Transcript-specific enrichment enables profiling rare cell states via scRNA-seq.

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing (scRNA-seq) identifies many rare populations of interest that express specific marker transcript combinations, traditional flow sorting limits our ability to enrich these populations for further profiling, including requiring cell surface markers with high-fidelity antibodies. Additionally, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers. To address these limitations, we describe Programmable Enrichment via RNA Flow-FISH by sequencing (PERFF-seq), a scalable assay that enables scRNA-seq profiling of subpopulations from complex cellular mixtures defined by the presence or absence of specific RNA transcripts. Across immune populations (n = 141,227 cells) and fresh-frozen and formalin-fixed paraffin-embedded brain tissue (n = 29,522 nuclei), we demonstrate the sorting logic that can be used to enrich for cell populations via RNA-based cytometry followed by high-throughput scRNA-seq. Our approach provides a rational, programmable method for studying rare populations identified by one or more marker transcripts.

Treatment and outcomes of IDH1-mutant gliomas in elderly patients.

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutations in both high- and low-grade gliomas are associated with an increase in survival compared with IDH-wild-type (IDHwt) tumors. A rare and understudied population is elderly individuals, ≥ 65 years of age, who have IDH1-R132H-mutant (IDHmt) gliomas. The objective of this paper was to characterize the institutions' experience with IDHmt gliomas in a patient population ≥ 65 years of age over the last 10 years. METHODS: A retrospective study of individuals ≥ 65 years of age with IDHmt gliomas treated between 2010 and 2020 at Memorial Sloan Kettering was performed. RESULTS: Twenty-five patients ≥ 65 years of age underwent resection or biopsy with a diagnosis of IDHmt glioma (52% WHO grade II, 32% WHO grade III, and 16% WHO grade IV). The most common presenting symptoms were seizure (28%) and motor or sensory deficits (24%). On preoperative MRI, 56% of tumors demonstrated contrast enhancement and 44% had no enhancement. Most patients underwent craniotomy for resection (n = 23, 92%), with subtotal resection achieved in the majority (16/23, 69.6%). Postoperative discharge location included home (64%), acute rehabilitation (16%), subacute rehabilitation (8%), and unknown (12%). Most patients received postoperative chemotherapy (72%) and radiation therapy (68%). The 2- and 5-year survival rates for the overall cohort were 83.1% (95% CI 69.3%-99.7%) and 69.7% (95% CI 53.2%-91.3%), respectively, with gross-total resection or near-total resection, contrast enhancement, and WHO grade significantly associated with survival. From the clinical sequencing data, no significant differences were identified between younger and older IDHmt cohorts. CONCLUSIONS: While IDH mutation in elderly patients may be rare, these patients have favorable survival relative to their IDHwt counterparts. Age at diagnosis should not be used in isolation to suggest a molecular IDHwt status or poor prognosis when guiding patient treatment decisions.

Orbital Exenteration for Craniofacial Lesions: A Systematic Review and Meta-Analysis of Patient Characteristics and Survival Outcomes.

BACKGROUND: The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the clinical outcomes of OE, including surgical outcomes and overall survival (OS). METHODS: Relevant articles were retrieved from Medline, Scopus, and Cochrane according to PRISMA guidelines. A systematic review and meta-analysis were conducted on the clinical characteristics, management, and outcomes. RESULTS: A total of 33 articles containing 957 patients who underwent OE for CFLs were included (weighted mean age: 64.3 years [95% CI: 59.9-68.7]; 58.3% were male). The most common lesion was squamous cell carcinoma (31.8%), and the most common symptom was disturbed vision/reduced visual acuity (22.5%). Of the patients, 302 (31.6%) had total OE, 248 (26.0%) had extended OE, and 87 (9.0%) had subtotal OE. Free flaps (33.3%), endosseous implants (22.8%), and split-thickness skin grafts (17.2%) were the most used reconstructive methods. Sino-orbital or sino-nasal fistula (22.6%), flap or graft failure (16.9%), and hyperostosis (13%) were the most reported complications. Regarding tumor recurrences, 38.6% were local, 32.3% were distant, and 6.7% were regional. The perineural invasion rate was 17.4%, while the lymphovascular invasion rate was 5.0%. Over a weighted mean follow-up period of 23.6 months (95% CI: 13.8-33.4), a weighted overall mortality rate of 39% (95% CI: 28-50%) was observed. The 5-year OS rate was 50% (median: 61 months [95% CI: 46-83]). The OS multivariable analysis did not show any significant findings. CONCLUSIONS: Although OE is a disfiguring procedure with devastating outcomes, it is a viable option for carefully selected patients with advanced CFLs. A patient-tailored approach based on tumor pathology, extension, and overall patient condition is warranted.

