Long-term outcome of primary clival chordomas: a single-center retrospective study with an emphasis on the timing of recurrences based on the primary treatment.

OBJECTIVE: This study aimed to provide data on extended outcomes in primary clival chordomas, focusing on progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective single-center analysis was conducted on patients with clival chordoma treated between 1987 and 2022 using surgery, stereotactic radiosurgery, or proton radiation therapy (PRT). RESULTS: The study included 100 patients (median age 44 years, 51% male). Surgery was performed using the endoscopic endonasal approach in 71 patients (71%). Gross-total resection (GTR) or near-total resection (NTR) was attained in 39 patients (39%). Postoperatively, new cranial nerve deficits occurred in 7%, CSF leak in 4%, and meningitis in none of the patients. Radiation therapy was performed in 79 patients (79%), with PRT in 50 patients (50%) as the primary treatment. During the median follow-up period of 73 (interquartile range [IQR] 38-132) months, 41 recurrences (41%) and 31 deaths (31%) were confirmed. Patients with GTR/NTR had a median PFS of 41 (IQR 24-70) months. Patients with subtotal resection or biopsy had a median PFS of 38 (IQR 16-97) months. The median PFS of patients who received radiation therapy was 43 (IQR 26-86) months, while that of patients who did not receive radiation therapy was 18 (IQR 5-62) months. The Kaplan-Meier method showed that patients with GTR/NTR (p = 0.007) and those who received radiation therapy (p < 0.001) had longer PFS than their counterparts. The PFS rates following primary treatment at 5, 10, 15, and 20 years were 51%, 25%, 17%, and 7%, respectively. The OS rates at the same intervals were 84%, 60%, 42%, and 34%, respectively. Multivariate Cox regression analysis showed that age < 44 years (p = 0.02), greater extent of resection (EOR; p = 0.03), and radiation therapy (p < 0.001) were associated with lower recurrence rates. Another multivariate analysis showed that age < 44 years (p = 0.01), greater EOR (p = 0.04), and freedom from recurrence (p = 0.02) were associated with lower mortality rates. Regarding pathology data, brachyury was positive in 98%, pan-cytokeratin in 93%, epithelial membrane antigen in 85%, and S100 in 74%. No immunohistochemical markers were associated with recurrence. CONCLUSIONS: In this study, younger age, maximal safe resection, and radiation therapy were important factors for longer PFS in patients with primary clival chordomas. Preventing recurrences played a crucial role in achieving longer OS.

Correlation of older age with better progression-free survival despite less aggressive resection in nonfunctioning pituitary adenomas.

OBJECTIVE: Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification. METHODS: This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50-59, 60-69, and ≥ 70 years. RESULTS: Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50-59 years, 85.0% in those 60-69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01-1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02-1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60-0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90-18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84-0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age. CONCLUSIONS: Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.

Predicting the need for occipitocervical fusion for patients with lower clival chordoma: a single-center retrospective study.

OBJECTIVE: To assess the impact of tumor extension into the occipital condyle (OC) in lower clival chordoma management and the need for occipito-cervical fusion (OCF). METHODS: A retrospective analysis was conducted on 35 patients with lower clival chordoma. The preoperative area of the intact OCs, Hounsfield units, and the integrity of the apical ligament and the tectorial membrane were assessed using preoperative imaging. RESULTS: Seven (20%) patients were in the OCF group. The OCF group exhibited a higher prevalence of preoperative pain in the neck or head (p = 0.006), ligament absence (p = 0.022), and increased propensity for postoperative wound issues (p = 0.022) than the non-OCF group. The OCF group had less intact OCs (p < 0.001) and higher spinal instability neoplastic score (p = 0.002) than the non-OCF group. All patients with intact OCs<60% underwent OCF, and those with OCs≥70% were treated without OCF. Those with OCs between 60% and 69% underwent OCF if the ligaments were eroded, and did not undergo OCF if the ligaments were intact. Treatment strategies varied, with endoscopic endonasal approach (EEA) alone being common. Radiation therapy was administered to 89% of patients. All three patients treated with OCF after tumor resection had wound issues; none treated with OCF before resection had wound issues. None developed atlanto-occipital instability. Survival rates did not significantly differ between groups. CONCLUSIONS: In the absence of mobility-related neck pain, patients with lower clival chordoma and intact OC≥60%, intact apical ligament, and intact tectorial membrane, may not require OCF.

