Incidence Of Moist Desquamation Research Articles

Mepitel Film for the prevention of acute radiation dermatitis in breast cancer: A randomized multi-centre open-label phase 3 trial

390226 Background: Radiation dermatitis (RD) is common in patients undergoing breast radiation treatment (RT), with worse RD in patients with large breasts and after mastectomy. Mepitel Film (MF), a silicone-based polyurethane film with Safetac technology, may reduce RD. We hypothesized that MF might play a role in preventing RD in this group of patients at risk. Methods: Patients were randomly assigned to receive MF or standard skin care (2:1 ratio). Patients with large breasts after lumpectomy (bra size ≥ 36 inches or cup size ≥ C) or after mastectomy were eligible. Stratification factors included surgery type (lumpectomy vs. mastectomy), dose fractionation (conventional vs. hypofractionated), and administration of boost/bolus. The primary endpoint was grade (G) 2 or 3 RD using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 during RT and within 3 months of completion of RT. Secondary endpoints included CTCAE G3, incidence of moist desquamation, use of topical antibiotic cream, and patient- (PROs) and clinician- (CRO) reported outcomes using the modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) and Skin Symptom Assessment (SSA). This study is registered with ClinicalTrials.gov (NCT04166799). Results: Between January 2020 and May 2022, 266 patients (66%) were randomly assigned to MF and 137 (34%) to standard care. After removing withdrawn patients, 376 patients were included in the modified intention-to-treat analysis. The incidence of G2 or 3 RD was significantly lower in MF patients compared to standard care (n = 39/251, 15.5%; 95% CI, 11.3-20.6% vs. n = 57/125, 45.6%; 95% CI, 36.7-54.8% respectively, odds ratio [OR]: 0.20, P < .0001). Benefits of MF over standard care remained significant in patients who developed G3 RD (n = 7, 2.8%; 95% CI, 1.1-5.7% vs. n = 17, 13.6%; 95% CI, 8.1-20.9%, OR: 0.19) and moist desquamation (n = 20, 8.0%; 95% CI, 4.9-12.0% vs. n = 24, 19.2%; 95% CI, 12.7-27.1%, OR: 0.36). When evaluating the combined patient and health care professional score using the RISRAS, the MF arm had significantly lower scores than standard care ( P < .0001); individual items on the RISRAS also favored MF for PROs (tenderness, discomfort of pain and burning sensation) and CROs (erythema and moist desquamation). Similarly, when assessed by the SSA, blistering/peeling, erythema, pigmentation, and edema in PROs, and pain/soreness, blistering/peeling, erythema, and pigmentation in CROs were significantly reduced in MF. Topical antibiotics were prescribed significantly less frequently in MF (23.1% vs. 43.2%, P < .0001). Three patients removed the film prematurely due to development of an allergic rash (n = 2) and excessive pruritis (n = 1). Conclusions: MF significantly reduces RD in breast cancer patients undergoing RT when compared to the standard care. We recommend changes to the clinical practice for RD prevention and inclusion of MF in high-risk patients in future guideline recommendations. Clinical trial information: NCT04166799.

A novel carbon-fibre adjustable reusable accessory (CARA) for supine breast positioning to reduce toxicity in breast adjuvant radiotherapy: a study protocol for a multicentre phase III randomized controlled trial

