Treatment Of Nonfunctioning Pituitary Adenomas Research Articles

Outcomes Associated With Stereotactic Radiosurgery After Multiple Resections of Nonfunctioning Pituitary Macroadenomas: An International, Multicenter Case Series

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections. METHODS: Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (≥2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan–Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism. RESULTS: Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone ≥2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P-value = .004). CONCLUSION: For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection.

Treatment of non-functioning pituitary adenoma with cabergoline: a systematic review and meta-analysis.

To make a systematic review and meta-analysis of studies evaluating the effect of cabergoline (CBG) in the treatment of non-functioning pituitary adenomas (NFPAs). The primary outcome was tumor shrinkage, using as cut-off a reduction of at least 20% of the NFPA size from baseline. The secondary outcomes were prevention of tumor progression, clinically required additional interventions and adverse events (AE). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Random meta-analysis for the proportion of tumor shrinkage, prevention of tumor progression, clinically required additional interventions and frequency of AE were conducted. Five studies were included. The meta-analysis of proportion was 19% for tumor shrinkage (95% CI 8-38%, 4 studies, 108 participants), 50% for prevention of tumor progression (95% CI 35-64%, 5 studies, 187 participants), 14% for clinically required additional interventions (95% CI 6-30%, 4 studies, 128 participants) and 2% for adverse events (95% CI 1-6%, 3 studies, 157 participants). Effect of CBG to promote tumor shrinkage in NFPAs was low, while prevention of tumor progression after surgery was seen in half of the cases, with a low frequency of adverse events. PROSPERO CRD42020206778.

Long-term hormonal and imaging outcomes of adjunctive gamma knife radiosurgery in non-functioning pituitary adenomas: a single center experience.

Gamma Knife Radiosurgery(GKRS) is an established modality for treatment of non-functioning pituitary adenomas(NFPA). The objective of the study was to assess long-term hormonal and imaging outcomes after adjunctive GKRS in patients with NFPA. A retrospective review of records of 109 patients with NFPA, from 1996 to 2020, who received adjunctive GKRS, was performed. Patients who had received GKRS as the primary modality of treatment for NFPA were not included. Sixty-three (57.8%) patients were available for follow up at our institute. The median follow-up period was 47months (range, 6-260). At a median time of 38months (range, 8-97), 25 (39.7%) patients developed ≥ 1 new pituitary hormone deficiency. Median time to cortisol deficiency was 38months (range, 8-55), thyroid hormone deficiency was 45.5months (range, 12-97) and gonadotropin deficiency was 45months (range, 21-75). The actuarial risk of developing a new pituitary hormone deficit at 1, 3, 5, 7, and 10years was 2.5%, 11%, 26.3%, 28% and 29.7%, respectively. Adenoma size decreased in 36 (57.1%) patients, remained unchanged in 19 (30.2%) patients, and increased in 8 (12.7%) patients. Overall tumor control rate was 87.3%. Endocrinopathy-Free Survival was 47.1%, and tumor Progression-Free Survival was 93.3%, at 5years. Five (4.6%) patients required additional treatment after GKRS. One (1.6%) patient each had worsening of headache, optic atrophy and cerebellar infarct after GKRS therapy. GKRS offers a safe adjunctive treatment modality, with satisfactory long-term preservation of hormone functions and a high rate of tumor control, in patients with NFPA.

Microsurgical versus endoscopic surgery for non-functioning pituitary adenomas: a retrospective study

