Is There Still a Role for Radiotherapy in Acromegaly?

Abstract

External radiotherapy (ideally 3-field radiotherapy with a daily fractional dose no higher than 1.8 Gy or conformal irradiation) has been used extensively in the treatment of acromegaly, and virtually all studies have documented a predictable but slow reduction in growth hormone (GH) excess, which is at its maximum in the first year after treatment (30–50%) and continues at an average rate of 10–15% thereafter in the long term. Therefore, achievement of ‘safe’ GH concentrations in an acceptable time interval after radiotherapy will be realized only in those patients who have lower GH concentrations prior to irradiation either as a result of mild disease or previous surgery. Recent studies have demonstrated the value of stereotactic radiotherapy (either as multiple arc X-irradiation or as ‘gamma knife’ therapy) in the post-surgical treatment of acromegaly or as salvage therapy for disease persisting after conventional external irradiation. The development of potent medical therapies for acromegaly (somatostatin analogues and the GH receptor antagonist) has called into question the role of radiotherapy in the treatment of this disease. However, even if the concept of primary, open-ended medical therapy for selected patients is accepted, reference to the success rates of surgery and response rates to somatostatin analogues indicates that approximately 10–20% of all patients with acromegaly will require consideration of radiotherapy for hormonal or tumour mass control. For these reasons, radiotherapy (both conventional external and stereotactic irradiation) continues to have a major role in controlling acromegaly in selected patients.

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

“…Patients with elevated IGF1 and normal GH/nadir GH are at risk of having persisting clinical manifestations of acromegaly and can therefore indeed benefit from the treatment with a GH receptor antagonist (24,25), while patients with elevated GH/nadir GH and normal IGF1 are at a risk of relapse of the tumour (22,23). The origin of discordance is likely to be that IGF1 and GH/nadir GH seem to represent two different aspects of acromegaly (26), and RT in general reduces rather than cures the hypersecretion of GH (3,24). Discordance is seen in up to 27% of acromegalic patients (22).…”

“…Conventional treatment of GH-secreting pituitary adenoma is primarily transsphenoidal surgery where cure or adequate control can be expected in O80% of cases when the tumour is within the sella (3). Besides the size and location of the tumour, the expertise of the surgeon is a determinant of the outcome of the surgery (4).…”

Radiation treatment strategies for acromegaly

“…In the case of pituitary adenomas, a standard dose of 160-180 cGy 4-5 times per week over 5-6 weeks for a total dose of 45-50 Gy is typically performed (Table 1). 69 Using strict remission definitions that began to be adapted in the mid-1990s of GH level below 2 ng/ ml and/or normalized IGF-I levels, most studies from the period 1997-2007 have reported remission rates of 35%-75% with CFR (Table 1). These remission rates typically take 10 years to achieve.…”

Optimalization and cost management of lanreotide-Autogel therapy in acromegaly

“…Therefore, adjuvant therapy is frequently necessary to achieve optimal IGF-I and GH control (1). External radiotherapy usually prevents tumor growth and reduces IGF-I and GH levels, but the slow onsetof action, the high incidence of hypopituitarism, and the cerebrovascular complications have minimized its role (4)(5)(6). Recent advances in the development of pharmacologic agents have permitted more efficacious medical treatment of persistent acromegaly, and these agents are also emerging as compelling options for primary therapy in selected patients (7).…”