Stereotactic radiosurgery for recurrent/residual nonfunctioning pituitary adenoma: a single-arm systematic review and meta-analysis.

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are a significant subtype of pituitary tumors, accounting for 30% of all pituitary tumors and 10-20% of intracranial tumors. The primary treatment for NFPAs is resection, but complete resection is often challenging due to the tumor's proximity to critical structures, leading to frequent recurrences. Stereotactic radiosurgery (SRS) has emerged as a viable treatment option for recurrent or residual NFPAs, but its long-term efficacy and safety profile require further investigation. METHODS: This systematic review followed PRISMA guidelines and included studies published up to February 2024. We searched MEDLINE, Embase, and Cochrane databases for studies evaluating SRS for recurrent/residual NFPAs. Inclusion criteria focused on studies reporting outcomes and complications of SRS, while exclusion criteria omitted case reports, case series, and non-English studies. Data extracted included demographic details, dosimetry parameters, and follow-up durations. The risk of bias was assessed using the ROBINS-I tool, and statistical analyses were performed using single-arm meta-analyses. RESULTS: A total of 24 studies involving 3,781 patients were included. The mean follow-up duration was 60 months. Tumor control was achieved in approximately 92.3% of patients. The risk of developing hypopituitarism post-SRS was 13.62%, while the risk for panhypopituitarism was 2.55%. New visual field deficits occurred in 3.94% of patients. Cranial nerve deficits were rare, with event rates below 1% for CN III, CN V, and CN VI. CONCLUSION: SRS is effective in managing recurrent or residual NFPAs, achieving high tumor control rates. However, the risk of hypopituitarism remains a significant concern, necessitating regular endocrinological monitoring. While generally safe, the potential for new visual field deficits and other cranial nerve deficits must be considered. SRS remains a valuable treatment option, but clinicians should be aware of its potential complications.

[Prospective longitudinal study on the evolution of autobiographical memory in patients irradiated for benign skull base tumour]. / Étude prospective longitudinale sur l'évolution de la mémoire autobiographique de patients irradiés pour une tumeur bénigne de la base du crâne.

PURPOSE: Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory. PATIENTS AND METHODS: From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability. RESULTS: Twelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the "TEMPau" test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study. CONCLUSION: Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results.

Efficacy and safety of radiosurgery in acromegaly.

Stereotactic radiosurgery (SRS) more and more frequently plays a crucial role in the treatment of acromegaly. We provide a systematic review of the literature and meta-analysis, according to PRISMA, on SRS for the management of growth hormone (GH)-secreting pituitary adenomas, including several radiosurgical techniques, with the aim of describing efficacy and safety of this treatment. A weighted random effects model was used to calculate pooled outcome estimates. From 346 abstract reviews, 27 retrospective studies were included. Despite the variability in hormonal remission criteria and the heterogeneity between treatment guidelines among included studies, most of them reported an endocrine remission rate between 40% and 60%. Random effects meta-analysis for overall endocrine remission and 5-year probability of remission estimate after SRS were 46% (95% CI: 39-53%) and of 48% (95% CI: 38-57%), respectively. Random effects meta-analysis for new hypopituitarism estimate after SRS was 23% (95% CI: 17-29%). Furthermore, incidence of radiation induced optic neuropathy after SRS ranged between 0% and 6% This meta-analysis confirms and quantifies safety and effectiveness of SRS to achieve endocrine remission after surgical management in acromegaly.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Single Versus Fractionated Gamma Knife Radiosurgery for Nonfunctioning Pituitary Adenomas Close to the Optic Pathway: A Multicenter Propensity Score Matched Study.

BACKGROUND AND OBJECTIVES: Gamma Knife radiosurgery (GKRS), typically administered in a single session (S-GKRS), is an effective treatment for nonfunctioning pituitary adenoma (NFPA). For lesions close to the optic pathway, the use of hypofractionated radiosurgery is growing. This study seeks to compare the results of S-GKRS vs fractionated-GKRS (F-GKRS) for NFPAs adjacent to the optic pathway. METHODS: Two cohorts of patients with residual or recurrent NFPAs in contact to the optic pathway were retrospectively included in this study: (1) a group of patients who underwent a 3-day course of F-GKRS in Europe and (2) a group of patients treated with S-GKRS in the United States. A propensity score matching (ratio 1:1) was carried out to obtain and compare 2 homogeneous groups of patients with NFPA. RESULTS: A total of 84 patients were included for analysis (42 in the S-GKRS cohort and 42 in the F-GKRS group). The 2 cohorts did not differ for age, sex, number of previous surgical procedure, tumor volume, and follow-up. The mean follow-up was 60.2 ± 37.0 months and 62.4 ± 37.4 months for F-GKRS and S-GKRS cohort, respectively ( P = .38). The overall tumor control at last follow-up was achieved in 95.2% and 92.9% of patients in F-GKRS and S-GKRS, respectively ( P = .64). The 1-year, 3-year, 5-year, and 7-year progression-free survival rate after F-GKRS was 100%, 97.1%, 97.1%, and 91%, respectively. In the S-GKRS sample, progression-free survival rates were 100%, 100%, 92.5%, and 92.5% at 1, 3, 5, and 7 years after treatment, respectively. Two patients (4.7%) from the F-GKRS cohort and 2 (4.7%) from the S-GKRS cohort sustained visual worsening after radiosurgery ( P = 1.0). CONCLUSION: In the management of NFPAs adjacent to the optic pathway both F-GKRS and S-GKRS had comparable outcomes and risks at 7 years. Future prospective studies including larger cohorts with longer follow-up are needed to confirm our results.