Examining the impact of cue similarity and fear learning on perceptual tuning.

Past research on the effects of associative aversive learning on discrimination acuity has shown mixed results, including increases, decreases, and no changes in discrimination ability. An animal study found that the type of learning experience determined the direction and extent of learning-induced changes. The current preregistered web-based study aimed to translate these findings to humans. Experiment 1 (N = 245) compared changes in stimulus discrimination between simple learning (only one oriented grating cue), coarse differential conditioning (physically distinct cues), and fine differential conditioning (physically similar cues) as well as to their three respective control groups. The discrimination task consisted of a two-alternative-forced-choice task with oriented grating stimuli. During learning, a specific orientation was paired with unpleasant pictures. Our analysis using generative modeling demonstrated weak to moderate evidence that aversive learning did not alter discrimination acuity in any of the groups. In a follow-up experiment (N = 121), we replicated these findings despite successful learning trajectories in all three groups and a more detailed assessment of discrimination acuity. Contrary to prior assumptions, our findings indicate that aversive learning does not enhance perceptual discrimination, and the presence of additional safety cues does not appear to moderate this effect.

Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis.

Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we show CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples. Meaningful clinico-genomic correlations are noted, namely EGFR alterations in leptomeningeal disease (LMD) and MYC amplifications in multifocal regional brain progression. Patients who developed early LMD frequently have had uncommon, multiple, and persistently detectable EGFR driver mutations. The distinct mutational patterns identified in BM specimens compared to other tissue sites suggest specific biologic underpinnings of intracranial progression.

The idiosyncratic nature of how individuals perceive, represent, and remember their surroundings and its impact on learning-based generalization.

The current study adopted a multimodal assessment approach to map the idiosyncratic nature of how individuals perceive, represent, and remember their surroundings and to investigate its impact on learning-based generalization. During an online differential conditioning paradigm, participants (n = 105) learned the pairing between a blue color patch (CS +) and an outcome (i.e., shock symbol) and the unpairing between a green color patch and the same outcome. After the learning task, the generalization of outcome expectancies was assessed to 14 stimuli spanning the entire blue-green color spectrum. Hereafter, a stimulus identification task assessed the ability to correctly identify the CS + among this stimulus range. Continuous and binary color category membership judgments of the stimuli were assessed preconditioning. We found that a response model with color perception and identification performance as sole predictors was preferred to contemporary approaches that use stimulus as a predictor. Interestingly, incorporating interindividual differences in color perception, CS identification, and color categories significantly improved the models' ability to account for different generalization patterns. Our findings suggest that insight into the idiosyncratic nature of how individuals perceive, represent, and remember their surroundings provides exciting opportunities to understand post-learning behaviors better. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Middle meningeal artery embolization using cone-beam computed tomography augmented guidance in patients with cancer.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of middle meningeal artery embolization (MMAE) performed under cone-beam computed tomography (CBCT) augmented guidance in patients with cancer. MATERIALS AND METHODS: Eleven patients with cancer (seven women, four men; median age, 75 years; age range: 42-87 years) who underwent 17 MMAEs under CBCT with a combination of particles and coils for chronic subdural hematoma (SDH) (n = 6), postoperative SDH (n = 3), or preoperative embolization of meningeal tumor (n = 2) from 2022 to 2023 were included. Technical success, fluoroscopy time (FT), reference dose (RD), kerma area product (KAP) were analyzed. Adverse events and outcomes were recorded. RESULTS: The technical success rate was 100% (17/17). Median MMAE procedure duration was 82 min (interquartile range [IQR]: 70, 95; range: 63-108 min). The median FT was 24 min (IQR: 15, 48; range: 21.5-37.5 min); the median RD was 364 mGy (IQR: 37, 684; range: 131.5-444.5 mGy); and the median KAP was 46.4 Gy.cm2 (9.6, 104.5; range: 30.2-56.6 Gy.cm2). No further interventions were needed. The adverse event rate was 9% (1/11), with one pseudoaneurysm at the puncture site in a patient with thrombocytopenia, which was treated by stenting. The median follow-up was 48 days (IQR; 14, 251; range: 18.5-91 days]. SDH reduced in 11 of 15 SDHs (73%) as evidenced by follow-up imaging, with a size reduction greater than 50% in 10/15 SDHs (67%) . CONCLUSION: MMAE under CBCT is a highly effective treatment option, but appropriate patient selection and careful consideration of potential risks and benefits is important for optimal patient outcomes.

