- Email: [email protected]
Section 4. Pituitary
Biomed Pharmacother 56 (2002) 178s–181s www.elsevier.com/locate/biopha
Mini review
Section 4. Pituitary Gamma knife radiosurgery for pituitary adenoma Masahiro Shin * Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Abstract For the treatment of pituitary adenomas, transsphenoidal surgery is established as a first choice of treatment. However, pituitary adenomas are often not curable with surgery alone, and further treatment including radiation therapy is required to control the disease. In this report, we review the literature of gamma knife radiosurgery for pituitary adenomas and discuss the efficacy of this modern technology. Radiosurgery achieved 85–100% of growth control rates with only mild and transient neurological complications in most cases. Endocrinological normalization was obtained in more than 65% of GH producing tumors. These hormonal control rates seemed to be slightly better in GH producing tumors compared to ACTH producing tumors. To normalize the excessive GH or ACTH levels, radiosurgery for functioning adenomas requires a relatively higher dose, ideally more than 35 Gy at tumor margin. However, the adjacent optic apparatus is less tolerable for irradiation, and the tumors have to be sufficiently separated from it to prevent the radiation-induced visual deficits. Therefore, the role of surgery should not be underevaluated, and even if radiosurgery alone may be able to achieve an excellent outcome in some cases, surgical resection will remain the primary treatment for pituitary adenomas. For high-risk patients or patients with residual tumors after transsphenoidal surgery, gamma knife radiosurgery can be a first choice of treatment, achieving both growth control and hormonal remission with minimum neurological complications, which is equivalent to conventional radiation therapy but with much less risk of radiation injury to the surrounding structures. © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Gamma knife; Stereotactic radiosurgery; Pituitary adenoma
1. Introduction For the treatment of pituitary adenomas, transsphenoidal surgery is established as one of the most reliable treatment modalities [2,3,5,20]. In most cases with microadenomas and many with macroadenomas, complete surgical resection using modern microsurgical techniques can achieve both of two aspects of the treatment goals: (1) reduction of tumor mass to protect surrounding structures from compression, and (2) the endocrinological cure of the symptoms caused by hormone secreting tumors [3,20]. However, in cases with functioning adenomas, many patients are already in poor physical condition caused by extended production of the excess pituitary hormones, and general anesthesia itself sometimes brings a certain risk for them. Also, they often
* Corresponding author. Tel.: +81-3-5800-8853; fax: +81-3-5800-8655. E-mail address: [email protected] (M. Shin). © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. PII: S 0 7 5 3 - 3 3 2 2 ( 0 2 ) 0 0 2 1 2 - 3
show invasion to surrounding structures including cavernous sinus, rendering the tumor surgically unresectable even in skilled hands [1,2,5,8,16]. When the functioning tumors remain within the cavernous sinus after transsphenoidal surgery, they continue to cause endocrinological symptoms, which necessitate further treatment. For such cases, conventional external radiation has been known to be effective, but it takes several years to achieve endocrinological remission and also carries a significant risk for panhypopituitarism or visual disturbances [7,9,12,18,19,21]. Since its introduction in neurosurgical fields, gamma knife radiosurgery has been widely adopted as a treatment modality for various intracranial lesions, and its efficacy and safety have been established over the past decade [4,6,9,11,13-15,17]. Particularly for the small benign tumors apparently carrying relatively high risk for surgical resection, radiosurgery has been used as a primary treatment, offering equivalent effectiveness with an acceptable risk of neurological complications [2,5,15,16], which has also been
M. Shin / Biomed Pharmacother 56 (2002) 178s–181s
179s
Fig. 1. The axial (A) and coronal (B) T1-weighted MRI showing a GH producing pituitary adenoma invading into cavernous sinus, and stereotactic radiosurgery was performed. The whole tumor volume was covered within 50% isodose line using the marginal dose of 30 Gy, while the visual pathway was irradiated with less than 10 Gy (C), and the internal carotid artery less than 30 Gy.
applied to the treatment of pituitary adenomas frequently as an alternative treatment modality. In this report, we review the past literature of gamma knife radiosurgery for pituitary adenomas and discuss the efficacy of this modern technology in the aspects of growth control and endocrinological remission of the tumors.
series of radiosurgery or conventional radiotherapy, for GH producing tumors, hormonal control was assigned when the serum GH level was below 10 mIU/l and the somatomedine C (SMC) level was below 450 ng/ml. For ACTH producing tumors, normalization of 24 h-urinary free cortisol level (<90 mg/d) was adopted as the criteria for hormonal control [4,6,11,13,14].
