• Chapter 5

    The purpose of the literature review in Chapter 5 was to determine the incidence of RON in acromegaly, and to establish risk factors associated with its occurrence. In the time period 1966-2002, 57 published series could be retrieved from Medline and Embase, in which the occurrence of RON after fractionated radiation therapy in acromegalic patients was reported. In this series RON developed in 25 out of 1845 patients yielding an incidence of 1.36%. Based on RON cases in these series and 12 case reports, information on total radiation dose and radiation fraction size was available in 32 patients who developed RON. RON was bilateral in 71% and unilateral in 29% of these patients. Visual acuity was reduced to less than 2/10 in 35 of 41 RON affected eyes. It is generally postulated that most cases of RON occur within 18 months after radiation therapy. In this review 27% of patients with RON developed this complication more than 18 months after radiation therapy with a range to 120 months. A radiation fractionation size greater than 2 Gray and/or a total radiation dose greater than 50 Gray are suggested to be risk factors for RON in general. In this review 50% of the patients with RON were treated with an assumed safe radiation therapy schedule. This suggests that other risk factors, including vascular compromise and GH-secreting pitui-tary adenoma itself contribute to RON occurrence. It was not possible to draw definite conclusions about age as a possible risk factor for RON development as suggested by others. Seventy-eight percent of the patients, in whom gender was reported, were female. Since the occurrence of acromegaly is not increased in females and it is unlikely that females are treated more frequently with radiation therapy than males, this would suggest that females are at an increased risk for the development of RON.
    RON is essentially considered as a diagnosis by exclusion. Using MRI with gadolineum, enhancement of the retro-orbital optic nerves and chiasm usually occurs probably as a consequence of a disrupted blood brain barrier within the optic nerves. This diagnostic approach is currently proposed to improve the diagnosis of RON. Until now there is no effective treatment for RON.
    With the current dose-fractionation policy in our department – 45 Gray in 1.8 Gray fractions are assumed “safe”- and with the introduction of advanced and emer-ging radiation delivery techniques, it is expected that these implementations will probably further decrease this serious side-effect of radiation therapy.

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