AimTo compare microsurgical technique (mTSS) and endoscopic technique (eTSS) in the treatment of non-functioning pituitary adenomas (NFPAs).MethodsWe retrospectively evaluated the charts of 50 patients who underwent either mTSS or eTSS for NFPA in the Department of Neurosurgery, University Hospital Hradec Kralove from 2013 to 2019. We enrolled all patients who were not treated by postoperative adjuvant radiotherapy and who underwent at least two regular postoperative magnetic resonance imaging (MRI) tests. We compared the groups in terms of the extent of resection, surgery duration, blood loss, complication rate, overall clinical effect on the endocrinological and ophthalmological deficit, and postoperative growth pattern of the residual tumor mass.ResultsThe mTSS group had significantly shorter surgical time (75 min vs 127 min, P < 0.001) and lower perioperative blood loss (156 mL vs 256 mL, P = 0.027). The groups did not significantly differ in the extent of resection, overall clinical or hormonal effect, and the complication rate. The extent of resection did not correlate with tumor consistency, while the tumor growth rate did not correlate with age or Ki-67 expression.ConclusionsThere was no major difference between the approaches in surgery radicality or safeness. However, eTSS remains the method of choice due to its potentially higher postoperative preservation of hormonal functions.

The natural history and treatment of non-functioning pituitary adenomas (non-functioning PitNETs).

Non-functioning pituitary adenomas, recently alternatively termed pituitary neuroendocrine tumours (NFpitNETs), are mostly benign neoplasms that are not associated with a hormonal hypersecretory syndrome. The clinical spectrum of NFpitNETs varies from completely asymptomatic to the development of panhypopituitarism and manifestations attributed to mass effects on nearby structures. NFpitNETs follow generally an indolent course, but in 5-10% of cases they exhibit more aggressive behaviour, characterised by rapid growth, invasiveness and early recurrence. The initial size of the adenoma, the presence of symptoms and the histological subtype are related to the natural course of NFpitNETs. Active surveillance is usually the strategy of choice in the case of an asymptomatic NFpitNET, while surgical resection is recommended in case of visual and/or neurological abnormalities or rapid tumour growth. Based on previous and emerging data, approximately 50% of patients show tumour growth, while 20% of patients with NF-macroadenomas on active surveillance may require further intervention during a follow-up period of 7 years. Adjuvant radiotherapy is usually considered for large residual tumours or recurrent and/or aggressive adenomas, but there is evidence that medical therapy, especially with cabergoline, can occasionally be beneficial, whereas newer molecular agents are under investigation. Thus, while highly effective medical therapy is awaited, a move towards a more conservative approach seems appropriate, at least until we have better molecular markers of progressiveness.

Regression of a nonfunctioning pituitary macroadenoma on the CDK4/6 inhibitor palbociclib: case report

A 71-year-old female patient was referred in 2013 for evaluation of an asymptomatic nonsecreting pituitary adenoma. The adenoma, measuring 13 mm in height by 10 mm in width, was discovered incidentally on imaging in 2012. Biochemical testing demonstrated a nonfunctioning adenoma. Given the relatively small lesion size and the lack of symptoms, observation was preferred over surgical intervention. The patient was monitored with routine MRI, which until 2016 demonstrated minimal growth. In early 2016, the patient developed recurrence of metastatic breast cancer and was treated with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor. This inhibitor acts on a pathway believed to be involved in pituitary adenoma tumorigenesis. One year after starting palbociclib, routine imaging demonstrated significant regression of her pituitary adenoma. The authors hypothesize that inhibition of the CDK4/6 pathway by palbociclib contributed to adenoma regression in this patient, and that palbociclib may represent a possible adjuvant therapy for the treatment of nonfunctioning pituitary adenomas.

Fibroblasts play a potential role in bone destruction via osteopontin related caldesmon expression and polymerization in human non-functioning pituitary adenomas

Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.

Low expression of secreted frizzled-related protein 2 and nuclear accumulation of β-catenin in aggressive nonfunctioning pituitary adenoma.

