Stereotactic Radiosurgery as the Initial Treatment for Patients with Nonfunctioning Pituitary Adenomas

doi:10.1016/j.wneu.2015.01.054

World Neurosurgery

Volume 83, Issue 6, June 2015, Pages 1173-1179

https://doi.org/10.1016/j.wneu.2015.01.054 Get rights and content

Objective

The aim of this study was to confirm the efficacy and safety of stereotactic radiosurgery as the initial treatment for patients with nonfunctioning pituitary adenomas (NFPAs) and to decide the optimum dose to achieve long-term tumor control as well as preservation of pituitary endocrine function.

Methods

The study was a single-center retrospective analysis of 16 patients with primary NFPAs that were treated with gamma knife surgery (GKS). Fifteen of 16 NFPAs were growing to the suprasellar region and slightly compressing or very close to the optic apparatus. Initial GKS was selected to avoid visual disturbance caused by further tumor growth that would require surgical resection under general anesthesia. The median tumor volume was 2.0 cm³, and the median tumor margin dose was 15 Gy.

Results

The median clinical follow-up period was 98 months. The last follow-up images demonstrated tumor regression in 15 patients and stable tumor in 1. No patient developed tumor progression. One patient who had pituitary apoplexy before treatment required hormone replacements 2 years after GKS. The other patients did not experience pituitary insufficiency requiring hormone–replacement therapy during the clinical follow-up period. No patient developed cranial nerve injury or radiation-induced neoplasm.

Conclusions

GKS is a safe and effective treatment option in patients with primary NFPAs, especially for patients with advanced age or comorbidity. Attention should be paid to late adverse radiation effects such as hypopituitarism, optic neuropathy, and radiation-induced neoplasms. However, stereotactic radiosurgery with a conformal treatment plan sparing the normal pituitary gland will contribute to avoidance of such complications as well as achievement of long-term tumor control.

Introduction

Currently, transsphenoidal surgery (TSS) is a common treatment for symptomatic nonfunctioning pituitary adenomas (NFPAs) 2, 4, 12, 24, 29, 30, whereas surveillance is preferred for asymptomatic NFPAs. When pituitary adenomas grow and compress the optic apparatus during the observation period, the patients need to decide whether to undergo TSS. If patients refuse surgery, they will develop visual disturbance and eventually might lose their vision. However, surgery under general anesthesia remains risky for older patients or ones with comorbidities. In this situation, stereotactic radiosurgery (SRS) is a reasonable treatment option, but it is not suitable for tumors that compress the optic apparatus because of dose limitation to the optic apparatus. Therefore, to safely treat NFPAs, prophylactic gamma knife surgery (GKS) before the development of visual disturbance has been performed for those patients who have NFPAs located close to the optic apparatus or growing on follow-up images. To date, there have been many reports demonstrating the efficacy of GKS for residual or recurrent NFPAs 5, 8, 13, 14, 19, 22, 25, 28, 33, 34, 35, 37. However, there is little information concerning initial treatment with GKS for patients harboring NFPAs (20). The aim of this study was to evaluate the safety and efficacy of GKS as the initial treatment for patients with NFPAs and whether SRS with a conformal treatment plan sparing the normal pituitary gland contributes to both long-term tumor control and preservation of pituitary endocrine function.

Section snippets

Patient Characteristics

This study was a single-center retrospective analysis of a prospectively maintained, Institutional Review Board–approved database. Patients harboring NFPAs treated with GKS as the initial treatment were evaluated. Inclusion criteria were 1) solid pituitary lesion on magnetic resonance imaging (MRI) scans and presumed pituitary adenomas, 2) no evidence of hormonal hypersecretion, and 3) no previous treatment. Patients who had any hypersecreting tumors, except mild hyperprolatinemia < 100 ng/dL,

Results

The median clinical follow-up period was 98 months (range, 12–213 months). The median radiological follow-up period was 86 months (12–155 months).

Indication for GKS as the Initial Treatment

Our treatment strategy for pituitary incidentalomas is basically identical with the Endocrine Society guidelines by Freda et al. (11). All patients included in this study had significant tumor growth of the pituitary incidentalomas and/or those close to the optic apparatus. For this subset of NFPAs, the guidelines on pituitary incidentaloma management suggest that surgery be considered. In this situation, we generally recommend TSS or surveillance when patients are asymptomatic. If TSS is

Conclusions

GKS was a safe and effective acceptable treatment option in patients with primary NFPAs, especially for patients with advanced age or comorbidity. During the follow-up period, no patient developed tumor enlargement with a median tumor volume reduction rate of 67%, and only 1 patient worsened pituitary endocrine function. However, attention should be paid to pituitary hormone deficiency, optic neuropathy, and radiation-induced neoplasms or vascular injuries in the long term, especially for young

References (38)