2. Treatment methods and dosimetry at radiosurgery Patients were fixed in the Leksell stereotactic head frame under administration of local anesthesia and underwent high-resolution stereotactic magnetic resonance imaging (MRI) with gadolinium-enhancement to obtain precise information on the shape, volume, and the three-dimensional coordinates of the tumors and the surrounding anatomic structures. The commercially available software, Leksell Gamma-Plan (Elekta instruments, Inc., Norcross, GA) was used for complex dose planning. The radiosurgical planning was done jointly by neurosurgeons and radiation oncologists. Radiosurgery was performed using a 201 source 60Co Gamma Knife (Elekta instruments). The day after radiosurgery, patients were discharged and could return to their daily lives without any neurological deterioration. For the purpose of growth control of the tumor, nonfunctioning adenomas were generally irradiated more than 12 Gy at the tumor margin [4,6,9,11,13-15,17], although a much higher irradiation dosage was required to achieve both growth control and hormonal remission, functioning pituitary adenomas were usually irradiated more than 25 Gy at the tumor margin [4,6,9,11,13-15,17]. The whole tumor was covered within 50–70% isodose lines. The prescribed marginal dose had to be decreased occasionally to keep the dose less than 10 Gy to the optic nerve, chiasma, and tract to avoid radiation-induced visual disturbances [9], and less than 30 Gy to the internal carotid artery (Fig. 1). The imaging studies were assessed independently by neuroradiologists and neurosurgeons. In the most reported
3. Growth control rates and endocrinological outcomes As the technology of radiographic imaging developed, pituitary adenomas could be clearly demonstrated on the MRI at radiosurgical dose planning, which remarkably improved the treatment outcome of gamma knife radiosurgery. In accordance with the previous literature of radiosurgery for pituitary adenomas, 85–100% of tumor control rates were achieved for 3–6 years, with only mild and transient neurological complications in most cases [4,6,9,11,13-15,17]. As well as the growth control rates, the rate of hormonal control has also remarkably improved. In recent reports, endocrinological normalization was obtained in more than 65% of GH producing tumors (Table 1). These hormonal control rates seemed to be slightly better in GH producing tumors compared to ACTH producing tumors [4,6,11,1315], probably because the GH producing adenomas were usually demarcated on the radiographic images better than the ACTH producing tumors (Table 1). Overall, the rate of endocrinological normalization was achieved in 50–70% of functioning adenomas at 3 years after radiosurgery, which was also similar to the results of conventional radiation therapy [12,18,19,21]. Because radiosurgery is a relatively new treatment modality, more studies with longer follow-up periods are awaited to confirm whether these results will still hold for several decades after the treatment.
180s
M. Shin / Biomed Pharmacother 56 (2002) 178s–181s
Table 1 Summary of endocrinological outcomes of functioning pituitary adenomas
GH producing adenoma Thoren et al. [17] Ganz et al. [4] Pollock et al. [14] Landolt et al. [9] Shin et al. [15] ACTH producing adenoma Martinez et al. [11] Shin et al. [15]
No. patients
Controlled (%) *
Improving (%)
Hypopituitarysm (%)
21 4 8 16 6
29.5 25.0 37.5 >65.0 66.7
38.1 75.0 37.5 – 33.3
9.5 0 0 NA 0
3 6
– 50.0
100 0
33.0 16.7 *
* Defined as both GH level <10 mIU/l and somatomedin C level <450 ng/ml for GH producing adenomas and as 24 hr-urinary free corticsol level less than 90 mg/d for ACTH producing adenomas. ** Only transient hypophyseal insufficiency and no permanent deterioration.
