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Analysis of non-genetic risk factors for adverse skin reactions to radiotherapy among 284 breast cancer patients.

OBJECTIVES: We analyzed non-genetic risk factors for adverse skin reactions to irradiation at 4 collaborating Japanese institutions, to design future investigation into genetic risk factors for adverse skin reactions to irradiation in a multicenter setting. METHODS: From April 2001, 284 breast cancer patients, who underwent radiotherapy with breast-conserving surgery, were enrolled from 4 collaborating institutions in Japan. We graded skin reactions according to international scoring systems. Clinical factors were tested against adverse effects. RESULTS: Grade 1+ skin reactions were observed in 261 (92%) of the patients in less than 3 months, 118 (42%) at 3 months, and 29 (10%) at 6 months in the late phase. Univariate analysis of treatment risk factors (such as the use of a multi-leaf colimeter, wedge-filter, or immobilization device) for skin reactions revealed a significant association (p< 0.0001). After a variable selection procedure with logistic regression, the institution, operative procedure, and magnitude of photon energy remained significantly associated with acute skin reactions. Only the institution was an explanatory variable for skin reactions at 3 and 6 months in the final logistic model. CONCLUSION: After stratification, substantial remaining variations in the occurrence of skin reactions of a given level suggested that individual genetic factors contribute markedly to individual radiosensitivity. Analysis of genetic factors associated with adverse effects would be possible by stratifying patients according to institution. Selection of eligible institutions, where appropriate treatment modalities could be performed, would also be possible when planning such a study.

Adult↗

Intensity and area increase of UVB-induced erythema: two variables used for studies of the influence of topically applied drugs.

The area of UV erythema produced by a small beam head was found to increase with increasing doses. The aim was to investigate whether measurement of the area could be a more useful indicator of UV-induced damage than classic visual grading. Topical pretreatment with all-trans retinoic acid (tretinoin) and betamethasone valerate was used to test the applicability of the method in pharmacological studies. We used a round outlet head (5 mm2) connected by optical fibre to a monochromatic irradiator, and doses ranging from 0.05 to 0.2 Joule of 300 mm UV light were applied to the skin of 6 healthy subjects. Erythemal area was calculated by the measurement of two diameters, and intensity was graded visually (0-6 scale). The area of the erythema correlated with the increase in intensity up to score 6. Area measurement was less subject to intra-investigators' variability than the intensity score. By multiplying intensity by area, a good indicator of UV-induced reactivity was obtained. Pretreatment with betamethasone valerate decreased the area of erythema, as did tretinoin 12 h after irradiation. Thus, area measurement of erythema is a useful adjunct to visual grading of UV-induced skin reactions.

Administration, Cutaneous↗

Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.

Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.

Animals↗

Male reproductive system in patients exposed to ionizing irradiation in the Chernobyl accident.

Twelve men with different forms and stages of chronic radiation dermatitis caused by accidental exposure to beta and gamma irradiation during and after the Chernobyl atomic power plant accident were examined. Two patients had impotentia coeundi, and the others reported various impairments of sexual function. One patient had aspermia, two patients had azoospermia, one had oligospermia, and four had normal sperm counts. In three samples abnormal forms of spermatozoa were increased. Sperm motility was decreased in 3 samples and was normal in another. Hormonal analyses demonstrated low testosterone plasma levels in two patients, an increase of follicle stimulating hormone (FSH) levels in six patients, and a decrease of luteinizing hormone (LH) in one patient. In one patient who showed an increase of plasma prolactin level, associated with low testosterone and LH, a microadenoma of the pituitary gland (prolactinoma) was detected. It would appear that there is an association between accidental exposure to ionizing radiation of varying severity and the impairment of exocrine and endocrine testicular function, sometimes resulting in long-lasting physiological and psychological problems.

Accidents↗

Radiation response modified by degradable starch microspheres. Experiments on the rat's foot.

Skin reaction in the rat's foot was used as an experimental method to evaluate the protective potential of profound temporary hypoxia against roentgen radiation produced by a linear accelerator. Hypoxia was induced by intraarterial injection of degradable starch microspheres. The irradiation dose needed to evoke a certain reaction in the hypoxic feet was 2.0 times the dose giving the same reaction in a control group. The results point towards a new technique of inducing local hypoxia in healthy tissues which need to be protected in an irradiation field.

Animals↗

Radiation recall dermatitis induced by edatrexate in a patient with breast cancer.

Enhancement of radiation injury to the skin and mucous membranes has been observed with a number of chemotherapeutic agents. A 32-year-old woman with metastatic breast cancer received local radiation therapy to the lumbosacral area. Six weeks later, systemic edatrexate therapy was initiated and a localized painful erythema with edema and a vesicular eruption occurred over the previous site of radiation therapy. Physicians should be aware that edatrexate can cause radiation recall, and that careful use of anti-inflammatory agents may allow continued chemotherapy treatment.

