 
6.1 Protection of Human Subjects 
 
 
The Investigator must ensure that patients or their legally acceptable 
representatives are clearly and fully informed about the purpose, potential risks 
and other critical issues regarding clinical trials in which they volunteer to 

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participate.  Preparation of the consent form is the responsibility of the 
Investigator and must include all elements required by CFR 21 Part 50.25 and 
the local IRB. 
6.2 Compliance with the Protocol and Protocol Revisions 
 
The study must be conducted as described in this approved protocol.  All 
revisions to the protocol must be provided to the PI.  The PI should not 
implement any deviation or change to the protocol without prior review and 
documented approval/favorable opinion from the IRB/IEC of an Amendment, 
except where necessary to eliminate an immediate hazard(s) to study patients. 
 
The investigator must ensure that patients or their legally acceptable 
representatives are clearly and fully informed about the purpose, potential risks 
and other critical issues regarding clinical trials in which they volunteer to 
participate.  Preparation of the consent form is the responsibility of the PI. 
 
 
7.0 DATA HANDLING AND RECORD KEEPING 
7.1 Confidentiality 
 
Information about study subjects will be kept confidential and managed 
according to the requirements of the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA).  Those regulations require a signed subject 
authorization informing the subject of the following: 
• What protected health information (PHI) will be collected from subjects in 
this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of 
their PHI. 
• In the event that a subject revokes authorization to collect or use PHI, the 
investigator, by regulation, retains the ability to use all information 
collected prior to the revocation of subject authorization.  For subjects that 
have revoked authorization to collect or use PHI, attempts should be 
made to obtain permission to collect at least vital status (i.e. that the 
subject is alive) at the end of their scheduled study period. 
Confidentiality will be maintained by keeping records in secure areas in the 
clinic. Patient-identifiable materials, such as laboratory tests and specimens will 
be kept in secure areas, i.e. Nurse’s station and/or freezer kept in lockable 
storage rooms. Computer files are accessible via password-protected computers 
that are kept in lockable rooms. All lab personnel that work with patient data or 

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samples have passed human subject protection courses, and certification of this 
is on file in the IRB office. 
7.2 Source Documents 
 
Source data is all information, original records of clinical findings, 
observations, or other activities in a clinical trial necessary for the reconstruction 
and evaluation of the trial.  Source data are contained in source documents.   
Examples of these original documents, and data records include: hospital 
records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries 
or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, subject files, and records kept at the pharmacy, at the 
laboratories, and at medico-technical departments involved in the clinical trial. 
Source documents will be stored as outline in “Confidentiality” in section 7.1 
above. 
 
 
7.3 Case Report Forms 
 
The Montefiore Electronic Medical Record will be used as the primary data 
collection instrument for the study.  
8.0 Data Safety and Monitoring Boards 
A Data Safety Monitoring Committee is being convened by Dr. Barrett Katz. 
They will have the responsibility for ensuring data and safety monitoring along 
with the PI who is ultimately responsible for the ongoing monitoring and safety of 
clinical protocols.  The primary functions of this DSMC are as follows: 
1. To review and ensure protocol compliance with dose escalation in phase I 
trials  
2. To review/assure protocol compliance for all trials that have two-stage 
phase II designs,  
3. Reviewing all internal and external serious adverse reports, investigator 
alerts, action letters, and other safety reports for trials being performed at 
AECC-affiliated institutions and;  
4. To implement and to determine the adequacy of DSM plans of all 
approved protocols.  
 
The committee will meet quarterly or more frequently as needed. This 
committee lead by Dr. Katz will review serious (grade 3 or higher) adverse events 
from this study.  In the event that the DSMC decides that a revision is warranted, 
the committee will immediately notify the principal investigator of this study.  The 
DSMC has the authority to close trials to patient accrual should the risk to 
patients be excessive or outweigh the potential benefits of the study.  All study 

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suspensions and closures will be forwarded to the IRB/CCI and study sponsor 
from the DSMC.   
 
9.0 ADVERSE EVENTS 
 
9.1 Adverse Event Definitions 
• AEs are defined as outlined by Albert Einstein College of Medicine’s 
“Reportable Events Policy.”[11] 
9.2 Adverse Event Reporting 
• AEs will be reported to the IRB as outlined by Albert Einstein College of 
Medicine’s “Reportable Events Policy.” 
 
