Author Correction: T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation.

In the version of this article initially published, in second paragraph of the second subsection of Results ('Peripheral licensing of CD4+ TH17 cells in Tbx21-/- hosts'), the figure citation ('Fig. 1c') in the sentence that begins "In addition to" was incorrect. The correct citation is 'Fig. 1d'.

T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation.

The transcription factor T-bet has been associated with increased susceptibility to systemic and organ-specific autoimmunity, but the mechanism by which T-bet expression promotes neuroinflammation remains unknown. In this study, we demonstrate a cardinal role of T-bet-dependent NKp46+ innate lymphoid cells (ILCs) in the initiation of CD4+ TH17-mediated neuroinflammation. Loss of T-bet specifically in NKp46+ ILCs profoundly impaired the ability of myelin-reactive TH17 cells to invade central nervous system (CNS) tissue and protected the mice from autoimmunity. T-bet-dependent NKp46+ ILCs localized in the meninges and acted as chief coordinators of meningeal inflammation by inducing the expression of proinflammatory cytokines, chemokines and matrix metalloproteinases, which together facilitated T cell entry into CNS parenchyma. Our findings uncover a detrimental role of T-bet-dependent NKp46+ ILCs in the development of CNS autoimmune disease.

Repeat stereotactic radiosurgery for progressive vestibular schwannomas after primary gamma knife radiosurgery.

PURPOSE: Limited data provides guidance on the management of vestibular schwannomas (VSs) that have progressed despite primary Gamma Knife radiosurgery (GKRS). The present article reports our long-term experience after repeat GKRS for VS with sustained progression after solely primary GKRS management. METHODS: A retrospective review of 1997 patients managed between 1987 and 2023 was conducted. Eighteen patients had sustained tumor progression after primary GKRS and underwent repeat GKRS. The median repeat GKRS margin dose was 11 Gy (IQR: 11-12), the median tumor volume was 2.0 cc (IQR: 1.3-6.3), and the median cochlear dose in patients with preserved hearing was 3.9 Gy (IQR: 3-4.1). The median time between initial and repeat GKRS was 65 months (IQR: 38-118). RESULTS: The median follow-up was 70 months (IQR: 23-101). After repeat GKRS, two patients had further tumor progression at 4 and 21 months and required partial resection of their tumors. The 10-year actuarial tumor control rate after repeat GKRS was 88%. Facial nerve function was preserved in 13 patients who had House-Brackmann grade 1 or 2 function at the time of repeat GKRS. Two patients with serviceable hearing preservation (Gardner-Robertson grade 1 or 2) at repeat GKRS retained that function afterwards. In patients with tinnitus, vestibular dysfunction, and trigeminal neuropathy, symptoms remained stable or improved for 16/16 patients, 12/15 patients, and 10/12 patients, respectively. One patient developed facial twitching in the absence of tumor growth 21 months after repeat GKRS. CONCLUSIONS: Repeat GKRS effectively controlled tumor growth and preserved cranial nerve outcomes in most patients whose VS had sustained progression after initial primary radiosurgery.

Stereotactic radiosurgery for patients with spinal metastases from prostate cancer.

PURPOSE: Spinal metastases may result in intractable pain, neurological deficit, and vertebral body collapse. There are only a few studies describing outcomes following spine stereotactic radiosurgery (SRS) specifically for prostate cancer metastases. METHODS: A prospectively collected database of patients with prostate cancer spinal metastases treated at the University of Pittsburgh Medical Center from 2003 to 2023 was analyzed. The primary outcome was local control (LC). Secondary outcomes were overall survival (OS), pain resolution, and adverse radiation effects (AREs). RESULTS: Thirty-seven patients and 51 lesions were identified. Fifteen lesions (29%) were previously resected and 34 lesions (67%) were previously irradiated. The median tumor volume was 37.0 cc (range: 2.9-263.3). A majority of lesions (71%) were treated in a single fraction (median 20 Gy, range: 14-22.5); multi-fractionated treatment consisted of 21-30 Gy in 2-5 fractions. Median follow-up was 12 months (range: 1-146). The 6-month, 1-year, and 2-year LC rates were 97%, 91%, and 91%, respectively. No tested prognostic factors were associated with LC, including hormone sensitivity. The 6-month, 1-year, and 2-year OS rates were 71%, 56%, and 32%; age > 70 years (p = 0.048) and tumor volume > 30 cc (p = 0.03) were associated with inferior rates of OS. Complete or partial pain response was observed in 58% of patients. There were 8 instances (16%) of AREs, 2 of which were vertebral compression fractures (4%). CONCLUSION: Radiosurgery as a primary or adjuvant treatment modality for prostate cancer spinal metastases confers durable LC and moderate pain relief with minimal toxicity. Further studies are warranted to optimize management in this patient population.