Radiotherapy and Mortality in Pituitary Adenomas.

BACKGROUND: Pituitary adenomas (PA), comprising 10-20% of intracranial tumors, are classified as functioning and non-functioning and are further divided by size. Non-functioning tumors cause mechanical symptoms while functioning ones result in hormonal hypersecretion syndromes. Initial treatment involves surgery, with medical treatment for prolactinomas. Radiotherapy (RT) is employed as an adjuvant treatment, with various modalities including conventional, stereotactic radiosurgery (SRS), and fractionated stereotactic RT (FSRT). Although effective, RT is associated with complications and toxicities such as hypopituitarism, optic neuritis, secondary CNS tumors, and neurocognitive deficits. AIM: Describe the information on mortality from radiotherapy as treatment of functioning PA. METHODS: A PubMed search spanning 2000-2017 was conducted for articles on pituitary RT. RESULTS: Conventional RT entails high-energy radiation over multiple sessions, while SRS delivers precise high doses in a single session. FSRT offers enhanced precision using a linear accelerator, delivering multiple doses. Optic structure proximity and tumor volume dictate RT modality. Studies have shown SRS and FSRT's efficacy in tumor and endocrine control, with variable risks and complications. Mortality rates in pituitary adenomas treated with RT have been evaluated, revealing complexities. Acromegaly, associated with increased mortality due to cerebrovascular disease, may result from RT. Irradiation of non-functioning pituitary macroadenomas also elevates cerebrovascular risk, while radiotherapy-induced hypopituitarism is associated with increased cardiovascular mortality. RT-induced damage is attributed to microvascular lesions and arteriolar changes. CONCLUSION: Modern techniques mitigate complications, and although safer, long-term studies are needed. Multidisciplinary evaluation guides the treatment decision, optimizing efficacy and minimizing risk, ultimately improving the patient's quality of life.

Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

BACKGROUND: Fractionated stereotactic radiotherapy (FSRT) is a common modality used to treat pituitary adenomas with good control rates. It is not known whether FSRT should be performed early or delayed until progression occurs. We compared FSRT in treating nonfunctional pituitary adenomas (NFPA) as an adjuvant (ADJ) or on-progression (PRG) therapy. METHODS: A retrospective review of patients who underwent FSRT for an NFPA between January 2004 and December 2022 at a single institution was performed. We compared endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment. RESULTS: Seventy-five patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumor control rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in 4 (11.4%) versus 7 (17.5%) new endocrinopathies and 2 (5.7%) versus 1 (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time to new endocrinopathy showed no difference between the 2 cohorts. The median time from surgery to new endocrinopathy was significantly different between ADJ and PRG, at 15.5 and 102.0 months, respectively. CONCLUSIONS: FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates and a low risk of developing new endocrinopathies and visual deficits. Delaying treatment delayed the development of new endocrinopathies, suggesting that observation with FSRT on tumor progression may delay the onset of hypopituitarism and maintain similar effectiveness in tumor control.

