Elsevier

World Neurosurgery

Volume 110, February 2018, Pages e534-e545
World Neurosurgery

Original Article
Postoperative Gamma Knife Radiosurgery for Cavernous Sinus–Invading Growth Hormone–Secreting Pituitary Adenomas

https://doi.org/10.1016/j.wneu.2017.11.043Get rights and content

Objective

We aimed to determine the long-term effects of Gamma knife radiosurgery (GKS) on remnants in the cavernous sinus (CS) after transsphenoidal surgery (TSS) for acromegaly and to identify its possible adverse effects.

Methods

Thirty patients who had remnant tumors only inside the CS after TSS and who consequently underwent GKS were included. They were followed for a median period of 47 months after GKS with regular hormonal and radiologic examinations.

Results

The mean tumor volume and margin dose irradiated by GKS was 3.7 cm3 and 26.2 Gy, respectively. Radiologic tumor control was identified in all patients, and no tumor regrowth or recurrent tumors were identified. For 14 patients who achieved endocrinologic remission, the median duration from GKS until remission was 35 months. The actuarial rates of remission at 2, 5, and 10 years were 7.1%, 43.6%, and 65.6%, respectively. The degree of decrease in the nadir GH level in the OGTT at 6 months after GKS was a statistically significant predictor of remission. Newly developed hypopituitarism frequently developed in a time-dependent manner. Radiation necrosis developed in 4 patients with relatively large remnant volumes.

Conclusions

GKS is an effective adjuvant treatment option for remnant tumors inside the CS after TSS. Maximal surgical resection, leaving minimal volume of remnants only inside the CS, allows the safe and sufficient delivery of a radiation dose to tumors, thereby increasing the possibility of remission. However, the risk of new hypopituitarism and radiation necrosis should be considered when tumors inside the CS are treated with GKS.

Introduction

Acromegaly is a neoplastic condition characterized by persistent growth hormone (GH) hypersecretion from pituitary adenoma (PA), which leads to a wide range of cardiovascular, respiratory, endocrine, and metabolic morbidities.1, 2 Transsphenoidal surgery (TSS) is the first-line treatment option for acromegaly. In contrast to endocrine-inactive PAs, leaving even a small residual tumor leads to the continuous hypersecretion of GH, and thus radical surgery is always required to achieve an endocrinologic cure. Most previous studies have reported 50%–90% remission rates, which are associated with the tumor size.3, 4, 5

The main factor that hinders remission is the presence of cavernous sinus (CS) invasion, which is encountered more frequently in acromegaly than other types of PA. However, exploration of the CS is always a risky procedure, and it is often impossible to achieve complete surgical resection, even by experienced surgeons. The presence of remnant tumors necessitates adjuvant therapy comprising pharmacologic or radiation treatment. Stereotactic radiosurgery, particularly gamma knife radiosurgery (GKS), is currently a major alternative treatment modality for residual or recurrent PAs. Many studies have reported the effectiveness of GKS for GH-secreting PA6, 7, 8 with endocrinologic remission rates of 42%–52%. However, various complications also have been reported, such as post-GKS hypopituitarism, visual deterioration, and radiation-induced brain necrosis.

In our series, it has been always our strategy to remove the intrasellar and suprasellar parts of the tumor completely to leave minimal remnants only inside the CS. Furthermore, tumors in the lateral compartment of the CS in the case of tumors encasing the internal carotid artery are also removed as much as possible to reduce the tumor volume for irradiation after GKS. Consequently, GKS always targets the remnants inside the CS while minimizing the radiation dose applied to nearby critical neuroanatomical structures. In this study, we describe our experiences of postoperative GKS for 30 GH-secreting PA remnants localized only inside the CS.