 
10.0 RISKS/BENEFITS 
 
• Anticipated risks (medical, social, psychological, and/or legal) 
o This protocol is considered greater than minimal risk, due to radiation 
exposure and the skin biopsy procedure.  
o The initial risk of radiotherapy is temporary discomfort and 
inconvenience during the treatment period.  
o This dose of radiotherapy may cause temporary hair loss at the 
treatment site for a few months. 
o The risk of acute or chronic radiation-induced dermatitis is thought to 
be very low with the dose of radiotherapy being employed in this study.    
o A risk of low-intermediate dose radiation is Radiation Induced Cancer 
(RIC) such as skin cancer (BCC, SCC, melanoma)[2]. In patients 
treated for benign disease with intermediate dose radiotherapy (Range 
3-50 Gy, mean approximately 20Gy), normal tissue side effects are 
rare or minimal. RIC risk is normally very small in adults (<1%) and 
decreases with increasing age.  
o Blood draw may cause discomfort, pain, and bruising.  
o Risks from skin biopsy may include temporary pain during the 
procedure, a small chance of infection, and the possibility that biopsy 
leaves a small scar.  
o A psychological risk is that the treatment will not have any clinical 
improvement. 
o Breach of confidentiality is a possible risk if data is lost or stolen.  
• How anticipated risks will be minimized  
o To minimize RIC risks- careful body positioning during radiotherapy 
and shielding of tissues outside of the intended treatment field will be 

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employed in a customized fashion for each patient.  In most cases, 
treatment with superficial forms of radiotherapy (electrons or surface 
brachytherapy) will be employed to minimize the volume of tissue 
irradiatied. 
o Lab tests and skin biopsy will be performed carefully, using standard 
safety measures. 
o Confidentiality will be maintained as described in Section 7.1. 
• Potential benefits 
o Potential benefits include disease improvement and potential 
remission, along with improved quality of life  

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11.0 REFERENCES 
 
 
1. 
Kimball, A.B., et al., Two Phase 3 Trials of Adalimumab for Hidradenitis 
Suppurativa. N Engl J Med, 2016. 375(5): p. 422-34. 
2. 
McKeown, S.R., et al., Radiotherapy for benign disease; assessing the risk of 
radiation-induced cancer following exposure to intermediate dose radiation. Br J 
Radiol, 2015. 88(1056): p. 20150405. 
3. 
Reichl, B., et al., DEGRO practical guidelines for radiotherapy of non-malignant 
disorders: Part I: physical principles, radiobiological mechanisms, and radiogenic 
risk. Strahlenther Onkol, 2015. 191(9): p. 701-9. 
4. 
Trombetta, M., E.D. Werts, and D. Parda, The role of radiotherapy in the 
treatment of hidradenitis suppurativa: case report and review of the literature. 
Dermatol Online J, 2010. 16(2): p. 16. 
5. 
Jemec, G.B., Clinical practice. Hidradenitis suppurativa. N Engl J Med, 2012. 
366(2): p. 158-64. 
6. 
CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. 
7. 
Cella, D., et al., The Patient-Reported Outcomes Measurement Information 
System (PROMIS) developed and tested its first wave of adult self-reported 
health outcome item banks: 2005-2008. J Clin Epidemiol, 2010. 63(11): p. 1179-
94. 
8. 
Cook, K.F., et al., PROMIS measures of pain, fatigue, negative affect, physical 
function, and social function demonstrated clinical validity across a range of 
chronic conditions. J Clin Epidemiol, 2016. 73: p. 89-102. 
9. 
Yost, K.J., et al., Minimally important differences were estimated for six Patient-
Reported Outcomes Measurement Information System-Cancer scales in 
advanced-stage cancer patients. J Clin Epidemiol, 2011. 64(5): p. 507-16. 
10. 
Wortsman, X., et al., Ultrasound in-depth characterization and staging of 
hidradenitis suppurativa. Dermatol Surg, 2013. 39(12): p. 1835-42. 
11. 
Reportable Events Policy .pdf. 
 

