Early Skin Response Research Articles

Comparison of the Thermal Reaction of Patients after Conserving Procedures and after Mastectomy to the Radiation Dose Obtained during Radiotherapy

The main aim of the study was to compare the temperature response of the body to the dose received during breast cancer radiotherapy. The control group consisted of 50 healthy volunteers. They underwent one thermographic examination and compared the temperatures between the left and right breasts. The research group consisted of 50 patients. Based on the treatment plan, the area PTV and isodose was marked on the thermograms. Five thermographs were performed in each patient (before radiotherapy and in each week of treatment). A qualitatively similar increase in mean temperature during treatment was observed in both subgroups in the analyzed areas. The highest increase in temperature was obtained in the third week of treatment. Compared with the value before treatment, the increase in the mean temperature in PTV in patients after partial surgery was 0.78 °C, these values are statistically significant p = 0.000055. In the case of post-mastectomy patients, 0.8 °C was obtained, these values are statistically significant p = 0.00369. In addition, strong correlation was calculated between isodoses read from treatment plans and isotherms obtained from the analysis of thermal images. In post-mastectomy patients for PTV r = 0.77, 30 Gy r = 0.94, 20 Gy r = 0.96, and 10 Gy r = 0.75. For patients after partial surgery for PTV r = 0.74, 30 Gy r = 0.89, 20 Gy r = 0.83, and 10 Gy r = 0.89. Infrared thermography seems to be a useful method of assessing the thermal response of the body to the dose received during radiotherapy of breast cancer and may be a clinically useful method of assessing the early skin response to radiation.

LBOVI-A-3Identification of skin biomarkers following testosterone administration in postmenopausal women

BACKGROUND/AIMS To pilot a pharmacodynamic (PD) model of short-term androgen administration that may be used to predict long-term effects of androgen administration in postmenopausal women. The study was specifically designed to identify biomarkers that evaluate early skin response to exogenous androgens. The clinical consequences of androgen administration include hirsutism and acne. Skin biopsies were performed to document morphological changes in the pilosebaceous unit (PSU) and gene expression changes (Taqman and microarray). Functional skin response was gauged by measuring sebum excretion rates (SER). METHODS A double-blind, randomized, placebo-controlled, parallel-group study was conducted in 36 healthy postmenopausal female subjects to identify early biomarkers of androgen administration. Subjects were randomized to receive either 2.5 mg of transdermal testosterone gel (TTG; AndroGel®), 300 μg of TTGtransdermal testosterone gel, or placebo gel, daily for 6 weeks in a 1:1:1 ratio. Skin biopsies were performed to document morphological changes in the pilosebaceous unit (PSU) and gene expression changes (Taqman and microarray). Five-mm skin punch biopsies were obtained from the back of subjects at baseline, after 6 weeks of treatment, and 4 weeks post treatment. Biopsies were analyzed for histological changes characterized by total sebaceous gland volume and sebocyte cell size. Skin biopsies were also analyzed for molecular skin changes using skin Taqman/microarray assays. Measurements of sebum excretion rates (SER) were obtained at baseline and after 6 weeks of treatment. RESULTS Six weeks of treatment with the 2.5-mg TTGdose of AndroGel® increased sebaceous gland volume on average by 42% (p=0.0410) and sebum excretion rateSER by 52% (p=0.0021) relative to placebo. Microarray and Taqman analyses on skin samples also demonstrated changes in the 2.5-mg TTG AndroGel® group. Histological and molecular findings were noted to be reversible 4 weeks after discontinuing therapy. Analysis of Total Sebaceous Gland Volume (106 μm3) at Week 6 (See Tables 1 and 2) Mean (SD) % Change from Baseline Treatment N Baseline Week 6 Mean (SD) LS Mean 95% CI Placebo 13 19.58 (32.51) 24.00 (32.27) 4.42 (33.53) 4.42 (−21.79, 30.63) 300 ug TTG 13 37.20 (39.16) 45.59 (47.20) 8.40 (51.97) 8.40 (−17.81, 34.61) 2.5 mg TTG 10 31.93 (36.34) 77.91 (71.76) 45.98 (53.01) 45.98 (16.10, 75.87) Analysis Results for SER at Week 6 Geometric Mean (CV) % Change from Baseline Treatment N Baseline Week 6 Geometric Mean (CV) Geometric LS Mean† 95% CI‡ Placebo 13 0.67 (0.52) 0.67 (0.51) −0.14 (0.29) −0.14 (18.22, −15.65) 300 ug TTG 12 0.81 (0.55) 0.89 (0.56) 10.80 (0.38) 10.80 (32.08, 7.05) 2.5 mg TTG 10 0.82 (0.43) 1.24 (0.42) 52.09 (0.22) 52.09 (84.37, 25.46) CONCLUSIONS TTG treatment is associated with marked increases in sebaceous gland volume and SER, consistent with side effects including hirsutism and acne. Biomarkers sufficiently robust to support using to test for androgen-mediated skin effects in postmenopausal women were identified. Clinical Pharmacology & Therapeutics (2005) 79, P84–P84; doi: 10.1016/j.clpt.2005.12.299

