Long term outcomes following surgery for pineal region tumors.

PURPOSE: Pineal region tumors are surgically demanding tumors to resect. Long term neuro-oncologic outcomes following surgical excision of tumors from this region have been underreported. We sought to define the long term outcomes of patients undergoing resection of pineal region tumors. METHODS: A retrospective analysis of a prospectively maintained database was performed on patients who underwent intended surgical excision of pineal region tumors. Overall survival (OS) and progression free survival (PFS) were the primary endpoints of this study. Factors associated with OS, PFS and the degree of resection were analyzed, along with 30-day complication rates and dependence on CSF diversion. RESULTS: Sixty-eight patients with a mean age of 30.9 ± 15.3 years were analyzed. The median clinical and radiographic follow-up was 95.7 and 48.2 months, respectively. The supracerebellar infratentorial and the occipital transtentorial corridors were utilized in the majority of cases (80.9%). The gross total resection (GTR) rate was 52.9% (n=36). The 5-year OS and PFS rates were 70.2% and 58.5%, respectively. Achieving GTR was associated with improved OS (HR 0.39, p = 0.03) and PFS (HR 0.4, p = 0.006). The 30-day mortality rate was 5.9%. The need for CSF diversion was high with 77.9% of patients requiring a shunt or ETV by last follow-up. CONCLUSIONS: This is the first modern surgical series providing long term follow-up for patients undergoing surgical resection of pineal region tumors. Obtaining a GTR of these challenging tumors is beneficial with regards to PFS/OS. Higher grade tumors have diminished PFS/OS and are treated with adjuvant chemotherapy and/or radiotherapy.

An efficient magnetic resonance image data quality screening dashboard.

PURPOSE: Complex data processing and curation for artificial intelligence applications rely on high-quality data sets for training and analysis. Manually reviewing images and their associated annotations is a very laborious task and existing quality control tools for data review are generally limited to raw images only. The purpose of this work was to develop an imaging informatics dashboard for the easy and fast review of processed magnetic resonance (MR) imaging data sets; we demonstrated its ability in a large-scale data review. METHODS: We developed a custom R Shiny dashboard that displays key static snapshots of each imaging study and its annotations. A graphical interface allows the structured entry of review data and download of tabulated review results. We evaluated the dashboard using two large data sets: 1380 processed MR imaging studies from our institution and 285 studies from the 2018 MICCAI Brain Tumor Segmentation Challenge (BraTS). RESULTS: Studies were reviewed at an average rate of 100/h using the dashboard, 10 times faster than using existing data viewers. For data from our institution, 1181 of the 1380 (86%) studies were of acceptable quality. The most commonly identified failure modes were tumor segmentation (9.6% of cases) and image registration (4.6% of cases). Tumor segmentation without visible errors on the dashboard had much better agreement with reference tumor volume measurements (root-mean-square error 12.2 cm3 ) than did segmentations with minor errors (20.5 cm3 ) or failed segmentations (27.4 cm3 ). In the BraTS data, 242 of 285 (85%) studies were acceptable quality after processing. Among the 43 cases that failed review, 14 had unacceptable raw image quality. CONCLUSION: Our dashboard provides a fast, effective tool for reviewing complex processed MR imaging data sets. It is freely available for download at https://github.com/EGates1/MRDQED.

Effects of systemic therapy and local therapy on outcomes of 873 breast cancer patients with metastatic breast cancer to brain: MD Anderson Cancer Center experience.