The identification of a specific molecular marker for aggressiveness of nonfunctioning pituitary adenomas (NFPAs) is urgently required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, low expression of secreted frizzled-related protein 2 (sFRP2) in NFPAs was demonstrated by reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemical analyses. The results confirmed an abnormal accumulation of free β-catenin in the nuclei of NFPAs, which is the core step for the activation of the Wnt canonical signaling pathway. Furthermore, cyclin D1 and c-Myc, the downstream proteins of the Wnt canonical signaling pathway, were overexpressed in aggressive NFPAs. These findings demonstrated the activation of the Wnt canonical signaling pathway in aggressive NFPAs. In addition, sFRP2 expression was observed to be inversely correlated to the aggressiveness of NFPAs. Therefore, sFRP2 may act as a tumor suppressor through modulation of the cellular cytosolic pool of β-catenin in NFPAs. Furthermore, the expression of sFRP2 may serve as a biomarker for NFPAs aggressiveness and prognosis.

Health-related quality of life in patients treated for nonfunctioning pituitary adenomas during the years 2000-2010.

The published data on health-related quality of life (HRQoL) after treatment of nonfunctioning pituitary adenomas (NFPAs) are conflicting. We evaluated HRQoL in a recent series of patients who had surgery for an NFPA. Cross-sectional study including a large control population. A HRQoL questionnaire (15D) was sent to all patients (n = 161) having undergone transsphenoidal surgery for NFPA in the years 2000-2010 at the Helsinki University Hospital. The 15D score and dimension scores of the study population (n = 137) were compared with those of a large (n = 4967) gender- and age-standardized control population. Possible independent predictors of HRQoL in the patients were estimated with multivariate regression analysis. Postoperatively, 57% of the patients had normal visual function. After a mean follow-up of 7·4 ± 3·2 years (mean ± SD), 62% suffered from hypopituitarism. Overall, HRQoL was near-normal in patients compared to controls (15D scores 0·885 ± 0·114 vs 0·903 ± 0·093, respectively, P = 0·07). On single dimensions, patients had impaired vision and sexual activity (both P < 0·0005), more depression and distress (both P < 0·005) and less discomfort and symptoms (P < 0·05). Age, body mass index, diabetes, depression and reoperation were independent predictors of impaired HRQoL (all P < 0·05). Thyroxine substitution was associated with impaired and hydrocortisone and testosterone substitution (males only) with better HRQoL (all P < 0·05). This recent series of NFPA patients demonstrates that overall HRQoL is near-normal after medium term follow-up; the most impaired dimensions were in vision and sexual activity. Comorbidities are strong predictors of impaired HRQoL.

Minimally Invasive Endoscopic Endonasal Transphenoid Approach for Resection of Pituitary Macroadenoma: Case Report and Literature Review

Background: Endoscopic endonasal transsphenoidal resection of pituitary adenomas is a common treatment modality used for the treatment of nonfunctioning pituitary adenomas due to its minimally invasive approach, excellent result yields and limited complications. Other treatment options, such as Gamma Knife radiosurgery (GKRS) can be considered as a suitable primary approach, however, GKRS is associated with a higher rate of treatment failure and tumor recurrence. Here we describe the case of recurrent pituitary macroadenoma post-radiosurgery treatment with Gamma Knife that was then treated via surgical resection with an endonasal endoscopic transsphenoidal approach. Case Description: We report the case of an 82 year-old male with a primary diagnosis of non-functioning pituitary macroadenoma. The patient presented with an initial complaint of an unrelated syncopal episode. During workup an incidental suprasellar mass was found and determined to be a nonfunctioning pituitary macroadenoma. The patient was initially treated with radiosurgery by Gamma Knife, however, 3 months later presented with an acute episode of headaches, nausea and vomiting, altered mental status, diplopia and a bitemporal hemianopsia. Work up and imaging revealed panhypopituitarism and a suprasellar mass. An endonasal endoscopic transsphenoidal approach was undertaken for resection. Conclusion: Various treatment modalities are available for the management of pituitary adenomas. Gamma Knife radiosurgery is a safe and effective treatment as a primary therapy as well as a co-adjuvant to surgical resection. However, there exists a probability of treatment failure and tumor recurrence with GKRS as well as attention should be paid to the adverse affects that can develop post-radiosurgery. Endoscopic transsphenoidal resection is a minimally invasive surgical procedure that can safely be employed as a treatment option for primary and recurrent pituitary macroadenomas.

