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A Critical Analysis of Pituitary Tumor Shrinkage during Primary Medical Therapy in Acromegaly

Department of Medicine, Cedars-Sinai Research Institute, David Geffen School of Medicine, University of California (S.M., V.B.), Los Angeles, California 90048; Zynx Health, Inc. (R.S., D.R.), Los Angeles, California 90024; Department of Medicine, Oregon Health & Science University (D.C.), Portland, Oregon 97205; Department of Medicine, Massachusetts General Hospital (A.K.), Boston, Massachusetts 02114; Department of Endocrinology, Hospital Bicetre (P.C.), Paris, France 94275; Department of Medicine, University of Virginia Health Science Center (M.L.V.), Charlottesville, Virginia 22901; Department of Medicine, New York University Medical Center (D.K.), New York, New York 10010; and Department of Medicine, Veterans Administration Medical Center, University of Michigan (A.B.), Ann Arbor, Michigan 48105

Address all correspondence and requests for reprints to: Dr. Shlomo Melmed, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048. E-mail: melmed{at}csmc.edu.

Context: Somatostatin analogs have been successfully used to treat patients with GH-secreting pituitary adenomas because they are safe, effective, and usually well tolerated. The results of studies evaluating acromegaly treatment with the somatostatin receptor ligands (SRLs), octreotide and lanreotide, have supported the use of these agents for primary medical therapy before or as an alternative to traditional interventions of surgery and radiotherapy in selected cases.

Evidence Acquisition: We therefore undertook a systematic literature overview to characterize the results of studies involving primary therapy with somatostatin analogs and their effects on pituitary tumor size. Because most studies in which pituitary tumor shrinkage has been assessed involve uncontrolled, open-label, prospective trials or retrospective case series, the lack of a control arm does not permit pooling of data in a metaanalytic fashion to determine tumor size reduction. Therefore, this systematic review was designed to document and stratify data by study design, summarize therapeutic regimens and patient characteristics, assess the percentage of patients showing changes in tumor size, and calculate the weighted average effect on size reduction.

Evidence Synthesis: Overall, for patients who experience significant shrinkage, an approximately 50% decrease in pituitary mass is achieved when a somatostatin analog is used exclusively or before surgery or radiotherapy. Fourteen studies (n = 424) provided a definition of significant tumor shrinkage, and the results showed that 36.6% (weighted mean percentage) of patients receiving primary SRL therapy for acromegaly experienced a significant reduction in tumor size. The weighted mean percent reduction in tumor size was 19.4% for those studies in which all patients received SRLs and change in tumor size was reported for all patients.

Conclusions: Clinical implications are discussed for patients in whom tumor size control with SRLs is an important objective, typically those who have failed surgery or are being treated with primary medical therapy with large tumors.

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