Spheno-orbital meningiomas (SOMs) are complicated tumors that involve multiple structures at initial presentation, such as the orbit, temporalis muscle, sphenoidal bone, cavernous sinus, and temporal ...or infratemporal fossa. The infiltrative growth and complexity of this type of meningioma make total resection impossible. In this study, the authors evaluated the surgical outcome of the endoscopic transorbital approach (eTOA) for SOM. In addition, they identified optimal indications for the use of eTOA and analyzed the feasibility of this approach as a minimally invasive surgery for SOMs of varying types and locations at presentation.
Between September 2016 and December 2019, the authors performed eTOA in 41 patients with SOM with or without orbital involvement at 3 independent tertiary institutions. The authors evaluated the surgical outcomes of eTOA for SOM and investigated several factors that affect the outcome, such as tumor volume, tumor location, and the presence of lateral orbitotomy. Gross-total resection (GTR) was defined as complete resection of the tumor or intended subtotal resection except the cavernous sinus. This study was undertaken as a multicenter project (006) of the Korean Society of Endoscopic Neurosurgery (KOSEN-006).
There were 41 patients (5 men and 36 women) with a median age of 52.0 years (range 24-73 years). Twenty-one patients had tumors that involved the orbital structure, while 14 patients had tumors that presented at the sphenoidal bone along with other structures, such as the cavernous sinus, temporal fossa, and infratemporal fossa. Fifteen patients had the globulous type of tumor and 26 patients had the en plaque type. Overall, GTR was achieved in 21 of 41 patients (51.2%), and complications included CSF leaks in 2 patients and wound complications in 2 patients. Multiple logistic regression analysis showed that the en plaque type of tumor, absence of lateral orbital rim osteotomy, involvement of the temporal floor or infratemporal fossa, and involvement of the orbit and medial one-third of the greater sphenoidal wing were closely associated with lower GTR rates (p < 0.05). Multivariate analysis revealed that the en plaque type of tumor and the absence of lateral orbital rim osteotomy were significant predictors for lower GTR rate.
The en plaque type of SOM remains a challenge despite advances in technique such as minimally invasive surgery. Overall, clinical outcome of eTOA for SOM was comparable to the transcranial surgery. To achieve GTR, eTOA is recommended, with additional lateral orbital rim osteotomy for globulous-type tumors, without involving the floor of the temporal and infratemporal fossa.
We evaluated changes in parafoveal and peripapillary vessel density in chiasmal compression after decompression surgery using optical coherence tomography angiography (OCT-A). Sixty-two eyes with ...chiasmal compression for which preoperative and postoperative (4-6 months) OCT, OCT-A, visual field (VF), and comprehensive ophthalmic data were available, and 44 healthy eyes were evaluated. Vessel densities of the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segment were assessed using OCT-A. The postoperative measurements were compared with preoperative data. Preoperative peripapillary retinal nerve fiber layer, macular ganglion cell-inner plexiform layer thickness, and vessel densities of SRCP and RPC segments in patients' eyes were significantly reduced compared to those of healthy controls (P < 0.0001, P < 0.0001, P = 0.0052, and P = 0.0085, respectively). Vessel densities were significantly decreased in the SRCP (P < 0.0001), DRCP (P = 0.0017), and RPC segments (P < 0.0001) after surgery compared to the preoperative values. Significant associations between the postoperative SRCP and DRCP vessel density changes and preoperative SRCP (r = - 0.3195, P = 0.0114) and DRCP (r = - 0.5165, P < 0.0001) vessel densities were found, respectively. There were also significant associations between postoperative SRCP vessel density changes and VF changes (r = - 0.2586, P = 0.0424). These findings indicate that decreased perfusion around the optic nerve head and on the macula associated with chiasmal compression could further progress after decompression surgery. Further functional and longer-term clinical studies are needed to elucidate the clinical implications of these findings.
Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved ...patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.
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•Distant recurrence predicts branched evolution of the paired tumors•Distant recurrence frequently involves divergence in key GBM driver alterations•Recurrent GBMs have more aberrations in core GBM driver pathways than initial GBMs•TMZ-induced hypermutation is rare in IDH1-wild-type primary GBMs
Kim et al. find that glioblastomas recurring at distant sites have driver genetic alterations very different from those of matched initial tumors. They also show that, in contrast to IDH1-mutated tumors, IDH1-wild-type primary glioblastomas rarely develop hypermutation following temozolomide treatment.
Precision medicine in cancer proposes that genomic characterization of tumors can inform personalized targeted therapies. However, this proposition is complicated by spatial and temporal ...heterogeneity. Here we study genomic and expression profiles across 127 multisector or longitudinal specimens from 52 individuals with glioblastoma (GBM). Using bulk and single-cell data, we find that samples from the same tumor mass share genomic and expression signatures, whereas geographically separated, multifocal tumors and/or long-term recurrent tumors are seeded from different clones. Chemical screening of patient-derived glioma cells (PDCs) shows that therapeutic response is associated with genetic similarity, and multifocal tumors that are enriched with PIK3CA mutations have a heterogeneous drug-response pattern. We show that targeting truncal events is more efficacious than targeting private events in reducing the tumor burden. In summary, this work demonstrates that evolutionary inference from integrated genomic analysis in multisector biopsies can inform targeted therapeutic interventions for patients with GBM.