Outcomes of treatments for patients with breast cancer brain metastasis (BCBM) remain suboptimal, especially for systemic therapy. To evaluate the effectiveness of systemic and local therapy (surgery [S], stereotactic radiosurgery [SRS] and whole brain radiotherapy [WBRT]) in BCBM patients, we analyzed the data of 873 BCBM patients from 1999 to 2012. The median overall survival (OS) and time to progression in the brain (TTP-b) after diagnosis of brain metastases (BM) were 9.1 and 7.1 months, respectively. WBRT prolonged OS in patients with multiple BM (hazard ratio [HR], 0.68; 95% CI, 0.52-0.88; P = .004). SRS alone, and surgery or SRS followed by WBRT (S/SRS + WBRT), were equivalent in OS and TTP-b (median OS, 14.9 vs 17.2 months; median TTP-b, 8.2 vs 8.6 months). Continued chemotherapy prolonged OS (HR, 0.35; 95% CI, 0.30-0.41; P < .001) and TTP-b (HR, 0.48; 95% CI, 0.33-0.70; P < .001), however, with no advantage of capecitabine over other chemotherapy agents used (median OS, 11.8 vs 12.4 months; median TTP-b, 7.2 vs 7.4 months). Patients receiving trastuzumab at diagnosis of BM, continuation of anti-HER2 therapy increased OS (HR, 0.53; 95% CI, 0.34-0.83; P = .005) and TTP-b (HR, 0.41; 95% CI, 0.23-0.74; P = .003); no additional benefit was seen with switching over between trastuzumab and lapatinib (median OS, 18.4 vs 22.7 months; median TTP-b: 7.4 vs 8.7 months). In conclusion, SRS or S/SRS + WBRT were equivalent for patients' OS and local control. Continuation systemic chemotherapy including anti-HER2 therapy improved OS and TTP-b with no demonstrable advantage of capecitabine and lapatinib over other agents of physicians' choice was observed.

Outcomes of orbital exenteration for craniofacial lesions.

BACKGROUND: Orbital exenteration (OE) is an ablative procedure used in the management of malignancies of the orbit of either primary or secondary origin. Publications evaluating this procedure have suffered from small patient numbers, heterogeneity of pathologies, and poor patient follow-up. The purpose of this study was to assess patient outcomes in a large cohort of patients undergoing OE at a tertiary cancer center. METHODS: A retrospective review was conducted of 180 consecutive patients who underwent OE at the authors' institution. Overall survival (OS) was the primary end point measured in the study. Time to locoregional recurrence (progression-free survival [PFS]) and disease-free survival were secondary end points. RESULTS: Between the years 1993 and 2011, 180 consecutive patients received OE for craniofacial malignancy at the authors' institution. The median follow-up for the cohort was 9.7 years (116 months). The median OS was 73 months, and the median PFS was 96 months. The presence of perineural invasion was associated with shorter OS (P = .01) and PFS (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter PFS than negative margins (P < .01) but with no change in OS (P = .15). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5), and there was 1 death observed (0.6%). CONCLUSIONS: Used judiciously in the setting of a multidisciplinary management plan, OE for tumor control is a safe therapy. LAY SUMMARY: Between the years 1993 and 2011, 180 consecutive patients received orbital exenteration for craniofacial malignancy at the MD Anderson Cancer Center. The median follow-up for the cohort was 9.7 years. The presence of perineural invasion was associated with shorter overall survival (P = .01) and progression-free survival (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter progression-free survival than negative margins (P < .01). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5).

Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development.

Breast cancer with brain metastases: clinicopathologic features, survival, and paired biomarker analysis.