The role of spine stereotactic radiosurgery for patients with breast cancer metastases.

PURPOSE: Breast cancer that metastasizes to the spine is associated with low quality of life and poor survival. Radiosurgery has an increasing role in this patient population. This single-institution (2003-2023) study analyzes clinical outcomes and prognostic factors for patients who underwent spinal stereotactic radiosurgery (SSRS) for metastatic breast cancer. METHODS: Ninety patients (155 unique breast cancer spinal metastases) were treated with SSRS. The median age was 57 years (range: 35-88), and the median KPS was 80 (range: 40-100). Forty-two (27%) lesions were managed surgically prior to radiosurgery. At SSRS, 75 (48%) lesions impinged or compressed the spinal cord per the epidural spinal cord scale (ESCC). Seventy-nine (51%) lesions were categorized as potentially unstable or unstable by the Spinal Instability Neoplastic Score (SINS). RESULTS: The median follow-up was 15 months (range: 1-183). The median single-session tumor volume was 25.4 cc (range: 2-197), and the median single-fraction prescription dose was 17 Gy (range: 12-25). Seven (5%) lesions locally progressed. The 1-, 2-, and 5-year local control rates were 98%, 97%, and 92%, respectively. The median overall survival (OS) for the cohort was 32 months (range: 2-183). The 1-, 2-, and 5-year OS rates were 72%, 53%, and 30%, respectively. On univariate analysis, KPS ≥ 80 (p = 0.009, HR: 0.51, 95% CI: 0.31-0.84) was associated with improved OS. Patient-reported pain improved (68%), remained stable (29%), or worsened (3%) following radiosurgery. Fifteen (10%) radiation-induced toxicities were reported. CONCLUSIONS: Spinal radiosurgery is a safe and highly effective long-term treatment modality for metastases to the spine that originate from breast cancer.

Outcomes after gamma knife radiosurgery for intraventricular meningiomas.

BACKGROUND: Intraventricular meningiomas (IVMs) are rare tumors with considerable treatment-associated morbidity due to their challenging location. Treatment with stereotactic radiosurgery (SRS) is sparsely reported in the literature. We describe our experience over the last 35 years using Gamma knife radiosurgery (GKRS) for IVMs. METHODS: We retrospectively reviewed the GKRS database identifying 2501 meningiomas treated at the University of Pittsburgh Medical Center over the last 35 years. Nineteen patients with (12 males, mean age = 53.2 years, range 14-84) 20 IVMs were identified. Headache was the most frequent presenting symptom (N = 12), and the trigone of the lateral ventricle was the most common location (N = 18). The median tumor volume was 4.8 cc (range, 0.8-17). The median margin dose was 14 Gy (range, 12-25) delivered at 50% isodose line. RESULTS: At a median follow-up of 63.1 months (range, 6-322.4) symptom control was achieved in 18 (94.7%) patients. The overall progression-free survival (PFS) was 95% at 5 years, and 85% at 10-years. After Log-rank test, patients who underwent GKRS within 12 months after diagnosis (vs. ≥ 12 months, X2: 4.455, p = 0.035), patients treated with primary GKRS without prior biopsy (vs. prior biopsy, X2: 4.000, p = 0.046), and patients with WHO grade I meningioma (vs. WHO II, X2: 9.000, p = 0.003) had a longer PFS. Imaging showed peritumoral edema in seven cases at a median of 10.5 (range, 6.13-24.3) months after GKRS. Only three of these patients were symptomatic and were successfully managed with oral medications. Cox´s regression revealed that a V12Gy ≥ 10 cc [HR: 10.09 (95% CI: 2.11-48.21), p = 0.004], and tumor volume ≥ 8 cc [HR: 5.87 (95% CI: 1.28-26.97), p = 0.023] were associated with a higher risk of peritumoral edema. CONCLUSION: GKRS is an effective and safe management option for intraventricular meningiomas. Early GKRS should be considered as a primary management modality for small and medium sized IVM and adjuvant management for residual IVMs.