BackgroundA novel device for supine positioning in breast radiotherapy for patients with large or pendulous breasts has been developed and tested in phase II studies. This trial is designed to assess the efficacy of the device to reduce skin toxicity and unwanted normal tissue dose in comparison to the current clinical standard for supine breast support during breast radiotherapy.MethodsPatients at high risk for moist desquamation, having infra-mammary fold or lateral ptosis, will be randomized into two arms. Patients in the control arm will receive breast radiotherapy with supine positioning using current standard of care. Patients in the experimental arm will be positioned supine with the novel device. The primary endpoint is the incidence of moist desquamation in the infra-mammary fold. We hypothesize a 20% reduction (from 50 to 30%) in the rate of moist desquamation in the study arm versus the control arm. For 80% power, two-tailed α = 0.05 and 10% loss to follow up, 110 patients will be assigned to each arm. The proportion of patients experiencing moist desquamation in the two arms will be compared using logistic regression adjusting for brassiere cup size, skin fold size, body mass index, smoking status, and dose fractionation schedule. An unadjusted comparison will also be made using the chi-square test, or Fisher’s exact test, if appropriate. Secondary endpoints include dose-volume statistics for the lung and heart, skin dose and clinical parameters including setup time, reproducibility, and staff experience with setup procedures. Patient-reported pain, skin condition interference with sleep and daily activities, and comfort during treatment are also secondary endpoints.DiscussionBased on results from earlier phase II studies, it is expected that the device-enabled elimination of infra-mammary fold should reduce toxicity and improve quality of life for this patient population. Earlier studies showed reduction in dose to organs at risk including lung and heart, indicating potential for other long-term benefits for patients using the device. This study is limited to acute skin toxicity, patient-reported outcomes, and clinical factors to inform integration of the device into standard breast radiotherapy procedures.Trial registrationClinicaltrials.gov identifier: NCT04257396. Registered February 6 2020.

Nigella sativa L. for prevention of acute radiation dermatitis in breast cancer: A randomized, double-blind, placebo-controlled, clinical trial

ObjectiveThe present study aimed to evaluate the effectiveness of Nigella sativa L. (N. sativa) extract on preventing the incidence of acute radiation dermatitis (ARD) in breast cancer patients. MethodsSixty-two breast cancer patients undergoing radiotherapy (RT) were randomly assigned to receiveN. sativa 5% gel or placebo. Patients were instructed to apply the medications twice daily during RT period. The severity of ARD, the incidence of moist desquamation, worst experienced pain, and skin-related quality of life (SRQOL) scores were assessed weekly during RT. ResultsPatients who were treated with the N. sativa gel developed ARD significantly less frequently compared to those who used the placebo (p < 0.05 for all weeks except week 2, p = 0.36). The incidence time of grade 2 and 3 of Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) toxicity was prolonged significantly with N. sativa gel as compared to placebo (35 vs. 29 days, p = 0.00 and 42 vs. 40 days, p = 0.01, respectively). Furthermore, the occurrence of moist desquamation was delayed in the N. sativa gel group compared with the placebo group (37 vs. 33 days, p = 0.01). The mean score of the worst pain that patients experienced in the placebo group was significantly higher than that of the N. sativa gel group at week 3 (2.5 ± 0.5 vs. 1.2 ± 0.3, p < 0.05). Nonetheless, the application of N. sativa gel had no significant effect on the SRQOL of patients at any week. ConclusionN. sativa extract significantly decreases the severity of ARD and delays the onset of moist desquamation in breast cancer patients.

Protocol Paper: A Randomized Trial of 2 Creams in the Skin Care of Patients Receiving Radiation Therapy for Breast Cancer in the Tropics.

Nurses working in a northern Australia Radiation Therapy Unit advise all patients undergoing radiation therapy to use a readily available nonprescription moisturizing cream to minimize the severity of radiation skin reactions. However, patients report that the cream is thick and difficult to use in the humid tropical climate, and nurses anecdotally suspect an increase in severe skin reactions during the summer months. This article presents the protocol for a randomized controlled trial that addressed a lack of evidence pertaining to the use of topical creams to prevent acute radiation skin reactions in a tropical climate. Two skin care creams were used in the trial. The trial's primary outcome measure was the incidence of moist desquamation during treatment and 1 month after treatment completion. The secondary outcome was the participants' acceptance of the allocated cream at similar time points. Recruitment to the trial has been completed. Findings of the research will be reported in a separate publication. This article presents the protocol for a randomized controlled trial that addresses a lack of evidence pertaining to the use of topical creams to prevent acute radiation skin reactions in a tropical climate. This protocol can be adapted by other researchers conducting practice-based research.