BACKGROUND: The aim of this study was to describe clinicopathologic features of patients with breast cancer brain metastasis (BCBM); to evaluate survival after diagnosis of BCBM; and to compare estrogen receptor (ER), progesterone receptor (PR), and HER2 expression in the paired primary and brain tumors. MATERIALS AND METHODS: We identified 140 consecutive patients who underwent craniotomy for BCBM (either for diagnostic purpose or with therapeutic intent) at the University of Texas MD Anderson Cancer Center between 2002 and 2009. RESULTS: Most patients had invasive ductal histology (91%), grade 3 tumors (67%), and positive axillary lymph node (64%). Of the tumors, 56% were ER-negative, 62% were PR-negative, 44% were HER2-positive, and 28% were triple negative (TN). Brain metastasis (BM) was solitary in 51% of patients. Median interval from breast cancer diagnosis to BM was 46 months; median survival after BM was 14.1 months. In the univariate analysis, younger age, solitary brain metastasis, and ER or PR positivity in the breast tumors were associated with longer survival. There was a statistical trend toward increased survival in HER2-positive patients compared with HER2-negative patients (18 vs. 11 months). In the multivariate analysis, predictors for longer survival included younger age, solitary brain lesion, and HER2 positivity in the breast cancer. Biomarkers were evaluated in paired primary and brain tumors in 35 patients for ER status, 34 for PR status, and 36 for HER2 status. Discordant rates were 28% for ER, 20% for PR, and 3% for HER2. CONCLUSION: Compared with unselected breast cancer patients at the same institution, patients with breast cancer who had brain metastases had a higher proportion of hormone receptor-negative, HER2-positive, and TN tumors. Younger age, solitary brain lesion, and HER2 expression were independent predictors of better survival in patients with BCBM. HER2 status was highly concordant between the paired primary and brain tumors, whereas changes of ER and PR status occurred in a substantial proportion of the patients. These findings are important for making effective treatment decisions for patients with BCBM.

Outcomes of arteriovenous grafts following simultaneous thrombectomy and stent graft placement across the venous anastomosis.

Arteriovenous grafts (AVGs) suffer from high thrombosis rates. It is not known whether placement of stent grafts at the venous anastomosis (VA) of thrombosed AVGs would impact future thrombosis. This is a retrospective study evaluating a group of AVGs that underwent endovascular thrombectomy with placement of a stent graft at their VA. The study period was a minimum of 1 year or until kidney transplantation or death. Primary and secondary AVG patency rates were obtained using Kaplan-Meier survival estimates. Demographic parameters were analyzed using Cox multivariate analysis. The effect of early vs. late first thrombosis was also studied. Sixty-six patients were included in the study. Of these, 53 (80%) experienced ≥1 thrombotic event during the study period. Thrombosis led to AVG loss in 26 (39%). The primary patency was 47%, 35%, and 21% at 3, 6, and 12 months, respectively. The assisted primary patency was 50%, 38%, and 25% at 3, 6, and 12 months, respectively. The secondary patency rate was 85%, 76%, and 72% at 3, 6, and 12 months, respectively. Thus, poor primary patency rates were observed despite stent graft placement at the VA. In addition, early thrombosis following stent graft placement was associated with worse AVG outcomes.

Impact of preoperative functional magnetic resonance imaging during awake craniotomy procedures for intraoperative guidance and complication avoidance.

BACKGROUND: We wanted to study the role of functional MRI (fMRI) in preventing neurological injury in awake craniotomy patients as this has not been previously studied. OBJECTIVES: To examine the role of fMRI as an intraoperative adjunct during awake craniotomy procedures. METHODS: Preoperative fMRI was carried out routinely in 214 patients undergoing awake craniotomy with direct cortical stimulation (DCS). RESULTS: In 40% of our cases (n = 85) fMRI was utilized for the intraoperative localization of the eloquent cortex. In the other 129 cases significant noise distortion, poor task performance and nonspecific BOLD activation precluded the surgeon from using the fMRI data. Compared with DCS, fMRI had a sensitivity and specificity, respectively, of 91 and 64% in Broca's area, 93 and 18% in Wernicke's area and 100 and 100% in motor areas. A new intraoperative neurological deficit during subcortical dissection was predictive of a worsened deficit following surgery (p < 0.001). The use of fMRI for intraoperative localization was, however, not significant in preventing worsened neurological deficits, both in the immediate postoperative period (p = 1.00) and at the 3-month follow-up (p = 0.42). CONCLUSIONS: The routine use of fMRI was not useful in identifying language sites as performed and, more importantly, practiced tasks failed to prevent neurological deficits following awake craniotomy procedures.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

REST regulates oncogenic properties of glioblastoma stem cells.

Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor repressor element 1 silencing transcription factor (REST), suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High REST-expressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low REST-expressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM.

Volumetric extent of resection and survival for recurrent atypical meningioma.