4. Comparison with outcomes of the conventional radiotherapy Conventional radiation therapy using a fractionated dose has been shown to achieve fairly good treatment outcomes both for tumor growth and endocrinological symptoms, and several studies posted 80–95% tumor control rate and 40–90% hormonal control rate [7,9,12,18,19,21]. However, the risk of radiation-induced hypopituitarism requiring permanent hormone replacement was relatively high, reaching 25–30% after approximately 50 Gy of fractionated external beam irradiation. In addition, visual disturbance caused by radiation is also noted in a few percent, and deterioration of neurocognitive function is reported to be observed in a
Fig. 2. A schema of our proposed strategy for functioning pituitary adenomas.
significant portion of the cases as well. Viability of radiosurgery as a treatment for pituitary adenomas depends on the comparison with conventional irradiation in those aspects. In the past literature of radiosurgically treated pituitary adenomas, the tumor control was achieved in 85–100% of the treated patients [4,6,9,11,13,14,15,17]. Therefore, in terms of tumor growth control, radiosurgery seems to have equivalent or possibly better results in treating pituitary adenomas than conventional radiation therapy [4,6,9,11,1315,17]. Also, the incidences of complication were extremely low, with only a few cases showing transient hypopituitarism. In combination with the fact that there was no visual dysfunction caused by radiosurgery, these results indicated
M. Shin / Biomed Pharmacother 56 (2002) 178s–181s
that adequately designed gamma knife radiosurgery is usually a safer treatment for pituitary adenomas than the conventional radiation therapy [9,12,18,19,21].
[3]
[4]
5. Roles of transsphenoidal surgery and radiosurgery
[5]
Needless to say, in the case where pituitary adenomas extend into suprasellar regions and compress the optic apparatus, leading to neurological symptoms, surgical resection should be recommended as a first choice of treatments. Although, in the treatment of pituitary adenomas invading the cavernous sinus, complete resection would not be possible in most cases, the role of surgery should not be underevaluated. Radiosurgery for functioning adenomas requires a relatively higher dose, ideally more than 35 Gy at tumor margin, to normalize the excessive GH or ACTH levels. However, the adjacent optic apparatus is less tolerable for irradiation [10], and the tumors have to be sufficiently separated from it to prevent the radiation-induced visual deficits. Therefore, the mass reduction by surgical resection is an important procedure that facilitates safer dose planning by creating sufficient space between the residual tumor and the critical neural structures [15]. Except for medical contraindication for surgery, the transsphenoidal resection will remain the primary treatment for invasive adenomas even if radiosurgery alone may be able to achieve an excellent outcome in some cases. However, for high-risk patients for general anesthesia or the patients with residual tumors after transsphenoidal surgery, gamma knife radiosurgery can be a first choice of treatment, successfully achieving both growth control and hormonal remission with minimum neurological complications (Fig. 2).
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
6. Conclusions
[16]
Although further accumulation of cases with longer follow-ups with this relatively new treatment modality is needed, stereotactic radiosurgery seems to be a valuable treatment modality for pituitary adenomas, achieving the successful growth control of the tumor and relatively earlier endocrinological normalization.
[17]
References
[20]
[1] [2]
Dolenc VV. Transcranial epidural approach to pituitary tumors extending beyond the sella. Neurosurgery 1997;41:542–52. Fahlbusch R, Buchfelder M. Transsphenoidal surgery of parasellar pituitary adenomas. Acta Neurochir (Wien) 1988;92:93–9.