S.C. Erridge et al.
Radiotherapy for pituitary adenomas: long-term efficacy and toxicity
Radiother Oncol
(2009)
J.O. Kim et al.
Long-term outcomes of fractionated stereotactic radiation therapy for pituitary adenomas at the BC Cancer Agency
Int J Radiat Oncol Biol Phys
(2013)
M. Loyo-Varela et al.
Pituitary tumor surgery: review of 3004 cases
World Neurosurg
(2013)
M.E. Molitch
Pituitary tumours: pituitary incidentalomas
Best Pract Res Clin Endocrinol Metab
(2009)
A.M. Pereira et al.
Treatment of nonfunctioning pituitary adenomas: what were the contributions of the last 10 years? A critical view
Ann Endocrinol (Paris)
(2012)
M.G.A. Sattler et al.
The incidence of second tumours and mortality in pituitary adenoma patients treated with postoperative radiotherapy versus surgery alone
Radiother Oncol
(2012)
G. Sicignano et al.
Dosimetric factors associated with pituitary function after Gamma Knife Surgery (GKS) of pituitary adenomas
Radiother Oncol
(2012)
K. Arita et al.
Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination
J Neurosurg
(2006)
M. Berker et al.
Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature
Pituitary
(2012)
M. Brada et al.
Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma
BMJ
(1992)

L. Chen et al.

A prospective study of nonfunctioning pituitary adenomas: presentation, management, and clinical outcome

J Neurooncol

(2011)

Y. Chen et al.

Gamma knife surgery for patients with volumetric classification of nonfunctioning pituitary adenomas: a systematic review and meta-analysis

Eur J Endocrinol

(2013)

K.H. Darzy et al.

Hypopituitarism following radiotherapy

Pituitary

(2009)

O.M. Dekkers et al.

The natural course of non-functioning pituitary macroadenomas

Eur J Endocrinol

(2007)

A.M.N. El-Shehaby et al.

Low-dose Gamma Knife surgery for nonfunctioning pituitary adenomas

J Neurosurg

(2012)

M.M. Fernández-Balsells et al.

Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis

J Clin Endocrinol Metab

(2011)

P.U. Freda et al.

Pituitary incidentaloma: an endocrine society clinical practice guideline

J Clin Endocrinol Metab

(2011)

J.A. Gondim et al.

Endoscopic endonasal approach for pituitary adenoma: surgical complications in 301 patients

Pituitary

(2011)

R. Gopalan et al.

Long-term outcomes after Gamma Knife radiosurgery for patients with a nonfunctioning pituitary adenoma

Neurosurgery

(2011)

Cited by (19)