Characterization of Central Nervous System Clinico-Genomic Outcomes in ALK-Positive Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Alectinib.

INTRODUCTION: Highly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT. METHODS: We retrospectively reviewed ALK fusion-positive NSCLC patients with BMs who received alectinib at the diagnosis of BM from 1/2012 and 5/2021. Outcome variables included intracranial progression-free survival (iPFS), overall survival (OS), duration of TKI therapy, and CNS response rates. Genomic characteristics from tumor specimens were assessed with MSK-IMPACT, a next-generation sequencing (NGS)-based genomic profiling assay. RESULTS: A total of 38 patients with 114 CNS lesions were included. Twelve of these patients also received contemporaneous LT (SRS, WBRT, or surgical resection). Maximal BM diameter in the TKI + LT group was greater (p < 0.003) but despite this difference, iPFS (TKI only, HR 1.21, 95 % CI 0.51-2.89; p = 0.66) and OS (TKI only, HR 5.99, 95 % CI 0.77-46.6; p = 0.052) were similar between groups and trended towards more favorable outcomes with the addition of LT. SMARCA4 co-alterations were associated with inferior OS (HR 8.76, 1.74-44.2; p = 0.009). CONCLUSIONS: Our study demonstrated that patients with ALK fusion-positive NSCLC treated with TKI + LT had larger BM and higher likelihood of pre-treatment neurologic symptoms. Despite these differences, iPFS was similar between groups. Results should be interpreted with caution as our study was limited by an underpowered sample size. SMARCA4 co-alterations were associated with inferior OS and these findings warrant further investigation.

A data-driven quality-score system for rating drug products and its implications for the health care industry.

The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products.

Individual differences in stimulus identification, rule induction, and generalization of learning.

In the field of stimulus generalization, an old yet unresolved discussion pertains to what extent stimulus misidentifications contribute to the pattern of conditioned responding. In this article, we perform cluster analysis on six datasets (four published datasets and two unpublished datasets, included N = 950) to examine the relationship between interindividual differences in (a) stimulus identification, (b) patterns of generalized responding, and (c) verbalized generalization rules. The datasets were obtained from online predictive learning tasks where participants learned associations between colored cues and the presence or absence of a hypothetical outcome. In these datasets, stimulus identification and expectancy ratings were assessed in separate phases to a range of colors varying between blue-green. Using cluster analyses on performance during stimulus identification, we identified different subgroups of participants (good vs. bad identifiers). In all six datasets, we found a close relationship between the pattern of stimulus identification and the shape of the expectancy gradient across the test dimension between the identified subgroups. Furthermore, participants classified as good identifiers were more likely to report a similarity generalization rule than a relational or linear rule, suggesting that individual differences in stimulus identification are related to individual differences in generalization rules. These findings suggest that greater consideration should be given to interindividual variability in stimulus identification, inductive rules, and their relationship in explaining patterns of generalized responses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Investigative needle core biopsies for multi-omics in Glioblastoma.

Glioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The role of investigative biopsies - tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses ('Multi-omics") has yet to be defined. Secondly, it is unknown whether comparatively small tissue samples from brain biopsies can yield sufficient information with such methods. Here we adapt stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue that was obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models in a separate patient cohort. Dataset integration across modalities showed good correspondence between spatial modalities, highlighted immune cell associated metabolic pathways and revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data, provide data rich insight into a patient's disease process and tumor immune microenvironment and can be of value in evaluating treatment responses. One sentence summary: Integrative multi-omics analysis of stereotactic needle core biopsies in glioblastoma.

Tumors Involving the Infratemporal Fossa: A Systematic Review of Clinical Characteristics and Treatment Outcomes.