Is Halcyon feasible for single thoracic or lumbar vertebral segment SBRT?

PURPOSE: Halcyon linear accelerators employ intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) techniques. The Halcyon offers translational, but not rotational, couch correction, which only allows a 3 degrees of freedom (3-DOF) correction. In contrast, the TrueBeam (TB) linear accelerator offers full 6-DOF corrections. This study aims to evaluate the difference in treatment plan quality for single thoracic or lumbar vertebral segment SBRT between the Halcyon and TB linear accelerators. In addition, this study will also investigate the effect of patient rotational setup errors on the final plan quality. METHODS: We analyzed 20 patients with a single-level spine metastasis located between the T7 and L5 vertebrae near the spinal canal. The median planning target volume was 52.0 cm3 (17.9-138.7 cm3 ). The median tumor diameter in the axial plane was 4.6 cm (range 1.7-6.8 cm), in the sagittal plane was 3.3 cm (range 2-5 cm). The prescription doses were either 12-16 Gy in 1 fraction or 18-24 Gy in 3 fractions. All patients were treated on the TB linear accelerator with a 2.5 mm Multi-Leaf Collimator (MLC) leaf width. Treatment plans were retrospectively created for the Halcyon, which has a 5 mm effective MLC leaf width. The 20 patients had a total of 50 treatments. Analysis of the 50 cone beam computed tomography (CBCT) scans showed average rotational setup errors of 0.6°, 1.2°, and 0.8° in pitch, yaw, and roll, respectively. Rotational error in roll was not considered in this study, as the original TB plans used a coplanar volumetric modulated arc therapy (VMAT) technique, and each 1° of roll will contribute an error of 1/360. If a plan has 3 arcs, the contribution from errors in roll will be < 0.1%. To simulate different patient setup errors, for each patient, 12 CT image datasets were generated in Velocity AI with different rotational combinations at a pitch and yaw of 1°, 2°, and 3°, respectively. We recalculated both the TB and Halcyon plans on these rotated images.  The dosimetric plan quality was evaluated based on the percent tumor coverage, the Conformity Index (CI), Gradient Index (GI), Homogeneity index (HI), the maximum dose to the cord/cauda, and the volume of the cord/cauda receiving 8, 10, and 12 Gy (V8Gy, V10Gy and V12Gy). Paired t-tests were performed between the original and rotated plans with a significance level of 0.05. RESULTS: The Eclipse based VMAT plans on Halcyon achieved a similar target coverage (92.3 ± 3.0% vs. 92.4 ± 3.3%, p = 0.82) and CI (1.0 ± 0.1 vs. 1.1 ± 0.2, p = 0.12) compared to the TB plans. The Gradient index of Halcyon is higher (3.96 ±0.8) than TB (3.85 ±0.7), but not statistically significant. The maximum dose to the spinal cord/cauda was comparable (11.1 ± 2.8 Gy vs. 11.4 ± 3.6 Gy, p = 0.39), as were the V8Gy, V10Gy and V12Gy to the cord/cauda. The dosimetric influence of patient rotational setup error was statistically insignificant for rotations of up to 1° pitch/yaw (with similar target coverage, CI, max cord/cauda dose and V8Gy, V10Gy, V12Gy for cord/cauda). The total number of monitor units (MUs) for Halcyon (4998 ± 1688) was comparable to that of TB (5463 ± 2155) (p = 0.09). CONCLUSIONS: The Halcyon VMAT plans for a single thoracic or lumbar spine metastasis were dosimetrically comparable to the TB plans. Patient rotation within 1° in the pitch and yaw directions, if corrected by translation, resulted in insignificant dosimetric effects. The Halcyon linear accelerator is an acceptable alternative to TB for the treatment of single thoracic or lumbar spinal level metastasis, but users need to be cautious about the patient rotational setup error.  It is advisable to select patients appropriately, including only those with the thoracic or lumbar spine involvement and keeping at least 2 mm separation between the target and the cord/cauda. More margin is needed if the distance between the isocenter and cord/cauda is larger. It is advisable to place the planning isocenter close to the spinal canal to further mitigate the rotational error. SUMMARY: We simulated various scenarios of patient setup errors with different rotational combinations of pitch and yaw with 1°, 2°, and 3°, respectively. Rotation was corrected with translation only to mimic the Halcyon treatment scenario. Using the Halcyon for treating a tumor in a single thoracic or lumbar vertebral segment is feasible, but caution should be noted in patients requiring rotational corrections of > 1° in the absence of 6-DOF correction capabilities.

