Acromegaly Radiation Therapy
Radiation was typically used to control tumor growth and to obtain eventual biochemical remission1. 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. 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 current AACE guidelines2.
On this page:
- 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 <5 ng/mL within 10 years posttreatment3,4.
Concomitant administration of pharmacologic agents is frequently necessary to effectively reduce GH levels or to effectively reduce GH levels until radiation achieves maximum therapeutic effects1.
Side effects of radiation can be serious, including:
- Panhypopituitarism-thyroid deficiencies, hypogonadism, and abnormal adrenal function5,6
- Damage to the optic nerve (in 1.5% of patients)7
- Development of second brain tumors (in 1.3% of patients)7
- Late necrosis of the brain, resulting in confusion and memory deficit8
| GH Levels After Radiotherapy4 | ||
|---|---|---|
| Postradiotherapy | 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
IGF-1 levels are rarely normalized, even when GH levels are reduced to <5 ng/mL.
- In one survey by Barkan et al (1997) only 2 of 38 (5%), patients treated with radiation gained normal IGF-1 levels9
- For the remaining 36 patients, IGF-1 remained elevated despite a mean plasma GH of 4.6 ng/mL
Postradiation Plasma GH and IGF-1 Levels
*P<0.01.
†P<0.05 (vs preradiation value).
Adapted with permission from Barkan et al9.
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 <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
- 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
- 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
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 (eg, 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 fails2.
Learn about treatment advantages and disadvantagesImportant Safety Information
Carcinoid Syndrome:
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and for the long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors in patients in whom initial treatment with immediate release Sandostatin® (octreotide acetate) Injection has been shown to be effective and tolerated.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (62%), gastrointestinal disorders (14% to 38%), and injection-site pain (20% to 50%). Hypoglycemia (4%), hyperglycemia (27%), sinus bradycardia (19%), conduction abnormalities (9%), and arrhythmias (3%) have been reported.
The controlled clinical trials that support the marketing clearance for Sandostatin® LAR Depot did not include determination of effect on tumor size or rate of growth. Sandostatin® LAR Depot is not indicated for tumor shrinkage.
Acromegaly
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. The goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (52%), gastrointestinal disorders (7% to 36%), and injection-site pain (2% to 11%). Hypoglycemia (2%), hyperglycemia (15%), and hypothyroidism (2%) have been reported. While not measured in acromegalic patients receiving Sandostatin® LAR Depot, ECG changes have been reported in patients receiving immediate release Sandostatin® Injection; the degree to which these abnormalities are related to octreotide acetate is not clear, as many acromegalics have cardiovascular disease. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
