Radiation Therapy
Radiation was typically used to control tumor growth and to obtain eventual biochemical remission (1). However, conventional fractionated radiation may take as long as 10 to 20 years to be fully effective in achieving biochemical control. Thus, the AACE guidelines (PDF 93KB) suggest radiation is appropriate as adjunctive therapy. Recent, more focused methods of delivering radiation, such as gamma knife, proton beam, and linear accelerator (Linac) have not been compared with conventional radiation, but initial reports suggest they may yield biochemical remission earlier than conventional radiation. Patients should be treated with medical therapy while awaiting the biochemical effects of radiation, in order to provide optimal disease control. Conventional radiation is associated with failure of the normal pituitary in up to 100% of patients with long-term follow-up, while 28% of patients developed hormone deficiency post gamma knife. This is an important contributing factor to the placement of radiation below medical therapy in the new AACE guidelines (2).
- Evaluating the Risks and Benefits
- IGF-1 Levels Rarely Normalized With Radiation
- Radiation Treatment Options
Evaluating the Risks and Benefits
When surgery fails or is contraindicated, radiation therapy can be considered. Factors for consideration in the use of radiation for acromegaly include:
- Delayed therapeutic effects — approximately 50% of patients achieve a reduction of GH circulating levels to less than 5 ng/mL within 10 years posttreatment (3, 4).
- Concomitant administration of pharmacologic agents is frequently necessary (1) to effectively reduce GH levels or to effectively reduce GH levels until radiation achieves maximum therapeutic effects.
- Side effects of radiation can be serious, including:
GH Levels After Radiotherapy (4)
| Post Radiotherapy | GH < 5 ng/mL | GH < 10 ng/mL |
|---|---|---|
| 1 yr | 2% | 10% |
| 5 yr | 28% | 60% |
| 10 yr | 58% | 73% |
| 15 yr | 72% | 80% |
| 20 yr | 88% | 90% |
IGF-1 Levels Rarely Normalized with Radiation
However, IGF-1 levels are rarely normalized, even when GH levels are reduced to <5 µg/L.
- In one survey by Barkan et al (1997) (9) only 2 of 38 (5%), patients treated with radiation gained normal IGF-1 levels.
- For the remaining 36 patients, IGF-1 remained elevated despite a mean plasma GH of 4.6 µg/L.
Post Radiation Plasma GH and IGF-1 Levels
Some studies indicate that radiotherapy may not be effective in lowering GH to safe levels in many patients, even after a long period of time. For example, Thalassinos et al reported data on 46 acromegalic patients who received external beam megavoltage radiotherapy and were followed for a mean of 7.6 years (range 2 to 22 years) (10).
- Following radiotherapy, basal GH levels decreased from a mean of 30.9 ng/mL to 11.5 ng/mL at 10 years of follow up.
- Only 27% of the patients (10/48) showed a decrease of GH levels to less than 2.5 ng/mL at their latest follow up.
- Thus, while radiotherapy was effective for decreasing GH hypersecretion, it seldom reduced GH levels to <2.5 ng/mL (10).
- Normalization of IGF-1 was achieved in only 29% (4/14) of the patients followed for at least 10 years and with IGF-1 levels available (10).
- Finally, 50% (5/10) of the patients followed for more than 10 years developed insufficient secretion of at least 1 of the anterior pituitary hormones (10).
Radiation Treatment Options
Radiation therapy may be provided as conventional (external-beam) irradiation, administered over a period of 4 to 6 weeks. Other approaches include:
- Heavy-particle (proton-beam) radiation
- Stereotactic radiosurgery (e.g., gamma-knife) using high-dose focused radiation
Because of its drawbacks and limitations (delayed effects, significant side effects, infrequent normalization of IGF-1, etc.), conventional radiotherapy may not be a desirable treatment option. Current AACE guidelines for the treatment of acromegaly state that radiation is recommended only if medical treatment fails (2).
References
- Consensus statement: benefits versus risks of medical therapy for acromegaly. Acromegaly Therapy Consensus Development Panel. Am J Med. 1994;97(5):468-73.
- AACE Medical Guidelines for Clinical Practice for the diagnosis and treatment of acromegaly. Endocr Pract. April 2004;10(3):213-25.
- Melmed S, Ho K, Klibanski A, et al, Clinical review 75: Recent advances in pathogenesis, diagnosis, and management of acromegaly. J Clin Endocrinol Metab. 1995;80(12):3395-402.
- Eastman RC, Gorden P, Glatstein E, et al, Radiation therapy of acromegaly. Endocrinol Metab Clin North Am. 1992;21(3):693-712.
- Constine LS, Woolf PD, Cann D, et al, Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med. 1993;328(2):87-94.
- Sheaves R, Pituitary irradiation for acromegaly., in Treating Acromegaly, J.A.H. Wass, Editor. 1994, Journal of Endocrinology Ltd: Bristol, UK. p. 103-108.
- Brada M, Rajan B, The toxicity of radiotherapy in the treatment of pituitary adenoma, in Treating Acromegaly, J.A.H. Wass, Editor. 1994, Journal of Endocrinology Ltd: Bristol, UK. p. 127-132.
- Jones A, Complications of radiotherapy for acromegaly, in Treating Acromegaly, J.A.H. Wass, Editor, Journal of Endocrinology Ltd: Bristol, UK. p. 115-125.
- Barkan AL, Halasz I, Dornfeld KJ, et al, Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab. 1997;82(10):3187-91.
- Thalassinos NC, Tsagarakis S, Ioannides G, et al, Megavoltage pituitary irradiation lowers but seldom leads to safe GH levels in acromegaly: a long-term follow-up study. Eur J Endocrinol. 1998;138(2):160-3.