Retrospective study of radiotherapy-induced skin reactions in breast cancer patients: Reduced incidence of moist desquamation with a hydroactive colloid gel versus dexpanthenol

PurposeDermatitis is a very frequent and distressing side effect of radiation therapy that may necessitate a treatment interruption when evolving towards more severe forms such as moist desquamation (MD). The aim of this study was to compare the efficacy of two topical agents, a dexpanthenol cream vs a hydroactive colloid gel combining absorbing and moisturising properties, in preventing MD in breast cancer patients. MethodsThis retrospective study compared two successive groups of breast cancer patients undergoing radiotherapy after breast-sparing surgery between 2008 and 2012. A group of 267 patients applied a 5% dexpanthenol cream on the irradiated zone throughout the course of their radiotherapy. Another group of 216 patients applied first the dexpanthenol cream then replaced it by the hydroactive colloid gel after 11–14 days of radiotherapy. Radiation treatment (total dose, technique, and equipment) was the same for the two groups. The clinical outcomes were the occurrence and time to onset of moist desquamation. Key resultsThe overall incidence of MD was significantly lower in patients who applied the hydroactive colloid gel (16%) than in those who applied the dexpanthenol cream (32%, odds-ratio = 0.35). Also, MD occurred significantly later with the hydroactive colloid gel than with the dexpanthenol cream (hazard ratio = 0.39). ConclusionsCompared with the dexpanthenol cream, the hydroactive colloid gel significantly reduced the risk of developing MD in patients undergoing radiotherapy for breast cancer. These promising results warrant further research on the efficacy of hydroactive colloid gels in managing radiation dermatitis.

Abstract 76: Rate of moist desquamation in patients receiving radiation for breast cancer after mastectomy versus breast conserving surgery.

Abstract OBJECTIVE: Although skin toxicity is expected to be more severe in the setting of post-mastectomy radiation (PMRT) compared to breast conserving surgery + intact breast radiation (BCT), the actual incidence of moist desquamation (MD) in patients treated with PMRT has not been well quantified. We prospectively determined rates of MD in patients treated with PMRT compared to BCT and identified risk factors for the development of MD. MATERIALS/ METHODS: 284 breast cancer patients enrolled on two parallel prospectively managed observational studies to assess skin reaction to RT (one in the setting of BCT and the other PMRT) were included in this analysis. All received tangential photons to the intact breast or chest wall (CW) following definitive surgery, with a dose of 45-50 Gy to the breast/CW +/- supraclavicular nodes (SCV). BCT patients had a 10 Gy lumpectomy cavity boost. PMRT patients received daily 0.5 cm bolus with a 10 Gy scar boost. Skin toxicities and rates of MD were rated by the treating physician on a weekly basis during RT, using the CTCAE v3.0 scale. Logistic regression analysis was used to assess risk factors associated with MD. RESULTS: Overall, 19% were black, 64% Hispanic white, and 17 % non-Hispanic white/other. Patients receiving PMRT were younger (median age 51.5 vs 57, p&amp;lt;.001), and had more advanced stage (0% vs 20.4% stage 0, 7% vs 46.9% stage I, 32.8% vs 26.1% stage II, and 60.3% v. 6.6% stage III, p&amp;lt;.0001), but there was no difference between the groups with respect to race, ethnicity, body mass index (BMI), or smoking status. In the BCT group, 23% of patients developed MD vs 55.2% in the PMRT group (p&amp;lt;0.0001). Other factors predictive of MD were increasing BMI (17.3% in BMI &amp;lt;25, 31.1% in BMI 25-29.9,37.2% in BMI &amp;gt;30, p=0.011), and increasing breast cancer stage (21.7% stage 0, 24.5% stage I, 29.5% stage II, 49% stage III, p=0.018). On multivariate analysis, the use of PMRT (OR 3.84, 95% CI 1.76-8.87, p=0.001) and increasing BMI (OR 2.42, 95% CI 1.10-5.30 (p=0.028) for BMI 25-29.9 vs &amp;lt;25; OR 3.10, 95% CI 1.46-6.59 (p=0.003) for BMI ≥30 vs &amp;lt;25) retained statistical significance as risk factors for MD, but stage was no longer significant. There was no difference in rate of MD by race or ethnicity. CONCLUSIONS: The rate of MD is more than double in patients receiving PMRT vs BCT, 55.2% vs 23%, even when accounting for increasing stage and BMI. This information is important in counseling our patients regarding the potential toxicities of adjuvant radiation treatment for breast cancer. Citation Format: Jean L. Wright, Cristiane Takita, Isildinha Reis, Wei Zhao, Jennifer J. Hu. Rate of moist desquamation in patients receiving radiation for breast cancer after mastectomy versus breast conserving surgery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 76. doi:10.1158/1538-7445.AM2013-76