Optimizing stereotactic radiosurgery in patients with recurrent or residual craniopharyngiomas.

PURPOSE: Stereotactic radiosurgery (SRS) is an important management strategy for residual and recurrent craniopharyngiomas. The current study evaluated the factors which affected tumor control and complications in craniopharyngioma SRS. METHODS: This study includes 53 consecutive patients who underwent single-session SRS for recurrent or residual craniopharyngiomas. The median age was 41 years with 28 male and 25 females. The median tumor volume was 0.63 cm3 and median margin dose was 12 Gy (range 9-25 Gy). RESULTS: The overall 3-, 5-, and 10-year survival rates were 97.8%, 92.7% and 88.5%. The overall 3-, 5-, and 10-year tumor control rates were 81.0%, 72.1%, and 53.4%. In univariate analysis, ≥ 3 mm distance from optic structures (p = 0.002), only solid or cystic tumor type (p = 0.037), and ≥ 12 Gy to ≥ 85% of the tumor (p < 0.001) were significantly associated with improved tumor control. In multivariate analysis, only solid or cystic tumor type, (p = 0.034), and ≥ 85% of the tumor receiving ≥ 12 Gy (p = 0.004) were significantly associated with better tumor control. When ≥ 85% of the tumor received ≥ 12 Gy the tumor control rates at 3-, 5-, and 10-year were 100%, 93.3%, and 93.3%. Higher conformity index was not associated with better tumor control. CONCLUSIONS: The tumor control rates after recurrent or residual craniopharyngiomas SRS were improved by ensuring that at least 85% of the tumor received ≥ 12 Gy even when the distance between the tumor and the optic system is < 3 mm. This concept refutes the conformity theory that a high conformity index is a critical feature of effective SRS.

Useful hearing preservation is improved in vestibular schwannoma patients who undergo stereotactic radiosurgery before further hearing deterioration ensues.

INTRODUCTION: The present study evaluates whether hearing deterioration during observation reduces serviceable hearing preservation rates after stereotactic radiosurgery (SRS) in vestibular schwannoma (VS) patients with useful hearing. METHODS: We retrospectively analyzed 1447 VS patients who underwent SRS between 1992 and 2017. We identified 100 VS patients who had Grade I Gardner- Robertson (GR) hearing at initial diagnosis but were observed without surgery or SRS. We compared hearing after SRS in 67 patients who retained GR Grade I hearing from initial diagnosis to SRS (the hearing maintenance or HM group) to 33 patients whose hearing worsened from GR grade I to grade II (the hearing deterioration or HD group). We also investigated whether a decline in pure tone average (PTA) or speech discrimination score (SDS) before SRS affected hearing preservation after SRS. RESULTS: The serviceable hearing (GR I and II) preservation in HM patients was 80%s, 63%, and 51% at 3, 5, and 10 years, respectively. The serviceable hearing preservation in HD patients was 40%, 33%, and 20% at 3, 5, and 10 years, respectively. In multivariate analysis, younger age (< 55 years, p = 0.045) and HM during observation (p = 0.001) improved serviceable hearing preservation rates. Patients whose PTA increased ≥ 15 dB (p = 0.024) or whose SDS declined ≥ 10% (p = 0.019) had reduced serviceable hearing preservation rates. CONCLUSIONS: Hearing deterioration during observation before SRS reduced long term hearing preservation rate in VS patients with GR grade I hearing at initial diagnosis. SRS before hearing deterioration was recommended for hearing preservation.

Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825.

BACKGROUND/PURPOSE: Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials. METHODS: This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825. RESULTS: Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males. CONCLUSIONS: A sex specific nomogram that assesses individualized survival probabilities (6-, 12- and 24-months) for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here- https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/ .

TCR Retrogenic Mice as a Model To Map Self-Tolerance Mechanisms to the Cancer Mucosa Antigen GUCY2C.

Characterizing self-tolerance mechanisms and their failure is critical to understand immune homeostasis, cancer immunity, and autoimmunity. However, examination of self-tolerance mechanisms has relied primarily on transgenic mice expressing TCRs targeting well-characterized, but nonphysiologic, model Ags, such as OVA and hemagglutinin. Identifying TCRs directed against bona fide self-antigens is made difficult by the extraordinary diversity of TCRs and the low prevalence of Ag-specific clones (<10-100 naive cells per organism), limiting dissection of tolerance mechanisms restricting immunity to self-proteins. In this study, we isolated and characterized TCRs recognizing the intestinal epithelial cell receptor and colorectal cancer Ag GUCY2C to establish a model to study self-antigen-specific tolerance mechanisms. GUCY2C-specific CD4+ effector T cells were isolated from immunized, nontolerant Gucy2c -/- mice. Next-generation sequencing identified GUCY2C-specific TCRs, which were engineered into CD4+ T cells in vitro to confirm TCR recognition of GUCY2C. Further, the generation of "retrogenic" mice by reconstitution with TCR-transduced hematopoietic stem cells resulted in normal CD4+ T cell development, responsiveness to immunization, and GUCY2C-induced tolerance in recipient mice, recapitulating observations in conventional models. This retrogenic model can be employed to define self-tolerance mechanisms restricting T and B cell responses to GUCY2C to optimize colorectal cancer immunotherapy without autoimmunity.

Radiotherapy of Parasellar Tumours.

Parasellar tumours represent a wide group of intracranial lesions, both benign and malignant. They may arise from several structures located within the parasellar area or they may infiltrate or metastasize this region. The treatment of the tumours located in these areas is challenging because of their complex anatomical location and their heterogenous histology. It often requires a multimodal approach, including surgery, radiation therapy (RT), and medical therapy. Due to the proximity of critical structures and the risks of side effects related to the procedure, a successful surgical resection is often not achievable. Thus, RT plays a crucial role in the treatment of several parasellar tumours. Conventional fractionated RT and modern radiation techniques, like stereotactic radiosurgery and proton beam RT, have become a standard management option, in particular for cases with residual or recurrent tumours after surgery and for those cases where surgery is contraindicated. This review examines the role of RT in parasellar tumours analysing several techniques, outcomes and side effects.

Primary or salvage stereotactic radiosurgery for brain metastatic small cell lung cancer.

PURPOSE: We evaluated the outcomes after stereotactic radiosurgery (SRS) for patients who developed new or progressive brain disease regardless of whether they had no prior radiation, PCI, or WBRT. METHODS: We retrospectively identified 90 SCLC patients who had SRS between 1991 and 2018. Thirty-one patients had no evidence of brain disease at the time of initial diagnosis but received prophylactic cranial irradiation. Twenty-six without initial brain disease underwent delayed SRS after brain disease was identified. Seventeen patients with synchronous systemic and brain disease underwent WBRT at the time of diagnosis. Fifteen patients had brain disease detected at the time of initial diagnosis and had initial SRS. RESULTS: We found no difference in overall survival between patients who received initial PCI or WBRT compared to patients treated with SRS alone at the time when brain metastases were identified. PCI was not associated with a longer duration between initial diagnosis and the development of brain metastasis. Local tumor control was achieved in 49 out of 58 patients who had follow up MRI available for review (84.5%). Actuarial local tumor control at 3, 6, and 12 months was calculated as 92%, 85%, and 80%, respectively. Radiation therapy (PCI or WBRT) before SRS was not associated with better or worse local tumor control. CONCLUSION: In this experience neither prior PCI nor WBRT improved survival or local tumor control in SCLC patients who underwent SRS for new or recurrent brain disease.