Bypass-Assisted Microsurgical Clipping for an Endovascular Treatment-Resistant Ruptured Internal Carotid-Posterior Communicating Artery Aneurysm, Recurring Two Decades Postinitial Clipping: 2-Dimensional Operative Video.

Salvage treatment of postclipping recurrent aneurysms remains challenging.1,2 The salvage microsurgical clipping is a possible intervention but sometimes difficult because of tissue adhesions around the aneurysm and previously installed clips; therefore, salvage coil embolization may have certain advantages.1-5 However, when coil embolization is not applicable,6 microsurgical clipping is a stand-alone curative treatment, requiring proficient and reliable microsurgical techniques. This article describes a unique case of a 70-year-old female patient complaining of a severe headache with subarachnoid hemorrhage due to a recurrent ruptured left internal carotid-posterior communicating artery aneurysm after microsurgical clipping 23 years ago. An initial attempt at coil embolization proved unsuccessful because of the aneurysm shape. Consequently, the salvage microsurgical clipping was planned. Given the additional time for trapping the internal carotid artery for the old clip removal, a superficial temporal artery-middle cerebral artery bypass was also planned. The operation entailed a superficial temporal artery-middle cerebral artery bypass, a Sylvian fissure dissection, the old clip removal, and aneurysm clipping. Intraoperatively, the complete aneurysm neck clipping was successfully performed without any complication, and patient postoperative course was uneventful. A wide surgical field should be obtained to be able to manipulate the aneurysm and old clip safely under a microscope. It is also important to temporarily trap the main artery to ensure removal of old clips and to prepare for intraprocedural ischemia using bypass after a precise assessment of hemodynamics before surgery. The patient provided informed consent for the procedure and the publication of the case along with its pertinent imaging, and this report was approved by the institutional review board at our hospital.

Safety evaluation of sinus patency after stereotactic radiosurgery for transverse-sigmoid sinus dural arteriovenous fistulas: implications of treatment options for patients with Borden type I fistulas.

OBJECTIVE: This study aimed to assess the efficacy and safety of stereotactic radiosurgery (SRS) in treating transverse-sigmoid sinus dural arteriovenous fistulas (TSS DAVFs), and to investigate post-SRS sinus patency, focusing on the risk factors associated with treated sinus occlusion. METHODS: Data from 34 patients treated with SRS between January 2006 and April 2023 were analyzed. Detailed angioarchitecture was confirmed using digital subtraction angiography before SRS. Angiography of the ipsilateral internal carotid artery and vertebral artery was performed to evaluate whether the involved side of the TSS was used for normal venous drainage. TSS stenosis was defined as sinus diameter < 50% of the normal proximal diameter. DAVF shunt obliteration, TSS occlusion, neurological status, and adverse events were also evaluated. RESULTS: Of the 34 patients, 21 had Borden type I and 14 had Borden type II DAVFs. The median age at SRS was 64 years (interquartile range 54-71 years), and the follow-up period was 31 months (interquartile range 15-94 months). Complete shunt obliteration was achieved in 24 (70.6%) patients. The cumulative 2-, 3-, and 5-year shunt obliteration rates were 49.6%, 71.2%, and 86.0%, respectively. Borden type I had higher obliteration rates (60.5%, 83.1%, and 94.4%, respectively) than Borden type II (41.7%, 51.4%, and 75.7%, respectively; p = 0.034). TSS occlusion occurred in 5 patients (14.7%). The cumulative 1-, 5-, and 10-year TSS occlusion rates were 2.9%, 8.3%, and 23.6%, respectively, across the entire cohort. All occlusions occurred exclusively in the sinuses that were not used for normal venous drainage. Cox proportional analyses revealed that TSS stenosis and the sinus not being used for normal venous drainage were significantly associated with a greater risk of TSS occlusion after SRS (HR 9.44, 95% CI 1.01-77.13; p = 0.049). CONCLUSIONS: SRS is effective and safe for TSS DAVF and results in favorable shunt obliteration, symptom improvement, and low complication rates. TSS occlusion after SRS is asymptomatic and is limited to sinuses that are not used for normal venous drainage.