Cost effectiveness of whole breast IMRT for reduction of moist desquamation

17004 Background: Cost minimization studies have compared conventional whole breast radiation therapy (C-WBRT) to whole breast intensity modulated radiation therapy (IMRT). Consistently, IMRT has proved to be far more expensive. The weakness of cost minimization studies is that they assume the outcomes and toxicities of the treatment modalities in question are identical. Data from a case- control trial and a recent randomized controlled trial show that IMRT reduces the incidence of moist desquamation. We performed an analysis to estimate the cost effectiveness of breast IMRT to prevent moist desquamation. Methods: The direct medical costs of C-WBRT and IMRT were estimated using the 2006 Medicare Fee Schedule. We assumed rates of moist desquamation of 48 to 31% in accordance with Pignol, et al., ASTRO 2006. The cost effectiveness ratio (additional dollars spent per case of desquamation avoided) was calculated under two circumstances: 1) every patient received IMRT, or 2) only those patients destined to desquamate were treated with IMRT. Results: The direct medical costs of C-WBRT are $7,948 vs. $29,790 for IMRT. Thus, the marginal cost of IMRT is $22,142. In circumstance 1, the marginal cost to avoid one case of desquamation is $130,247. In circumstance 2, this cost is $62,518. Conclusions: The two circumstances described above are extremes that bound the range of cost estimates. Patient risk factors for desquamation, such as large breast size, can be used to identify high risk patients, obviating the need to treat all patients with IMRT. However, perfect prospective identification of all patients destined to desquamate is unlikely. Instead, the true marginal cost to avoid one case of moist desquamation will lie between $62,518 and $130,247. This cost may be too high to justify the benefit of reduced acute skin toxicity, but it is likely that the benefits of IMRT have been underestimated. IMRT may shorten the duration of moist desquamation. Late effects such as breast fibrosis and color variegation of the skin caused by desquamation as well as dose to the heart and lungs may be decreased by IMRT. If new data support these benefits, then IMRT may become a more cost effective option. No significant financial relationships to disclose.

Effects of Lipochromin and Levosinum in the modulation of radiation-induced injury to pig skin.

Pig skin was used as a model to study the effectiveness of two topically applied creams, Lipochromin and Levosinum, in modifying the development of both early and late radiation damage to pig skin. Irradiated skin sites that received daily topical application of Levosinum or Lipochromin after exposure were compared with sites on the contralateral flank of the same animal that received irradiation only. Irradiation was with graded doses of 90Sr/90Y beta-rays. Incidence of moist desquamation (acute) and ischaemic dermal necrosis (late) were used as end-points. The latency period for the development of moist desquamation and its healing time was also assessed. The latency period for the development of moist desquamation in this model ranged from 4.00-6.75 weeks. There was no significant difference between the cream treatment and control sites. Application of Levosinum shortened the healing time of moist desquamation at each dose level by 5-10 days. In three out of four dose levels used, this shortening of the healing time was statistically significant (p < 0.03). Treatment with these topical applications also reduced the incidence of late dermal necrosis and increased the ED50 values for the incidence of dermal necrosis. This increase in ED50 values was equivalent to a dose modification factor of 1.11-1.13.