OBJECTIVE: In recurrent atypical meningioma, the survival impact of volumetric extent of resection (vEOR) and residual tumor volume (RTV) has not been previously studied. METHODS: The authors performed a retrospective vEOR analysis of patients with recurrent World Health Organization grade II meningiomas treated with reresection from 2000 to 2019. The Kaplan-Meier method and multivariate Cox regression analysis were used to study progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-nine patients with a median follow-up duration of 95 (95% CI 42-148) months were included. The median (range) vEOR was 100% (32%-100%) and the mean ± SD was 90.7% ± 15.3%. Among patients who underwent gross-total resection (GTR) (n = 32 [54%]), Simpson grade I and II resections were achieved in 23 (72%) and 9 (28%) patients, respectively. Among patients who underwent subtotal resection (n = 27 [46%]), the median (range) RTV was 4.3 (0.3-40) cm3. The 1-, 2-, and 5-year actuarial PFS rates for the cohort were 76%, 56%, and 34%, respectively. The 1-, 2-, and 5-year actuarial OS rates for the cohort were 98%, 78%, and 60%, respectively. Variables reflecting EOR significantly impacted both PFS and OS in multivariate analysis: GTR (p < 0.01) was significantly associated with longer PFS, and lower Simpson grade (p = 0.04) was significantly associated with longer OS. Additional factors including RTV, Ki-67 index, and pretreatment and posttreatment history also impacted survival outcomes (p < 0.05). CONCLUSIONS: EOR and Simpson grade were independently associated with survival outcomes in patients with recurrent atypical meningioma. These findings support the practice of thorough reresection for maximal cytoreduction in appropriate surgical candidates.

Postoperative Management of Recurrence After Radiosurgery and Surgical Resection for Brain Metastases and Predicting Benefit From Adjuvant Radiation.

Stereotactic radiosurgery (SRS) is often used as upfront treatment for brain metastases. Progression or radionecrosis after SRS is common and can prompt resection. However, postoperative management strategies after resection for SRS failure vary widely, and no standard practice has been established. In this approved study, we retrospectively reviewed patients who received SRS for a brain metastasis followed by resection of the same lesion. We extracted patient-, disease-, and treatment-related variables and information on disease-related outcomes. Univariate and multivariate analyses of clinicopathologic variables were used to create a model to predict factors associated with local failure (LF). A total of 225 patients with brain metastases treated with SRS from 2009 to 2017 followed by surgical resection were identified. Overall, 65% of cases had gross total resection (GTR) on postoperative imaging review. Twenty-one patients (9.3%) received adjuvant radiation therapy to the surgical cavity, and 204 (90.7%) were observed. Of these 204 patients, 118 had GTR with evidence of tumor within the pathology specimen. With a median follow-up of 13 months after resection, 47 patients (40%) developed LF after surgery. After salvage resection of a brain metastasis initially treated with SRS, the observed LF rate was 40% among those who had a GTR and evidence of tumor on pathologic examination. This LF rate is sufficiently high that adjuvant radiation to the surgical bed after salvage resection should be considered in these cases when there is tumor in the pathology, even after a GTR.

Subependymomas of the fourth ventricle: To operate or not to operate?

BACKGROUND: There is a paucity of literature regarding the clinical characteristics and management of subependymomas of the fourth ventricle due to their rarity. Here, we describe the operative and non-operative management and outcomes of patients with such tumors. METHODS: This retrospective single-institution case series was gathered after Institutional Review Board (IRB) approval. Patients diagnosed with a subependymoma of the fourth ventricle between 1993 and 2021 were identified. Clinical, radiology and pathology reports along with magnetic resonance imaging (MRI) images were reviewed. RESULTS: Patients identified (n = 20), showed a male predominance (n = 14). They underwent surgery (n = 9) with resection and histopathological confirmation of subependymoma or were followed with imaging surveillance (n = 11). The median age at diagnosis was 51.5 years. Median tumor volume for the operative cohort was 8.64 cm3 and median length of follow-up was 65.8 months. Median tumor volume for the non-operative cohort was 0.96 cm3 and median length of follow-up was 78 months. No tumor recurrence post-resection was noted in the operative group, and no tumor growth from baseline was noted in the non-operative group. Most patients (89 %) in the operative group had symptoms at diagnosis, all of which improved post-resection. No patients were symptomatic in the non-operative group. CONCLUSIONS: Surgical resection is safe and is associated with alleviation of presenting symptoms in patients with large tumors. Observation and routine surveillance are warranted for smaller, asymptomatic tumors.

Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience.

Background: Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults. Methods: From a single-institution dataset of 200 adult patients diagnosed with medulloblastoma during 1978-2017, those with recurrence were analyzed for clinical features, treatment, and outcome. Results: Of the 200 patients, 82 (41%) with median age of 29 years (18-59) had recurrence after a median follow-up time of 8.4 years (95% CI = 7.1, 10.3). Of these, 30 (37%) were standard-risk, 31 (38%) were high-risk, and 21 (26%) had unknown-risk diseases at the time of initial diagnosis. Forty-eight (58%) presented with recurrence outside the posterior fossa, of whom 35 (43%) had distant recurrence only. Median Progression-free survival (PFS) and OS from initial surgery were 33.5 and 62.4 months, respectively. Neither PFS nor OS from initial diagnosis differed between the standard-risk and high-risk groups in those who experience recurrence (P = .505 and .463, respectively). Median OS from first recurrence was 20.3 months, also with no difference between the standard-risk and high-risk groups (P = .518). Recurrences were treated with combinations of re-resection (20 patients; 25%), systemic chemotherapy (61 patients; 76%), radiation (29 patients; 36%), stem cell transplant (6 patients; 8%), and intrathecal chemotherapy (4 patients; 5%). Patients who received radiation at recurrence had better OS (32.9 months) than those who did not (19.2 months) (P = .034). Conclusions: Recurrent medulloblastoma in adults has a poor prognosis irrespective of initial risk stratification. Recurrence commonly arises outside the posterior fossa years after initial diagnosis.

Butterfly glioblastomas: a retrospective review and qualitative assessment of outcomes.

To address a paucity of literature and treatment guidelines regarding the management of butterfly glioblastomas, we performed a ten year retrospective analysis of data from twenty-three consecutive patients treated for this disease at a single institution. Clinical characteristics and outcomes were assessed. Median age was 59 years; 52 % were female; median preoperative Karnofsky performance score (KPS) was 80. Twelve patients underwent biopsy and eleven underwent surgical decompression. The median tumor volume for the biopsy group was 60.6 cm(3) and for the surgically decompressed group 40.5 cm(3). In the biopsy group, five patients received adjuvant therapy but one died prior to its completion; two died prior to the initiation of adjuvant therapy and five were lost to follow up. In the surgical decompression group, seven patients received adjuvant therapy, one died prior to the initiation of adjuvant therapy, two were treated with palliative measures only, and one was lost to follow up. Kaplan-Meier estimates of overall median post surgical-survival of the whole group was 180 days, the biopsy group 48 days, and the surgically decompressed group 265 days (p = 0.14). Our results show that there was a higher median survival in the surgically decompressed group; but a direct correlation could not be established, and that the median KPS did not improve in either group after treatment. A larger multicenter review is required to quantitatively assess the factors, including tumor biomarkers that are associated with patient outcome.

Initial experience with the use of an expandable titanium cage as a vertebral body replacement in patients with tumors of the spinal column: a report of 95 patients.

