Eighty-two consecutive patients with moderate-to-severe and active Graves' ophthalmopathy were randomly treated with orbital radiotherapy combined with either oral (prednisone; starting dose, 100 mg/d; withdrawal after 5 months) or iv (methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals) glucocorticoids. The two groups did not differ for age, gender, duration of hyperthyroidism and ophthalmopathy, prevalence of smokers, thyroid volume, and pretreatment ocular conditions. Both groups of patients received radioiodine therapy shortly before treatment for Graves' ophthalmopathy. Follow-up lasted for 12 months. A significant reduction in proptosis (from 23.2 +/- 3.0 to 21.6 +/- 1.2 mm in the iv glucocorticoid group, P < 0.0001; and from 23 +/- 1.8 to 21.7 +/- 1.8 mm in oral glucocorticoid group, P < 0.0001) and in lid width (from 13.3 +/- 2.5 to 11.8 +/- 2.2 mm, and from 13.6 +/- 2.0 to 11.5 +/- 1.9 mm, respectively; P < 0.001 in both cases) occurred, with no difference between the two groups. Diplopia significantly improved in both groups: it disappeared in 13 of 27 (48.1%) iv glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral glucocorticoid patients (P < 0.03). The degree of amelioration of diplopia did not significantly differ between the two groups (P = 0.82). Optic neuropathy improved in 11 of 14 iv glucocorticoid (P < 0.01) and only in 3 of 9 oral glucocorticoid (P = 0.57) patients, with no significant difference in these outcomes. The Clinical Activity Score decreased from 4.5 +/- 1.2 to 1.7 +/- 1.0 (P < 0.0001) in the iv glucocorticoid group and from 4.2 +/- 1.1 to 2.2 +/- 1.2 (P < 0.0001) in the oral glucocorticoid group; final Clinical Activity Score was significantly lower in iv glucocorticoid than in oral glucocorticoid patients (P < 0.01). By self-assessment evaluation, 35 (85.3%) iv glucocorticoid and 30 (73.2%) oral glucocorticoid patients reported an improvement of ocular conditions (P = 0.27). Overall, both treatments produced favorable effects in most patients, but responders in the iv glucocorticoid group (36 of 41, 87.8%) were more than in the oral glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv glucocorticoid treatment was better tolerated than oral glucocorticoid treatment. Side effects occurred in 23 (56.1%) iv glucocorticoid and 35 (85.4%) oral glucocorticoid patients (P < 0.01); in particular, cushingoid features developed in 5 of the former and 35 of the latter patients. One iv glucocorticoid patient had severe hepatitis of undetermined origin at the end of glucocorticoid treatment, followed by spontaneous recovery. In conclusion, high-dose iv glucocorticoid and oral glucocorticoid (associated with orbital radiotherapy) are effective in the management of severe Graves' ophthalmopathy, but the iv route seems to be more effective and better tolerated than the oral route and associated with a lower rate of side effects.

We investigated the long-term side-effects of orbital radiotherapy (OR) in 204 patients with Graves' ophthalmopathy (GO), irradiated from 1972-1996 [44 by cobalt unit (CU) and 160 by linear accelerator (LA), mostly combined with glucocorticoids], with a 5- to 25-yr follow-up (median, 11 yr). Cataract was observed in 21 patients (10%) 3-21 yr after OR, with a higher (not significant) prevalence in CU-treated patients (18% vs. 8% in LA-treated patients). The prevalence of cataract was higher, although not significantly, in CU-treated patients aged less than 60 yr, but not in LA-treated patients, compared with the general population. Mild, asymptomatic retinopathy was observed in 1 of 7 patients (14%) with diabetes and hypertension, in 1 of 31 patients (3%) with hypertension alone, and in 0 of 11 patients with diabetes alone. No tumors were observed in 157 patients submitted to computed tomography scan of orbital and adjacent regions. In conclusion, OR is a safe treatment, not associated with an increased frequency of cataract, provided a high voltage apparatus is used. Hypertension, especially if associated with diabetes, may represent a relative contraindication, as it may cause retinopathy. Although no secondary tumors were detected, due to the long latency of radiation-induced tumors, OR should be restricted to patients older than 35 yr.

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Combined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side-effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty-four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20-30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5.9; the final score was 3.2, with a change of -2.7 (P less than 0.001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra-ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side-effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple or recurrent squamous cell skin carcinoma is a rare tumor in the aged. These patients are currently treated with 5-fluorouracil (5-FU) cream as a local chemotherapy; in cases in which the disease progresses, few treatments are available. Two reports deal with the treatment of progressive squamous cell skin carcinoma with systemic 5-FU, but in only eight patients age less than 70 years. We prospectively investigated oral 5-FU therapy in 14 consecutive patients (average age 76 1/2 years) with histologically proven squamous cell skin carcinoma. The disease was aggressive, multiple, or recurrent and had not been eradicated by surgery, radiation therapy, topical 5-FU cream, and non-5-FU chemotherapy. Oral 5-FU was administered as mannitol-coated 5-FU tablets at the daily dose of 175 mg/m2 for 3 weeks every 5 weeks. Toxicity, effectiveness, quality of life, and compliance to therapy were evaluated. Total cycles amounted to 55 (range: 2-6, mean: 4 for each patient) at an average dose intensity of 740 mg/m2/week for from 12 to 36 weeks. Only gastrointestinal toxicity World Health grade I occurred. Quality of life and compliance to therapy were 90%. Therapy induced measurable improvement in nine patients (64.3%): two partial remissions (14.3%), three minimal remissions (21.4%), and four arrests of disease (28.6%) with a median duration of 30+ months. The study ended because of a lack of patients. We can conclude that, if elderly patients require chemotherapy because of progressive multiple or advanced squamous cell skin carcinoma, appreciable results may be obtained with oral 5-FU as a single agent.