The effect of evening primrose oil on the radiation response and blood flow of mouse normal and tumour tissue

Purpose : To investigate the effect of the oral administration of evening primrose oil on the radiation response and the blood flow of normal tissue and a tumour in BALB/c mice. Methods and materials : Aliquots of evening primrose oil were fed to BALB/c mice daily and the radiation response of the skin was assessed by the determination of ED 50 values for the incidence of moist desquamation, using probit analysis. Tumour radiosensitivity was investigated by determining the growth delay caused by irradiation of a transplantable rhabdomyosarcoma. The 86 RbCl uptake technique was used to determine the blood flow in normal foot and tumour tissue. The fatty-acid content of red blood cells, plasma and tumour tissue was measured using gas chromatography. Results : Daily evening primrose oil dietary supplementation reduced the sensitivity of skin to radiation-induced moist desquamation and prevented the radiation-associated increase in blood flow that was observed in this tissue. No modification of tumour blood flow or of tumour sensitivity to radiation resulted from evening primrose oil supplementation of mice. Evening primrose oil supplementation resulted in changes in plasma levels of linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA). These changes were contingent on whether the mice had been irradiated or not. In red blood cells evening primrose oil supplementation increased the GLA level of unirradiated mice and the LA level at 20 days after irradiation. There were no changes in tumour fatty-acid levels as a result of evening primrose oil treatment. Conclusions : Daily evening primrose oil supplementation reduced the sensitivity of skin to radiation-induced moist desquamation but did not alter tumour sensitivity to radiation.

Acute and late morbidity of using a breast positioning ring in women with large/pendulous breasts

Purpose: To assess acute and late effects of radiation therapy in women with breast cancer treated with a breast positioning ring. Materials and methods: Fifty-six patients with large and/or pendulous breasts were irradiated using a breast positioning ring. The incidence of acute morbidity was correlated with patient weight and breast ‘size’. Cosmesis was scored at ≥1 year following radiation therapy by the patients. Dose changes in the buildup region under the ring were measured using a computer-controlled scanning system. Results: Moist desquamation (MD) occurred in 60.7% (34/56) of patients treated with the breast ring. The incidence of MD was more common in patients with larger breasts ( P=0.08), the severity necessitating a treatment interruption in 5 out of 56 (9%) patients. Cosmesis at ≥1 year following radiation therapy was scored as ≥ good by all patients. The surface dose under the ring was approximately 85% of the D max dose. Conclusions: The incidence or severity of acute MD in patients treated with a breast positioning ring appears high in patients with large pendulous breasts, and might be related in part, to the increased skin dose due to the positioning ring. To date, there appears to be no significant late normal tissue effects in patients treated with the positioning ring. Additional follow up is needed to assess the long-term consequences of the ring on cosmesis.

The Kinetics of Repair of Sublethal Radiation-Induced Damage in Pig Skin: Studies with Multiple Interfraction Intervals

The kinetics of the repair of radiation-induced sublethal damage (SLD) was studied for the epidermis of the pig. A total of either 7 or 14 interfraction intervals with incomplete repair was achieved by giving 28 fractions either as 7 x 2 fractions/day plus a top-up dose of 17 Gy (half tolerance) or as 14 x 2 fractions/day. The dose per fraction ranged from 1.96-4.82 Gy. A total of 9 intervals ranging from 0.17 h up to 8 h between fractions was used. The incidence of moist desquamation, as an estimate of acute epidermal response, was used as an end point to establish dose-effect relationships. The data were analyzed using either the incomplete repair model of Thames, assuming mono-exponential repair kinetics, or a modified version of the incomplete repair model, assuming bi-exponential repair of sublethal damage. Both methods of analysis allowed for the longer overnight interval between fractions. Analysis assuming mono-exponential repair gave a T1/2 of 0.74 h for the combined data, although there was a trend toward a longer half-time when only the longer interfraction intervals ( > 1.0 h) were used in the analysis. A further analysis using the modified version of an incomplete repair model gave a fast and a slow component of repair with significantly different half-times of 0.09 and 4.5 h, respectively. Varying the number of incomplete repair intervals by replacing half the number of fractions with a single half-tolerance top-up dose did not modify the kinetics of repair significantly, in terms of either the repair half-times or the proportion of repair associated with a fast and slow component. Reanalysis of data published previously for 3 and 4 fractions using the modified incomplete repair model again resulted in two components of repair, represented by the significantly different half-times of 0.17 and 3.0 h. These values were similar to those obtained from the multiple-fraction experiment. These data clearly demonstrate that an acutely responding tissue is associated with a long T1/2 for the repair of SLD which is independent of the dose per fraction. For accelerated fractionation schedules in the clinic, using multiple fractions per day, these results suggest a need to control the intervals between fractions carefully and when appropriate to reduce the total dose to avoid serious normal-tissue complications.

