Recurrent Pituitary Adenomas Research Articles

Endoscopic Transmaxillary Transposition of Temporalis Flap for Recurrent Cerebrospinal Fluid Leak Closure.

Objective To describe the technique of endoscopic transmaxillary temporalis muscle flap transposition for the repair of a persistent postoperative sphenoidal cerebrospinal fluid leak. Design The repair of a recurrent cerebrospinal fluid leak for a patient who had undergone endoscopic transsphenoidal excision of an invasive silent corticotroph Hardy C and Knosp Grade IV pituitary adenoma was undertaken. The patient had completed postoperative radiotherapy for the residual tumor and presented with cerebrospinal fluid leak, 1 year later. The initial two attempts to repair the cerebrospinal fluid leak with free grafts failed. Therefore, an endoscopic transmaxillary transposition of the temporalis muscle flap was attempted to stop the cerebrospinal fluid leak. Results The endoscopic transmaxillary transposition of the vascularized temporalis muscle flap onto the cerebrospinal fluid leak repair site resulted in successful closure of the cerebrospinal fluid leak. Conclusion Endoscopic transmaxillary transposition of the temporalis flap resulted in closure of recurrent cerebrospinal fluid leak in a patient with recurrent pituitary adenoma, who had undergone previous surgery and radiotherapy. This technique has advantages over the endoscopic transpterygoid transposition of the same flap and could be used as a complementary technique in selected patients.

HTERT promoter methylation in pituitary adenomas

Telomerase reverse transcriptase (TERT) expression is a hallmark in tumorigenesis and upregulated due to mutations and methylation of the human (h)TERT promoter. As mutations are rare but methylation is common in pituitary adenomas (PA), we determined promoter methylation and its clinical impact in 85 primary and 15 recurrent PA by methylation-specific PCR. 40 females (47%) and 45 males (53%) with a median age of 53 years harboring micro-, macro-, and giant adenomas in 12, 82, and 6% were included (prolactinomas, corticotroph, somatotroph, gonadotroph, thyreotroph, plurihormonal, and null cell adenomas in 11, 18, 10, 29, 1, 10, and 21%, respectively). In primary diagnosed tumors, methylation rate was 27% and higher in males than in females (40 vs. 13%, p = 0.001) after uni- and multivariate analyses. Methylation differed among PA subtypes (0-42%, p = n.s.) and was not significantly correlated with tumor size, cavernous sinus invasion, or serum hormone levels. Ki67 labeling index and recurrence (N = 16, 19%) were independent of methylation. In recurrent tumors, methylation was similar to primary PA (N = 5/15, 33%) and remained unchanged along follow-up. Thus, while being commonly observed in PA, hTERT promoter methylation is stable along follow-up and independent of most clinical variables, PA subtype, proliferation, and without prognostic value.

Intracranial violation by nasotracheal suction catheter in a patient with a history of transsphenoidal surgery.

A 37-year-old woman underwent transsphenoidal surgery for recurrent pituitary adenoma. Postoperatively, she had a prolonged intensive care unit stay and repeated tracheal intubations because of inadequate airway reflexes. On postoperative day 25, she had difficulty maintaining her airway, and the nursing staff attempted orotracheal suctioning, which failed. Nasotracheal suctioning was then performed. Her level of consciousness declined, warranting reintubation. Computed tomography showed diffuse pneumocephalus and a new parenchymal hemorrhage. The only temporally related event was use of a nasotracheal catheter. This case suggests that nasotracheal suctioning may not be safe in patients who have recently undergone transsphenoidal procedures.

Incidental uptake of (18)F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer.

BackgroundPositron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases.ResultsIn 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma.Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.ConclusionsTo the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.

Clinicopathological study of recurrent pituitary adenomas: a five-year preliminary review

Pituitary adenomas are benign, slow-growing tumors of the pituitary gland that are most successfully treated with surgical removal. However, pituitary adenoma recurrence after surgery can occur. We aim to evaluate the clinical and pathological predictors of recurrent pituitary adenomas. Here we review 160 cases of pituitary adenomas operated 2009–2013. We found 20 patients who presented with tumor recurrence and a second operation had been undertaken. The clinicopathological data of these cases were reviewed.