Clinical characteristics and treatment outcome of 485 patients with nonfunctioning pituitary macroadenomas.

Background. Nonfunctioning pituitary adenomas (NFPAs) are the most common benign lesions of the pituitary gland. Objective. To describe our experience with the management of NFPA. Study Design and Methods. Retrospective evaluation of NFPA patients managed between 2008 and 2013. We analyzed data regarding clinical presentation, imaging diagnosis, hormonal status, surgical, radiotherapeutic, and pharmacological treatment, and outcome. Results. 485 patients (54% men, mean age 53 ± 14 years) were followed for a median of 6.5 years. Visual field abnormalities and headaches were the presenting complaints in 87% and 66%, respectively. The diagnosis of NFPA was made incidentally in 6.2%, and 8% presented with clinical evidence of apoplexy. All patients harbored macroadenomas, with a median volume of 10306 mm3; 57.9% had supra- or parasellar invasion and 19.6% had tumors larger than 4 cm. Central hypothyroidism, hypogonadism, and hypocortisolism were present in 47.2%, 35.9%, and 27.4%, respectively. Surgical resection was performed at least once in 85.7%. Tumor persistence was documented in 27% and was related to the size and invasiveness of the lesion. In selected cases, radiotherapy proved to be effective in controlling or preventing tumor growth. Conclusions. The diagnosis and treatment of NFPA are complex and require a multidisciplinary approach.

Patients with adrenal insufficiency hate their medication: concerns and stronger beliefs about the necessity of hydrocortisone intake are associated with more negative illness perceptions.

Patients with adrenal insufficiency (AI) require daily and life-long hydrocortisone substitution with risks of under- and overreplacement, the necessity to adjust the dose in stressful situations, and a lack of clinical and biochemical parameters to assess optimal dosing. The spectrum of medication beliefs in patients with AI is currently unknown. The objective of the study was to examine the possible association between illness perceptions and medication beliefs about hydrocortisone (HC) in patients with AI. This was a cross-sectional evaluation of illness perceptions and medication beliefs in 107 patients with primary AI (n = 49), secondary AI after the treatment of Cushing's syndrome (n = 29), or treatment of nonfunctioning pituitary adenoma (n = 29). The Illness Perception Questionnaire-Revised and the Beliefs about Medicines Questionnaire were used for the assessment. Stronger beliefs about the necessity of HC and stronger concerns about the adverse effects of HC were associated with attribution of more symptoms to AI, to the perception of AI being more cyclical, to the perception of more negative consequences of AI, and to the presence of stronger emotional representations (all P < .05). Furthermore, stronger beliefs about the necessity of HC intake were associated with feelings of less personal control over AI (P < .05). Stronger concerns about the adverse effects of HC were associated with lower perceived treatment control and lower illness coherence (both P < .05). In addition, patients with Cushing's syndrome reported stronger beliefs regarding the necessity of taking HC, compared with patients with Addison's disease (P = .039) or nonfunctioning pituitary adenoma (P < .001). Specific beliefs about the necessity of hydrocortisone replacement and concerns about its adverse effects were strongly associated with more negative illness perceptions. These specific beliefs differed, depending on the etiology of AI. These results need to be taken into account in the treatment of patients with AI and may serve to enable the development of psychosocial education/self-management programs aiming at improving quality of life.