Use of a CT simulator in radiotherapy treatment planning for breast conserving therapy

A CT simulator (CT-S) is a real-time, CT-linked, 3-D treatment planning system, which consists of a CT scanner, a multi-image display, a treatment planning device with real-time visual optimization, and a laser beam projector. This system was clinically evaluated in 339 Stage 0,I and II breast cancers in 337 patients who received breast conserving therapy. Following quadrantectomy or wide excision with complete axillary dissection, a total of 50 Gy was delivered to the ipsilateral breast using 60Co γ-rays. In patients with involved surgical margins, boost electron irradiation was also given. Treatment planning could be accomplished within 40–50 min using the CT-S. The parameters for the tangential portals could be optimized for each patient, and the wedge filters and the electron energy for boost irradiation could be appropriately selected. The incidence of moist desquamation and depigmentation at the areola was slightly decreased with the use of wedge filters. During the follow-up for 2–71 months (median, 22 months), local recurrence and symptomatic radiation pneumonitis occurred in one patient each. The CT-S appears to be useful for the individualized optimization of tangential irradiation fields in breast conserving therapy.

Protection of Pig Epidermis against Radiation-induced Damage by the Infusion of BW12C

BW12C, which was developed as an agent for the treatment of sickle cell anaemia, increases the binding of oxygen to haemoglobin and hence reduces the availability of oxygen to tissues. Due to these changes in oxygen availability BW12C could act as a protector against radiation-induced injury to normal tissues. In this study the potential value of BW12C, as a radioprotector, was studied in the irradiated epidermis of the pig. The infusion of BW12C caused an instant left shift of the oxygen dissociation curve, an effect that lasted for approximately 1.5 h. This left shift in the oxygen dissociation curves increased with increasing dose of the drug. There appeared to be no long-term systemic effects produced by doses of 20-100 mg/kg of BW12C. In the first 90 min after the infusion of BW12C skin fields were irradiated with single doses of beta-rays from strontium-90 plaques. The incidence of moist desquamation was used as an endpoint for assessing the severity of the radiation response. With animals breathing approximately 70% oxygen in the anaesthetic gas mixture, the ED50 values for moist desquamation were 30-31 Gy after a dose of 30 and 50 mg/kg, and 37-38 Gy for 75 and 100 mg/kg doses of BW12C. These ED50 values were significantly higher than the value of 27.3 Gy for radiation alone. This indicated dose modification factors (DMF) with mean values of approximately 1.13 and approximately 1.40 for irradiation following the infusion of low (30-50 mg/kg) and high (75-100 mg/kg) doses of the drug, respectively. With the animals breathing air (approximately 21% of oxygen) in the 2% halothane anaesthesia gas mixture, irradiation in the presence of 30 and 50 mg/kg of BW12C resulted in ED50 values of approximately 39 Gy for moist desquamation, which was significantly higher than the value of 31.2 Gy for radiation alone. Surprisingly, a higher dose of 75 mg/kg of BW12C resulted in a lower ED50 value for moist desquamation of 34.38 Gy. Irradiation in the presence of a dose of 100 mg/kg of BW12C produced an ED50 value which was not significantly different from that for radiation alone. In the situation where animals were breathing air (approximately 21% oxygen) during irradiation a DMF of 1.14 was obtained for irradiation alone, when the results were compared with those for irradiation alone with approximately 70% oxygen in the anaesthetic gas mixture.(ABSTRACT TRUNCATED AT 400 WORDS)