[18]
[19]
[21]
181s
Freda PU, Wardlaw SL, Post KD. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 1998;89:353–8. Ganz JC, Backlund EO, Thorsen FA. The effects of gamma knife surgery of pituitary adenomas on tumor growth and endocrinopathies. Stereotact Funct Neurosurg 1993;61(Suppl):30–7. Hashimoto N, Kikuchi H. Transsphenoidal approach to infrasellar tumors involving the cavernous sinus. J Neurosurg 1990;73:513–7. Hayashi M, Izawa M, Hiyama H, et al. Gamma knife radiosurgery for pituitary adenomas. Stereotact Funct Neurosurg 1999;72(Suppl): 111–8. Kliman B, Kjellberg RN, Swisher B, et al. Proton beam therapy of acromegaly: a 20-year experience. In: Black PM, Zervas NT, Ridgway EC, et al., editors. Secretary tumors of the pituitary gland. progress in endocrine research and therapy, vol. 1. New York: Raven Press; 1984. p. 191–211. Knosp E, Steiner E, Kitz K, et al. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 1993; 33:610–8. Landolt AM, Haller D, Lomax N, et al. Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy. J Neurosurg 1998;88:1002–8. Leber KA, Bergloff J, Pendl G. Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg 1998;88:43–50. Martinez R, Bravo G, Burzaco J, et al. Pituitary tumors and gamma knife surgery: clinical experience with more than two years of follow-up. Stereotact Funct Neurosurg 1998;70(Suppl):110–8. McCord MW, Buatti JM, Fennell EM, et al. Radiotherapy for pituitary adenoma: long-term outcome and sequelae. Int J Radiat Oncol Biol Phys 1997;39:437–44. Morange-Ramos I, Regis J, Andrieu JM, et al. Gamma-knife surgery for secreting pituitary adenomas. Acta Neurochir (Wien) 1998;140: 437–43. Pollock BE, Kondziolka D, Lunsford LD, et al. Stereotactic radiosurgery for pituitary adenomas: imaging, visual, and endocrine results. Acta Neurochir 1994;62(Suppl):33–8. Shin M, Kurita H, Sasaki T, et al. Stereotactic radiosurgery for piutitary adenoma invading into cavernous sinus. J Neurosurg 2000;93(Suppl 3):2–5. Tamiya T, Ono Y, Date I, et al. Extradural temporopolar approach for giant pituitary adenomas invading the cavernous sinus and parasellar regions. No. Shinkei Geka 1998;26:803–11. Thoren M, Rahn T, Guo WY, et al. Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of growth hormoneproducing pituitary tumors. Neurosurgery 1991;29:663–8. Tsang RW, Brierley JD, Panzarella T, et al. Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. Int J Radiat Oncol Biol Phys 1994;30:557–65. Tsang RW, Brierley JD, Panzarella T, et al. Role of radiation therapy in clinical hormonally-active pituitary adenomas. Radiother Oncol 1996;41:45–53. Watson JC, Shawker TH, Nieman LK, et al. Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing’s disease and no demonstrable pituitary tumor on magnetic resonance imaging. J Neurosurg 1998;89:927–32. Zierhut D, Flentje M, Adolph J, et al. External radiotherapy of pituitary adenomas. Int J Radiat Oncol Biol Phys 1995;33:307–14.
Mini review
Section 4. Pituitary Gamma knife radiosurgery for pituitary adenoma Masahiro Shin * Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Abstract For the treatment of pituitary adenomas, transsphenoidal surgery is established as a first choice of treatment. However, pituitary adenomas are often not curable with surgery alone, and further treatment including radiation therapy is required to control the disease. In this report, we review the literature of gamma knife radiosurgery for pituitary adenomas and discuss the efficacy of this modern technology. Radiosurgery achieved 85–100% of growth control rates with only mild and transient neurological complications in most cases. Endocrinological normalization was obtained in more than 65% of GH producing tumors. These hormonal control rates seemed to be slightly better in GH producing tumors compared to ACTH producing tumors. To normalize the excessive GH or ACTH levels, radiosurgery for functioning adenomas requires a relatively higher dose, ideally more than 35 Gy at tumor margin. However, the adjacent optic apparatus is less tolerable for irradiation, and the tumors have to be sufficiently separated from it to prevent the radiation-induced visual deficits. Therefore, the role of surgery should not be underevaluated, and even if radiosurgery alone may be able to achieve an excellent outcome in some cases, surgical resection will remain the primary treatment for pituitary adenomas. For high-risk patients or patients with residual tumors after transsphenoidal surgery, gamma knife radiosurgery can be a first choice of treatment, achieving both growth control and hormonal remission with minimum neurological complications, which is equivalent to conventional radiation therapy but with much less risk of radiation injury to the surrounding structures. © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Gamma knife; Stereotactic radiosurgery; Pituitary adenoma
1. Introduction For the treatment of pituitary adenomas, transsphenoidal surgery is established as one of the most reliable treatment modalities [2,3,5,20]. In most cases with microadenomas and many with macroadenomas, complete surgical resection using modern microsurgical techniques can achieve both of two aspects of the treatment goals: (1) reduction of tumor mass to protect surrounding structures from compression, and (2) the endocrinological cure of the symptoms caused by hormone secreting tumors [3,20]. However, in cases with functioning adenomas, many patients are already in poor physical condition caused by extended production of the excess pituitary hormones, and general anesthesia itself sometimes brings a certain risk for them. Also, they often