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

The aim of this study was to scrutinize the literature to determine the efficacy and safety of gamma knife surgery (GKS) for the treatment of nonfunctioning pituitary adenomas (NFPAs) with volumetric classification. Electronic databases including MedLine, PubMed, and Cochrane Central were searched. The literature related to patients with NFPAs treated with GKS was collected. Eligible studies reported on the rate of tumor control (RTC), the rate of radiosurgery-induced optic neuropathy injury (RRIONI), the rate of radiosurgery-induced endocrinological deficits (RRIED), and other parameters. A total of 17 studies met the criteria. based on the tumor volume, nfpas were divided into three groups: the RTC of group I (93 patients) with tumor volumes <2 ml was 99% (95% CI 96-100%), the RRIONI was 1% (95% CI 0-4%), and the RRIED was 1% (95% CI 0-4%). The RTC of group II (301 patients) with volumes from 2 to 4 ml was 96% (95% CI 92-99%), the RRIONI was 0 (95% CI 0-2%), and RRIED was 7% (95% CI 2-14%). The RTC of group III (531 patients) with volumes larger than 4 ml was 91% (95% CI 89-94%), the RRIONI was 2% (95% CI 0-5%), and the RRIED was 22% (95% CI 14-31%). There were significant differences in the RTC and in the RRIED among the three groups (P<0.001), indicating that there were higher RRIED and lower RTC with the increase of tumor volume. NFPAs, according to tumor volume classification, need stratification for GKS treatment. GKS is the optimal choice for the treatment of group II NFPAs. Patients with residual tumor volumes of <4 ml will benefit most from GKS treatment.

Low-dose Gamma Knife surgery for nonfunctioning pituitary adenomas

The primary concern when performing Gamma Knife surgery for pituitary adenoma is preservation of vision and pituitary function while achieving tumor growth control. Higher prescribed radiation doses are typically correlated with higher incidences of postradiosurgical hormone deficiencies. The goal of the present study was to retrospectively analyze the feasibility of using a lower prescribed radiation dose in the treatment of nonfunctioning pituitary adenomas and the effect of this dose on vision, pituitary function, and tumor growth control. The study was conducted in 38 patients with nonfunctioning pituitary adenomas, who were treated between January 2002 and July 2008. Twenty-one patients were available for follow-up (13 men and 8 women). The mean follow-up period was 44 months (range 24-90 months). Nineteen patients had previously undergone surgery. Pituitary dysfunction developed after surgery in 3 patients. One patient had an abnormal pituitary hormone profile before radiosurgery due to an attack of pituitary apoplexy. Visual field defects were present in 12 patients. The prescribed radiation dose was 12 Gy in all patients. The tumor volume ranged from 0.5 to 11.8 cm(3) (mean 4.8 cm(3)). The maximum dose to the visual pathway was kept below 10 Gy. The mean maximum dose delivered to the visual pathway was 7.9 Gy. The patients were followed up for a period of 24 to 90 months (mean 44 months). The size of the tumor decreased in 11 patients (52%) and remained stable in 9 patients (43%). In 1 patient there was tumor growth outside the previous radiation field (on the contralateral side). Among the 12 patients with visual field defects, 9 (75%) experienced an improvement and the remaining patients' vision remained stable. In only 4 patients was the visual improvement associated with tumor shrinkage. The hormone profile remained normal in all patients except for the 4 patients who had pituitary dysfunction before radiosurgery. The 12-Gy prescribed dose used in this study seems to be sufficient for producing tumor control while sparing the patient from radiation-induced pituitary dysfunction. In addition, visual improvement was reported in a number of cases. A larger series and longer follow-up are required to confirm these results.

Predictors for visual dysfunction in nonfunctioning pituitary adenomas – implications for neurosurgical management

