A validated LC-MS/MS method for determination of neuro-pharmacokinetic behavior of niraparib in brain tumor patients.

Niraparib is a potent and orally bioavailable inhibitor of poly (ADP-ribose) polymerase (PARP) with high specificity for isoforms 1 and 2. It has been approved by the U.S. Food and Drug Administration for ovarian cancer maintenance therapy and is currently under development for various cancers, including glioblastoma. To assess central nervous system (CNS) penetration of niraparib in glioblastoma patients, a novel bioanalytical method was developed to measure total and unbound niraparib levels in human brain tumor tissue and cerebrospinal fluid (CSF). The method was validated using plasma as a surrogate matrix over the concentration range of 1-10,000 nM on an LC-MS/MS system. The MS/MS detection was conducted in positive electrospray ionization mode, while chromatography was performed using a Kinetex™ PS C18 column with a total 3.5-minute gradient elution run time. The maximum coefficient of variation for both intra- and inter-day precision was 10.6%, with accuracy ranging from 92.8% - 118.5% across all matrices. Niraparib was stable in human brain homogenate for at least 6 hours at room temperature (RT) and 32 days at -20°C, as well as in stock and working solutions for at least 21 hours (RT) and 278 days (4°C). Equilibrium dialysis experiments revealed the fractions unbound of 0.05 and 0.16 for niraparib in human brain and plasma, respectively. The validated method is currently employed to assess niraparib levels in human glioblastoma tissue, CSF, and plasma in an ongoing trial on newly diagnosed glioblastoma and recurrent IDH1/2(+) ATRX mutant glioma patients (NCT05076513). Initial results of calculated total (Kp) and unbound (Kp,uu) tumor-to-plasma partition coefficients indicate significant brain penetration ability of niraparib in glioblastoma patients.

Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

OBJECTIVE: Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration-cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied. METHODS: Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0-2) and a high tumor probability (HTP) group (scores 3-5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated. RESULTS: Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86-0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40-0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40-0.83]) and HTP group (0.68 [0.39-0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group. CONCLUSIONS: CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

Miniature line-scanned dual-axis confocal microscope for versatile clinical use.

A miniature optical-sectioning fluorescence microscope with high sensitivity and resolution would enable non-invasive and real-time tissue inspection, with potential use cases including early disease detection and intraoperative guidance. Previously, we developed a miniature MEMS-based dual-axis confocal (DAC) microscope that enabled video-rate optically sectioned in vivo microscopy of human tissues. However, the device's clinical utility was limited due to a small field of view, a non-adjustable working distance, and a lack of a sterilization strategy. In our latest design, we have made improvements to achieve a 2x increase in the field of view (600 × 300 µm) and an adjustable working distance range of 150 µm over a wide range of excitation/emission wavelengths (488-750 nm), all while maintaining a high frame rate of 15 frames per second (fps). Furthermore, the device is designed to image through a disposable sterile plastic drape for convenient clinical use. We rigorously characterize the performance of the device and show example images of ex vivo tissues to demonstrate the optical performance of our new design, including fixed mouse skin and human prostate, as well as fresh mouse kidney, mouse intestine, and human head and neck surgical specimens with corresponding H&E histology. These improvements will facilitate clinical testing and translation.

Quisinostat is a brain-penetrant radiosensitizer in glioblastoma.

Histone deacetylase (HDAC) inhibitors have garnered considerable interest for the treatment of adult and pediatric malignant brain tumors. However, owing to their broad-spectrum nature and inability to effectively penetrate the blood-brain barrier, HDAC inhibitors have failed to provide substantial clinical benefit to patients with glioblastoma (GBM) to date. Moreover, global inhibition of HDACs results in widespread toxicity, highlighting the need for selective isoform targeting. Although no isoform-specific HDAC inhibitors are currently available, the second-generation hydroxamic acid-based HDAC inhibitor quisinostat possesses subnanomolar specificity for class I HDAC isoforms, particularly HDAC1 and HDAC2. It has been shown that HDAC1 is the essential HDAC in GBM. This study analyzed the neuropharmacokinetic, pharmacodynamic, and radiation-sensitizing properties of quisinostat in preclinical models of GBM. It was found that quisinostat is a well-tolerated and brain-penetrant molecule that extended survival when administered in combination with radiation in vivo. The pharmacokinetic-pharmacodynamic-efficacy relationship was established by correlating free drug concentrations and evidence of target modulation in the brain with survival benefit. Together, these data provide a strong rationale for clinical development of quisinostat as a radiosensitizer for the treatment of GBM.

Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review.

BACKGROUND: Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials. METHODS: We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. The followings were key words for the literature search as index terms or free-text words: "phase II trials", "glioblastoma", and "two-stage design". We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. RESULTS: Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Most trials (90%) used Simon's two-stage designs. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. CONCLUSIONS: Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials.

Simultaneous determination of LY3214996, abemaciclib, and M2 and M20 metabolites in human plasma, cerebrospinal fluid, and brain tumor by LC-MS/MS.

A sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the quantification of total and unbound concentrations of LY3214996, an extracellular signal-regulated kinase inhibitor; abemaciclib, a cyclin-dependent kinase 4/6 inhibitor; and abemaciclib active metabolites, M2 and M20, in human plasma, brain tumor, and cerebrospinal fluid samples. The method was validated over a concentration range of 0.2-500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex™ F5 column. Detection was performed on a Sciex QTRAP 6500+ mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. The intra- and inter-batch accuracy as well as the precision of the method for all matrices was within ±20% and ≤20% at the lower limit of quantification, and within ±15% and ≤15% for other quality control levels for all analytes. The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis. The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.

Perioperative Complication Profile of Skull Base Meningioma Resection in Older versus Younger Adult Patients.

Objectives To better understand the risk-benefit profile of skull base meningioma resection in older patients, we compared perioperative complications among older and younger patients. Design Present study is based on retrospective outcomes comparison. Setting The study was conducted at a single neurosurgery institute at a quaternary center. Participants All older (age ≥ 65 years) and younger (<65 years) adult patients treated with World Health Organization grade 1 skull base meningiomas (2008-2017). Main Outcome Measures Perioperative complications and patient functional status are the primary outcomes of this study. Results The analysis included 287 patients, 102 older and 185 younger, with a mean (standard deviation [SD]) age of 72 (5) years and 51 (9) years ( p < 0.01). Older patients were more likely to have hypertension ( p < 0.01) and type 2 diabetes mellitus ( p = 0.01) but other patient and tumor factors did not differ ( p ≥ 0.14). Postoperative medical complications were not significantly different in older versus younger patients (10.8 [11/102] vs. 4.3% [8/185]; p = 0.06) nor were postoperative surgical complications (13.7 [14/102] vs. 10.8% [20/185]; p = 0.46). Following anterior skull base meningioma resection, diabetes insipidus (DI) was more common in older versus younger patients (14 [5/37] vs. 2% [1/64]; p = 0.01). Among older patients, a decreasing preoperative Karnofsky performance status score independently predicted perioperative complications by logistic regression analysis ( p = 0.02). Permanent neurologic deficits were not significantly different in older versus younger patients (12.7 [13/102] vs. 10.3% [19/185]; p = 0.52). Conclusion The overall perioperative complication profile of older and younger patients was similar after skull base meningioma resection. Older patients were more likely to experience DI after anterior skull base meningioma resection. Decreasing functional status in older patients predicted perioperative complications.

Residual Tumor Volume and Tumor Progression after Subtotal Resection and Observation of WHO Grade I Skull Base Meningiomas.

