Y Greenman1, O Cooper2, I Yaish3, E Robenshtok4, N Sagiv3, T Jonas-Kimchi5, X Yuan6, A Gertych6, I Shimon4, Z Ram7, S Melmed2, N Stern8. 1. Institute of Endocrinology, Metabolism and HypertensionTel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel yonagr@tlvmc.gov.il. 2. Pituitary CenterCedars Sinai Medical Center, Los Angeles, California, USA. 3. Institute of Endocrinology, Metabolism and HypertensionTel Aviv Sourasky Medical Center, Tel Aviv, Israel. 4. Institute of Endocrinology and MetabolismRabin Medical Center, Petah Tikva, Israel Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel. 5. Neuroradiology UnitTel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel. 6. Department of PathologyCedars Sinai Medical Center, Los Angeles, California, USA. 7. Department of NeurosurgeryTel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel. 8. Institute of Endocrinology, Metabolism and HypertensionTel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel.
Abstract
OBJECTIVE: Clinically nonfunctioning pituitary adenoma (NFPA) remains the only pituitary tumor subtype for which no effective medical therapy is available or recommended. We evaluated dopamine agonist (DA) therapy for preventing growth of postsurgical pituitary tumor remnants. DESIGN: The study design included historical cohort analysis of clinical results at two pituitary referral centers with different standard practices for postoperative NFPA management: DA therapy or conservative follow-up. METHODS: Seventy-nine patients followed for 8.8±6.5 years were treated with DA, initiated upon residual tumor detection on postoperative MRI (preventive treatment (PT) group, n=55), or when tumor growth was subsequently detected during follow-up (remedial treatment (RT) group, n=24). The control group (n=60) received no medication. Tumoral dopamine and estrogen receptor expression assessed by quantitative RT-PCR and immunostaining were correlated with response to treatment. RESULTS: Tumor mass decreased, remained stable, or enlarged, respectively, in 38, 49, and 13% of patients in the PT group, and in 0, 53, and 47% of control subjects; shrinkage or stabilization was achieved in 58% of enlarging tumors in the RT group, P < 0.0001.Fifteen-year progression-free survival rate was 0.805, 0.24, and 0.04, respectively, for PT, RT, and control groups (P<0.001). About 42% of patients in the control group required additional surgery or radiotherapy, compared with 38 and 13% subjects in the RT and PT groups, respectively (P=0.002). Outcome measures were not related to NFPA D2R abundance. CONCLUSIONS: Dopamine agonist therapy in patients with NFPA is associated with decreased prevalence of residual tumor enlargement after transsphenoidal surgical resection.
OBJECTIVE: Clinically nonfunctioning pituitary adenoma (NFPA) remains the only pituitary tumor subtype for which no effective medical therapy is available or recommended. We evaluated dopamine agonist (DA) therapy for preventing growth of postsurgical pituitary tumor remnants. DESIGN: The study design included historical cohort analysis of clinical results at two pituitary referral centers with different standard practices for postoperative NFPA management: DA therapy or conservative follow-up. METHODS: Seventy-nine patients followed for 8.8±6.5 years were treated with DA, initiated upon residual tumor detection on postoperative MRI (preventive treatment (PT) group, n=55), or when tumor growth was subsequently detected during follow-up (remedial treatment (RT) group, n=24). The control group (n=60) received no medication. Tumoral dopamine and estrogen receptor expression assessed by quantitative RT-PCR and immunostaining were correlated with response to treatment. RESULTS:Tumor mass decreased, remained stable, or enlarged, respectively, in 38, 49, and 13% of patients in the PT group, and in 0, 53, and 47% of control subjects; shrinkage or stabilization was achieved in 58% of enlarging tumors in the RT group, P < 0.0001.Fifteen-year progression-free survival rate was 0.805, 0.24, and 0.04, respectively, for PT, RT, and control groups (P<0.001). About 42% of patients in the control group required additional surgery or radiotherapy, compared with 38 and 13% subjects in the RT and PT groups, respectively (P=0.002). Outcome measures were not related to NFPA D2R abundance. CONCLUSIONS:Dopamine agonist therapy in patients with NFPA is associated with decreased prevalence of residual tumor enlargement after transsphenoidal surgical resection.
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