Glioblastoma multiforme (GBM) is the most aggressive form of cancer that begins within the brain; generally, the patient has a dismal prognosis and limited therapeutic options. Signal transducer and ...activator of transcription 3 (STAT3) is a critical mediator of tumorigenesis, tumor progression, and suppression of anti-tumor immunity in GBM. In a high percentage of GBM cells and tumor microenvironments, persistent activation of STAT3 induces cell proliferation, anti-apoptosis, glioma stem cell maintenance, tumor invasion, angiogenesis, and immune evasion. This makes STAT3 an attractive therapeutic target and a prognostic indicator in GBM. Targeting STAT3 affords an opportunity to disrupt multiple pro-oncogenic pathways at a single molecular hub. Unfortunately, there are no successful STAT3 inhibitors currently in clinical trials. However, strong clinical evidence implicating STAT3 as a major factor in GBM justifies the identification of safe and effective strategies for inhibiting STAT3.
Hypermutagenesis refers to marked increase in the number of mutations due to continuous mutagenic process. Hypermutated tumors, have being found in several tumor types, are associated with inherited ...or acquired alterations in the DNA repair pathways. Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide(TMZ)‐induced mutagenesis. In our study, we have identified a rare subset of treatment‐naïve adult gliomas with de novo hypermutator phenotype and explored the evolution of spontaneous and treatment‐induced hypermutagenesis. We conducted Whole‐Exome Sequencing (WES), Whole‐Transcriptome Sequencing (WTS), and Single‐Cell Sequencing (SCS) of TMZ‐naïve and post‐TMZ‐treated hypermutated tumors to identify distinct clinical or genomic manifestations that contribute to the development of hypermutation in untreated adult gliomas. TMZ‐naïve hypermutated tumors were marked by absence of IDH1 somatic mutation and MGMT promoter (pMGMT) methylation, two genomic traits that were significantly associated with the TMZ‐induced hypermutagenic event in glioblastoma, and harbored inherited alterations in the mismatch repair (MMR) machinery. The immediate family members of the TMZ‐naive hypermutated glioma patients were also previous diagnosed with cancer development history, suggesting that germline dysfunction of the MMR pathway could potentially pose hereditary risk to genetic predisposition of carcinogenesis in gliomas. Lastly, both TMZ‐naïve and post‐TMZ‐treated hypermutated tumors exhibited a significant accumulation of neoantigen loads, suggesting immunotherapeutic alternatives. Our results present new and unique understanding of hypermutagenic process in adult gliomas and an important step towards clinical implication of immunotherapy in glioma treatment.
What's new?
Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide (TMZ)‐induced mutagenesis, leading to therapeutic resistance. Here, the authors identified a rare subset of pre‐treatment adult glioma patients with de novo hypermutator phenotype. TMZ‐naïve hypermutated tumors lacked somatic mutation of IDH1 and MGMT promoter methylation, and harbored both germline and somatic dysregulation of mismatch repair machinery encoding genes. Patients with TMZ‐naïve hypermutagenesis demonstrated high incidence of cancer‐development history in their immediate family members. Both TMZ‐naïve and post‐TMZ treated hypermutated tumors exhibited a significant accumulatin of neoantigen loads, pointing towards potential implementation of immunotherapy.
We have quantitatively evaluated the macular and peripapillary microvascular changes in eyes with chiasmal compression caused by brain tumors compared with healthy control eyes using optical ...coherence tomography angiography (OCT-A) and correlated them with other ocular parameters. This cross-sectional study involved the analysis of 36 eyes of 36 patients with chiasmal compression and age and refractive error-matched 35 healthy control eyes. OCT-A was used to generate microvascular images of the superficial and deep retinal capillary plexus (SRCP, DRCP) and the radial peripapillary capillary (RPC) segment in the macula and peripapillary areas. Automated segmentation and vessel density measurements facilitated the analysis of each layer. Macular OCT-A analysis revealed a significant reduction in vessel density in the SRCP (P = 0.004) of the nasal quadrant (P < 0.001) and in the same quadrant of the DRCP (P = 0.019) in the eyes with chiasmal compression compared with the control eyes. The RPC segment vessel density has also been significantly reduced in the eyes with chiasmal compression (P < 0.001). The RPC segment and the SRCP vessel densities were correlated with the peripapillary retinal nerve fiber layer and the ganglion cell layer complex thicknesses. The RPC segment and the nasal quadrant SRCP and the DRCP vessel densities were correlated with visual field defect. Significant microvascular alterations have been detected in the eyes with chiasmal compression compared with the control eyes. This study confirmed that chiasmal compression caused by brain tumors not only induced a loss of ganglion cells but also resulted in intra-retinal microvascular changes.