Objective This study investigated the impact of residual tumor volume (RTV) on tumor progression after subtotal resection and observation of WHO grade I skull base meningiomas. Study Design This study is a retrospective volumetric analysis. Setting This study was conducted at a single institution. Participants Patients who underwent subtotal resection of a WHO grade I skull base meningioma and postsurgical observation (July 1, 2007-July 1, 2017). Main Outcome Measure The main outcome was radiographic tumor progression. Results Sixty patients with residual skull base meningiomas were analyzed. The median (interquartile range) RTV was 1.3 (5.3) cm 3 . Tumor progression occurred in 23 patients (38.3%) at a mean duration of 28.6 months postsurgery. The 1-, 3-, and 5-year actuarial progression-free survival (PFS) rates were 98.3, 58.6, and 48.7%, respectively. The Cox multivariate analysis identified increasing RTV ( p = 0.01) and history of more than 1 previous surgery ( p = 0.03) as independent predictors of tumor progression. In a Kaplan-Meier analysis for PFS, the RTV threshold of 3 cm 3 maximized log-rank testing significance between groups of patients dichotomized at 0.5 cm 3 thresholds ( p < 0.01). The 3-year actuarial PFS rates for meningiomas with RTV ≤3 cm 3 and >3 cm 3 were 76.2 and 32.1%, respectively. When RTV >3 cm 3 was entered as a covariate in the Cox model, it was the only factor independently associated with tumor progression ( p < 0.01). Conclusion RTV was associated with tumor progression after subtotal resection of WHO grade I skull base meningioma in this cohort. An RTV threshold of 3 cm 3 was identified that minimized progression of the residual tumor when gross total resection was not safe or feasible.

A Window of Opportunity to Overcome Therapeutic Failure in Neuro-Oncology.

Glioblastoma is the most common primary malignant brain neoplasm and it remains one of the most difficult-to-treat human cancers despite decades of discovery and translational and clinical research. Many advances have been made in our understanding of the genetics and epigenetics of gliomas in general; yet, there remains an urgent need to develop novel agents that will improve the survival of patients with this deadly disease. What sets glioblastoma apart from all other cancers is that it develops and spreads within an organ that renders tumor cells inaccessible to most systemically administered agents because of the presence of the blood-brain barrier. Inadequate drug penetration into the central nervous system is often cited as the most common cause of trial failure in neuro-oncology, and even so-called brain-penetrant therapeutics may not reach biologically relevant concentrations in tumor cells. Evaluation of the pharmacokinetics and pharmacodynamics of a novel therapy is a cornerstone of drug development, but few trials for glioma therapeutics have incorporated these basic elements in an organ-specific manner. Window-of-opportunity clinical trial designs can provide early insight into the biological plausibility of a novel therapeutic strategy in the clinical setting. A variety of window-of-opportunity trial designs, which take into account the limited access to treated tissue and the challenges with obtaining pretreatment control tissues, have been used for the initial development of traditional and targeted small-molecule drugs and biologic therapies, including immunotherapies and oncolytic viral therapies. Early-stage development of glioma therapeutics should include a window-of-opportunity component whenever feasible.

A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma.

PURPOSE: Ceritinib is an orally bioavailable, small-molecule inhibitor of anaplastic lympoma kinase (ALK), insulin-like growth factor 1 receptor (IGFR1), and focal adhesion kinase (FAK), which are highly expressed in glioblastoma and many brain metastases. Preclinical and clinical studies indicate that ceritinib has antitumor activity in central nervous system (CNS) malignancies. This phase 0 trial measured the tumor pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in patients with brain metastasis or recurrent glioblastoma. PATIENTS AND METHODS: Preoperative patients with brain tumors demonstrating high expression of pSTAT5b/pFAK/pIGFR1 were administered ceritinib for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at predefined timepoints following the final dose. Total and unbound drug concentrations were determined using LC-MS/MS. In treated tumor and matched archival tissues, tumor PD was quantified through IHC analysis of pALK, pSTAT5b, pFAK, pIGFR1, and pIRS1. RESULTS: Ten patients (3 brain metastasis, 7 glioblastoma) were enrolled and no dose-limiting toxicities were observed. Ceritinib was highly bound to human plasma protein [median fraction unbound (Fu), 1.4%] and to brain tumor tissue (median Fu, 0.051% and 0.045% in gadolinium-enhancing and -nonenhancing regions respectively). Median unbound concentrations in enhancing and nonenhancing tumor were 0.048 and 0.006 µmol/L, respectively. Median unbound tumor-to-plasma ratios were 2.86 and 0.33 in enhancing and nonenhancing tumor, respectively. No changes in PD biomarkers were observed in the treated tumor samples as compared to matched archival tumor tissue. CONCLUSIONS: Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastases and patients with recurrent glioblastoma were insufficient for target modulation.

Nonredundant, isoform-specific roles of HDAC1 in glioma stem cells.