Incidence of and risk factors for chronic subdural hematoma after endoscopic endonasal surgery: quantitative analysis of pneumocephalus.

OBJECTIVE: Chronic subdural hematoma (CSDH) is known to occur after endoscopic endonasal surgery (EES); however, the detailed clinical picture remains unclear. In this study, the authors aimed to examine the incidence of and risk factors for post-EES CSDH, with a focus on the quantitative evaluation of postoperative pneumocephalus. METHODS: The authors retrospectively collected data on consecutive patients who, between November 2016 and December 2022, had undergone EES during which intraoperative cerebrospinal fluid (CSF) leakage occurred. Using CT images obtained immediately after surgery (CT0), the authors measured the extent of pneumocephalus in detail. The locations of pneumocephalus were divided into two groups: remote and local. Remote pneumocephalus was further subdivided into convexity and ventricular. The incidence of post-EES CSDH was calculated, and its risk factors were analyzed. RESULTS: Among the 159 EES patients included in the study, Esposito grade 1, 2, and 3 intraoperative CSF leakage was confirmed in 22 (14%), 27 (17%), and 110 (69%) patients, respectively. CSDH occurred in 6 patients (3.8%). One patient (0.6%) required unilateral burr hole surgery, whereas the hematomas spontaneously disappeared in the others. All CSDHs occurred in patients with Esposito grade 3 CSF leakage and convexity pneumocephalus on CT0. In the multivariate analysis of 149 sides with convexity pneumocephalus on CT0, the product of the diameter and the thickness of convexity pneumocephalus on CT0 was significantly associated with subsequent CSDH (OR 1.21, 95% CI 1.06-1.38, p = 0.004). Using a cutoff value of 10 cm2, CSDH development could be predicted with a sensitivity of 0.82 and specificity of 0.74. CONCLUSIONS: The incidence of post-EES CSDH is acceptably low, and surgery is rarely required. Patients with extensive convexity pneumocephalus on immediate postoperative CT are prone to develop CSDH and thus should be carefully monitored.

Long-term geometric quality assurance of radiation focal point and cone-beam computed tomography for Gamma Knife radiosurgery system.

To investigate the geometric accuracy of the radiation focal point (RFP) and cone-beam computed tomography (CBCT) over long-term periods for the ICON Leksell Gamma Knife radiosurgery system. This phantom study utilized the ICON quality assurance tool plus, and the phantom was manually set on the patient position system before the implementation of treatment for patients. The deviation of the RFP position from the unit center point (UCP) and the positions of the four ball bearings (BBs) in the CBCT from the reference position were automatically analyzed. During 544 days, a total of 269 analyses were performed on different days. The mean ± standard deviation (SD) of the deviation between measured RFP and UCP was 0.01 ± 0.03, 0.01 ± 0.03, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively. The deviations with offset values after the cobalt-60 source replacement (0.00 ± 0.03, -0.01 ± 0.01, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively) were significantly (p = 0.001) smaller than those before the replacement (0.02 ± 0.03, 0.02 ± 0.01, and -0.02 ± 0.01 mm in the X, Y, and Z directions, respectively). The overall mean ± SD of four BBs was -0.03 ± 0.03, -0.01 ± 0.05, and 0.01 ± 0.03 mm in the X, Y, and Z directions, respectively. Geometric positional accuracy was ensured to be within 0.1 mm on most days over a long-term period of more than 500 days.

Role of stereotactic radiosurgery for recurrent skull base acinic cell carcinoma: illustrative case.