BACKGROUND: Infratemporal fossa (ITF) tumors represent various pathologies and are seldom described in the literature, reflecting their rarity. Here we review the literature on tumors invading ITF and describe patient characteristics, treatment strategies, and clinical outcomes. METHODS: Relevant articles were retrieved from PubMed, Scopus, and Cochrane. A systematic review and meta-analysis were conducted on the clinical presentation, treatment protocols, and clinical outcomes. RESULT: A total of 27 articles containing 106 patients with ITF tumors (median tumor size: 24.3 cm3 [interquartile range, 15.2-42 cm3]) were included (median age: 46 years [interquartile range, 32-55 years]; 59.4% were males]). Of the confirmed tumor pathology data, schwannomas (n = 24; 26.1%) and meningiomas (n = 13; 14.1%) were the most common tumors. Facial hypoesthesia (n = 22; 18.5%), auricular/preauricular pain (n = 20; 16.8%), and headaches (n = 11; 9.2%) were the most common presenting symptoms. Of patients who had surgical resection (n = 97; 95.1%), 70 (73.7%) had transcranial surgery (TCS) and 25 (26.3%) had endoscopic endonasal surgery (EES). Among available details on the extent of resection (n = 84), gross-total resection (GTR) was achieved in 62 (73.8%), and 5 (6.0%) had biopsy only. Thirty-five (33.0%) patients had postoperative complications. Among cases with available data on reconstruction techniques (n = 8), four (50%) had adipofascial antero-lateral thigh flap, three (37.5%) had latissimus dorsi free flap, and one (12.5%) had antero-lateral thigh flap. Fourteen (13.2%) patients had adjuvant chemotherapy, and sixteen (15.1%) had adjuvant radiotherapy. During a median follow-up time of 28 months (IQR, 12.25-45.75 months), 15 (14.2%) patients had recurrences, and 18 (17.0%) patients died. The median overall survival (OS) time was 36 months (95% confidence interval: 29-41 months), and the 5-year progression-free survival (PFS) rate was 61%. CONCLUSION: Various tumor types with different biological characteristics invade the ITF. The present study describes patient demographics, clinical presentation, management, and outcomes. Depending on the tumor type and patient condition, patient-tailored management is recommended to optimize treatment outcomes.

Neoadjuvant Stereotactic Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis of the Literature and Ongoing Clinical Trials.

BACKGROUND: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. METHODS: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. RESULTS: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9-57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7-60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1-10) post-NaSRT. Median follow-up was 19.2-months (range, 1-41.3). Actuarial post-treatment rates were 4% (95%CI: 2-6%) for symptomatic radiation necrosis, 15% (95%CI: 12-18%) and 47% (95%CI: 42-52%) for local and distant recurrences, 6% (95%CI: 3-8%) for leptomeningeal metastases, 81% (95%CI: 75-87%) and 59% (95%CI: 54-63%) for 1-year local tumor control and overall survival. CONCLUSION: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.

Adenoid Cystic Carcinoma (ACC) Infiltrating the Skull Base: A Systematic Review of Clinical Characteristics and Management Strategies.

BACKGROUND/AIM: To systematically review the patient characteristics and management approaches of adenoid cystic carcinoma (ACC) infiltrating the skull base. MATERIALS AND METHODS: According to PRISMA guidelines, PubMed, Scopus, and Cochrane were searched to retrieve studies reporting management protocols and survival outcomes of patients with skull base ACCs. Patient characteristics, management strategies, and outcomes were investigated. RESULTS: The review encompassed 17 studies involving 171 patients, with a female predominance (57.9%) and a mean age of 49±7.12 years. ACCs mostly infiltrated the paranasal sinus (22.2%), cavernous sinus (8.8%), and nasopharynx (7.1%). Perineural invasion was reported in 6.4% of cases. Facial pain, nasal obstruction, and facial paresthesia were the most common symptoms. Surgical resection (45.6%) was favored over biopsy (12.2%). Employing the free flap technique (4.7%), surgical reconstruction of the bony defect after resection was performed using abdominal and anterior thigh muscle grafts in 1.8% of patients each. As adjuvant management, 22.8% of cases had radiotherapy and 14.6% received chemotherapy. Recurrence of skull base ACCs occurred in 26.9% of cases during a mean follow up-time of 30.8±1.8 months. CONCLUSION: Skull base ACCs pose a surgical challenge mainly due to their proximity to critical neurovascular structures and aggressive behavior. Surgical resection and radiotherapy are shown to be safe and effective treatment modalities. The dismal prognosis and limited data on non-surgical strategies highlight the need for further evaluation of the current management paradigm and upraising innovative therapies to improve patient mortality and quality of life.