Pituitary adenomas
2022, Progress in Brain Research
Citation Excerpt :
The tumor control rate was 100%. The median prescription dose in this series was 15 Gy with a range between 10 and 34 Gy, but the tumors were smaller with a median volume of 2 cm3 and with a range of 0.2–8.4 cm3 (Hasegawa et al., 2015). It has long been well recognized that even radical surgery of what used to be called a chromophobe pituitary adenoma might well be followed by recurrence.
Pituitary adenomas produce a complex collection of disorders. Some are incidental findings. Some distort local anatomical structures which can lead to disorders of vision or hormone production. Some produce excesses of hormones which can be either life threatening or clinically distressing. The management requires the expertise of a variety of experts who plan together. No single treatment is universally successful in controlling these conditions. Medical, biochemical, surgical and radiosurgical management can all have parts to play. Coordinate co-operation between specialists will provide patients with the best available treatment.
Single- and Multi-Fraction Stereotactic Radiosurgery Dose Tolerances of the Optic Pathways
2021, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
PubMed searches were performed for reports published from 1990 through June 2015 (the search criteria are detailed in the Online Appendix, available at https://doi.org/10.1016/j.ijrobp.2018.01.053). Studies included in the analyses (8, 16-50) reported visual endpoints after SRS/fSRS, as well as information about dose to the optic apparatus (also described as optic nerve, chiasm, and/or anterior visual pathway). The optic apparatus dose must have been reported in patients (if any) who developed RION and in the study population (either explicitly reported, or able to be estimated).
Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.
Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).
Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy.
Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.
Long-Term Follow-Up Studies of Gamma Knife Radiosurgery for Postsurgical Nonfunctioning Pituitary Adenomas
2019, World Neurosurgery
Citation Excerpt :
In multiple reputed Gamma Knife centers, GKRS for NFPAs1,5-15 has proved to be a safe and effective treatment modality. In Table 2,1,5-17 the long-term tumor control rate of GKRS for NFPAs is summarized to be 89.6%–100%, and the actuarial progression-free survival at 3, 5, and 10 years was 93%–100%, 88.2%–97%, and 76%–92%, respectively. The median tumor recurrence time after GKRS in this cohort was 5.0 years (mean, 5.1 years; range, 1–13 years).
The aim of this study was to evaluate the long-term clinical outcomes of Gamma Knife radiosurgery (GKRS) for residual and recurrent nonfunctioning pituitary adenomas (NFPAs) after surgery and the role of GKRS in the management of NFPAs.
Between January 2000 and December 2010, 204 patients with residual or recurrent NFPAs undergoing GKRS were enrolled in this study according to the inclusion criteria. The median age of the patients was 48 years (mean, 48 years; range, 14–79 years). The median tumor volume was 3.3 mL (mean, 5.2 mL; range, 0.3–26.4 mL). The median margin dose was 14 Gy (mean, 14 Gy; range, 9–18 Gy). The median maximum dose was 31 Gy (mean, 30 Gy; 20–40 Gy). The median duration of follow-up was 86 months (mean, 88 months; range, 12–213 months).
Of these 204 patients, the latest follow-up magnetic resonance imaging studies showed tumor regression in 102 patients (50%), tumor stability in 81 patients (40%), and tumor enlargement in 21 patients (10%). The tumor control rate of this cohort was 90%. The cumulative progression-free survival at 3, 5, 8, 10, and 15 years was 97%, 95%, 92%, 92%, and 81%, respectively. Thirty-seven patients (18%) developed new-onset hypopituitarism, with 1 patient experiencing panhypopituitarism. Five patients (2.5%) presented with new or worsening visual dysfunction without tumor growth. No new cranial nerve dysfunction was shown and no second brain tumor was identified.
GKRS provided high tumor control and a low complication rate in our long-term follow-up. We recommend that early GKRS should be considered the routine adjuvant treatment for residual NFPAs approximately 6 months after subtotal surgical resection.
Magnetic resonance diffusion tensor imaging study of rhesus optic nerve radiation injury caused by a single dose/fractionation scheme stereotactic radiosurgery at an early stage
2016, Journal of Neuroradiology
Radiation-induced optic neuropathy (RION) is a devastating late complication of radiotherapy. However, research on the imaging performance of RION is not sufficient. The aim of this study was to investigate the performance of magnetic resonance diffusion tensor imaging (DTI) early after injury of the optic nerve of rhesus monkeys by a single-dose/fractionation-scheme of stereotactic radiosurgery (SRS).
The intraorbital optic nerve contour of 5 rhesus monkeys was acquired by magnetic resonance imaging (MRI). Then, the unilateral intraorbital optic nerves of 5 rhesus monkeys were injured by gamma knife surgery (GKS) with a single-dose/fractionation scheme (marginal dose of 15 Gy, 50% isodose curve). DTI was performed before the irradiation and 1 week, 2 weeks, 4 weeks, and 24 weeks after injury to obtain the cross-sectional area, and the fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD) and radial diffusivity (RD) values.
The cross-sectional area of the injured optic nerve exhibited significant atrophy 24 weeks after SRS. FA declined 1 week after injury; this value then increased slightly but remained lower than before injury (P < 0.05). AD began to decline in the 2 weeks after injury and gradually disappeared (P < 0.05).
SRS with a single-dose/fractionation scheme (marginal dose of 15 Gy, 50% isodose curve) on the unilateral intraorbital optic nerve can induce RION. DTI can detect RION at an early stage. FA and AD are useful indicators for RION diagnosis. In the early stage, the primary site of RION may be the vascular endothelium.
Radiation-Induced Retinopathy and Optic Neuropathy after Radiation Therapy for Brain, Head, and Neck Tumors: A Systematic Review
2023, Cancers
Pituitary adenoma in the elderly: surgical outcomes and treatment trends in the United States
2022, Journal of Neurosurgery

View all citing articles on Scopus

: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

View full text

Peer-Review ReportStereotactic Radiosurgery as the Initial Treatment for Patients with Nonfunctioning Pituitary Adenomas

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Patient Characteristics

Results

Indication for GKS as the Initial Treatment

Conclusions

Radiother Oncol

Int J Radiat Oncol Biol Phys

World Neurosurg

Best Pract Res Clin Endocrinol Metab

Ann Endocrinol (Paris)

Radiother Oncol

Radiother Oncol

Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination

J Neurosurg

Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature

Pituitary

Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma

BMJ

A prospective study of nonfunctioning pituitary adenomas: presentation, management, and clinical outcome

J Neurooncol

Gamma knife surgery for patients with volumetric classification of nonfunctioning pituitary adenomas: a systematic review and meta-analysis

Eur J Endocrinol

Hypopituitarism following radiotherapy

Pituitary

The natural course of non-functioning pituitary macroadenomas

Eur J Endocrinol

Low-dose Gamma Knife surgery for nonfunctioning pituitary adenomas

J Neurosurg

Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis

J Clin Endocrinol Metab

Pituitary incidentaloma: an endocrine society clinical practice guideline

J Clin Endocrinol Metab

Endoscopic endonasal approach for pituitary adenoma: surgical complications in 301 patients

Pituitary

Long-term outcomes after Gamma Knife radiosurgery for patients with a nonfunctioning pituitary adenoma

Neurosurgery

Peer-Review Report
Stereotactic Radiosurgery as the Initial Treatment for Patients with Nonfunctioning Pituitary Adenomas