A Comparison of the Radiation Response of the Epidermis in Two Strains of Pig

The response of the epidermis was compared in two strains of pig, the English Large White and the Göttinger Miniature, after irradiation with 90Sr beta rays. The effects of two types of anesthesia were also tested in pigs of each strain, a volatile gas mixture of approximately 70% oxygen, approximately 30% nitrous oxide, and 2% halothane, and an intravenously administered narcotic azaperon/etimodat with the animals breathing air. Strain- and anesthetic-related changes were compared on the basis of dose-effect curves for the incidence of moist desquamation from which ED50 values (+/- SE) were determined, i.e., the dose required to produce this effect in 50% of the fields irradiated. For English Large White pigs anesthetized with the volatile gas mixture, an ED50 of 27.32 +/- 0.52 Gy was obtained for moist desquamation. Irradiation with the azaperon/etomidat anesthesia in this strain of pig produced a significantly higher ED50 of 33.36 +/- 0.76 Gy (P less than 0.001). This appeared to be related to the fact that the animals were breathing air, i.e., a lower oxygen concentration (approximately 21%), at the time of irradiation. For the Göttinger Miniature pig the ED50 values for moist desquamation were 38.93 +/- 3.12 Gy and 43.36 +/- 1.34 Gy while using the gaseous anesthetic mixture and the azaperon/etomidat anesthesia with the animals breathing air, respectively. These ED50 values are 10-11 Gy higher than those obtained for the English Large White pig under identical conditions of anesthesia, which resulted in a strain difference ratio of approximately 1.35. Radiation under the volatile gas mixture anesthesia resulted in a uniform irradiation response over the skin of the flank in both strains of pig. Radiation under azaperon/etomidat anesthesia resulted in a nonuniform skin response over the flank. The ED50 for moist desquamation was significantly higher in dorsal sites on the flank compared with the ventral area of English Large White pigs; a similar trend was seen in Göttinger Miniature pigs. This difference in the radiosensitivity over the flank skin while the animals are under azaperon/etomidat anesthesia at the time of irradiation was associated with the animals breathing air and is in agreement with findings published previously for animals under halothane anesthesia and breathing air.

Modification of the radiation response of pig skin by manipulation of tissue oxygen tension using anesthetics and administration of BW12C.

The importance of tissue oxygen tension on radiosensitivity was studied by examining modifications in the incidence of moist desquamation in pig skin after irradiation with strontium-90 plaques. The effects were analyzed using quantal dose-response data and comparisons were made using ED50 values for moist desquamation. Under standard anesthetic conditions of 2% halothane, approximately 70% oxygen, and approximately 30% nitrous oxide, the ED50 value (+/- SE) for moist desquamation was 27.32 +/- 0.52 Gy with no significant variation in radiosensitivity between dorsal, lateral, and ventral skin sites on the flank. Irradiation with 2% halothane and air increased the ED50 to 31.25 +/- 0.94 Gy, primarily due to an increased radioresistance of the dorsal sites. When combined with BW12C, a drug which binds oxygen selectively to hemoglobin and hence reduced the oxygen availability to tissues, a further increase in the ED50 values was observed. This was approximately 39 Gy with BW12C concentrations of 30 mg/kg and 50 mg/kg b.w. of BW12C, indicating a dose modification factor (DMF) of approximately 1.26. However, when animals were breathing the standard gas mixture, this DMF was reduced to 1.15 for 30 mg/kg of BW12C, indicating that a higher level of oxygen partly counteracted the effects of the drug in these studies with BW12C. The greatest variability in radiosensitivity was seen in the dorsal fields. This suggested complex physiological adaptation, a phenomenon that might also explain the absence of any modification of the radiation response when 100 mg/kg of BW12C was used.