Despite ample experience with surgical treatment of nonfunctioning pituitary adenomas, objective data defining the risk for visual compromise depending on the suprasellar extension in pituitary adenomas are sparse. We measured the suprasellar extension of 98 newly diagnosed suprasellar nonfunctioning pituitary adenomas on sagittal and coronal magnetic resonance images using reference lines for the skull base level. In addition, the position of the optic chiasm in relation to the suprasellar adenoma was assessed. The findings were correlated with the degree of visual dysfunction and with the type of visual field defects (VFD). Seventy per cent of the patients suffered from VFD. The most frequent perimetric findings were bilateral (81·2%) or unilateral (10·1%) temporal hemifield defects. For the coronal view, a suprasellar extension of 12 mm was a practicable cut-off value for emergence of visual disturbances (87·0% sensitivity, 72·4% specificity). For the sagittal view, 8-mm suprasellar extension was a suitable cut-off for appearance of chiasma syndrome (87·0% sensitivity, 75·9% specificity). In five of seven cases without a chiasma syndrome despite a suprasellar extension >12 (coronal) and 8 mm (sagittal), the optic chiasm was found in an anterior position. No correlation was found between the position of the chiasm (i.e. anterior, superior or posterior) and the type of VFD (P = 0·647). A highly significant correlation was found between the decline of visual acuity and the suprasellar adenoma extension (P < 0·0001). Cut-off values possess a high sensitivity and specificity for imminent visual disturbances and are helpful for clinical decision-making. A delayed emergence of visual dysfunction may be observed with an anterior position of the optic chiasm.

Short-term treatment with cabergoline can lead to tumor shrinkage in patients with nonfunctioning pituitary adenomas

This study was carried out to evaluate the effectiveness of cabergoline in the treatment of nonfunctioning pituitary adenomas (NFPA), in a short-term follow-up period. Nineteen patients (10 men and 9 women) followed at the University Hospital of Brasilia and harboring nonfunctioning pituitary macroadenomas were enrolled in the study. Eleven patients were previously submitted to transsphenoidal surgery, and in 8 patients no previous treatment had been instituted. Their response to the use of cabergoline (2mg/week) by 6months was evaluated. Significant tumor shrinkage (above 25% from baseline tumor volume) was observed in 6 (31.6%) of the 19 patients, and no adverse effects were observed during treatment. In 9 patients (47.4%), a reduction in tumor volume of at least 10% was noted, whereas tumor growth was observed in four patients (increase above 25% was only observed in one patient). Cabergoline (2mg/week) can lead to significant tumor shrinkage in NFPA in a considerable number of patients, and this effect can be observed early (6months after starting medication). Thus, this therapeutic strategy may be a low cost and safe alternative for treatment of NFPA in patients with remnant or recurrent tumor after transsphenoidal surgery or in those not operated by contraindications or refusal to surgical procedure.

Treatment of nonfunctioning pituitary adenomas: What were the contributions of the last 10 years? A critical view

Objectives.– All evidence for treatment and follow-up for nonfunctioning pituitary adenomas (NFMA) is based on observational studies. The objective was to critically review the contributions of the last 10years on treatment of NFMA. Materials and methods.– Systematic review. Results.– Transsphenoidal surgery remains the cornerstone of treatment of NFMA. When compared to the microsurgical procedure, some, but not all, studies favor endoscopy, but endocrinological outcome is not different. Radiosurgery results in a high and durable rate of tumor control, including in those previously treated by conventional radiotherapy, but the risk of developing hypopituitarism is comparable to the risk after conventional radiotherapy. In selected patients without visual field defects, a wait-and-see approach with frequent evaluation of visual fields is possible, without the risk of irreversibly compromising visual function. Tumor progression in NFMA is difficult to predict, but the MIB-1 LI is clinically useful and is indicative of invasiveness, but does not predict recurrence. To date, the potential contribution of other proliferation markers still requires further validation, and effective medical treatment strategies are not available. New features are the role of temozolomide and rapamicin as potential therapeutical targets, combined with octreotide. Although chimeric sst-DA analogues effectively inhibit proliferation in vitro, the effects of these molecules have not yet been evaluated in clinical trials with patients with NFMA. Conclusion.– Surgery, followed by radiotherapy or radiosurgery in case of remnant or recurrence, remains the cornerstone of treatment of NFMA. Currently, medical treatment cannot yet be incorporated in routine clinical practice.