BACKGROUND: Acinic cell carcinomas (AcCCs), rare malignancies of the salivary glands, often recur and metastasize, particularly in the skull base. Conventional radical resection can be invasive for skull base AcCCs adjacent to cranial nerves and major vasculature, and the effectiveness of stereotactic radiosurgery (SRS) as an alternative is not well established. OBSERVATIONS: This case report details the application of SRS for recurrent skull base AcCCs. A 71-year-old male with a history of resection for a right mandibular AcCC 23 years earlier experienced tumor recurrence involving the right cavernous sinus and nasal cavity. He underwent endoscopic transnasal surgery followed by SRS targeting different tumor locations-the cavernous sinus to the pterygopalatine fossa, maxillary sinus, and clivus-each with a prescribed dose of 20 Gy to the 40% to 50% isodose line. After the first skull base metastasis, additional sessions of localized SRS after endoscopic surgery led to a 12-year survival without sequela. LESSONS: This is a report indicating that SRS for skull base AcCCs can achieve favorable local control, functional preservation, and long-term survival. SRS may be suitable for skull base AcCC given the lesion's tendency toward multiple local recurrences. Further investigation is needed to validate the treatment's efficacy.

Ki-67 labeling index predicts tumor progression patterns and survival in patients with atypical meningiomas following stereotactic radiosurgery.

PURPOSE: This study investigated whether Ki-67 labeling index (LI) correlated with clinical outcomes after SRS for atypical meningiomas. METHODS: This retrospective study examined 39 patients with atypical meningiomas who underwent SRS over a 10-year study period. Ki-67 LI was categorized into 3 groups: low (< 5%), intermediate (5%-10%), and high (> 10%). Local tumor control rates (LCRs), progression-free rates (PFRs), disease-specific survival (DSS) rates, and adverse radiation-induced events (AREs) were evaluated. RESULTS: The median follow-up periods were 26 months. SRS was performed at a median prescription dose of 18 Gy for tumors with a median Ki-67 LI of 9.6%. The 3-year LCRs were 100%, 74%, and 25% in the low, intermediate, and high LI groups, respectively (p = 0.011). The 3-year PFRs were 100%, 40%, and 0% in the low, intermediate, and high LI groups (p = 0.003). The 5-year DSS rates were 100%, 89%, and 50% in the low, intermediate, and high LI groups (p = 0.019). Multivariable Cox proportional hazard analysis showed a significant correlation of high LI with lower LCR (hazard ratio [HR], 3.92; 95% confidence interval [CI] 1.18-13.04, p = 0.026), lower PFR (HR 3.80; 95% CI 1.46-9.88, p = 0.006), and shorter DSS (HR 6.55; 95% CI 1.19-35.95, p = 0.031) compared with intermediate LI. The ARE rates were minimal (8%) in the entire group. CONCLUSION: Patients with high Ki-67 LI showed significantly more tumor progression and tumor-related death. Ki-67 LI might offer valuable predictive insights for the post-SRS management of atypical meningiomas.

Clinical presentation, role of surgery and prognosis in spinal astrocytoma: Cohort study.

Spinal astrocytoma is a rare neoplasm with discouraging prognosis, which accounts for 6-8 % of total intramedullary spinal tumors. As this is a rare entity, details of the clinical and molecular features have not been fully unraveled. We evaluated the radiologic findings, perioperative clinical presentation, histopathological features and treatment response in a single institution series of 37 consecutive cases of spinal astrocytomas (WHO grades 1 to 4). We identified 8, 16, 8, and 5 patients with grade 1, 2, 3, and 4 lesions, respectively, from 1988 to 2017. Peak ages were youngest in grade 1, followed in order by grades 4, 3 and 2. Whereas all cases of grade 1 and 4 enhanced with contrast, less than half of the cases of grade 2 tumors enhanced (44 %). Grade 3 tumors had a higher rate of multiplicity at presentation (50 %). A concomitant brain lesion at presentation was present in 14 % and 43 % of grade 2 and 3 lesions, respectively. Progression-free and overall survival were worse in grades 3 and 4 compared to grade 2 lesions but no significant difference was observed between grade 3 and 4. Many patients (16-of-36) experienced new neurological deficits postoperatively regardless of grade. Most patients (88 %) required postoperative rehabilitation, and 61 % were not discharged to home. Discharge destination closely correlated with age (p = 0.002). These clinical findings may be useful in understanding the clinical phenotype and improving the management of this rare disease.