Glioblastoma (GBM) is characterized by an aberrant yet druggable epigenetic landscape. One major family of epigenetic regulators, the histone deacetylases (HDACs), are considered promising therapeutic targets for GBM due to their repressive influences on transcription. Although HDACs share redundant functions and common substrates, the unique isoform-specific roles of different HDACs in GBM remain unclear. In neural stem cells, HDAC2 is the indispensable deacetylase to ensure normal brain development and survival in the absence of HDAC1. Surprisingly, we find that HDAC1 is the essential class I deacetylase in glioma stem cells, and its loss is not compensated for by HDAC2. Using cell-based and biochemical assays, transcriptomic analyses, and patient-derived xenograft models, we find that knockdown of HDAC1 alone has profound effects on the glioma stem cell phenotype in a p53-dependent manner. We demonstrate marked suppression in tumor growth upon targeting of HDAC1 and identify compensatory pathways that provide insights into combination therapies for GBM. Our study highlights the importance of HDAC1 in GBM and the need to develop isoform-specific drugs.

Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling.

BACKGROUND: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. METHODS: Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. RESULTS: Potentially meaningful associations (p<0.1, Fisher's exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. CONCLUSIONS: GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB.

Three-Dimensional Printable Conductive Semi-Interpenetrating Polymer Network Hydrogel for Neural Tissue Applications.

Intrinsically conducting polymers (ICPs) are widely used to fabricate biomaterials; their application in neural tissue engineering, however, is severely limited because of their hydrophobicity and insufficient mechanical properties. For these reasons, soft conductive polymer hydrogels (CPHs) are recently developed, resulting in a water-based system with tissue-like mechanical, biological, and electrical properties. The strategy of incorporating ICPs as a conductive component into CPHs is recently explored by synthesizing the hydrogel around ICP chains, thus forming a semi-interpenetrating polymer network (semi-IPN). In this work, a novel conductive semi-IPN hydrogel is designed and synthesized. The hybrid hydrogel is based on a poly(N-isopropylacrylamide-co-N-isopropylmethacrylamide) hydrogel where polythiophene is introduced as an ICP to provide the system with good electrical properties. The fabrication of the hybrid hydrogel in an aqueous medium is made possible by modifying and synthesizing the monomers of polythiophene to ensure water solubility. The morphological, chemical, thermal, electrical, electrochemical, and mechanical properties of semi-IPNs were fully investigated. Additionally, the biological response of neural progenitor cells and mesenchymal stem cells in contact with the conductive semi-IPN was evaluated in terms of neural differentiation and proliferation. Lastly, the potential of the hydrogel solution as a 3D printing ink was evaluated through the 3D laser printing method. The presented results revealed that the proposed 3D printable conductive semi-IPN system is a good candidate as a scaffold for neural tissue applications.

Surgical strategy for insular glioma.

PURPOSE: The goal of this article is to review the outcomes of insular glioma surgery and discuss strategies to minimize postoperative morbidity. METHODS: The authors reviewed the published literature on low- and high-grade insular gliomas with a focus on glioma biology, insular anatomy, and surgical technique. RESULTS: Maximal safe resection of insular gliomas is associated with improved survival and is the primary goal of surgery. Protecting patient speech and motor function during insular glioma resection requires versatile integration of insular anatomy, cortical mapping, and microsurgical technique. Both the transsylvian and transcortical corridors to the insula are associated with low morbidity profiles, but the transcortical approach with intraoperative mapping is more favorable for gliomas within the posterior insular region. CONCLUSIONS: Surgical strategy for insular gliomas is dependent on biological, anatomical, and clinical factors. Technical mastery integrated with intraoperative technologies can optimize surgical results.

Quantitative protein expression of blood-brain barrier transporters in the vasculature of brain metastases of patients with lung and breast cancer.