Craniopharyngiomas Invading the Ventricular System: A Systematic Review.

BACKGROUND/AIM: Craniopharyngiomas involving the ventricular system are rare but pose significant surgical challenges. We systematically reviewed the literature on craniopharyngiomas invading the ventricles (CP-V). MATERIALS AND METHODS: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched to include studies reporting clinical data of patients with CP-Vs. Clinico-radiological features, management, and treatment outcomes were analyzed. RESULTS: We included 73 studies encompassing 407 patients. Patients were mostly male (61.5%), presenting with headache (57.9%) and/or endocrine disorders (52.1%). CP-Vs mostly involved the third ventricle (96.3%), followed by the lateral ventricles (2.9%), and the fourth ventricle (1%). Tumors had cystic components in 59% of cases and were mostly adamantinomatous (70.8%). Open resection was performed in 232 cases (57%), mostly with trans-lamina terminalis (36.6%) and trans-callosal (31.9%) approaches. Endoscopic resection was performed in 169 cases (41.5%), mostly with trans-sphenoidal (74.6%) and transventricular (24.9%) approaches. Gross-total tumor resection was obtained in most cases (62.9%). Adjuvant radiotherapy was delivered in 22.8% cases. A total of 178 patients experienced persistent complications, mostly including diabetes insipidus (47.1%) and panhypopituitarism (12.7%), not significantly different after open versus endoscopic resection (p=0.117). Symptom improvement was obtained in 88% of cases. CP-Vs recurrences were reported in 94 patients (23.1%), with median progression-free survival of 13.5 months (range=0.5-252.0 months). Fifty-nine patients died (14.5%), with median overall survival of 32.0 months (range=0.5-252.0 months), significantly longer after endoscopic resection than open resection (p=0.019). CONCLUSION: CP-Vs are uncommon and challenging entities. Surgical resection is feasible, but patient-tailored selection of open/endoscopic approaches is necessary to achieve optimal outcomes and minimize complication risks.

Gliomas Infiltrating the Corpus Callosum: A Systematic Review of the Literature.

Background: Gliomas infiltrating the corpus callosum (G-I-CC) majorly impact patient quality-of-life, but maximally safe tumor resection is challenging. We systematically reviewed the literature on G-I-CC. Methods: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with G-I-CC. Clinicopathological features, treatments, and outcomes were analyzed. Results: We included 52 studies comprising 683 patients. Most patients experienced headache (33%), cognitive decline (18.7%), and seizures (17.7%). Tumors mostly infiltrated the corpus callosum genu (44.2%) with bilateral extension (85.4%) into frontal (68.3%) or parietal (8.9%) lobes. Most G-I-CC were glioblastomas (84.5%) with IDH-wildtype (84.9%) and unmethylated MGMT promoter (53.5%). Resection (76.7%) was preferred over biopsy (23.3%), mostly gross-total (33.8%) and subtotal (32.5%). The tumor-infiltrated corpus callosum was resected in 57.8% of cases. Radiation was delivered in 65.8% of patients and temozolomide in 68.3%. Median follow-up was 12 months (range, 0.1−116). In total, 142 patients (31.8%) experienced post-surgical complications, including transient supplementary motor area syndrome (5.1%) and persistent motor deficits (4.3%) or abulia (2.5%). Post-treatment symptom improvement was reported in 42.9% of patients. No differences in rates of complications (p = 0.231) and symptom improvement (p = 0.375) were found in cases with resected versus preserved corpus callosum. Recurrences occurred in 40.9% of cases, with median progression-free survival of 9 months (0.1−72). Median overall survival was 10.7 months (range, 0.1−116), significantly longer in low-grade tumors (p = 0.013) and after resection (p < 0.001), especially gross-total (p = 0.041) in patients with high-grade tumors. Conclusions: G-I-CC show clinicopathological patterns comparable to other more frequent gliomas. Maximally safe resection significantly improves survival with low rates of persistent complications.