Long term results of primary radiosurgery for vestibular schwannomas.

BACKGROUND: Stereotactic radiosurgery (SRS) has become a primary option for management for both newly diagnosed vestibular schwannomas (VS), as well as VS that enlarge after initial observation. METHODS: A retrospective review of our prospectively maintained data base found 871 patients who underwent Gamma knife® SRS as their initial (primary) management between 1987 and 2008. Follow-up ranged from 1-25 years (median = 5.2 years) Median tumor volume was 0.9 cc (0.02-36) and median margin dose was 13 Gy (12-25). RESULTS: Progression free survival (PFS) after SRS was 97% at 3 years, 95% at 5 years, and 94% at 10 years. Freedom from delayed surgical resection was found in 98.7% of patients. Smaller tumor volume was significantly associated with improved PFS. There were 326 patients with serviceable hearing (Gardner-Robertson 1 or 2) at the time of SRS with audiological follow-up of ≥ 1 year. Serviceable hearing preservation rates after SRS were 89.8% at 1 year, 76.9% at 3 years, 68.4% at 5 years, 62.5% at 7 years, and 51.4% at 10 years. Factors associated with improved serviceable hearing preservation included younger age, Gardner-Robertson grade 1 at SRS, and absence of subjective complaints of dysequilibrium or vertigo (vestibulopathy). Fifty-one patients (5.8%) developed trigeminal neuropathy. Fourteen (1.6%) developed a transient House-Brackmann grade 2 or 3 facial neuropathy. CONCLUSIONS: In this report with extended follow-up, primary SRS achieved tumor growth control in 94% of patients. Optimization of long- term cranial nerve outcomes remains an important achievement of this management strategy for VS.

Cranial nerve outcomes after primary stereotactic radiosurgery for symptomatic skull base meningiomas.

OBJECTIVE: To evaluate cranial nerve (CN) outcomes after primary stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. METHODS: From our prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12 month follow up. Median age at the time of SRS was 58 years. Median follow up was 58 months (range 12-300 months), Median tumor volume treated with SRS was 5.9 cm3 (range 0.5-37.5 cm3), and median margin dose was 13 Gy (range 9-20Gy). RESULTS: Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58 months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10 years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10 years. CONCLUSION: Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit.

Management of nonfunctioning pituitary tumors: radiotherapy.

External beam radiotherapy (RT) is an essential part of the management of intracranial tumors and has been used in treating pituitary adenomas for more than five decades. It has been demonstrated that conventional RT for postoperative residual or progressive nonfunctioning pituitary adenomas (NFAs) present an excellent long-term local tumor control, although its use has been limited because of the potential late toxicity related to radiation treatments. Recent advances in radiation techniques have led to more accurate treatments, rendering obsolete many commonly held views of the "old" radiotherapy. New techniques include intensity modulated radiotherapy, volumetric-modulated arc therapy, and stereotactic techniques, either stereotactic radiosurgery or fractionated stereotactic radiotherapy. New techniques allow the delivering of higher radiation doses to the target with rapid dose fall-off in the surrounding normal tissues, and potentially limiting the long term toxicity of radiation. In this review, we present a critical analysis of the most recent available literature on the use of radiation in patients with NFAs, focusing particularly on the efficacy and safety of radiation stereotactic techniques.

A Case of Symptomatic Granular Cell Tumor of the Pituitary Treated with Stereotactic Radiosurgery.

BACKGROUND: Granular cell tumors (GCT) of the pituitary are rare. Surgery is considered the primary management option. However, complete resection is often difficult, and surgery is associated with high rates of postoperative complications. AIMS: To report a unique case of pituitary GCT treated with stereotactic radiosurgery (SRS). CASE DESCRIPTION: We report a case of a 40-year-old female with endocrine dysfunction who underwent stereotactic biopsy and then SRS for the management of a suprasellar granular cell tumor. Over the ensuing 10 years, tumor regression was observed. Thirteen years after SRS, the patient remained asymptomatic; however, follow-up MRI demonstrated tumor progression. Fifteen years after SRS, the patient required endoscopic endonasal surgery after developing a new optic neuropathy. Her images demonstrated further tumor growth beyond the targeted area. CONCLUSION: SRS resulted in long-term tumor control without additional endocrine dysfunction, but the onset of new optic neuropathy associated with delayed tumor growth prompted surgical decompression.