* Corresponding author. Tel.: +81-3-5800-8853; fax: +81-3-5800-8655. E-mail address: [email protected] (M. Shin). © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. PII: S 0 7 5 3 - 3 3 2 2 ( 0 2 ) 0 0 2 1 2 - 3
show invasion to surrounding structures including cavernous sinus, rendering the tumor surgically unresectable even in skilled hands [1,2,5,8,16]. When the functioning tumors remain within the cavernous sinus after transsphenoidal surgery, they continue to cause endocrinological symptoms, which necessitate further treatment. For such cases, conventional external radiation has been known to be effective, but it takes several years to achieve endocrinological remission and also carries a significant risk for panhypopituitarism or visual disturbances [7,9,12,18,19,21]. Since its introduction in neurosurgical fields, gamma knife radiosurgery has been widely adopted as a treatment modality for various intracranial lesions, and its efficacy and safety have been established over the past decade [4,6,9,11,13-15,17]. Particularly for the small benign tumors apparently carrying relatively high risk for surgical resection, radiosurgery has been used as a primary treatment, offering equivalent effectiveness with an acceptable risk of neurological complications [2,5,15,16], which has also been
M. Shin / Biomed Pharmacother 56 (2002) 178s–181s
179s
Fig. 1. The axial (A) and coronal (B) T1-weighted MRI showing a GH producing pituitary adenoma invading into cavernous sinus, and stereotactic radiosurgery was performed. The whole tumor volume was covered within 50% isodose line using the marginal dose of 30 Gy, while the visual pathway was irradiated with less than 10 Gy (C), and the internal carotid artery less than 30 Gy.
applied to the treatment of pituitary adenomas frequently as an alternative treatment modality. In this report, we review the past literature of gamma knife radiosurgery for pituitary adenomas and discuss the efficacy of this modern technology in the aspects of growth control and endocrinological remission of the tumors.
series of radiosurgery or conventional radiotherapy, for GH producing tumors, hormonal control was assigned when the serum GH level was below 10 mIU/l and the somatomedine C (SMC) level was below 450 ng/ml. For ACTH producing tumors, normalization of 24 h-urinary free cortisol level (<90 mg/d) was adopted as the criteria for hormonal control [4,6,11,13,14].
2. Treatment methods and dosimetry at radiosurgery Patients were fixed in the Leksell stereotactic head frame under administration of local anesthesia and underwent high-resolution stereotactic magnetic resonance imaging (MRI) with gadolinium-enhancement to obtain precise information on the shape, volume, and the three-dimensional coordinates of the tumors and the surrounding anatomic structures. The commercially available software, Leksell Gamma-Plan (Elekta instruments, Inc., Norcross, GA) was used for complex dose planning. The radiosurgical planning was done jointly by neurosurgeons and radiation oncologists. Radiosurgery was performed using a 201 source 60Co Gamma Knife (Elekta instruments). The day after radiosurgery, patients were discharged and could return to their daily lives without any neurological deterioration. For the purpose of growth control of the tumor, nonfunctioning adenomas were generally irradiated more than 12 Gy at the tumor margin [4,6,9,11,13-15,17], although a much higher irradiation dosage was required to achieve both growth control and hormonal remission, functioning pituitary adenomas were usually irradiated more than 25 Gy at the tumor margin [4,6,9,11,13-15,17]. The whole tumor was covered within 50–70% isodose lines. The prescribed marginal dose had to be decreased occasionally to keep the dose less than 10 Gy to the optic nerve, chiasma, and tract to avoid radiation-induced visual disturbances [9], and less than 30 Gy to the internal carotid artery (Fig. 1). The imaging studies were assessed independently by neuroradiologists and neurosurgeons. In the most reported
3. Growth control rates and endocrinological outcomes As the technology of radiographic imaging developed, pituitary adenomas could be clearly demonstrated on the MRI at radiosurgical dose planning, which remarkably improved the treatment outcome of gamma knife radiosurgery. In accordance with the previous literature of radiosurgery for pituitary adenomas, 85–100% of tumor control rates were achieved for 3–6 years, with only mild and transient neurological complications in most cases [4,6,9,11,13-15,17]. As well as the growth control rates, the rate of hormonal control has also remarkably improved. In recent reports, endocrinological normalization was obtained in more than 65% of GH producing tumors (Table 1). These hormonal control rates seemed to be slightly better in GH producing tumors compared to ACTH producing tumors [4,6,11,1315], probably because the GH producing adenomas were usually demarcated on the radiographic images better than the ACTH producing tumors (Table 1). Overall, the rate of endocrinological normalization was achieved in 50–70% of functioning adenomas at 3 years after radiosurgery, which was also similar to the results of conventional radiation therapy [12,18,19,21]. Because radiosurgery is a relatively new treatment modality, more studies with longer follow-up periods are awaited to confirm whether these results will still hold for several decades after the treatment.
