Purpose
To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We ...analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures.
Methods
The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications.
Results
The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (
p
= 0.019), and T8 dominant group than T4 dominant group (
p
= 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps.
Conclusions
Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain ...tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture (p = 0.0147) and craniotomy design (p = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered ...to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. Methods Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups. Results We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression. Conclusions This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies. Keywords: Glioma, Telomere maintenance mechanism, TERT, ALT
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei ...RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.
OBJECTIVE The endoscopic endonasal approach (EEA) is commonly used for the treatment of craniopharyngioma; therefore, it is essential to analyze outcomes in order to understand the benefits and ...drawbacks. The goal of this paper was to evaluate the clinical features and outcomes associated with this treatment approach. METHODS From July 2010 to March 2016, 82 adult craniopharyngioma patients underwent an EEA at the authors' institution. Of these cases, intraoperative records and immediate postoperative MR images were available for 68 patients. The patients underwent systemized endocrinological evaluation. Eighteen of 68 patients who underwent EEA for recurrence or regrowth of residual lesions after previous surgical management were excluded in the analysis of the anatomical tumor classification. The authors retrospectively analyzed preoperative clinical features and previous anatomical classifications, focusing on the relationship of the pituitary stalk and tumor, to determine predictive factors for the clinical outcome, such as the extent of resection, visual function, endocrinological function, recurrence rate, and complications. RESULTS The mean tumor size was 2.5 cm (3.1 cm for primary tumors and 1.9 cm for recurrent lesions). Gross-total resection (GTR) was achieved in 62 (91.1%) patients (48 96.0% patients with primary tumors and 14 77.8% patients with recurrent tumors). The rate of GTR was higher in the primary group than in the group with recurrence (p = 0.038). The overall pre- and postoperative visual impairment scale (VIS) scores were 40.8 and 22.1, respectively (50.9 and 14.3 in the primary group and 30.7 and 29.9 in patients with recurrence, respectively). The improvement rate in VIS score was higher in the primary group than in the recurrent group (p = 0.001). Endocrinological function was improved in 4 patients (5.9%) and deteriorated in 32 of 68 patients (47.1%). Tumor invasion into the center of the pituitary stalk affected the postoperative outcomes most significantly. Cognitive dysfunction was observed in 22 patients before surgery and improved in 20 patients (90.9%) after surgery. Hydrocephalus was found in 7 patients and resolved after surgery in all cases. CSF leakage occurred in 2 (2.9%) of 68 patients and was repaired by revision surgery in both patients. Ten patients without CSF leakage also received antibiotics for the treatment of meningitis. The infection rate was higher in the recurrent group. Postoperative endocrinological evaluation showed no deficits in 12 patients and panhypopituitarism in 55 patients. The remaining patient had growth hormone deficiency. Forty-three patients had new-onset diabetes insipidus, and 1 patient had persistent diabetes insipidus after surgery. There were 2 (2.9%) cases of recurrence during the mean 30.7-month follow-up period; one patient underwent radiosurgery and the other underwent reoperation. CONCLUSIONS The EEA resulted in excellent surgical outcomes and acceptable morbidity rates, regardless of the anatomical location of the tumor. Invasion of the craniopharyngioma into the center of the pituitary stalk has strong predictive power for postoperative endocrinological outcome.
A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors ...retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution.
Ninety-two patients with petroclival meningiomas were treated surgically at the authors' institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1-368 months) and 105 months (range 1-348 months), respectively.
A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively.
The authors' preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.
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.
We evaluated the prognostic factors for hearing outcomes after stereotactic radiosurgery (SRS) for unilateral sporadic intracanalicular vestibular schwannomas (IC-VSs) as a clinical homogeneous group ...of VSs.
Sixty consecutive patients with unilateral sporadic IC-VSs, defined as tumors in the internal acoustic canal, and serviceable hearing (Gardner-Roberson grade 1 or 2) were treated with SRS as an initial treatment. The mean tumor volume was 0.34±0.03 cm3 (range, 0.03-1.00 cm3), and the mean marginal dose was 12.2±0.1 Gy (range, 11.5-13.0 Gy). The median follow-up duration was 62 months (range, 36-141 months).
The actuarial rates of serviceable hearing preservation were 70%, 63%, and 55% at 1, 2, and 5 years after SRS, respectively. In multivariate analysis, transient volume expansion of ≥20% from initial tumor size was a statistically significant risk factor for loss of serviceable hearing and hearing deterioration (increase of pure tone average≥20 dB) (odds ratio=7.638; 95% confidence interval, 2.317-25.181; P=.001 and odds ratio=3.507; 95% confidence interval, 1.228-10.018; P=.019, respectively). The cochlear radiation dose did not reach statistical significance.
Transient volume expansion after SRS for VSs seems to be correlated with hearing deterioration when defined properly in a clinically homogeneous group of patients.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Abstract Background The extended endoscopic endonasal approach (EEA) to the anterior cranial base is used for the resection of craniopharyngiomas. Objective We present clinical experience and ...outcomes utilizing EEA for craniopharyngiomas. Methods A total of 116 patients in two remote institutions were enrolled in this retrospective study. Surgical, endocrinological and ophthalmological outcomes were assessed. Results The mean follow-up was 35 months (range, 1–115). Gross total resection (GTR), near total resection (NTR, >95%), and subtotal resection (STR) were achieved in 46%, 39%, and 15% of the patients, respectively. Surgery performed after 2010 was the only variable significantly associated with greater extent of resection, which might be explained by the learning curve. Overall tumor recurrence rate was 15.5%, with a median interval until recurrence of 14.5 months (range, 3–58). Extent of resection was significantly associated with recurrence-free survival ( P =0.0116). Those who underwent NTR/STR followed by adjuvant radiotherapy had a similar median recurrence-free survival rate compared to those that underwent GTR (26.5 vs 20 months, P =0.167). Endocrinological examination revealed that 47.4% of patients experienced worsening of anterior pituitary function following surgery while 25.5% developed new-onset diabetes insipidus. Of the 89 patients with preoperative visual deficits, 68 (76.4%) experienced improvement in visual field assessment. Conclusion EEA is effective for the surgical resection of craniopharyngiomas, resulting in high rates of visual improvement and low complication rates. Adjuvant radiotherapy is a useful method for tumor control after incomplete resection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Degree of resection and visual outcome are the main concerns in the surgical resection of tuberculum sellae meningioma (TSM). In addition to the transcranial approach (TCA), the endoscopic endonasal ...approach (EEA) has been used increasingly. However, the controversy regarding the optimal surgical approach is not clearly resolved.
We compared the surgical outcomes of each approach for TSMs from 44 patients receiving EEA and 40 patients receiving TCA in 2 institutions between 2004 and 2015. We analyzed the surgical outcomes and affecting factors for the relapse of tumor and visual outcome.
Gross total resection rates and relapse-free survival were not different between the 2 groups; however, the locations of residual or recurred tumor definitely differed. All recurrences in the TCA group were in the sella turcica, whereas residual tumors in EEA group were mainly located at lateral or superior to the clinoid process. The complete or partial improvement rate of visual function in the EEA group was 97.7%, but 9 patients (23.7%) in the TCA group experienced visual deterioration after surgery. EEA and younger age (<55 years) were associated with favorable visual outcome. Cerebrospinal fluid leakage occurred in only one case in the EEA group.
Surgical approaches do not affect the gross total resection rates, but the locations of residual tumor or recurrence differ according to surgical approaches. EEA is superior to TCA in visual outcome. At least in pure TSMs, the trend seems to be shifting in favor of EEA, considering the huge difference in visual outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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