OBJECTIVE: Vertebral body resection to treat spine tumors necessitates reconstruction to maintain spinal stability. The durability of reconstruction may be a challenge in cancer patients as treatment with chemotherapy and/or radiation coupled with poor nutritional status may compromise bone quality. We present a series of patients who underwent implantation of an expandable titanium cage (ETC) for reconstruction after vertebral body resection for primary or metastatic spine tumors. We report the functional outcome, assess the durability of reconstruction, and describe complications associated with this procedure. METHODS: A retrospective review of patients undergoing placement of ETC after vertebrectomy for spinal tumor at our institution was performed. RESULTS: From September 2001 to August 2006, 95 patients underwent implantation of an ETC for reconstruction of the anterior spinal column following vertebrectomy for tumor (75 one-level, 19 two-level, 1 three-level). All patients underwent spinal stabilization as well. The median survival after surgery was 13.7 months; 23 patients had primary spinal tumors and 72 had metastatic tumors. Numerical pain scores were significantly improved postoperatively indicating a palliative benefit. No new neurological deficits were noted postoperatively, except when intentional neurological sacrifice was performed for oncologic reasons. Median height correction of 14% (range 0-118%) and median improvement in sagittal alignment of 6° (range 0-28°) were demonstrated on immediate postoperative imaging. Three patients experienced hardware related complications, one of which had posterior migration of the ETC. On postoperative imaging, 12 patients demonstrated subsidence of greater than 1 mm, but none required operative revision. CONCLUSION: Use of an ETC for spinal reconstruction in patients with spinal tumors is safe, decreases pain associated with pathologic fracture, protects neurologic function, and is durable. We found a very low incidence of cage-related construct failures and no significant problems with subsidence.

Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas.

OBJECTIVE: Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors' institution they have increasingly used a circumferential, perilesional, sulcus-guided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome. METHODS: The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher's exact test. Multivariate analyses were performed using multivariate logistic regression. RESULTS: Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1-2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR. CONCLUSIONS: The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.

Bcl-2 promotes malignant progression in a PDGF-B-dependent murine model of oligodendroglioma.

A significant subset of gliomas arises after activation of the proproliferative platelet-derived growth factor (PDGF) pathway. The progression of low-grade gliomas to more malignant tumors may be due to oncogenic cellular programs combining with those suppressing apoptosis. Antiapoptotic genes are overexpressed in a variety of cancers, and the antiapoptotic gene, BCL2, is associated with treatment resistance and tumor recurrence in gliomas. However, the impact of antiapoptotic gene expression to tumor formation and progression is unclear. We overexpressed Bcl-2 in a PDGFB-dependent mouse model of oligodendroglioma, a common glioma subtype, to assess its effect in vivo. We hypothesized that the antiapoptotic effect would complement the proproliferative effect of PDGFB to promote tumor formation and progression to anaplastic oligodendroglioma (AO). Here, we show that coexpression of PDGFB and Bcl-2 results in a higher overall tumor formation rate compared to PDGFB alone. Coexpression of PDGFB and Bcl-2 promotes progression to AO with prominent foci of necrosis, a feature of high-grade gliomas. Median tumor latency was shorter in mice injected with PDGFB and Bcl-2 compared to those injected with PDGFB alone. Although independent expression of Bcl-2 was insufficient to induce tumors, suppression of apoptosis (detected by cleaved caspase-3 expression) was more pronounced in AOs induced by PDGFB and Bcl-2 compared to those induced by PDGFB alone. Tumor cell proliferation (detected by phosphohistone H3 activity) was also more robust in high-grade tumors induced by PDGFB and Bcl-2. Our results indicate that suppressed apoptosis enhances oligodendroglioma formation and engenders a more malignant phenotype.

Impact of Multi-modality Monitoring Using Direct Electrical Stimulation to Determine Corticospinal Tract Shift and Integrity in Tumors using the Intraoperative MRI.