Treatment outcomes of single-fraction stereotactic radiosurgery for adenoid cystic carcinoma: a case series of 55 patients.

PURPOSE: This study aimed to analyze the treatment outcomes of single-fraction stereotactic radiosurgery (SRS) for adenoid cystic carcinoma patients. METHODS: Retrospective analysis was conducted for 55 patients with 66 lesions. SRS intentions were categorized as definitive, adjuvant, salvage, and palliative. Tumor control was defined as local (within 50% isodose line), marginal (outside 50% isodose line), and distant (metastasis outside head/neck). RESULTS: The median age was 60 years (range 21-85), with 53% males. Tumor origin was head/neck for 88% and trachea/lung for 12%. 61% were recurrent lesions. Median interval from diagnosis to SRS was 14 months. Preceding surgery was performed in 30%. SRS was administered as definitive (30 lesions), adjuvant (13), salvage (19), and palliative (4). SRS was used as a boost to external beam radiation therapy (EBRT) in 39%. Concurrent chemotherapy was administered in 26%. 5-, 10-, and 15-year local control rates were 60%, 33%, and 27%, respectively; local/marginal control rates were 29%, 13%, and 10%. For recurrent lesions treated with SRS without EBRT, 5-year local control rate was 14%, and local/marginal control rate was 5%. For recurrent lesions treated with SRS and EBRT, 5-year local control rate was 100%, and local/marginal control rate was 40%. The rate of distant failure after SRS was 40%. Older age and distant metastasis before SRS were negative factors for overall survival. CONCLUSION: SRS provided a high rate of local tumor control, but marginal failure was frequent. Integrating SRS with added EBRT exhibits potential for enhancing local and local/marginal tumor control, particularly in recurrent cases.

Inferior Petrosal Sinus Sampling Tumor Lateralization and the Surgical Treatment of Cushing Disease: A Meta-Analysis and Systematic Review.

OBJECTIVE: To determine whether accurate inferior petrosal sinus sampling (IPSS) tumor lateralization is associated with improved clinical outcomes following the surgical treatment of Cushing disease. METHODS: The presented study was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data regarding patient demographics, IPSS tumor lateralization, and postoperative endocrinologic outcomes were abstracted and pooled with random effects meta-analysis models. Additional meta-regression models were used to examine the association between the accuracy of IPSS tumor lateralization and postoperative outcomes (recurrence/persistence or remission/cure). Statistical analyses were performed using the Comprehensive Meta-Analysis software (significance of P < 0.05). RESULTS: Seventeen eligible articles were identified, yielding data on 461 patients. Within average follow-up duration (∼59 months), the rate of correct IPSS tumor lateralization was 69% [95% confidence interval: 61%, 76%], and the rate of postoperative remission/cure was 78% [67%, 86%]. Preoperative IPSS tumor lateralization was concordant with magnetic resonance imaging lateralization for 53% of patients [40%, 66%]. There was no significant association between the rate of correct IPSS tumor lateralization and postoperative remission/cure among study-level data (P = 0.735). Additionally, there was no association among subgroup analyses for studies using stimulatory agents during IPSS (corticotropin-releasing hormone or desmopressin, P = 0.635), nor among subgroup analyses for adult (P = 0.363) and pediatric (P = 0.931) patients. CONCLUSIONS: Limited data suggest that the rate of correct IPSS tumor lateralization may not be positively associated with postoperative remission or cure in patients with Cushing disease. These findings bring into question the utility of IPSS tumor lateralization in the context of preoperative planning and surgical approach rather than confirming a pituitary source.

Longitudinal treatment outcomes of recurrent clival chordomas: a single-center retrospective study.