Purpose
To compare postoperative macular thickness measurements of inner and outer retinal layers in eyes of patients with chiasmal compression with or without visual field (VF) recovery and healthy ...controls using optical coherence tomography (OCT).
Methods
Macular spectral‐domain OCT has been used for the auto‐segmentation of images obtained from 100 eyes affected with chiasmal compression compared with 100 healthy controls enrolled in this study. We have divided eyes with chiasmal compression into two groups: group 1 characterized by VF recovery after tumour excision and group 2 showing partial or no recovery of VF. The thickness of the macular retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer (PRL), inner retinal layer (IRL) and outer retinal layer (ORL) was segmented. The correlation between macular RNFL (mRNFL) and functional parameters has been analysed.
Results
Both groups 1 and 2 showed significant thinning of RNFL, GCL, IPL and IRL in all quadrants. However, no significant changes have been detected in PRL and ORL of patients in either group compared with healthy controls. A significant thickening was detected in INL and ONL of group 2 compared with healthy controls and group 1. Postoperative mRNFL thickness is significantly correlated with VF defects and visual acuity except temporal quadrant.
Conclusions
Eyes with chiasmal compression showed thinning of the inner retinal layers with thickening of the INL and ONL in patients with partial to no recovery of VF. The changes in retinal microstructures are well‐correlated with functional recovery. Further studies are needed to reveal the clinical implications of these findings in patients with chiasmal compression.
OBJECTIVEThe authors conducted this retrospective study to investigate the clinical outcomes of intracranial solitary fibrous tumor (SFT) and hemangiopericytoma (HPC), defined according to the 2016 ...WHO classification of central nervous system (CNS) tumors.METHODSHistopathologically proven intracranial SFT and HPC cases treated in the period from June 1996 to September 2014 were retrospectively reviewed and analyzed. Two neuropathologists reviewed pathological slides and regraded the specimens according to the 2016 WHO classification. Factors associated with progression-free survival (PFS) and overall survival (OS) were statistically evaluated with uni- and multivariate analyses.RESULTSThe records of 47 patients-10 with SFT, 33 with HPC, and 4 with anaplastic HPC-were reviewed. A malignant transition from conventional SFT to WHO grade III SFT/HPC was observed in 2 cases, and 13 HPC cases were assigned grade III SFT/HPC. Mean and median follow-ups were 114.6 and 94.7 months, respectively (range 7.1-366.7 months). Gross-total resection (GTR) was significantly associated with longer PFS and OS (p = 0.012 for both), and adjuvant radiation therapy versus no such therapy led to significantly longer PFS (p = 0.018). Extracranial metastases to the liver, bone, lung, spine, and kidney occurred in 10 patients (21.3%). Grade III SFT/HPC was strongly correlated with the development of extracranial metastases (p = 0.031).CONCLUSIONSThe 2016 WHO classification of CNS tumors reflected the different types of pathological malignant progression and clinical outcomes better than prior classifications. Gross-total resection should be the primary treatment goal in patients with SFT/HPC, regardless of the pathological grade, and radiation can be administered as adjuvant therapy for patients with SFT/HPC that shows an aggressive phenotype or that is not treated with GTR.
The endoscopic endonasal approach (EEA) and the transcranial approach (TCA) are good options for the treatment of tuberculum sellae (TS) meningiomas. The objective of this study was to identify the ...key anatomical features in TS meningiomas and compare the two surgical approaches.
The authors retrospectively reviewed clinical data in 178 patients with TS meningiomas treated at 3 institutions between January 2010 and July 2016. Patients with tumors encasing the internal carotid artery or anterior cerebral artery or involving the anterior clinoid process or cavernous sinus were excluded. Tumors were classified as high-lying or low-lying based on their location, and involvement of the optic canal was evaluated. The surgical outcomes of EEA and TCA were analyzed according to the relevant anatomical features.
During the study period, 84 patients underwent EEA and 94 patients underwent TCA. Based on preoperative MR images, 43 (24.2%) meningiomas were classified as high-lying tumors, 126 (70.8%) as low-lying, and 9 (5.0%) as nonspecific. Gross-total resection (GTR) was performed in 145 patients (81.5%); the GTR rate did not differ significantly between the EEA and TCA groups. Of 157 patients with preoperative visual disturbance, 140 had improved or stable vision postoperatively. However, 17 patients (9.6%) experienced some visual deterioration after surgery. The TCA group had a worse visual outcome than the EEA group in patients with preoperative optic canal involvement (77.6% vs 93.2%, p = 0.019), whereas there was no significant difference in visual outcome based on whether tumors were high-lying or low-lying.
The results of this study support EEA over TCA, at least with respect to visual improvement with acceptable complications, although TCA is still an effective approach for TS meningioma.
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