INTRODUCTION: Preserving the integrity of the corticospinal tract (CST) while maximizing the extent of tumor resection is one of the key principles of brain tumor surgery to prevent new neurologic deficits. Our goal was to determine the impact of the use of perioperative diffusion tensor imaging (DTI) fiber-tracking protocols for location of the CSTs, in conjunction with intraoperative direct electrical stimulation (DES) on patient neurologic outcomes. The role of combining DES and CST shift in intraoperative magnetic resonance imaging (iMRI) to enhance extent of resection (EOR) has not been studied previously. METHODS: A total of 53 patients underwent resection of tumors adjacent to the motor gyrus and the underlying CST between June 5, 2009, and April 16, 2013. All cases were performed in the iMRI (BrainSuite 1.5 T). Preoperative DTI mapping and intraoperative cortical and subcortical DES including postoperative DTI mapping were performed in all patients. There were 32 men and 21 women with 40 high-grade gliomas (76%), 4 low-grade gliomas (8%), and 9 (17%) metastases. Thirty-four patients (64%) were newly diagnosed, and 19 (36%) had a previous resection. There were 31 (59%) right-sided and 22 (42%) left-sided tumors. Eighteen patients (34%) had a re-resection after the first intraoperative scan. Most patients had motor-only mapping, and one patient had both speech and motor mapping. Relative to the resection margin, the CST after the first iMRI was designated as having an outward shift (OS), inward shift (IS), or no shift (NS). RESULTS: A gross total resection (GTR) was achieved in 41 patients (77%), subtotal resection in 4 (7.5%), and a partial resection in 8 (15%). Eighteen patients had a re-resection, and the mean EOR increased from 84% to 95% (p = 0.002). Of the 18 patients, 7 had an IS, 8 an OS, and in 3 NS was noted. More patients in the OS group had a GTR compared with the IS or NS groups (p = 0.004). Patients were divided into four groups based on the proximity of the tumor to the CST as measured from the preoperative scan. Group 1 (32%) included patients whose tumors were 0 to 5 mm from the CST based on preoperative scans; group 2 (28%), 6 to 10 mm; group 3 (13%), 11 to 15 mm; and group 4 (26%), 16 to 20 mm, respectively. Patients in group 4 had fewer neurologic complications compared with other groups at 1 and 3 months postoperatively (p = 0.001 and p = 0.007, respectively) despite achieving a similar degree of resection (p = 0.61). Furthermore, the current of intraoperative DES was correlated to the distance of the tumor to the CST, and the regression equation showed a close linear relationship between the two parameters. CONCLUSIONS: Combining information about intraoperative CST and DES in the iMRI can enhance resection in brain tumors (77% had a GTR). The relative relationship between the positions of the CST to the resection cavity can be a dynamic process that could further influence the surgeon's decision about the stimulation parameters and EOR. Also, the patients with an OS of the CST relative to the resection cavity had a GTR comparable with the other groups.

Alterations in Functional Connectomics Associated With Neurocognitive Changes Following Glioma Resection.

BACKGROUND: Decline in neurocognitive functioning (NCF) often occurs following brain tumor resection. Functional connectomics have shown how neurologic insults disrupt cerebral networks underlying NCF, though studies involving patients with brain tumors are lacking. OBJECTIVE: To investigate the impact of brain tumor resection upon the connectome and relationships with NCF outcome in the early postoperative period. METHODS: A total of 15 right-handed adults with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessment before and after awake tumor resection. Graph theoretical analysis was applied to rs-fMRI connectivity matrices to calculate network properties. Network properties and NCF measures were compared across the pre- to postoperative periods with matched pairs Wilcoxon signed-rank tests. Associations between pre- to postoperative change in network and NCF measures were determined with Spearman rank-order correlations (ρ). RESULTS: A majority of the sample showed postoperative decline on 1 or more NCF measures. Significant postoperative NCF decline was found across measures of verbal memory, processing speed, executive functioning, receptive language, and a composite index. Regarding connectomic properties, betweenness centrality and assortativity were significantly smaller postoperatively, and reductions in these measures were associated with better NCF outcomes. Significant inverse associations (ρ = -.51 to -.78, all P < .05) were observed between change in language, executive functioning, and learning and memory, and alterations in segregation, centrality, and resilience network properties. CONCLUSION: Decline in NCF was common shortly following resection of glioma involving eloquent brain regions, most frequently in verbal learning/memory and executive functioning. Better postoperative outcomes accompanied reductions in centrality and resilience connectomic measures.