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Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study.

BACKGROUND: Radiation dermatitis is a common side-effect of radiation therapy, but there is no current consensus about its appropriate therapy. OBJECTIVES: To compare treatment with topical 0.1% methylprednisolone vs. 0.5% dexpanthenol in a cohort of patients undergoing fractionated radiation therapy for breast cancer. METHODS: In a randomized, double-blind design, treatment was initiated at the beginning of radiation therapy and continued for 2 weeks after termination of radiation. Outcomes were compared by three different measures: clinical (symptom score), functional (transepidermal water loss, TEWL) and subjective (quality of life, QOL). RESULTS: In a preliminary cohort of untreated patients undergoing radiation therapy, clinical signs and TEWL levels increased progressively during radiation therapy, reaching highest values at 5 and 4 weeks, respectively. Although neither topical treatment reduced the incidence of radiation dermatitis, both delayed the emergence of greatest clinical and TEWL scores until approximately 6 and 5 weeks, respectively. With topical corticosteroids, clinical symptoms and TEWL were less pronounced than with dexpanthenol. Whereas general QOL improved after completion of radiation therapy, skin-related QOL declined. However, the skin-related QOL decline could be at least in part reversed by use of topical corticosteroid vs. dexpanthenol-containing emollient. CONCLUSIONS: We provide evidence that prophylactic and ongoing use of topical therapy with either topical corticosteroid or a dexpanthenol-containing emollient ameliorates, but does not prevent radiation dermatitis. Our data suggest, but do not prove, a benefit of a topical corticosteroid vs. a dexpanthenol-containing emollient. Further controlled studies with larger cohorts will be needed to determine optimal forms of topical therapy for radiation dermatitis.

Acute Disease↗

Dermatomyositis with elevated serum hyaluronate.

We report two Japanese patients with dermatomyositis whose serum hyaluronate levels were correlated with their disease activities. The diagnosis of one patient was primary idiopathic dermatomyositis, and that of the second patient was dermatomyositis associated with neoplasia. The serum hyaluronate level of the former patient was decreased by systemic corticosteroid therapy, and that of the latter patient decreased following the surgical resection of mammary carcinoma and subsequent chemotherapy. The disease activity of each patient was greatly improved after these therapies. The longitudinal measurement of serum hyaluronate concentration may be useful to estimate the disease activity of patients with dermatomyositis whose initial serum levels of hyaluronate are elevated.

Adult↗

Chronic lymphocytic alveolitis with migrating pulmonary infiltrates after localized chest wall irradiation.

In a number of patients, radiotherapy following surgery for breast carcinoma may induce radiation injury to the lungs. This has classically been divided into an early radiation pneumonitis and a late fibrosis, both confined to the irradiated lung volume. However we observed a female patient who similarly to other recent reports in the literature developed a recurring pneumonitis migrating from one lung to the other after radiotherapy for breast carcinoma. This migratory BOOP (bronchiolitis obliterans organizing pneumonia) was characterized by a lymphocytic alveolitis and responded well to corticosteroids. Clinicians should be aware of the possibility of a lymphocytic pneumonitis in both lungs after unilateral thoracic irradiation and recognize the distinctive features of fever, cough, dyspnoea and malaise in order to start an effective treatment with corticosteroids. They should also be aware of the high tendency for recurrence when tapering off.

Anti-Inflammatory Agents↗

Induction of p53 expression in skin by radiotherapy and UV radiation: a randomized study.

BACKGROUND: p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or gamma-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast. METHODS: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided. RESULTS: In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (r(s) =.78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses. CONCLUSIONS: Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatitis.

Aged↗

Bronchiolitis obliterans organizing pneumonia syndrome primed by radiation therapy to the breast. The Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires (GERM"O"P)

Reports of bronchiolitis obliterans organizing pneumonia (BOOP) occurring in women after radiation therapy for breast cancer have suggested that radiation to the lung could participate in the development of BOOP. We now describe the clinical, radiographic, functional, and bronchoalveolar lavage characteristics of this syndrome in a series of 15 patients reported to the Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P) in France. All 15 women (60 +/- 6 yr of age) fulfilled the following inclusion criteria: (1) radiation therapy to the breast within 12 mo, (2) general and/or respiratory symptoms lasting for at least 2 wk, (3) lung infiltrates outside the radiation port, and (4) no specific cause. The patients presented with fever, nonproductive cough, mild dyspnea, and peripheral alveolar opacities on chest radiograph with a characteristic migratory pattern. In five patients, BOOP was found at lung pathologic analysis. In all the patients dramatic improvement was obtained with corticosteroids, but relapses occurred in 12 patients while tapering or after stopping corticosteroids. This report demonstrates that a characteristic BOOP syndrome may occur after radiation therapy to the breast, including tangential radiation to the lung, thus suggesting that radiation therapy may prime the development of BOOP.

Aged↗

A randomized, phase III, double-blind, placebo-controlled trial of intrapleural instillation of methylprednisolone acetate in the management of malignant pleural effusion.