This study determined absolute transporter protein abundances in isolated microvessels of human noncancerous cerebral cortex as well as brain metastases of patients with lung and breast cancer, using a validated targeted proteomics approach. As compared with those in microvessels of noncancerous cerebral cortex, the median protein abundances of glucose transporter 1 (a brain endothelial marker) and sodium-potassium pump (Na/K ATPase, a plasma membrane marker) were decreased by ~ 80% in brain metastasis microvessels. The major efflux transporters (ABCB1 and ABCG2) fell to undetectable in microvessels of more than 80% of brain metastasis specimens. Monocarboxylate transporter 1 was undetectable in microvessels of more than 80% of brain metastases, whereas large neutral amino acid transporter 1 levels remained unchanged. In conclusion, the integrity of the physical and biochemical barrier with respect to transporter protein expression is largely disrupted in brain metastasis tumor vasculatures. Differential transporter protein abundances at the blood-brain barrier and blood-brain tumor barrier provided mechanistic and quantitative basis for prediction of heterogeneous drug penetration into human brain and brain tumors, which is critical not only to the understanding of the success or failure of systemic chemotherapy in the treatment of brain tumors but also to the development of more effective therapeutic strategies.

Physiologically Based Pharmacokinetic Modeling of Central Nervous System Pharmacokinetics of CDK4/6 Inhibitors to Guide Selection of Drug and Dosing Regimen for Brain Cancer Treatment.

A better understanding of the human central nervous system (CNS) pharmacokinetics is critical to the selection of the right drug and refinement of dosing regimen for more effective treatment of primary and metastatic brain cancer. Using the physiologically-based pharmacokinetic (PBPK) modeling approach, we systematically compared the CNS pharmacokinetics of three cyclin D-cyclin dependent kinase 4 and 6 (CDK4/6) inhibitors (ribociclib, palbociclib, and abemaciclib) in patients with cancer. A PBPK model platform was developed and verified for predicting plasma and CNS pharmacokinetics. Target engagement ratio (TER), defined as the ratio of the average steady-state unbound drug brain concentration to the in vitro half-maximal inhibitory concentration (IC50 ) for CDK4/6 inhibition, was used as a crude predictor of efficacy. As compared with ribociclib and palbociclib, abemaciclib penetrated into the human brain to a larger extent, but at a slower rate, and was retained in the brain longer. Following the standard dosing regimens, the predicted CDK4/6 TERs were 26/5.2 for abemaciclib, 2.4/0.62 for ribociclib, and 0.36/0.27 for palbociclib. Simulations suggested that abemaciclib achieved comparable TERs following twice daily or daily dosing; ribociclib may sufficiently inhibit both CDK4 and CDK6 at the maximum tolerated dose; whereas, palbociclib achieved TERs < 0.5 even at a dose 50% higher than the standard dose. In conclusion, the PBPK modeling, supported by available preclinical and clinical evidence, suggests that abemaciclib is the best CDK4/6 inhibitor for brain cancer treatment, whereas palbociclib is not recommended. The model refined dosing regimen is 300 mg daily on a 4-weeks-on schedule for abemaciclib, and 900 mg daily on a 3-weeks-on/1-week-off schedule for ribociclib.

Sterile Gelatin Film Reduces Cortical Injury Associated With Brain Tumor Re-Resection.

BACKGROUND: Recurrent intracranial tumors frequently require re-resection. Dural adhesions to the cortex increase the morbidity and duration of these revision craniotomies. OBJECTIVE: To describe the use of commercially available sterile gelatin film to prevent meningocerebral adhesions and decrease the rate of surgically induced ischemia from revision craniotomy. METHODS: This retrospective cohort study examined patients with recurrent glioma, meningioma, and metastasis who underwent re-resection at least 30 d following their initial tumor resection. Cortical surface tissue ischemia after re-resection on diffusion-weighted magnetic resonance imaging was compared for patients with (gelatin film group) and without (nongelatin film group) a history of gelatin film placement at the conclusion of their initial tumor resection. RESULTS: A total of 84 patients in the gelatin film group were compared to 86 patients in the nongelatin film group. Patient age, sex, tumor pathology, tumor volume, tumor eloquence, laterality of surgical approach, history of radiotherapy, and time interval between resections did not differ between groups. Radiographic evidence of cortical ischemia following reoperation was less prevalent in the gelatin film group (13.1% vs 32.6%; P < .01). In multivariate logistic regression analysis, no gelatin film (P < .01) and larger tumor size (P = .02) predicted cortical surface ischemia following revision craniotomy. Postoperative complications in the gelatin film and nongelatin film group otherwise did not differ. CONCLUSION: Routine placement of commercially available sterile gelatin film on the cortex prior to dural closure is associated with decreased surgically induced tissue ischemia at the time of revision tumor craniotomy.