An Exploratory Evaluation of Biomarkers in Blister Fluid in Healthy Volunteers and Irradiated Skin

BACKGROUND:

Blister fluid has been used to measure cytokine expression, proteomic profiles, and
pharmacokinetics in a variety of disease states.

Blister fluid inside radiation treatment fields has been shown to have altered expression of
cytokines and products of collagen metabolism.

Evaluation of blister fluid in normal skin inside and outside the radiation field may allow
the development of a minimally invasive marker of radiation exposure or damage induced by
radiation in irradiated skin.

OBJECTIVES:

This protocol will evaluate the ability to determine a cytokine pattern and global changes at
the protein level measured in blister fluid that correlates with radiation exposure, absorbed
skin dose, or skin toxicity from patients receiving radiation.

ELIGIBILITY:

Patients in whom radiotherapy is required for standard management of their breast or prostate
cancer.

Healthy volunteers with no history of cutaneous inflammatory condition of the skin such as
eczema, or psoriasis.

DESIGN:

This protocol is designed to evaluate blister fluid in and out of the radiation field in
patients that are receiving radiation therapy and in healthy volunteers.

Patients will undergo blister induction and blister fluid collection prior to treatment
outside of the radiation field, and after completion of radiation within the radiation field.

Blisters will be induced in a non-sun exposed area and if possible in matched sites (i.e.
left and right).

- ELIGIBILITY CRITERIA

ELIGIBILITY CRITERIA FOR PATIENTS RECEIVING RADIOTHERAPY:

INCLUSION CRITERIA:

1. Histological diagnosis: Pathologically confirmed diagnosis of 1) invasive breast
cancer, 2) ductal carcinoma in situ, or 3) adenocarcinoma of the prostate.

2. Patients in whom the management of the histologic diagnosis will include radiation
treatment as part of standard clinical management.

3. Patients in whom the extent of disease is considered local or locoregional (i.e.
requiring definitive radiotherapy to the breast or prostate).

4. Patients must be older than 18 years of age.

5. Patients must have a primary medical or surgical oncologist in the community or at NCI
who is willing to collaborate with the ROB staff in the clinical management of the
patient.

6. Patients of childbearing or child- fathering potential must be willing to use a
medically acceptable form of birth control, which includes abstinence, while they are
being treated with radiotherapy on this study.

7. Patients must have an ECOG performance status of 0-2 and a life expectancy greater
than 12 months.

EXCLUSION CRITERIA:

1. Patients with a history of chronic skin disease such as psoriasis, eczema, or history
of keloid formation.

2. Patients requiring concurrent use of topical steroids

3. Patients requiring concurrent use of glucocorticoid therapy.

4. Patients who have received topical or systemic chemotherapy within 4 weeks of
enrollment (not including hormonal agents such as antiandrogens, GnRH agonists,
aromatase inhibitors, tamoxifen, and similar agents) are excluded.

5. Patients requiring concurrent chemotherapy with radiotherapy except as noted in
(Protocol section 2.3.1) are excluded.

6. Patients with a history of lupus erythematosis, scleroderma, ataxia telengiectasia or
other known hypersensitivity to therapeutic radiation.

7. Patients with prior radiotherapy to the site which would be used for blister
induction.

8. Patients who are pregnant because of the potential mutagenic effects of radiation on a
developing fetus or newborn.

9. Patients with unrelated systemic illness which in the judgment of the Principal
Investigator (PI) would compromise the patient s ability to tolerate this therapy or
are likely to interfere with the study procedures or results.

10. Patients who are in the estimation of the PI, deemed unable or unlikely to adhere to
protocol treatment.

11. Patients with significant skin atrophy that would interfere with blister formation.

12. Breast cancer patients in whom the site of radiotherapy includes a myocutaneous flap
or skin graft.

ELIGIBILITY CRITERIA FOR HEALTHY VOLUNTEERS:

INCLUSION CRITERIA:

1. Healthy volunteers older than 18 years of age.

2. Ability to provide informed consent.

EXCLUSION CRITERIA:

1. History of chronic skin disease such as psoriasis, eczema, or history of keloid
formation.

2. Concurrent use of glucocorticoid therapy.

3. History of lupus erythematosis, scleroderma, ataxia telengiectasia or other known
hypersensitivity to therapeutic radiation.

4. Prior radiotherapy to the site which would be used for blister induction (for benign
or malignant causes).

5. Unrelated systemic illness which in the judgment of the Principal Investigator (PI)
would compromise the patient s ability to tolerate blister induction or are likely to
interfere with blister healing, the study procedures, or the study results.

6. Darkly pigmented skin in whom pigmentation changes are a likely complication

7. Significant skin atrophy that would interfere with blister formation.