STUDY OBJECTIVES: To determine if intrapleural administration of methylprednisolone acetate (MA) after therapeutic thoracentesis for symptomatic malignant pleural effusion improved time to repeat thoracentesis for symptom control, quality of life (QOL), and dyspnea. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A tertiary care cancer treatment center in Edmonton, AB, Canada. PATIENT SELECTION: Patients with symptomatic pleural effusions secondary to disseminated malignancy requiring therapeutic thoracentesis for symptom control. INTERVENTIONS: Sixty-seven patients underwent ultrasound-guided therapeutic thoracentesis for management of symptomatic malignant pleural effusion. Patients were randomly and blindly assigned to either 160 mg (8 mL) of MA or 8 mL of saline solution instilled into the pleural space. Patients were followed up for 6 weeks to determine the time to repeat therapeutic thoracentesis. All patients completed the Functional Assessment of Cancer Therapy-General (FACT-G) QOL questionnaire and a dyspnea visual analog scale (VAS) at baseline and again 2 weeks later. MEASUREMENTS AND RESULTS: Thirty-three patients received MA, and 34 patients received placebo; baseline characteristics for the two groups were similar, apart from a slightly higher use of concurrent systemic therapy in the placebo group. At 6 weeks follow-up, 50% of MA-treated patients required repeat thoracentesis compared to 56% of placebo-treated patients (not significant [NS]). The mean of the individual FACT-G change scores (2 weeks - baseline) was similar in the two groups (NS). VAS scores improved for both groups over the 2-week period, but the mean change scores (2 weeks - baseline) were not statistically different. CONCLUSION: Despite previous case series describing benefit from intrapleural MA in malignant pleural effusion, this controlled study of intrapleural MA instillation did not delay reaccumulation of symptomatic pleural effusion compared to placebo, nor were differences in QOL or dyspnea observed.

Anti-Inflammatory Agents↗

Treatment of chronic idiopathic urticaria with topical steroids. An open trial.

Twenty-three patients with chronic idiopathic urticaria and 3 patients with urticaria pigmentosa received a 2-week treatment with daily application of potent topical steroid using plastic occlusion. Seventy per cent of the chronic urticaria patients had a statistically significant, immediate response, which, however, did not last until the final evaluation after 1.5 years. Relapse occurred after on average 3 weeks, but 39% reported less severity. The 3 patients with urticaria pigmentosa remained free from attacks for 6 to 9 months, after which they gradually relapsed. Two women were diagnosed during the follow-up period to have a carcinoma of the breast, and one patient developed systemic lupus erythematosus.

Administration, Topical↗

A descriptive study of pulmonary complications after postoperative radiation therapy in node-positive stage II breast cancer.

This study was conducted to assess the frequencies of symptomatic pulmonary complications following adjuvant postoperative radiotherapy using different treatment techniques in patients with Stage II node-positive breast cancer. During 1991-1993, 177 patients were referred to the Radiotherapy Department of Stockholm Söder Hospital; 144 after modified radical mastectomy and 33 after partial mastectomy. The records of these patients were studied retrospectively for clinically diagnosed radiotherapy-induced lung complications 1-7 months after treatment. Thirty-three of 138 patients (24%) irradiated after modified radical mastectomy developed pulmonary complications and 20 (14%) of these were diagnosed as severe, i.e. needing medical treatment with corticosteroids. No statistically significant difference could be found between the different electron energies used for treating the chest wall and the frequency of respiratory side-effects. Eighteen of 33 patients completed the prescribed treatment after partial mastectomy. Nine of these 18 patients (50%) developed pulmonary complications and 4 (22%) developed severe reactions. Fifteen patients received alternative treatments. With the techniques used after partial mastectomy the median central lung distance was 32 mm among the patients who experienced respiratory side-effects compared with 25 mm among the patients who were not affected (p = 0.03). This study identifies acute/subacute pulmonary side-effects as a clinically significant problem. Prospective follow-up with lung function tests, identification of risk factors, and individual lung dose volume histograms is warranted to assess the long-term implications.

Adult↗

[Migratory pneumonitis similar to bronchiolitis obliterans organizing pneumonia after conservative treatment of breast cancer: a case report].

We report the case of a 63-year-old woman who developed cough and fever with migratory lung infiltrates three months after completion of right breast irradiation following conservative surgery. Lung infiltrates were initially localized in the irradiated area, but later spread to unirradiated areas in both lungs. No cause of migratory pneumonitis other than irradiation was found, and we clinically diagnosed this case as radiation-induced migratory pneumonitis similar to BOOP, without lung biopsy. Steroid therapy resulted incomplete resolution of lung infiltrates. The reported case clearly differed from typical radiation pneumonitis. We suggest that lung irradiation might trigger the development of migratory pneumonitis with a clinical pattern similar to that of BOOP.

Anti-Inflammatory Agents↗

[Pulmonary radiation injury manifested by signs of bronchiolitis obliterans with organizing pneumonia after postoperative breast cancer radiotherapy].