OBJECTIVE: The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality. METHODS: A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors' institution between 1990 and 2022. RESULTS: A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18-79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36-62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1-8), and the median (IQR) time to the first recurrence was 29 (9-51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0-245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54-82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038-0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01-1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11-51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence. CONCLUSIONS: Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.

The clinical presentation of PIT1 positive pituitary neuroendocrine tumor immunonegative for growth hormone, prolactin, and thyroid stimulating hormone with analysis of clinical and immunostaining dissociation.

BACKGROUND: PIT1 is a pituitary transcription factor that is associated with either growth hormone (GH), prolactin (PRL), or thyroid-stimulating hormone (TSH) production. However, PIT1-positive pituitary neuroendocrine tumors (PitNETs) are occasionally immunonegative for GH, PRL, and TSH. This paper describes the clinical presentation of PIT1 positive however immunonegative PitNETs. METHODS: We conducted a retrospective analysis, identifying 228 PIT1-positive PitNET patients between 2017 and 2022. Out of these, ten (4%) tested negative for GH, PRL, and TSH. Functioning PitNETs were defined as those causing hormonal excess symptoms or hormonal overproduction. RESULTS: As for 10 patients immunonegative for all three hormones however PIT1-positive, the mean ( ± standard deviation) age was 46 ± 13 years with 70% women. Six patients exhibited signs of excess GH or PRL, and three had visual problems. Additionally, one patient had secondary hypothyroidism and adrenal insufficiency resulting from the mass effect. All tumors were macroadenoma, with a median volume of 2.1 cm3 (range, 0.8-17.5 cm3). Gross total resection was attained in six patients by trans-sphenoidal surgery. Postoperatively, eight patients experienced clinical improvement: three in vision, two in amenorrhea, two in headache, and one in acromegaly symptoms. Biochemical improvement was observed in six patients, with all experiencing remission in hormonal excess and one showing improvement in secondary hypothyroidism. Stereotactic radiosurgery was performed in three patients. CONCLUSIONS: Patients with functioning PitNETs may exhibit PIT1 staining without GH, PRL, or TSH staining. Hormonally active tumors exist in this patient population; therefore, close endocrine follow-up is necessary despite the lack of staining for GH, PRL, and TSH.

Long-term outcomes of stereotactic radiosurgery for intracranial schwannoma in neurofibromatosis type 2: a genetic analysis perspective.

PURPOSE: Neurofibromatosis type 2 (NF2) is intractable because of multiple tumors involving the nervous system and is clinically diverse and genotype-dependent. Stereotactic radiosurgery (SRS) for NF2-associated schwannomas remains controversial. We aimed to investigate the association between radiosurgical outcomes and mutation types in NF2-associated schwannomas. METHODS: This single-institute retrospective study included consecutive NF2 patients with intracranial schwannomas treated with SRS. The patients' types of germline mutations ("Truncating," "Large deletion," "Splice site," "Missense," and "Mosaic") and Halliday's genetic severity scores were examined, and the associations with progression-free rate (PFR) and overall survival (OS) were analyzed. RESULTS: The study enrolled 14 patients with NF2 with 22 associated intracranial schwannomas (median follow-up, 102 months).　The PFRs in the entire cohort were 95% at 5 years and 90% at 10-20 years. The PFRs tended to be worse in patients with truncating mutation exons 2-13 than in those with other mutation types (91% at 5 years and 82% at 10-20 years vs. 100% at 10-20 years, P = 0.140). The OSs were 89% for patients aged 40 years and 74% for those aged 60 years in the entire cohort and significantly lower in genetic severity group 3 than in the other groups (100% vs. 50% for those aged 35 years; P = 0.016). CONCLUSION: SRS achieved excellent PFR for NF2-associated intracranial schwannomas in the mild (group 2A) and moderate (group 2B) groups. SRS necessitates careful consideration for the severe group (group 3), especially in cases with NF2 truncating mutation exons 2-13.

Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel.

Background: Despite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies. Case presentation: We report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach. Conclusion: Gene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.

Autologous Osteochondral Grafts for Knee Osteochondral Diseases Result in Good Patient-Reported Outcomes in Patients Older Than 60 Years.