Dose- and Source-Size-Related Changes in the Late Response of Pig Skin to Irradiation with Single Doses of β Radiation from Sources of Differing Energy

Late radiation damage to pig skin has been assessed at 104 weeks after exposure to sources of 90Sr/90Y (Emax 2.2 MeV) and 170Tm (Emax 0.9 MeV). Damage was assessed from measurements of dermal thickness in histological sections of irradiated skin and was compared with that of unirradiated skin to establish the relative reduction in dermal thickness. The size of the source varied from 0.1 to 40.0 mm in diameter; this covered the range of source sizes designed to simulate exposure to radioactive "hot" particles (< or = 1.0 mm diameter) up to the lower range of field size that patients may be exposed to in radiotherapy treatments. Radiation doses were measured using an extrapolation chamber with a collecting electrode of 1.1 mm2, and thus the quoted doses represent an average dose over this area. For the larger 90Sr/90Y sources of > or = 5 mm diameter and the larger 170Tm sources of > or = 2 mm diameter there was no evidence, based on levels of damage consistent with a > or = 10, > or = 20, > or = 30, and > or = 40% reduction in relative dermal thickness, for any effect of source size on the ED50 value for each of these specified levels of effect. However, there was a marked effect of beta-particle energy; the skin surface doses associated with the ED50 values (+/- SE) for a > or = 20% reduction in relative dermal thickness were approximately 12 and approximately 40 Gy for 90Sr/90Y and 170Tm, respectively. This difference in skin surface dose for an equivalent level of dermal injury reflects the variation in the depth dose from these two beta-particle emitters. These skin surface doses, for what was considered to be a clinically detectable dermal effect, were below the ED10 for the early skin response of moist desquamation. This supports the selection of late dermal thinning as the effect on which to base dose limits in radiation protection for more generalized larger area skin exposures. In comparison, single exposures to a small area, from sources designed to simulate those from hot particles, reinforced the view that acute ulceration should be the effect on which dose limitation is based. Either the isoeffect doses for a clinically detectable reduction in relative dermal thickness of > or = 20%, following a single exposure to a small area, were higher than the ED10 for acute ulceration or the area of skin showing dermal thinning was so small that it was not considered to be detrimental.

The relationship of acute to late skin injury in 2 and 5 fraction/week γ-ray therapy

Areas of pigs' skin were exposed to fractionated doses of y-rays, and their acute and late (several months) responses were measured as desquamation and degree of contraction, respectively. The purpose was to measure the relative changes in acute and late response when the dose fractionation pattern of a 6.5 week treatment was changed from five times to twice weekly. It was found that NSD formula did not predict isoeffect for reduced numbers of dose-fractions. Moreover, early skin response did not predict the magnitude of late damage when dose-fractionation was altered from conventional daily routines. Specifically, 200 rad five times weekly was equivalent, for acute response, to a dose greater than 435 rad twice weekly ( p < 0.01), whereas, for late response, equivalence was achieved at a dose less than 360 rad twice weekly ( p < 0.0526).

Skin tolerance to fractionated x-irradiation in the pig--how good a predictor is the NSD formula?

Abstract Fields on the flanks of domestic swine were irradiated with 250 kVp X rays in courses of one, six, or 30 fractions. The acute skin response was scored quantitatively using a numerical scheme. Late skin tolerance, up to one year after exposure, was determined by the presence or absence of skin necrosis in the irradiated fields. The Nominal Standard Dose was a poor predictor for early skin response; an approximately 30 per cent higher equivalent dose was required when administered in six fractions over 18 days to produce either dry or moist desquamation, than was required when given in 30 fractions over 39 days. The difference was even greater when compared with single radiation doses. Late skin tolerance was not closely correlated with the level of early response, but skin necrosis was well predicted by the NSD formula. These data in the pig correlate well with clinically determined late skin tolerance in three large radiotherapy centres. For a 64 cm2 skin field, however, skin tolerance in the pig...