Pineal Region Gliomas: A Systematic Review of Clinical Features and Treatment Outcomes.

BACKGROUND/AIM: To review the current literature on pineal region gliomas, summarizing the clinical characteristics and treatment outcomes. MATERIALS AND METHODS: PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Comprehensive clinical characteristic review and survival analysis were conducted. RESULTS: Twelve studies describing 81 patients were included. The median age was 39 years (male=54.3%). Fifty patients (61.7%) had obstructive hydrocephalus requiring cerebrospinal fluid diversion with either ventriculoperitoneal shunt (VPS) (40.0%) or endoscopic third ventriculostomy (ETV) (24.0%). Patients who underwent VPS had significant survival benefits compared to ETV (p<0.05). All patients in our review underwent surgery, and gross-total resection (≥98%) was achieved in 34.6%. The supracerebellar infratentorial approach was the most employed surgical approach (62.3%). Chemotherapy was administered in 32.1% of cases, and radiotherapy in 40.7%. The median overall survival (OS) was 12 months, and the overall one-year survival rate was 60%. CONCLUSION: This study could not establish a correlation between the extent of tumor resection and positive treatment outcomes. However, among cases with hydrocephalus, patients who underwent VPS placement had better survival as compared to ETV.

Metastases in the Pineal Region: A Systematic Review of Clinical Features, Management Strategies, and Survival Outcomes.

BACKGROUND: Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases. METHODS: PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed. RESULTS: We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P < 0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence. CONCLUSIONS: Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.

Primary Skull Base Chondrosarcomas: A Systematic Review.

BACKGROUND: Primary skull base chondrosarcomas (SBCs) can severely affect patients' quality of life. Surgical-resection and radiotherapy are feasible but may cause debilitating complications. We systematically reviewed the literature on primary SBCs. METHODS: PubMed, EMBASE, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with primary SBCs. Clinical characteristics, management strategies, and treatment outcomes were analyzed. RESULTS: We included 33 studies comprising 1307 patients. Primary SBCs mostly involved the middle-fossa (72.7%), infiltrating the cavernous-sinus in 42.4% of patients. Cranial-neuropathies were reported in 810 patients (62%). Surgical-resection (93.3%) was preferred over biopsy (6.6%). The most frequent open surgical approaches were frontotemporal-orbitozygomatic (17.6%) and pterional (11.9%), and 111 patients (21.3%) underwent endoscopic-endonasal resection. Post-surgical cerebrospinal-fluid leaks occurred in 36 patients (6.5%). Radiotherapy was delivered in 1018 patients (77.9%): photon-based (41.4%), proton-based (64.2%), and carbon-based (13.1%). Severe post-radiotherapy complications, mostly hypopituitarism (15.4%) and hearing loss (7.1%) were experienced by 251 patients (30.7%). Post-treatment symptom-improvement (46.7%) and reduced/stable tumor volumes (85.4%) showed no differences based on radiotherapy-protocols (p = 0.165; p = 0.062). Median follow-up was 67-months (range, 0.1-376). SBCs recurrences were reported in 211 cases (16.1%). The 5-year and 10-year progression-free survival rates were 84.3% and 67.4%, and overall survival rates were 94% and 84%. CONCLUSION: Surgical-resection and radiotherapy are effective treatments in primary SBCs, with acceptable complication rates and favorable local tumor control.

Multimodality durable salvage of recurrent brain metastases refractory to LITT, SRS and immunotherapy with resection and cesium-131 brachytherapy: case report and literature review.

Brain metastases (BrM) are treated with multimodality therapy, however the optimal combination and timing of modalities in the setting of recurrent tumours that have failed prior treatments remain poorly defined. We present a case of a patient with biopsy-confirmed renal cell carcinoma BrM with good performance status initially treated with laser interstitial thermal ablation therapy (LITT) followed by stereotactic radiosurgery and dual checkpoint inhibitor immunotherapy. He subsequently developed rapid in-field recurrence which was treated with salvage surgical resection and implantation of intracavitary cesium-131 brachytherapy. The patient's disease remained stable through 18 months postoperatively. This case illustrates the range of options available and provides a combination salvage therapy strategy in a select group of locally recurrent patients who have exhausted conventional treatment options.