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12.0 APPENDICES 
 
Appendix A: Photos 
 
 
 
Persistent HS Hurley Stage 3 Lesions on the buttocks of two patients.  

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Appendix B: Relevant Skin and Subcutaneous Tissue CTCAE Items[6] 
 
Skin and Subcutaneous Tissue Disorders 
 
Grade 
Adverse 
Event 
1 
2 
3 
4 
5 
Bullous 
dermatitis 
Asymptomatic; 
blisters covering  
 
Blisters covering 
10 - 30% BSA; 
painful blisters; 
limiting 
instrumental ADL 
 
Blisters 
covering >30% 
BSA; limiting 
self care ADL 
 
Blisters 
covering 
>30% BSA; 
associated 
with fluid or 
electrolyte 
abnormalities; 
ICU care or 
burn unit 
indicated 
Death 
 
Dry Skin 
Covering <10% 
BSA and no 
associated 
erythema or 
pruritus 
 
Covering 10 - 
30% BSA and 
associated with 
erythema or 
pruritus; limiting 
instrumental ADL 
Covering >30% 
BSA and 
associated with 
pruritus; limiting 
self care ADL 
 
 
 
Pain of 
Skin 
Mild pain 
Moderate pain; 
limiting 
instrumental ADL 
Severe pain, 
limiting self 
care 
 
 
Pruritus 
Mild or localized; 
topical intervention 
indicated 
 
Intense or 
widespread; 
intermittent; skin 
changes from 
scratching (e.g., 
edema, 
papulation, 
excoriations, 
lichenification, 
oozing/crusts); 
oral intervention 
indicated; limiting 
instrumental ADL 
 
Intense or 
widespread; 
constant; 
limiting self 
care ADL or 
sleep; oral 
corticosteroid 
or 
immunosuppre
ssive therapy 
indicated 
 
 
 
Skin 
hyperpigme
ntation 
Hyperpigmentation 
covering <10% 
BSA, no 
psychosocial 
impact  
Hyperpigmentati
on covering 
>10% BSA; 
associated 
psychosocial 
- 
 
 

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impact 
 
Skin 
hypopigme
ntation 
Hypopigmentation 
or depigmentation 
covering  
<10% BSA; no 
psychosocial 
impact 
Hypopigmentatio
n or 
depigmentation 
covering >10% 
BSA; associated 
psychosocial 
impact 
 
 
 
 
Skin 
induration 
Mild induration, 
able to move skin 
parallel to plane 
(sliding) and 
perpendicular to 
skin (pinching up) 
 
Moderate 
induration, able 
to slide skin, 
unable to pinch 
skin; limiting 
instrumental ADL 
 
Severe 
induration, 
unable to slide 
or pinch skin; 
limiting joint 
movement or 
orifice (e.g., 
mouth, anus); 
limiting self 
care ADL 
 
Generalized; 
associated 
with signs or 
symptoms of 
impaired 
breathing or 
feeding 
 
Death 
 
Skin 
ulceration 
Combined area of 
ulcers <1 cm; 
nonblanchable 
erythema of intact 
skin with 
associated warmth 
or edema 
 
 
Combined area 
of ulcers 1 - 2 
cm; partial 
thickness skin 
loss involving 
skin or 
subcutaneous fat 
 
Combined area 
of ulcers >2 
cm; full-
thickness skin 
loss involving 
damage to or 
necrosis of 
subcutaneous 
tissue that may 
extend down to 
fascia 
 
Any size ulcer 
with extensive 
destruction, 
tissue 
necrosis, or 
damage to 
muscle, bone, 
or supporting 
structures with 
or without full 
thickness skin 
loss 
 
 
 

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Appendix C: PROMIS – Pain Interference 
 
 
 
 
 
 
 
 
 
 

18 
Version 1.2 2/5/2017 
 

19 
Version 1.2 2/5/2017 
 
Appendix D: PROMIS- Physical Functioning 
 
 
 
 
 
 
 
 

20 
Version 1.2 2/5/2017 
 
 
 
 
 
 

21 
Version 1.2 2/5/2017 
 
Appendix E: DLQI 
 

22 
Version 1.2 2/5/2017 
 
Appendix F: Ultrasound Criteria for Diagnosis & Staging Hidradenitis 
Suppurativa [10]