Estimating the Risks of Adverse Radiation Effects After Gamma Knife Radiosurgery for Arteriovenous Malformations.

BACKGROUND AND PURPOSE: We evaluated risk factors associated with the development of adverse radiation effects (ARE) after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs). METHODS: We evaluated 755 patients with AVM who underwent a single Gamma Knife SRS procedure with at least a 2-year minimum follow-up. Eighty-seven patients (12%) underwent previous resection and 128 (17%) had previous embolization. The median target volume was 3.6 mL (range, 0.1-26.3 mL). The median margin dose was 20 Gy (range, 13-27 Gy). RESULTS: Fifty-five patients (7%) developed symptomatic ARE at a median follow-up of 75 months. The cumulative rates of symptomatic ARE were 3.2%, 5.8%, 6.7%, and 7.5% at 1, 2, 3, and 5 years, respectively. Factors associated with a higher rate of developing symptomatic ARE included larger AVM volume, higher margin dose, larger 12-Gy volume, higher Spetzler-Martin grade, and higher radiosurgery-based score. The rates of developing symptomatic ARE were higher in the brain stem (22%) or thalamus (16%), compared with AVMs located in other brain locations (4%-8%). Nineteen patients (3%) sustained irreversible new neurological deficits related to ARE, and 1 patient died. The rates of irreversible symptomatic ARE were 0.8%, 1.9%, 2.1%, and 2.8% at 1, 2, 3, and 5 years, respectively. The 5-year cumulative rates of irreversible symptomatic ARE were 9.1% in thalamus, 12.1% in brain stem, and 1.4% in other locations. CONCLUSIONS: The knowledge of ARE risk rates after AVM radiosurgery can assist informed consent for patients with AVM, their families, and healthcare providers.

Stereotactic radiosurgery for essential tremor: Retrospective analysis of a 19-year experience.

BACKGROUND: Essential Tremor (ET) is a common movement disorder that can be disabling. Initial treatment is in the form of medical therapies. Patients with medically refractory ET seek surgical intervention which include radiofrequency thalamotomy, deep brain stimulation, and radiosurgical thalamotomy. Radiosurgical thalamotomy is a minimally invasive surgical option which is especially valuable for elderly and high surgical risk patients. OBJECTIVE: The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory essential tremor. METHODS: During a 19-year period (1996-2015), 73 patients underwent gamma knife thalamotomy for intractable essential tremor. A median central dose of 140 Gy (range, 130-150) was delivered to the nucleus ventralis intermedius through a single 4-mm isocenter. We used the Fahn-Tolosa-Marin clinical tremor rating scale to score tremor, handwriting, drawing, and ability to drink fluids. The median time to last follow-up was 28 months (range, 6-152). RESULTS: After gamma knife thalamotomy, 93.2% improved in tremor. Forty-four patients (60.3%) experienced tremor arrest or barely perceptible tremor. Eighteen patients (24.7%) noted tremor arrest and complete restoration of motor function. Tremor improvement was sustained at last follow-up in 96% of patients who experience tremor relief. Mean tremor score improved from 3.19 before to 1.27 after gamma knife thalamotomy (P < 0.0001). Mean handwriting score improved from 2.97 to 1.25 (P < 0.0001). Mean drawing score improved from 3.16 to 1.26 (P < 0.0001). Mean drinking score improved from 3.14 to 1.56 (P < 0.0001). Imaging follow-up showed three types of lesions: enhancing lesion, streaking along internal capsule on fluid-attenuated inversion recovery, and significant reactive changes. Three patients (4%) experienced temporary adverse radiation effects. CONCLUSION: Radiosurgery is a safe and valuable treatment option for medically refractory essential tremor, especially for the elderly or those with high surgical risk for DBS or radiofrequency thalamotomy. © 2017 International Parkinson and Movement Disorder Society.

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61-0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63-0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.