Feasibility and outcome of re-irradiation in the treatment of multiply recurrent pituitary adenomas

This study evaluates the toxicity and outcomes of re-irradiation to the sella for pituitary adenomas. Patients diagnosed with a pituitary adenoma and treated with two or more courses of radiation treatment (RT) to the sella were retrospectively analyzed for: initial diagnosis, including histological type and functional status; RT modality, technique, dose, and fractionation; treatment with surgery, endocrine agents, and chemotherapy; toxicity of RT including radiation-induced optic neuropathy, radionecrosis, and radiation-induced neoplasms; and outcomes including local control, distant metastasis, biochemical control of functional tumors, and vital status at last follow-up. We identified 15 patients with non-functioning pituitary adenoma (n = 6), Cushing's disease (CD) (n = 5), acromegaly (n = 3), and prolactinoma (n = 1). Initial RT was delivered using opposed lateral fields in 8 (53%), intensity-modulated radiation therapy (IMRT) in 4 (27%), fractionated stereotactic radiation therapy (FSRT) in 1 (6.7%), and stereotactic radiosurgery (SRS) in 2. The median dose was 49.5 Gy for fractionated RT and 15-25 Gy for SRS. Re-irradiation was performed a median of 5.8 years after initial RT, and delivered using lateral opposed beams (n = 1), IMRT (n = 4), linear-accelerator based SRS (n = 3), FSRT (n = 3), gamma knife surgery (n = 2), and yttrium-90 brachytherapy (n = 1). The median dose of re-irradiation was 45 Gy (range 27.9-54 Gy) for fractionated RT and 18 Gy for SRS. Radiation-induced optic neuropathy (RION) was observed in 2 (13.3%) patients, 6 months and 14 years after re-irradiation; the 5-year rate of RION was 9 %. Temporal lobe necrosis (TLN) occurred in two patients (13.3%), both of whom had received SRS. The 2- and 5-year rates of TLN were 10 and 28%. Actuarial local control rates at 2 and 5 years were 80 and 58%, respectively. Biochemical remission occurred in one of three patients with CD. Four patients (27%) ultimately developed pituitary carcinoma. Re-irradiation is a feasible treatment option for local control in patients with recalcitrant pituitary adenomas, with acceptable rates of RION and TLN given the lack of options that may be available otherwise. Re-irradiation, however, did not control hormonal hypersecretion.

Expression of somatostatin receptors, angiogenesis and proliferation markers in pituitary adenomas: an immunohistochemical study with diagnostic and therapeutic implications

Pituitary adenomas are common intracranial neoplasms that generate symptoms as a result of either mass effect or the increased production of pituitary hormones. Although mostly benign, these tumours can be associated with considerable morbidity. We investigated a panel of immunohistochemical preparations to identify potential therapeutic targets and surrogate markers of clinical outcome. Tumour tissue from 25 patients was evaluated for immunohistochemical expression of somatostatin receptors 1‒5, von Willebrand-factor (vWF), interleukin-8 (IL-8), vascular endothelial growth factor receptor 2 (VEGFR-2), kinesin spindle protein (Eg5) and MIB-1 (Ki-67), and its relationship with clinical features was analysed. The proliferation marker MIB-1 (Ki-67) was the only marker predictive of adenoma recurrence. Of note, 67% of all relapses were associated with tumours showing luteinising hormone expression. All pituitary adenomas showed variable somatostatin receptor, IL-8, Eg5, vWF and VEGFR-2 expression; a relationship between these parameters and clinical outcome could not be demonstrated in this cohort. This study validates MIB-1 (Ki-67) as a reliable marker of tumour recurrence in pituitary adenomas. Considering the consistently increased expression of Eg5, IL-8, VEGFR-2, somatostatin receptors and vWF in these tumours, further investigation as potential therapeutic targets is warranted.

Functional Pituitary Adenoma Recurrence After Surgical Resection

ituitary adenoma is the third most commonly diagnosed primary brain tumor after meningioma and glioma. PituiP tary adenomas account for 14.1% of all primary intracranial neoplasms (4). Surgical resection is the preferred primary treatment for many pituitary adenomas. Up to one third of surgically resected tumors will recur, usually in the first 5 years after surgery (8). The indications for and preferred methods of treating recurrent pituitary adenomas vary with type of tumor. Either nonfunctional pituitary adenomas or functional (endocrinologically active) pituitary adenomas (FPA) may cause symptoms of mass effect at recurrence requiring treatment. The latter may need treatment for symptomatic elevated serum hormone levels regardless of tumor size, which may require further treatment. Predicting which pituitary tumors are more likely to recur is of extreme clinical importance in guiding the intensity of clinical, radiologic, and hormonal follow-up and the need for adjuvant therapy after surgical resection.