Purpose: This study aims to examine the clinical autologous osteochondral grafts (AOG) outcomes for knee osteochondral diseases at operative ages >60 years, and to determine whether patients are able to sit straight in Japanese style after AOG. Methods: All patients who underwent AOG for knee osteochondral diseases between November 2001 and April 2018 were retrospectively identified. The inclusion criteria were AOG only without osteotomy, operative ages between 60 and 79 years, >2 years of follow-up, and involved femorotibial angle between 169° and 179° (normal alignment). Patients who underwent osteotomy to improve knee alignment and patients with inflammatory diseases such as rheumatoid arthritis were excluded. The patients' knee symptoms and their clinical outcome were evaluated according to the criteria of the knee scoring system of the Japanese Orthopedic Association (JOA), International Knee Documentation Committee (IKDC) subjective score, and the ability of straight sitting in Japanese style. Results: This study enrolled 57 cases and 60 knee joints during the study period. The follow-up ratio was 85.1%. Moreover, 14 men and 43 women and 29 right and 31 left knee joints were included in this study. The mean operative age and mean follow-up period were 67.8 years (range 60-76 years) and 81.1 months (range 24-167 months), respectively. In addition, the study involved 30 cases and 32 knee joints (60s group), and 27 cases and 28 knee joints (70s group). Moreover, 34 cases and 36 knee joints had osteonecrosis (ON group), and 23 cases and 24 knee joints had cartilage injury (CI group). The IKDC subjective and JOA scores in both the 60s and 70s groups showed significant differences: 2 years after AOG ＞at the follow-up period, ＞at the preoperative period. The scores in both the CI and ON groups showed similar significant differences. Furthermore, 8.3% and 53.5% of the patients could sit straight in Japanese style at the preoperative period and 2 years after AOG, respectively. Conclusion: Even if the patient's operative age was >60 years, the AOG only for their knee osteochondral diseases had good clinical outcomes, including the ability to sit straight in Japanese style. Level of Evidence: IV, Therapeutic case series Key words: autologous osteochondral grafts, aged patients, clinical outcome, knee joint, straight sitting in Japanese style.

Comparison of Tumor Control After Stereotactic Radiosurgery or Pencil Beam Proton Therapy for Newly Diagnosed Clival Chordomas: A Single-Center Retrospective Study.

OBJECTIVE: To compare outcomes of proton radiation therapy (PRT), stereotactic radiosurgery (SRS), and x-ray-based radiation with an SRS boost (XRT + SRS) for newly diagnosed clival chordoma. METHODS: Consecutive patients who underwent PRT or SRS in our facility were retrospectively reviewed. RESULTS: A total of 59 patients were identified (PRT, 36; SRS, 11; XRT + SRS, 12). The mean age (± standard deviation) was 46 ± 20 years, with 54% being male. The mean tumor diameter (± standard deviation) was 3.7 ± 1.5 cm, and 21 (36%) involved the lower clivus. Gross total or near-total resection was attained in 27 patients (46%), all of whom received PRT. PRT was administered with a median prescribed dose of 70.8 Gy (range, 66.0-76.0). SRS involved a median marginal dose of 16 Gy (range, 14-20) and a median maximal dose of 36 Gy (range, 30-45). The XRT + SRS group was treated with an SRS marginal dose of 12.5 Gy (range, 10-20), a maximal dose of 27 Gy (range, 20-40), and an XRT prescription dose of 50.4 Gy (range, 45.0-59.4). Fifteen recurrences were observed (PRT, 6; SRS, 5; XRT + SRS, 4). For the entire cohort (n = 59), recurrence was associated with the degree of resection (P = 0.042), but not with radiation groups (P = 0.98). For patients after subtotal resection or biopsy (n = 32), the SRS ± XRT group was associated with few recurrences (hazard ratio, 0.260; 95% confidence interval, 0.069-0.98; P = 0.046). CONCLUSIONS: Patients after subtotal resection or biopsy may benefit from the incorporation of SRS.