Stereotactic radiosurgery may yield favorable remission response rates in patients with acromegaly with a low rate of adverse events, according to data published in the Journal of Clinical Endocrinology and Metabolism.
- Surgical resection is currently the primary treatment for patients with acromegaly, according to researchers. The rates of endocrine remission relate to tumor size, degree of invasiveness and surgical expertise, the researchers wrote.
They conducted a retrospective review of 136 patients (mean age, 44 years) withacromegaly treated with stereotactic radiosurgery at the University of Virginia. Gamma Knife radiosurgery data were collected from 1989 to 2012.
Follow-up data at 61.5 months indicated that 65.4% of the patients reached remission of acromegaly, with a mean time to remission of 27.5 months.
Specifically, there was a 31.7% remission rate at 2 years, 64.5% at 4 years, 73.4% at 6 years and 82.6% at 8 years after radiosurgery, according to data.
After the withdrawal of growth hormone or insulin-like growth factor I medications, patients with an oral glucose tolerance test GH level <1 ng/mL or normal IGF-I were considered to be in remission, researchers wrote.
Favorable prognostic factors for remission included higher radiation combined with maximum dose and lower initial IGF-I levels, according to data.
“Hypothalamic-pituitary dysfunction is the most common intermediate to late complication of [stereotactic radiosurgery] of pituitary adenomas. In our series, 31.6% patients developed new hormone deficiency at a median of 50.5 months following radiosurgery,” researchers wrote.
Two patients (1.5%) developed panhypopituitarism. Other risk factors for pituitary hormone deficiencies included a margin dose >25 G and tumor volume >2.5 mL. An adverse radiation effect was observed in one patient, visual deterioration in four, and new oculomotor nerve palsy in one. Seven patients who reached remission after surgery developed a recurrence of the disease at 42 months.
John D. Carmichael
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Acromegaly is a difficult disease to treat in many cases. The patients’ clinical experiences range from those which are mild and straight-forward to those with aggressive tumors, very challenging biochemistry, and disease attributes that require multimodal therapy. It’s good to see a large study like this reporting on radiotherapy outcomes and safety, which is one part of our treatment armamentarium.
The response rates that they report are encouraging in terms of the biochemistry because there are patients who do require more aggressive treatment than just surgery or medication.
I think the difficulties of such a study are that long-term follow-up is challenged with treatment performed through a tertiary referral center, and as they acknowledge in their paper, they rely on other endocrinologists’ data in some cases and are unable to obtain complete data sets. This might be one of the shortcomings of the study: that sometimes, the tests that you want to complete don’t always get done in terms of both safety assessments and assessments of recurrence.
In general, they compare their findings to both prior radiosurgery techniques and to prior conventional radiotherapy. I think that many people are hoping that the gamma knife radiosurgery will have significantly improved response rates and a better safety profile in terms of hypopituitarism and damage to adjacent structures.
The authors have shown that their response rates are satisfactory enough to consider radiosurgery as a viable treatment. Unfortunately, the hypopituitarism demonstrated in these patients is comparable to prior reports of radiotherapy-induced hypopituitarism and practitioners are concerned about this adverse effect. These data are not going to make gamma knife radiosurgery more appealing to those who are concerned about the effects of hypopituitarism. The use of radiotherapy is a divisive topic in the treatment of patients with acromegaly and physicians have very strong opinions about the use and the timing of this mode of therapy. Some may utilize it earlier on in the care of patients, so that a patient will directly be treated with radiosurgery after failed transsphenoidal surgery, as many of the patients were in this study. Alternatively, one may use radiosurgery only in those resistant to medical therapy and unable to gain biochemical or tumor control.
The follow-up for patients treated with radiosurgery does require longer duration of observation and while this group has some of the longest follow-up compared to other studies, nevertheless more time is required for safety assessments such as development of secondary tumors and hypopituitarism.
- John D. Carmichael, MD
- Assistant Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism at the David Geffen School of Medicine at the University of California, Los Angeles; and
Staff Physician of Endocrinology/Metabolism at Cedars-Sinai Medical Center
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