180s
M. Shin / Biomed Pharmacother 56 (2002) 178s–181s
Table 1 Summary of endocrinological outcomes of functioning pituitary adenomas
GH producing adenoma Thoren et al. [17] Ganz et al. [4] Pollock et al. [14] Landolt et al. [9] Shin et al. [15] ACTH producing adenoma Martinez et al. [11] Shin et al. [15]
No. patients
Controlled (%) *
Improving (%)
Hypopituitarysm (%)
21 4 8 16 6
29.5 25.0 37.5 >65.0 66.7
38.1 75.0 37.5 – 33.3
9.5 0 0 NA 0
3 6
– 50.0
100 0
33.0 16.7 *
* Defined as both GH level <10 mIU/l and somatomedin C level <450 ng/ml for GH producing adenomas and as 24 hr-urinary free corticsol level less than 90 mg/d for ACTH producing adenomas. ** Only transient hypophyseal insufficiency and no permanent deterioration.
4. Comparison with outcomes of the conventional radiotherapy Conventional radiation therapy using a fractionated dose has been shown to achieve fairly good treatment outcomes both for tumor growth and endocrinological symptoms, and several studies posted 80–95% tumor control rate and 40–90% hormonal control rate [7,9,12,18,19,21]. However, the risk of radiation-induced hypopituitarism requiring permanent hormone replacement was relatively high, reaching 25–30% after approximately 50 Gy of fractionated external beam irradiation. In addition, visual disturbance caused by radiation is also noted in a few percent, and deterioration of neurocognitive function is reported to be observed in a
Fig. 2. A schema of our proposed strategy for functioning pituitary adenomas.
significant portion of the cases as well. Viability of radiosurgery as a treatment for pituitary adenomas depends on the comparison with conventional irradiation in those aspects. In the past literature of radiosurgically treated pituitary adenomas, the tumor control was achieved in 85–100% of the treated patients [4,6,9,11,13,14,15,17]. Therefore, in terms of tumor growth control, radiosurgery seems to have equivalent or possibly better results in treating pituitary adenomas than conventional radiation therapy [4,6,9,11,1315,17]. Also, the incidences of complication were extremely low, with only a few cases showing transient hypopituitarism. In combination with the fact that there was no visual dysfunction caused by radiosurgery, these results indicated
M. Shin / Biomed Pharmacother 56 (2002) 178s–181s
that adequately designed gamma knife radiosurgery is usually a safer treatment for pituitary adenomas than the conventional radiation therapy [9,12,18,19,21].
[3]
[4]
5. Roles of transsphenoidal surgery and radiosurgery
[5]
Needless to say, in the case where pituitary adenomas extend into suprasellar regions and compress the optic apparatus, leading to neurological symptoms, surgical resection should be recommended as a first choice of treatments. Although, in the treatment of pituitary adenomas invading the cavernous sinus, complete resection would not be possible in most cases, the role of surgery should not be underevaluated. Radiosurgery for functioning adenomas requires a relatively higher dose, ideally more than 35 Gy at tumor margin, to normalize the excessive GH or ACTH levels. However, the adjacent optic apparatus is less tolerable for irradiation [10], and the tumors have to be sufficiently separated from it to prevent the radiation-induced visual deficits. Therefore, the mass reduction by surgical resection is an important procedure that facilitates safer dose planning by creating sufficient space between the residual tumor and the critical neural structures [15]. Except for medical contraindication for surgery, the transsphenoidal resection will remain the primary treatment for invasive adenomas even if radiosurgery alone may be able to achieve an excellent outcome in some cases. However, for high-risk patients for general anesthesia or the patients with residual tumors after transsphenoidal surgery, gamma knife radiosurgery can be a first choice of treatment, successfully achieving both growth control and hormonal remission with minimum neurological complications (Fig. 2).