A single centre’s experience of stereotactic radiosurgery and radiotherapy for non-functioning pituitary adenomas with the Linear Accelerator (Linac)

Non-functioning pituitary adenomas are primarily a surgically managed pathology, but recurrence or regrowth is not uncommon. Previous large series have retrospectively validated the use of the Gamma Knife (GK) as an adjuvant treatment. To our knowledge, we present the largest case series to date with the Linear Accelerator (Linac) for the management of this pathology. In this study we review the clinical course of 118 patients, 51 of whom had stereotactic radiosurgery (SRS) and 67 who had fractionated stereotactic radiotherapy (FSRT); the discriminatory feature being proximity to the optic chiasm. For comparison purposes a population of 53 patients who had conventional radiotherapy (CRT) is included. The local control rates at 5years for SRS, FRST and CRT were 100%, 93% and 87% respectively. Treatment-related morbidity was low. These data confirm that Linac SRS and FSRT are safe and effective for the treatment of non-functioning pituitary adenomas.

Hypofractionated stereotactic radiotherapy with CyberKnife for nonfunctioning pituitary adenoma: high local control with low toxicity

The aim was to evaluate the clinical outcome of hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for nonfunctioning pituitary adenoma. From October 2000 to March 2009, 100 patients with nonfunctioning pituitary adenoma were treated with hypofractionated SRT. Forty-three patients were male, and 57 were female. The patient's ages ranged from 16 to 82 years (median, 59 years). Five patients were medically inoperable, and 1 refused surgery; the remaining 94 were recurrent cases or those receiving postoperative adjuvant SRT. No patients had a history of previous cranial radiotherapy. Tumor volume ranged from 0.7 to 64.3 mL (median, 5.1 mL). The marginal doses were 17.0 to 21.0 Gy for the 3-fraction schedule and 22.0 to 25.0 Gy for the 5-fraction schedule. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for living patients was 33 months (range, 18-118.5 months). The 3-year overall survival and local control rates were 98% and 98%, respectively. In-field and out-field tumor regrowth were observed in 3 and 2 patients, respectively. Transient cyst enlargement occurred in 3 cases. A post-SRT grade 2 visual disorder occurred in 1 patient. Symptomatic post-SRT hypopituitarism was observed in 3 of 74 patients who had not received hormone replacement therapy after surgery. CyberKnife SRT involving 21 Gy in 3 fractions or 25 Gy in 5 fractions is safe and effective for surgical treatment of nonfunctioning pituitary adenoma. Hypofractionated SRT appears useful for protecting the visual nerve and neuroendocrine function, especially for tumors located near the optic pathways and large tumors.

Outcomes of surgical treatment for nonfunctioning pituitary adenomas: a systematic review and meta‐analysis

Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta-analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision. We searched MEDLINE, EMBASE and Cochrane CENTRAL, queried experts and reviewed the reference list of included publications. Eligible studies were comparative and noncomparative longitudinal studies that enroled patients with NFPA who underwent surgery (alone or in combination with other therapies). Reviewers, working independently and in duplicate, determined study eligibility with adequate reproducibility and extracted descriptive, quality and outcome data. Risks, relative risks (RR) and 95% confidence intervals (CIs) were estimated from each study and pooled using random-effects meta-analysis. Most included studies were uncontrolled case series in which patients received a combination of surgery and radiotherapy. The overall quality of the evidence was very low. Median follow-up was 4·29 years. When surgery was not combined with radiotherapy, there was an increased risk of tumour recurrence (RR 1·97; 95% CI, 1·15-3·35). Complications were more likely with the transcranial than with the transsphenoidal approach (mortality RR 4·89; 95% CI, 3·15-6·47; new anterior pituitary deficits RR 4·90; 95% CI, 2·94-7·82; and persistent diabetes insipidus RR 2·50; 95% CI, 1·05-5·35). Overall, transsphenoidal surgery had fairly low perioperative mortality (≤ 1%) and low complication rate (≤ 5% for all patient-important outcomes), but only less than a third of the patients had improvement in pituitary function. Observational evidence supports the association between a combined approach of transsphenoidal surgery with radiotherapy and improvements in visual field defects and reduction in tumour recurrence.