Low- vs. high-dose radiotherapy in Graves’ ophthalmopathy: a retrospective comparison of long-term results

Abstract

Purpose Radiotherapy represents an effective treatment option in Graves’ ophthalmopathy (GO), leading to palliation of clinical symptoms. However, there are only a limited number of trials comparing the effectiveness of low- vs. high-dose radiotherapy. Methods We analyzed 127 patients treated with radiotherapy for stage 3/4 GO (NOSPECS classification). Patients were treated with single doses of 2.0 Gy (cumulative dose 20 Gy) until 2007, afterwards a single dose of 0.8 Gy (cumulative dose 4.8 Gy) was applied. With a median follow-up-time of 9.0 years, the treatment efficacy (overall improvement, sense of eye pressure, lid edema, ocular motility, exophthalmos, subjective vision, and diplopia) and adverse effects were analyzed by a standardized survey. Results Overall, 63.8% described improvement of symptoms after radiotherapy. No significant differences in overall treatment response and improvement of main outcome measures between low- or high-dose radiotherapy treatments are detectable, while low-dose radiotherapy leads significantly more often to retreatment (13.1% vs. 1.7%, p = 0.016). The main independent predictor of treatment response is the presence of lid edema (odds ratio, OR, 3.53; p = 0.006). Conclusion At long-term follow-up, the majority of patients reported palliation of symptoms with limited adverse effects, suggesting clinical effectiveness of radiotherapy for amelioration of GO symptoms independent of low- or high-dose radiotherapy.

Reply to: Longer treatment time and lower radiation doses—an alternative for Graves’ ophthalmopathy treatment

“…Importantly, in a post-hoc analysis, when excluding the patients who were treated with a second course of radiotherapy, the difference in reported side effects between the low- and high-dose arm lost statistical significance ( p = 0.215). Thus, we have presented a possible and plausible reason for the increased rate of adverse effects [ 2 ]. Nevertheless, we cannot fully exclude further radiobiologic, methodologic, or unknown factors, which cannot be proven by our data.…”

“…This may include the unexpected observation of increased side effects in the low-dose arm, for which we provide an explanation in the form of increased second treatment courses, but which might only be definitively clarified by future studies on radiotherapy in Graves’ orbitopathy. While a prospective randomized design of course provides the best level of evidence and largely excludes potential biases, this has rarely been feasible in Graves’ orbitopathy [ 5 , 6 ], especially not for such long follow-up periods, as presented in our trial [ 2 ]. Therefore, other study designs have to be pursued to address the important areas of uncertainty.…”