Multicenter Evaluation of the Effect of Upfront Radiosurgery on Residual Growth Hormone-secreting Pituitary Adenoma
Multicenter Evaluation of the Effect of Upfront Radiosurgery on Residual Growth Hormone-secreting Pituitary Adenoma
In this study, the investigators hypothesize that upfront gamma knife radiosurgery with drug
 therapy is superior in the treatment of growth hormone-secreting pituitary tumors after
 primary surgical treatment compared with the drug therapy alone. This study can provide
 useful clinical information in the treatment of patients with acromegaly.
Acromegaly is often caused by growth hormone (GH)-secreting pituitary adenoma and causes
 anatomic changes in the body and various metabolic disorders caused by increased GH and
 insulin-like growth factor-1 (IGF1). Surgical treatment of pituitary tumors is the preferred
 standard of care, but only 40-70% of patients can be treated with surgical treatment alone.
 In many cases, complete resection of the tumor is not possible and the hormone imbalance
 persists after surgery. After surgical treatment, several additional treatments are needed to
 prevent hypersecretion of GH and to normalize blood levels of IGF-1.

 As first-line treatment after surgical resection, there are typically drug therapy and
 radiation therapy. The most common used drugs are octreotide and lanreotide, which are growth
 hormone analogues. However, according to the recent guideline, the endocrine remission rate
 obtained from post-operative drug therapy is only 17-35%. Although clinical trials are
 underway for new drugs, the burden of expensive drug costs, recurrence during drug
 withdrawal, and drug side effects remains major drawbacks. There is a need for therapeutic
 intervention to reduce the dose and duration of therapy, to prevent tumor recurrence, and to
 achieve rapid endocrinologic remission.

 Stereotactic radiosurgery (SRS), such as gamma knife radiosurgery, has been actively
 introduced worldwide to control residual pituitary tumors and has been applied to more than
 200 cases of intractable acromegaly. The effect of SRS on endocrine remission in patients who
 did not receive endocrine therapy was confirmed in the literature. In a study of 136 patients
 who underwent preoperative radiotherapy followed by more than 5 years of follow-up, 65.4% of
 patients reported endocrine remission. According to the recently published meta-analysis, SRS
 showed 93-100% tumor growth control and size reduction within 5 to 10 years after surgery.
 The endocrinologic remission rate was reported to be 40-60% at 5 years.

 To date, SRS has been recommended for the treatment of growth hormone - secreting pituitary
 tumors in cases where surgical removal is not feasible from the beginning or if drug
 treatment fails after surgical removal. Only the retrospective study of SRS was performed and
 no prospective study was conducted at all. However, many institutions already prefer
 preemptive SRS treatment for residual tumor after surgery and have been practiced in many
 patients. Therefore, prospective clinical trials are needed to establish the basis for
 upfront SRS and establish the treatment strategy for patients who do not have endocrine
 remission after surgical treatment of GH secretory pituitary tumor.
Inclusion Criteria:

 -  Among patients with acromegaly due to growth hormone secreting pituitary adenoma who
 underwent primary surgical resection, patients who fail to achieve endocrinologic
 remission at 3 months after surgery.

 -  On brain MRI scan at 3months after surgery, residual tumor is confirmed by clinicians

 -  the definition of endocrinologic remission

 1. random growth hormone level < 2.5 ug/L

 2. normalization of age-matched insulin growth factor-1 level

 Exclusion Criteria:

 -  patients with contraindication of stereotactic radiosurgery; e.g. pregnancy or
 planning pregnancy, or claustrophobia

 -  recurrent pituitary adenoma

 -  limited life expectancy due to systemic disease; e.g. malignant tumor, genetic
 disease, and terminal stage of renal or hepatic failure

 -  disability to clinic visit due to postoperative complications