Clinical Investigations
Place of radiotherapy in the treatment of Graves’ orbitopathy

Presented at the 39th ASTRO Meeting, Orlando, FL, October 1997.
https://doi.org/10.1016/S0360-3016(98)00405-2Get rights and content

Abstract

Purpose: The aim of this study is to evaluate the response of Graves’ orbitopathy to irradiation, and to specify the prognostic factors allowing one to better define the indications of orbital radiotherapy.

Methods and Materials: From 1977 to 1996, 199 patients received bilateral orbital irradiation delivering 20 Gy in 10 fractions and 2 weeks for a progressive Graves’ orbitopathy. 195 patients were seen between 1 and 6 months after radiotherapy. The different symptoms were studied and their response to radiation was analyzed. Factors such as age, sex, evolution of thyroid disease, history of symptoms, and previous or combined treatments were analyzed.

Results: The results revealed that 50 patients (26%) had a good or excellent response, 98 (50%) had a partial response, 37 (19%) were stable, 10 (5%) had a progression of disease. The signs that best responded to radiotherapy were the infiltration of soft tissues and the corneal involvement. Responses of proptosis or oculomotor disorders were more complete when these signs were not advanced at the time of treatment. Irradiation seemed to have the same efficacy when applied as first-line treatment or after failure of corticosteroids. Neither modality of treatment of hyperthyroidism nor thyroid status at the time of orbital irradiation modified the results. The best results were recorded for early or moderately advanced presentation (p = 0.05). Patients treated within a delay of 7 months after the beginning of the ophthalmopathy had better responses than patients treated later (p = 0.10).

Conclusion: Radiation therapy was successful in Graves’ orbitopathy by stopping the progression of disease in almost all cases, by improving the comfort of patients, by obtaining objective responses, and by avoiding surgical treatments particularly when signs were moderate.

Introduction

In Graves’ disease, ophthalmologic modifications occur frequently, however clinical expression is found in only one-third of the cases and only in 5 to 10% of the patients will the modifications evolve into a malignant form 1, 2. The mechanism of this disease might be an immunological disturbance consisting of edema of the orbital tissues with lymphocytic infiltration and deposits of mucopolysaccharides. The aspect of the patient is usually modified by inflammatory eye and lids, proptosis, and hypertrophy of oculomotor muscles. At the beginning, these abnormalities are regressive and intermittent, however, in time they can evolve into fat fibrosis and fibrous atrophy of the muscles. Optical neuropathy is partly related to compressive phenomena and to the blockage of the venous drainage during the edematous phase (3).

In its malignant form, orbitopathy has an unpredictable evolution. The onset of ophthalmopathy is within 18 months of the date of diagnosis of hyperthyroidism in 85% of cases. Ophthalmopathy can also precede the diagnosis of hyperthyroidism. The modalities of treatment of hyperthyroidism include radioactive iodine, surgery, or antithyroid drugs which may have consequences on the ophthalmologic evolution (4). The apparent relation may also be due to a chronological delay between the natural evolution of the ophthalmopathy and the effects of hyperthyroidism treatment 5, 6. Simple follow-up of discrete forms is possible thanks to spontaneous regressive evolution in 90% of cases within 18 to 24 months. In its severe forms whether untreated or treated with delay, regression is usually incomplete and leaves aesthetic and functional after-effects with lack of lid occlusion or oculomotor dysfunction. The most progressive forms can lead to blindness because of optic neuropathy. The unpredictable natural evolution of the disease makes treatment evaluations very difficult.

The treatment of Graves’ orbitopathy usually includes corticosteroids, immunosuppressors, plasmatic exchanges, surgical orbital decompression, and radiotherapy.

Radiotherapy introduced during the 1940s 7, 8 involved the orbital region and the pituitary gland; however, since 1973 (9), it has been admitted that orbital radiotherapy alone yielded equivalent results.

A modified Werner classification of the eye changes of Graves’ disease was recommended by the American Thyroid Association; in short, NO SPECS was used 10, 11. The accuracy of this classification is under discussion 12, 13 but it was found to be helpful for this retrospective study over 20 years, with heterogeneous ophthalmologic data. Associated with the measurement of ocular tension, it facilitates the description of the patient’s ophthalmologic status and comparative examinations during evolution can be made (Table 1). In this study the report of the results and a part of the discussion concerning clinical features will be organized according to the NO SPECS classification of the signs. This classification can be easily performed from a detailed ophthalmologic examination including the record of lid retraction, exophthalmometry (Hertel), examination of the ocular mobility and of the cornea, evaluation of visual acuity, fundoscopy, and ocular tension measurement.

In the course of this 20-year experience, indications for radiotherapy became clearer: for the last 10 years, the majority of the irradiated patients have been those with predominant edematous signs 14, 15. The aim of this study is to verify the pertinence of indications and to measure as well as possible the real impact of orbital radiotherapy.

Section snippets

Methods and materials

The study included 199 patients treated from 1977 to 1996 in the Radiotherapy Department of Centre Alexis Vautrin, Nancy (France) by orbital irradiation for progressive or invalidating Graves’ orbitopathy. All patients were treated in the same manner, in supine position, immobilized by a mask in thermoformed Plexiglas. Clinical target volume (CTV) was limited to the retrobulbar orbital content, sparing the lenses, the lacrymal glands, and the sella turcica. A dose of 20 Gy was delivered in 10

Patients’ characteristics

The study included 199 patients with 195 evaluable patients after the treatment. The population included 143 females (72%) and 56 males (28%). The median age was 49 years with a range of 20 to 90 years. Half of the patients were aged between 40 and 60 years (98 cases). The thyroid pathology was documented in all cases: it included a pure Graves’ disease in 175 cases, thyroiditis with hypothyroidism in 10 cases, ophthalmologic Mean’s syndrome without detectable dysthyroidism in 9 cases (5 males

Discussion

In this study, the overall results were consistent with other experiences although excellent results were less frequent 13, 17, 18, 19, 20, 21, 22, 23, 24, 25. In general, progressions were rare, ranging from 0% to 16%. Classes of signs improvement were comparable (Table 5). The issue concerning orbital irradiation therapy is still unclear: the modalities, the efficacy, the potential adverse side effects remain unresolved. These different elements were examined, with the aim of giving more

Conclusion

Given its good results and tolerance, radiotherapy can be proposed as first-line treatment for patients with a severe progressive form of thyroid ophthalmopathy. In moderate forms, it should be used alone. In marked forms, corticosteroids might improve the results but the best modality of prescription remains unknown. Some reservations can be applied to young patients because of the potential risk of radio-induced tumors and to diabetic patients who are at a higher risk of radiation

Acknowledgements

The authors express their gratitude to Dr. A. Taghian, and to M. Bollet for their helpful comments on this manuscript.

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