Fractionated stereotactic radiosurgery using the Novalis system for the management of pituitary adenomas close to the optic apparatus

Radiosurgery has been proven to be an effective treatment for residual or recurrent pituitary adenomas after surgery. However, it causes severe complications when the optic apparatus is irradiated over the tolerance dose. In this study, we analyzed the feasibility of fractionated stereotactic radiosurgery to treat pituitary tumors close to the optic apparatus. Thirty-four patients from June 2006 to June 2011 with recurrent or residual pituitary adenomas close to (<3mm) the optic apparatus were treated with fractionated stereotactic radiosurgery. Three fractions with a total dose of 2100cGy were applied to the tumors. Imaging, examination of vision, and estimation of hormone level were regularly performed before and after radiosurgery. The mean tumor volume before fractioned stereotactic radiosurgery was 5.06±3.08cm3 (range: 0.82–12.69cm3). After a mean follow up of 36.8±15.7months (range: 16–72months), tumor size was reduced in seven (20.6%) patients and remained the same in the other 27 (79.4%) patients. Vision was improved in one patient and remained stable in the rest. Only one patient developed transient post-treatment diplopia. This study suggests that fractionated stereotactic radiosurgery is safe for treating pituitary adenomas close to the optic apparatus. Studies with more patients and longer follow-up are required to draw definite conclusions.

Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas

The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas. We report on 37consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4Gy (range 45-52.2Gy), 5 × 1.8Gy weekly. The mean PTV was 22.8ccm (range 2.0-78.3ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination. Tumor control was 91.9 % for a median follow-up time of 57months (range 2-111months). Before FSRT partial hypopituitarism was present in 41 % of patients, while 35 % had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had anterior panhypopituitarism. Visual acuity was stable in 76 % of patients, improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35patients (95 %), improved in one and worsened in 1patient (2.7 %). FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors.

Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness

Introduction and objective The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67.

Hepatocellular carcinoma metastasis to the brain mimicking primary pituitary tumor around the sella turcica.

We report on two cases of hepatocellular carcinoma (HCC) with metastasis to the cavernous sinus and sphenoid sinus. Both cases presented with diplopia and retro-orbital headache and both underwent surgery for a primary pituitary gland tumor. After surgery, both cases were diagnosed with metastases from HCC. Case 1 was a 67-year-old male with a history of HCC who was referred to our hospital for pituitary tumor surgery. The tumor appeared to be in the sella turcica and to invade the sphenoid sinus and right cavernous sinus. Transnasal transsphenoidal surgery (TSS) was performed. The tumor was postoperatively diagnosed by histology to be a metastatic pituitary tumor from HCC. Radiotherapy was administered to the metastatic site. Case 2 was a 58-year-old male with a history of TSS for a pituitary tumor 16years previously. He was referred to our hospital for TSS for a recurrent pituitary adenoma. TSS was performed twice in 3months. During a preoperative general examination, HCC and chronic hepatitis B were revealed. TSS was performed initially, followed by arterial infusion chemotherapy. After TSS, the pituitary tumor was diagnosed by histology to be a metastasis from HCC. As with Case 1, radiotherapy was administered to the metastasis. Most tumors in the sella turcica are pituitary adenomas, although some cases of metastatic pituitary tumors and skull base metastases have been reported. Distant metastases generally have a poor prognosis; however, surgery to the metastatic site can effectively control symptoms caused by the metastatic tumor.

A Novel Technique for Pedicled Nasoseptal Flap Takedown in Revision Skull Base Surgery

Objective To describe a novel technique of using the CO2 laser for a revision pedicled nasoseptal flap (PNSF) takedown. Patient Patient with a pituitary adenoma recurrence that had undergone an endoscopic skull base resection with a nasoseptal flap repair 3 years prior. Procedure Flap edges and bony defect are examined using an image-guidance probe to identify the full extent of the defect. The CO2 laser fiber is used to incise through to the underlying skull base. The flap is then elevated from its most distal portion toward the pedicle, using the laser to cut adhesions away from the underlying dura. The skull base defect is then repaired with an onlay graft of acellular dermis, then the PNSF. Results The laser was adept at dissecting through mucosa to the underlying bone and at dissecting the underside of the flap from the posterior adhesions and intradural structures safely. Conclusion The novel use of the of the CO2 laser for the flap takedown was very effective at safely making the mucosal cuts and dissecting the flap from the underlying structures. The nasoseptal flap takedown can be a technically challenging procedure that was made easier by the use of the CO2 laser.

Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness

Introduction and objectiveThe ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67. Materials and methodsIn this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46±36 months. ResultsExtrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st–3rd quartile: 0.000–0.089] NCN vs. 0.135 [0.105–0.159] NCN, p=0.04). IGF1R expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69±3.84 NCN vs. 5.44±3.55 NCN, p=0.014). ConclusionsOur results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples.

Feasibility of Endoscopic Endonasal Approach for Recurrent Pituitary Adenomas after Microscopic Trans-Sphenoidal Approach

ObjectiveThe surgical approach for recurrent pituitary adenoma after trans-sphenoidal approach (TSA) is challenging. We report the outcomes of the endoscopic TSA for recurrent pituitary adenoma after microscopic TSA.MethodsFrom February 2010 to February 2013, endoscopic TSA was performed for removal of 30 recurrent pituitary adenomas after microscopic TSA. Twenty-seven (90%) patients had a clinically non-functioning pituitary adenoma. Twenty-four (80%) patients suffered from a visual disturbance related to tumor growth. The clinical features and surgical outcomes were retrospectively analyzed for the ophthalmological, endocrinological, and oncological aspects.ResultsThe mean tumor volume was 11.7 cm3, and gross total resection was achieved in 50% of patients. The volumetric analysis based on the postoperative MR showed that the mean extent of resection rates were 90%. Vision was improved in 19 (79%) of 24 patients with visual symptoms, and endocrinological cure was achieved in all of three functioning pituitary adenomas; however, the post-operative follow-up endocrinological examination revealed a new endocrinological deficit in one patient. Two patients required antibiotics management for post-operative meningitis.ConclusionThe endoscopic TSA can be an effective treatment option for recurrent pituitary adenoma after microscopic TSA with acceptable outcome.

Endoscopic Surgery of Cavernous Sinus Tumors Originating from the Extradura

In the present study, we explored the effects of various endoscopic approaches in patients with cavernous sinus (CS) tumors. Five endoscopic approaches, including the endoscopic transseptal transsphenoidal approach, extended endoscopic transseptal transsphenoidal approach, extended transnasal transmaxillary approach, extranasal extended maxillary sinus approach, and endoscopic transnasal transpterygoid approach, were selected for the resection of CS tumors from 36 patients. Thirty gross total tumors and 6 subtotal tumors were removed. After a follow-up period of 6 months to 3 years, 30 patients were determined to be recurrence-free, and 2 patients had unchanged residual tumors. One patient with a recurrent pituitary adenoma underwent a second surgery, and 1 patient with chordoma died because of an intracavernous carotid artery rupture 18 months after the operation. Various endoscopic approaches tailored to the origin and extent of the CS tumor were proven efficacious for the maximal and precise removal of CS tumors while avoiding vital structures.

Towards an integrated molecular and clinical strategy to predict early recurrence in surgically resected non-functional pituitary adenomas

Pituitary adenomas (PA) are histologically benign tumors of the sella that are capable of recurrence following resection. No mechanism exists to predict accurately the risk of recurrence in patients with PA following successful gross total surgical resection. We used microarray-based gene expression profiling to search for genotypically distinct subgroups of non-functional PA associated with the early recurrent phenotype. Rigorous phenotypic controls were used to select four patients with PA with early (<12months) recurrence and seven patients with non-recurrent PA for comparative molecular analysis. Seventy genes with differential expression patterns between the phenotypic groups were identified, although this required some relaxation of rigid multiple-testing corrections. While some of these genes may therefore represent statistical false discoveries attributable to limited sample size, the CHL1 gene has a differential expression patterns that suggests a potential role as a predictor of recurrence phenotype. Transcriptome-level differences between early recurrent and non-recurrent non-functional PA appear to be subtle, although CHL1 expression may be a candidate for further study as a class discriminator. This suggests two possibilities with regard to recurrence; (i) that microscopic residual disease unidentifiable either by the surgeon or by current neuroimaging strategies may serve as a focus for early recurrence or that biological differences in recurrence phenotypes may occur outside of the transcriptome. These findings are useful for focusing future investigations into the clinical and biological mechanisms of PA recurrence as well as for development of strategies designed to predict prospectively these recurrence phenotypes.