Volumetric Assessment of Nonfunctional Pituitary Adenoma Treated With Stereotactic Radiosurgery: An Assessment of Long-Term Response.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is widely used to manage recurrent or residual nonfunctioning pituitary adenomas (NFPAs). Studies on the long-term volumetric response of NFPAs to SRS are lacking. Such a post-SRS volumetric study will allow us to set up appropriate radiographic follow-up protocols and predict tumor volumetric response. METHODS: Two providers independently performed volumetric analyses on 54 patients who underwent single-session SRS for a recurrent/residual NFPA. In the case of discrepancy between their results, the final volume was confirmed by an independent third provider. Volumetry was performed on the 1-, 3-, 5-, 7-, and 10-year follow-up neuroimaging studies. RESULTS: Most patients showed a favorable volumetric response, with 87% (47/54) showing tumor regression and 13% (7/54) showing tumor stability at 10 years. Year 3 post-SRS volumetric results correlated (R 2 = 0.82, 0.63, 0.56) with 5-, 7-, and 10-year outcomes. The mean interval volumetric reduction was 17% on year 1; further interval volumetric reduction was 17%, 9%, 4%, and 9% on years 3, 5, 7, and 10, respectively. CONCLUSION: Year 3 post-SRS volumetric response of patients with residual or recurrent NFPAs is predictive of their 7-10-year follow-up response. For patients demonstrating NFPA regression in the first 1-3 years, interval follow-up MRI's can likely be performed at 2-year periods unless otherwise clinically indicated. Further studies are needed to better define the volumetric response to adenomas more than a decade after SRS.

The Role of Stereotactic Radiosurgery for Functioning and Nonfunctioning Pituitary Adenomas.

Pituitary adenomas are benign brain tumors that comprise 10%-20% of all central nervous system neoplasms. In recent years, stereotactic radiosurgery (SRS) has emerged as a highly effective treatment option in the management of functioning and nonfunctioning adenomas. It is associated with tumor control rates frequently ranging from 80% to 90% in published reports. While permanent morbidity is uncommon, potential side effects include endocrine dysfunction, visual field deficits, and cranial nerve neuropathies. In patients where single fraction SRS would pose an unacceptable risk (e.g. large lesion size or close proximity to the optic apparatus), hypofractionated SRS delivered in 1-5 fractions is a potential treatment option; however, available data are limited. A comprehensive literature search of PubMed/MEDLINE, CINAHL, Embase, and the Cochrane Library was conducted to identify articles reporting on the use of SRS in functioning and nonfunctioning pituitary adenomas.

Contemporary radiotherapy and radiosurgery techniques for refractory pituitary adenomas.

The pituitary gland is a potential site for a range of pathologies, for which treatment can involve resection and/or ionizing radiation. Modern stereotactic radiosurgery (SRS) involves highly conformal radiation, allowing for the delivery of high doses to the tumor while simultaneously sparing nearby healthy structures. SRS has become a standard treatment option for residual or recurrent pituitary adenomas. It has been used for both functioning and nonfunctioning pituitary adenomas, with reported local tumor control over 90% and moderate rates of endocrine remission in functioning adenomas. We aim to briefly review the existing indictions and supporting literature for the use of SRS for refractory adenomas.

Effects of Neuroanatomic Structural Distances on Pituitary Function After Stereotactic Radiosurgery: A Multicenter Study.

BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

Biological and Therapeutic Implications of the Tumor Microenvironment in Pituitary Adenomas.

Pituitary adenomas (PAs) are neoplasms derived from the endocrine cells of the anterior pituitary gland. Most frequently, they are benign tumors, but may sometimes display an aggressive course, and in some cases metastasize. Their biology, including their wide range of behavior, is only partly understood. In terms of therapeutic targeting, most PAs are easily treated with available medical treatments, surgery, and sometimes radiotherapy. Nevertheless, gonadotroph adenomas lack medical therapeutic options, and treatment of aggressive PAs and pituitary carcinomas remains challenging. Here, we present an overview of the implications of the tumor microenvironment in PAs, reviewing its composition and function, as well as published cases that have been treated thus far using tumor microenvironment-targeting therapies. Additionally, we discuss emerging views, such as the concept of nonangiogenic tumors, and present perspectives regarding treatments that may represent future potential therapeutic options. Tumor-infiltrating lymphocytes, tumor-associated macrophages, folliculostellate cells, tumor-associated fibroblasts, angiogenesis, as well as the extracellular matrix and its remodeling, all have complex roles in the biology of PAs. They have been linked to hormone production/secretion, size, invasion, proliferation, progression/recurrence, and treatment response in PAs. From a therapeutic perspective, immune-checkpoint inhibitors and bevacizumab have already shown a degree of efficacy in aggressive PAs and pituitary carcinomas, and the use of numerous other tumor microenvironment-targeting therapies can be foreseen. In conclusion, similar to other cancers, understanding the tumor microenvironment improves our understanding of PA biology beyond genetics and epigenetics, and constitutes an important tool for developing future therapies.