Adult↗

Total skin electron irradiation: efficacy in early mycosis fungoides.

The rare, indolent, but lethal malignancy, mycosis fungoides (MF), is amenable to durable remissions if treated topically at an early stage with nitrogen mustard, PUVA, or radiotherapy. A modification of conventional therapeutic irradiation which utilizes electron beams rather than photons, has been in use since 1951. This method, termed total skin electron irradiation (TSEI), has achieved consistently good CR rates (95-100%) at a variety of centres in the U.S.A., England, France, and Italy, despite troublesome differences in staging systems. In northern Israel we have treated 37 MF patients with TSEI during the past 13 years. All 21 of our early stage patients achieved CR, which is no longer regarded as an unusual result. However, most workers in the field acknowledge that issues of optimal dosing and curative potency remain unresolved.

Adult↗

Prophylactic beclomethasone spray to the skin during postoperative radiotherapy of carcinoma breast: a prospective randomized study.

BACKGROUND AND AIMS: Radiation induced wet desquamation of skin in carcinoma breast patients is a painful condition. In this study topical beclomethasone dipropionate spray was used as prophylaxis with the purpose of reducing risk of the wet desquamation of skin in irradiated field. MATERIALS AND METHODS: Sixty patients of carcinoma breast were planned for postoperative loco regional radiotherapy (50 Gy in 25 fraction over five weeks) were prospectively randomized into two groups (1) steroid group-patients were advised to use beclomethasone dipropionate spray in irradiated axilla from day one of radiotherapy, (2) control group-patients were not allowed to use any topical agent in irradiated area. Radiation induced skin reaction was noted in terms of erythema, dry desquamation and wet desquamation weekly till end of prescribed 50 Gy dose of the radiation therapy. STATISTICAL METHOD: Chi-square test was used to see the statistical significance of the difference in wet desquamation between two arms of the study. Chi-square value and P-value was calculated for the difference of wet desquamation in two study arms. RESULT: In steroid group 4/30 (13.33%) patients developed wet desquamation of the axillary skin at the end of the radiotherapy. For the control group, this figure was 11/30 (36.66%). The difference in wet desquamation of the axillary skin in the two groups was statistically significant (P-value = 0.0369). CONCLUSION: Topical steroid (beclomethasone dipropionate spray) for skin during radiotherapy significantly reduces the risk of wet desquamation of the skin.

Adult↗

Recall of radiation pneumonitis after intrapleural administration of doxorubicin.

A 67-year-old woman developed a malignant pleural effusion 18 months after radical mastectomy and radiotherapy for carcinoma of the breast. After drainage, 30 mg of doxorubicin was instilled into the pleural cavity. Thirty-six hours later, she developed fever, dyspnoea, and erythema in the area of the previous radiotherapy field; patchy intrapulmonary opacities were evident on chest X-ray film. These features resolved over two weeks after treatment with prednisone and frusemide. We believe that this represents a radiation-recall phenomenon.

Aged↗

Care of the patient and management of complications after percutaneous coronary artery interventions.

Certain aspects of patient management are common with conventional balloon angioplasty and newer coronary artery interventions. These aspects include the evaluation of chest pain or treatment of acute vessel closure shortly after the intervention, management of the vascular access site (especially if complications occur), prevention and treatment of contrast-induced renal dysfunction, and the use of anticoagulant or antiplatelet agents after the procedure. However, some aspects of management vary among techniques. Several different drug therapies are indicated after these procedures, but pharmacologic therapy for restenosis has been largely unsuccessful. Placement of an intracoronary stent decreases the frequency of restenosis and subsequent revascularization procedures, and functional testing may be of value in some patients after coronary artery interventions. It is important for the specialist in internal medicine to have a firm working knowledge of the various aspects of care that are required because their role in management is increasing.

Angioplasty, Balloon, Coronary↗

Adriamycin and enhanced radiation reaction in normal esophagus and skin.

Clinical evaluation of 10 patients with small cell carcinoma of the lung treated with radiotherapy and periodic cycles of combination chemotherapy with cyclophosphamide, vincristine, and adriamycin showed frequent and occasionally severe esophageal and skin reactions. Eight of the 10 patients had esophagitis, four required supportive intravenous fluids, and two subsequently developed esophageal narrowing and stricture formation. Recurrent esophagitis with augmentation of injury in the recently irradiated esophagus was observed 11 times in eight of the 10 patients after cycles of chemotherapy, and contributed to the sustained toxicity seen in two patients. Dermatitis in the form of moist desquamation was observed in five of the patients at very low doses of supervoltage radiation therapy. Acute pulmonary reactions was notably absent. This combination of chemotherapy, particularly adriamycin, potentiates the effect of radiotherapy on the normal esophagus and skin, and further implicates the radiosensitizing property of adriamycin.

Carcinoma, Small Cell↗