A 67-year-old woman underwent surgery for cancer of both breasts (right: mastectomy, left: conserving surgery), and received 60 Gy radiation to the left postoperative breast. Three months later, cough and fever developed. A chest radiograph demonstrated infiltrative shadows in the left lung field. Transbronchial lung biopsy specimens disclosed organizing exudates in the alveolar spaces and bronchioles. After treatment with prednisolone, the clinical symptoms and radiographic infiltrates disappeared. This was a case of pulmonary radiation injury pathologically manifested by signs of bronchiolitis obliterans with organizing pneumonia.

Aged↗

[A case of migratory air space infiltration after radiation therapy for breast cancer].

A 54-year-old woman underwent conserving surgery for right breast cancer, and received a cumulative dose of 50 Gy of radiation therapy to the remaining part of the right breast. About five months after the termination of irradiation, cough and low-grade fever developed. The chest radiograph showed an infiltrative shadow in the right lung field. Organizing pneumonia was identified in the transbronchial lung biopsy specimen. After prednisolone was given to the patient the clinical symptoms and infiltrates seen in the radiograph disappeared. In the course of tapering the prednisolone dose, new infiltrative shadows developed in the upper right lung and the left lung. The histologic changes were shown by transbronchial lung biopsy to be organizing pneumonia. The increased dose of prednisolone resulted in the rapid improvement of the clinical symptoms and chest radiograph abnormalities. This case suggests that breast radiation after conserving surgery for breast cancer may cause a pathologic process similar to that of bronchiolitis obliterans organizing pneumonia.

Air↗

[Clinical study of bronchiolitis obliterans organizing pneumonia (BOOP) primed by radiation for breast cancer].

Bronchiolitis obliterans organizing pneumonia (BOOP) primed by radiation therapy for the breast cancer (BOOP-RT/BC) has been recognized recently. In this study, we reported 9 such cases and discussed steroid therapy. Mean radiation dose and interval from completion of radiation therapy to the appearance of BOOP-RT/BC were 47.3 Gy and 5.6 months respectively. BOOP-RT/BC recurrence was observed by 5 episodes in 3 of 9 cases (recurrence rate was 33%). Steroid therapy showed a remarkable improvement in both primary and recurrent disease, and no residual symptom or BOOP shadow was detectable at the end of the observation except for shadows due to radiation fibrosis. All but one patient were prescribed prednisolone, with a mean initial dose of 32.5 mg/day and a mean treatment duration of 46.7 weeks. One patient improved without treatment. No case suffered from respiratory failure which needed mechanical ventilation or was motile. Considering these findings and the fact that almost all patients are middle aged or senior women who are susceptible to osteoporosis, we conclude that steroid therapy for BOOP-RT/BC should be carefully considered.

Adult↗

[Medical therapy of pain in oncology].

The authors report data concerning their study on the incidence of pain in advanced neoplastic patients and on the natural history of this symptom. They also report their experience in the treatment of solid tumours with non steroidal antiinflammatory drugs (Zomepirac, acetylsalicylic acid, Diflunisal, Ketoprofen) with a synthetic progestin (Medroxyprogesterone Acetate employed by authors at high or at very high doses for the first time) and with morphine hydrochloride used by oral, rectal, sublingual and nasal route. The authors also indicate the correct strategy of employing these drugs and criteria of evaluating their effectiveness.

Anti-Inflammatory Agents↗

[Bullous lichen sclerosus after radiotherapy].

BACKGROUND: Bullous lichen sclerosus is an uncommon observation after radiotherapy and can be misdiagnosed as a radiodermitis or recurrence of the neoplasia. CASE REPORT: Two women developed bullous lichen sclerosus after radiotherapy. The delay after radiotherapy was 4 months and 10 years respectively. Irradiation dose was 60 and 64 grays. The lesions covered more than the irradiated zone in one case. Stabilization or regression of the lesions was obtained with cases I topical corticosteroids, with acitretine in one case. DISCUSSION: These cases, and similar cases reported in the literature, underline the fact that the condition has only been reported in women. This is probably because of the nature of the neoplasias treated (breast cancer in 20 cases and cervical cancer in 1). The delay to onset of the skin lesions are quite variable. Lichen sclerosus or morphea may be observed in the irradiated zone but may also appear at a distance. These lesions are not associated with recurrence of the initial cancer. As no association between breast cancer and localized sclerodermia has been found, the causal role is probably played by radiotherapy, producing a Koebner phenomena in predisposed tissue.

Administration, Topical↗

Postradiation morphea.

We describe a 54-year-old woman who developed right breast morphea after radiotherapy following a lumpectomy for infiltrating lobular carcinoma. Skin biopsy confirmed the histological features of morphea. Treatment was initiated with both topical and intralesional steroid, resulting in marked improvement. Morphea following radiotherapy is an infrequently recognized phenomenon. However, when diagnosed early it may be effectively managed with local steroid treatment.

Administration, Topical↗