Role of biological effective dose for prediction of endocrine remission in acromegaly patients treated with stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery (SRS) can be used in acromegaly patients to achieve endocrine remission. In this study we evaluate the biological effective dose (BED) as a predictor of SRS outcomes for acromegaly. METHOD: This retrospective, single-center study included patients treated with single-fraction SRS with growth hormone secreting pituitary adenomas and available endocrine follow-up. Kaplan-Meier analysis was used to study endocrine remission, new pituitary deficit, and tumor control. Cox analyses were performed using two models [margin dose (model 2) versus BED (model 1)]. RESULTS: Sixty-seven patients (53.7% male) with a median age of 46.8 years (IQR 21.2) were treated using a median dose of 25 Gy (IQR 5), and a median BED of 171.9Gy2.47 (IQR 66.0). Five (7.5%) were treated without stopping antisecretory medication. The cumulative probability of maintained endocrine remission off suppressive medications was 62.5% [47.9-73.0] at 3 years and 76.5% [61.0-85.9] at 5 years. IGF1i > 1.5 was a predictor of treatment failure [Hazard ratio (HR) 0.40 (0.21-0.79) in model 1, p = 0.00783]. Margin dose > 22 Gy [HR 2.33 (1.06-5.13), p = 0.03593] or a BED > 170Gy2.47 [HR 2.02 (1.06-3.86), p = 0.03370] were associated with endocrine remission. The cumulative probability of new hypopituitarism after SRS was 36.8% (CI 95% 22.4-45.9) at 3 years and 53.2% (CI 95% 35.6-66) at 5 years. BED or margin dose were not associated with new hypopituitarism. CONCLUSION: BED is a strong predictor of endocrine remission in patients treated with SRS. Dose planning and optimization of the BED to > 170Gy2.47 give a greater probability of endocrine remission in acromegalic patients.

Management after initial surgery of nonfunctioning pituitary adenoma: surveillance, radiotherapy or surgery?

INTRODUCTION: The first line of treatment for nonfunctioning pituitary adenoma (NFPA) is surgery. Adjuvant radiotherapy or surveillance and new treatment (second surgical operation or salvage radiotherapy) in case of recurrence are options discussed at the multidisciplinary tumor board. The purpose of this study was to evaluate the therapeutic outcome for each option. METHODS: The records of 256 patients followed with NFPA between 2007 and 2018 were retrospectively reviewed. Mean age at initial surgery was 55 years [18-86]. Post-operative MRI found a residual tumor in 87% of patients. Mean follow-up was 12.1 years [0.8-42.7]. RESULTS: After initial surgery, 40 patients had adjuvant radiotherapy. At 5, 10 and 15 years progression-free survival (PFS) was significantly different after surgery alone (77%, 58% and 40%) compared to surgery and adjuvant radiotherapy (84%, 78% and 78%) (HR = 0.24 [0-0.53] p < 0.0005). Overall, after first, second or third surgical operation, 69 patients had adjuvant radiotherapy and 41 salvage radiotherapy. Five-year PFS was similar for adjuvant (90%) and salvage radiotherapy (97%) (p = 0.62). After a second surgical operation, 62% and 71% of patients were irradiated after 2 and 5 years respectively. The risk of corticotropic and thyrotropic deficiency rates were 38% and 59% after second or third surgical operation and 40% and 73% after radiotherapy. Brain tumors occurred in 4 patients: 1 meningioma present at initial surgery, and after radiotherapy, 1 neurinoma which appeared at 5 years, 1 glioblastoma at 13 years and 1 meningioma at 20 years. CONCLUSION: Among patients treated by surgery for NFPA, a "wait-and-see" attitude should be an option since adjuvant radiotherapy is not superior to salvage radiotherapy. However, in case of recurrence or progression, the authors recommended delivery of salvage radiotherapy to avoid a second surgical operation.

Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance.

BACKGROUND: Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. METHODS: In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls. FINDINGS: Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2·18 (95% CI 1·31-3·62, p<0·0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2·1% for the controls at 20 years. INTERPRETATION: Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. FUNDING: Pfizer.

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience.

OBJECTIVE: We aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter. METHODS: We retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi. RESULTS: The median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005). CONCLUSION: Overall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.

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

PURPOSE: 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. METHODS: 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. RESULTS: Sixty-three (57.8%) patients were available for follow up at our institute. The median follow-up period was 47 months (range, 6-260). At a median time of 38 months (range, 8-97), 25 (39.7%) patients developed ≥ 1 new pituitary hormone deficiency. Median time to cortisol deficiency was 38 months (range, 8-55), thyroid hormone deficiency was 45.5 months (range, 12-97) and gonadotropin deficiency was 45 months (range, 21-75). The actuarial risk of developing a new pituitary hormone deficit at 1, 3, 5, 7, and 10 years 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 5 years. 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. CONCLUSION: 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.