Pituitary lymphoma developing within pituitary adenoma

Lymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with a history of pituitary adenoma was diagnosed with diffuse large B-cell lymphoma (DLBCL) of the left ocular adnexa, which was successfully treated by standard chemotherapy and local radiotherapy. Eight months later, he complained of diplopia and bitemporal hemianopia. Brain magnetic resonance imaging detected a suprasellar tumor. Transsphenoidal biopsy of the mass was performed, and histopathological examination revealed DLBCL admixed with pituitary adenoma. On a review of the literature, we found that pituitary lymphoma developing within adenoma is a recurrent phenomenon. The composite tumor is likely to be characterized by suprasellar involvement and presentation of visual disturbances. Moreover, in the present case, the suprasellar tumor remained visible after autologous peripheral stem cell transplant, likely due to the residual pituitary adenoma. We therefore recommend that refractory pituitary lymphoma should be vigorously biopsied in search of possibly underlying adenoma.

Cranial nerve dysfunction following Gamma Knife surgery for pituitary adenomas: long-term incidence and risk factors

Gamma Knife surgery (GKS) has become a significant component of neurosurgical treatment for recurrent secretory and nonsecretory pituitary adenomas. Although the long-term risks of visual dysfunction following microsurgical resection of pituitary adenomas has been well studied, the comparable risk following radiosurgery is not well defined. This study evaluates the long-term risks of ophthalmological dysfunction following GKS for recurrent pituitary adenomas. An analysis of 217 patients with recurrent secretory (n = 131) and nonsecretory (n = 86) pituitary adenomas was performed to determine the incidence of and risk factors for subsequent development of visual dysfunction. Patients underwent ophthalmological evaluation as part of post-GKS follow-up to assess for new or worsened cranial nerve II, III, IV, or VI palsies. The median follow-up duration was 32 months. The median maximal dose was 50 Gy, and the median peripheral dose was 23 Gy. A univariate analysis was performed to assess for risk factors of visual dysfunction post-GKS. Nine patients (4%) developed new visual dysfunctions, and these occurred within 6 hours to 34 months following radiosurgery. None of these 9 patients had tumor growth on post-GKS neuroimaging studies. Three of these patients had permanent deficits whereas in 6 the deficits resolved. Five of the 9 patients had prior GKS or radiotherapy, which resulted in a significant increase in the incidence of cranial nerve dysfunction (p = 0.0008). An increased number of isocenters (7.1 vs 5.0, p = 0.048) was statistically related to the development of visual dysfunction. Maximal dose, margin dose, optic apparatus dose, tumor volume, cavernous sinus involvement, and suprasellar extension were not significantly related to visual dysfunction (p >0.05). Neurological and ophthalmological assessment in addition to routine neuroimaging and endocrinological follow-up are important to perform following GKS. Patients with a history of radiosurgery or radiation therapy are at higher risk of cranial nerve deficits. Also, a reduction in the number of isocenters delivered, along with volume treated, particularly in the patients with secretory tumors, appears to be the most reasonable strategy to minimize the risk to the visual system when treating recurrent pituitary adenomas with stereotactic radiosurgery.

LINAC-radiosurgery for nonsecreting pituitary adenomas

Stereotactic linear accelerator-based radiosurgery (LINAC-RS) is increasingly used for microsurgically inaccessible or recurrent pituitary adenomas. This single-center study evaluates the long-term follow-up after LINAC-RS of nonsecreting pituitary adenomas (NSA). Between 1992 and August 2008, 65 patients with NSA were treated. Patient treatment and follow-up were conducted according to a prospective protocol. Indications for LINAC-RS were (1) tumor recurrence or (2) residual tumor. Three patients were treated primarily. For analysis of prognostic factors, patients were grouped according to epidemiological or treatment-associated characteristics. A total of 61 patients with a follow-up ≥ 12 months (median 83 months, range 15-186 months, longest follow-up of published radiosurgery series) were evaluated with regard to their clinical, radiological, and endocrinological course. The median tumor volume was 3.5 ml (± 4.3 ml, range 0.3-17.3 ml) treated with a median surface and maximum dose of 13.0 Gy and 29.7 Gy, respectively. Local tumor control was achieved in 98%. One patient died of unrelated cause after 36 months and 1 patient developed a radiation-induced seizure disorder. Visual complications did not occur. In 37 of 41 patients (90.2%), pituitary function remained stable. Maximum dose to the pituitary ≤ 16 Gy and female gender were positive prognostic factors for the preservation of pituitary function. LINAC-RS is a minimally invasive, safe, and effective treatment for recurrent NSA or microsurgically inaccessible residual tumor. LINAC-RS yielded a high rate of local long-term tumor control with a small number of radiation-induced side effects.