Analysis of Disease Control in Acromegaly Treated With Radiosurgery
Object. Stereotactic radiosurgery (SRS) has emerged as an adjuvant radiation-based therapy for pituitary adenomas. Here, the authors present a systematic analysis of SRS for growth hormone–secreting adenomas to characterize the efficacy of SRS in the treatment of acromegaly.
Methods. A comprehensive search of the English language literature revealed 970 patients with new, recurrent, or persistent acromegaly that had been treated using SRS along with assessable and quantifiable outcome data. Articles published between June 1998 and September 2009 were included in the analysis. Patient outcome data were aggregated and investigated based on tumor size, radiosurgery dose, and clinical outcomes both with and without medication.
Results. The overall disease control rate without medication was 48%–53%, and the overall disease control rate with or without medication was 73%. The overall mean duration of the reported follow-up was 48.5 ± 25.8 months. The mean overall tumor volume in this analysis was 2.11 ± 1.16 cm. The Pearson product-moment correlation coefficient for tumor volume and cure rate was not significant (r = 0.0668, p = 0.8546).
Conclusions. Data from this analysis suggest that tumor size may not be a significant prognostic factor in disease control after radiosurgery for acromegaly. The overall disease control rate was approximately 48% without suppressive medications after radiosurgery for acromegaly. With the advancement of increasingly sophisticated stereotactic planning and tumor targeting, the precision of radiosurgery may continue to improve in the treatment of acromegaly.
Acromegaly is an endocrine disorder characterized by the excess production of GH, generally by hypersecreting pituitary adenomas, resulting in progressive somatic disfigurement and increased morbidity and death due to the systemic effects of organ overgrowth. The control of GH and its primary mediator IGF-I has been associated with a reduction in the mortality risk.
Historically, the primary treatment for GH-producing pituitary adenomas has been resection and/or medical management. The reported rates of biochemical cure following surgical removal has varied based on tumor size and the definition of a cure, but is generally considered to range from 75%–95% for microadenomas and 40%–68% for macroadenomas. Note that the latter lesion type affects the majority of patients. Remission rates achieved using purely medical therapies have improved over the past decade, with several studies reporting biochemical control in approximately 70% of patients. But current medical therapies, such as somatostatin analogs and GH antagonists, must be taken lifelong and are costly.
Radiation treatment has typically been used when surgery is not an option or has left residual tumor and/or when medical therapy has failed. Stereotactic radiosurgery has largely supplanted traditional external beam radiation therapy for pituitary adenomas. Through the use of stereotactic precision, beams of radiation are delivered specifically to the target tissue, thereby avoiding surrounding normal neuronal tissue. The efficacy of SRS as well as surgery for the treatment of GH-secreting pituitary tumors is debated largely because of inconsistent methods of analysis and endocrine criteria throughout the past decade of studies. Furthermore, the criteria defining "remission" and "cure" have evolved and become more stringent over time. Earlier studies assessing only serum GH levels are now considered wholly inadequate. A recent consensus from the Acromegaly Consensus Group regarding the criteria for cure in acromegaly has further tightened the level of endocrine remission, requiring a normal age-adjusted IGF-I level plus GH levels dropping below 1 ng/ml with the oral glucose tolerance test. Pure outcome analyses of sole surgical, medical, or radiation treatment for acromegaly are important but do not necessarily reflect current clinical management protocols, since more than one are often used. From the patient's perspective, what is desired is endocrinological control.
Here, we summarize the most recent data regarding the SRS treatment of GH-secreting adenomas to characterize the efficacy of SRS in the treatment of acromegaly. In addition to compiling data pertaining to disease remission, our goal was to assess the rate of disease control in patients continuing medical therapy after SRS.
Abstract and Introduction
Abstract
Object. Stereotactic radiosurgery (SRS) has emerged as an adjuvant radiation-based therapy for pituitary adenomas. Here, the authors present a systematic analysis of SRS for growth hormone–secreting adenomas to characterize the efficacy of SRS in the treatment of acromegaly.
Methods. A comprehensive search of the English language literature revealed 970 patients with new, recurrent, or persistent acromegaly that had been treated using SRS along with assessable and quantifiable outcome data. Articles published between June 1998 and September 2009 were included in the analysis. Patient outcome data were aggregated and investigated based on tumor size, radiosurgery dose, and clinical outcomes both with and without medication.
Results. The overall disease control rate without medication was 48%–53%, and the overall disease control rate with or without medication was 73%. The overall mean duration of the reported follow-up was 48.5 ± 25.8 months. The mean overall tumor volume in this analysis was 2.11 ± 1.16 cm. The Pearson product-moment correlation coefficient for tumor volume and cure rate was not significant (r = 0.0668, p = 0.8546).
Conclusions. Data from this analysis suggest that tumor size may not be a significant prognostic factor in disease control after radiosurgery for acromegaly. The overall disease control rate was approximately 48% without suppressive medications after radiosurgery for acromegaly. With the advancement of increasingly sophisticated stereotactic planning and tumor targeting, the precision of radiosurgery may continue to improve in the treatment of acromegaly.
Introduction
Acromegaly is an endocrine disorder characterized by the excess production of GH, generally by hypersecreting pituitary adenomas, resulting in progressive somatic disfigurement and increased morbidity and death due to the systemic effects of organ overgrowth. The control of GH and its primary mediator IGF-I has been associated with a reduction in the mortality risk.
Historically, the primary treatment for GH-producing pituitary adenomas has been resection and/or medical management. The reported rates of biochemical cure following surgical removal has varied based on tumor size and the definition of a cure, but is generally considered to range from 75%–95% for microadenomas and 40%–68% for macroadenomas. Note that the latter lesion type affects the majority of patients. Remission rates achieved using purely medical therapies have improved over the past decade, with several studies reporting biochemical control in approximately 70% of patients. But current medical therapies, such as somatostatin analogs and GH antagonists, must be taken lifelong and are costly.
Radiation treatment has typically been used when surgery is not an option or has left residual tumor and/or when medical therapy has failed. Stereotactic radiosurgery has largely supplanted traditional external beam radiation therapy for pituitary adenomas. Through the use of stereotactic precision, beams of radiation are delivered specifically to the target tissue, thereby avoiding surrounding normal neuronal tissue. The efficacy of SRS as well as surgery for the treatment of GH-secreting pituitary tumors is debated largely because of inconsistent methods of analysis and endocrine criteria throughout the past decade of studies. Furthermore, the criteria defining "remission" and "cure" have evolved and become more stringent over time. Earlier studies assessing only serum GH levels are now considered wholly inadequate. A recent consensus from the Acromegaly Consensus Group regarding the criteria for cure in acromegaly has further tightened the level of endocrine remission, requiring a normal age-adjusted IGF-I level plus GH levels dropping below 1 ng/ml with the oral glucose tolerance test. Pure outcome analyses of sole surgical, medical, or radiation treatment for acromegaly are important but do not necessarily reflect current clinical management protocols, since more than one are often used. From the patient's perspective, what is desired is endocrinological control.
Here, we summarize the most recent data regarding the SRS treatment of GH-secreting adenomas to characterize the efficacy of SRS in the treatment of acromegaly. In addition to compiling data pertaining to disease remission, our goal was to assess the rate of disease control in patients continuing medical therapy after SRS.
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