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
6. Conclusions
[16]
Although further accumulation of cases with longer follow-ups with this relatively new treatment modality is needed, stereotactic radiosurgery seems to be a valuable treatment modality for pituitary adenomas, achieving the successful growth control of the tumor and relatively earlier endocrinological normalization.
[17]
References
[20]
[1] [2]
Dolenc VV. Transcranial epidural approach to pituitary tumors extending beyond the sella. Neurosurgery 1997;41:542–52. Fahlbusch R, Buchfelder M. Transsphenoidal surgery of parasellar pituitary adenomas. Acta Neurochir (Wien) 1988;92:93–9.
[18]
[19]
[21]
181s
Freda PU, Wardlaw SL, Post KD. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 1998;89:353–8. Ganz JC, Backlund EO, Thorsen FA. The effects of gamma knife surgery of pituitary adenomas on tumor growth and endocrinopathies. Stereotact Funct Neurosurg 1993;61(Suppl):30–7. Hashimoto N, Kikuchi H. Transsphenoidal approach to infrasellar tumors involving the cavernous sinus. J Neurosurg 1990;73:513–7. Hayashi M, Izawa M, Hiyama H, et al. Gamma knife radiosurgery for pituitary adenomas. Stereotact Funct Neurosurg 1999;72(Suppl): 111–8. Kliman B, Kjellberg RN, Swisher B, et al. Proton beam therapy of acromegaly: a 20-year experience. In: Black PM, Zervas NT, Ridgway EC, et al., editors. Secretary tumors of the pituitary gland. progress in endocrine research and therapy, vol. 1. New York: Raven Press; 1984. p. 191–211. Knosp E, Steiner E, Kitz K, et al. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 1993; 33:610–8. Landolt AM, Haller D, Lomax N, et al. Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy. J Neurosurg 1998;88:1002–8. Leber KA, Bergloff J, Pendl G. Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg 1998;88:43–50. Martinez R, Bravo G, Burzaco J, et al. Pituitary tumors and gamma knife surgery: clinical experience with more than two years of follow-up. Stereotact Funct Neurosurg 1998;70(Suppl):110–8. McCord MW, Buatti JM, Fennell EM, et al. Radiotherapy for pituitary adenoma: long-term outcome and sequelae. Int J Radiat Oncol Biol Phys 1997;39:437–44. Morange-Ramos I, Regis J, Andrieu JM, et al. Gamma-knife surgery for secreting pituitary adenomas. Acta Neurochir (Wien) 1998;140: 437–43. Pollock BE, Kondziolka D, Lunsford LD, et al. Stereotactic radiosurgery for pituitary adenomas: imaging, visual, and endocrine results. Acta Neurochir 1994;62(Suppl):33–8. Shin M, Kurita H, Sasaki T, et al. Stereotactic radiosurgery for piutitary adenoma invading into cavernous sinus. J Neurosurg 2000;93(Suppl 3):2–5. Tamiya T, Ono Y, Date I, et al. Extradural temporopolar approach for giant pituitary adenomas invading the cavernous sinus and parasellar regions. No. Shinkei Geka 1998;26:803–11. Thoren M, Rahn T, Guo WY, et al. Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of growth hormoneproducing pituitary tumors. Neurosurgery 1991;29:663–8. Tsang RW, Brierley JD, Panzarella T, et al. Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. Int J Radiat Oncol Biol Phys 1994;30:557–65. Tsang RW, Brierley JD, Panzarella T, et al. Role of radiation therapy in clinical hormonally-active pituitary adenomas. Radiother Oncol 1996;41:45–53. Watson JC, Shawker TH, Nieman LK, et al. Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing’s disease and no demonstrable pituitary tumor on magnetic resonance imaging. J Neurosurg 1998;89:927–32. Zierhut D, Flentje M, Adolph J, et al. External radiotherapy of pituitary adenomas. Int J Radiat Oncol Biol Phys 1995;33:307–14.