Section snippets

Patient Population and TSS Procedure

We reviewed a pituitary tumor database comprising 507 patients with acromegaly who underwent TSS between 1995 and 2014 by our senior neurosurgeon (S.H.K.). All patients were diagnosed as having GH-secreting PAs based on positive results in the oral glucose tolerance test (OGTT) as well as their insulin-like growth factor-1 (IGF-1) level and sellar dynamic magnetic resonance imaging (MRI). The diagnosis was confirmed by histopathologic examination in all patients. This study was approved by the

Patient Characteristics

The patient characteristics are summarized in Table 1. This study included 23 women and 7 men with a mean age of 39.0 years (range, 22–63 years). Only 1 patient (patient 1) underwent U-type GKS. C-type GKS was used for radiosurgical procedures in 10 patients (patients 2–11). In the other 19 patients (patients 12–30), the latest model of GKS, Perfexion, was used. GKS was performed at a mean interval of 18.2 months (range, 1–114 months) after TSS. In total, 19 patients (61.3%) underwent GKS

Discussion

Surgical treatment is the first-line option even for CS-invading GH-secreting tumors because many of them can possibly be cured by surgery alone. As the result of advances in surgical techniques and equipment, the chance of cure by TSS alone has reached 70% for GH-secreting PAs.12 However, it is still very challenging to achieve remission when CS invasion is present, and thus this is regarded as the most significant unfavorable prognostic factor for remission. According to our experience,

Conclusions

Maximal surgical resection, leaving the minimal remnant volume only inside the CS, facilitates the safe and sufficient delivery of a radiation dose to target tumors, thereby increasing the possibility of remission. After GKS, new hypopituitarism may develop in a time-dependent manner, where it mainly affects the TSH, LH/FSH, and ACTH axes, rather than PRL. The risk of radiation necrosis in the temporal lobe should be considered if a relatively large tumor remains in the lateral compartment of

Acknowledgments

The authors thank Juyoon Park, R.N., M.P.H., O.C.N., Min Kyeong Jang, R.N., Sung Ja Kang, R.N., and Bok Soon Lee, R.N., Pituitary Tumor Center; Ji Hyoun An, R.N., Gamma Knife Center; and Soo Yeon Choi, M.P.H., Department of Medical Recording for their tremendous effort in performing the endocrinologic tests and data acquisition for such a long follow-up duration.

References (23)

  • F. Castinetti et al.

    Radiotherapy and radiosurgery of pituitary adenomas

    Presse Med

    (2009)
  • A. Colao et al.

    Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients

    J Clin Endocrinol Metab

    (2006)
  • S. Melmed

    Medical progress: acromegaly

    N Engl J Med

    (2006)
  • E. Erturk et al.

    Outcome of surgery for acromegaly performed by different surgeons: importance of surgical experience

    Pituitary

    (2005)
  • P. Nomikos et al.

    The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical 'cure'

    Eur J Endocrinol

    (2005)
  • I. Shimon et al.

    Transsphenoidal surgery for acromegaly: endocrinological follow-up of 98 patients

    Neurosurgery

    (2001)
  • M. Losa et al.

    The role of stereotactic radiotherapy in patients with growth hormone-secreting pituitary adenoma

    J Clin Endocrinol Metab

    (2008)
  • B.E. Pollock et al.

    Radiosurgery of growth hormone-producing pituitary adenomas: factors associated with biochemical remission

    J Neurosurg

    (2007)
  • B.E. Pollock et al.

    Results of stereotactic radiosurgery in patients with hormone-producing pituitary adenomas: factors associated with endocrine normalization

    J Neurosurg

    (2002)
  • C.R. Ku et al.

    Surgical and endocrinological outcomes in the treatment of growth hormone-secreting pituitary adenomas according to the shift of surgical paradigm

    Neurosurgery

    (2012)
  • E.H. Kim et al.

    Predicting long-term remission by measuring immediate postoperative growth hormone levels and oral glucose tolerance test in acromegaly

    Neurosurgery

    (2012)
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    Conflict of interest statement: This study was supported by a grant from a faculty research grant of Yonsei University College of Medicine for 2013 (6–2014–0050).

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