bluuebunny/crossref_metadata_2025_split huggingface dataset:
SURG-15. RIGHT FRONTAL-PARIETAL PILOCYTIC ASTROCYTOMA WHO GRADE I ASSOCIATED WITH HEMORRHAGIC COMPONENT AND ESSENTIAL HYPERTENSION IN AN ADULT
Authors: Kamabu Larrey , Kiryabwire Joel 
Published: November 2023

Abstract
Pilocytic astrocytoma (PA) is a primary glial neoplasm and low-grade tumor. After total resection, the prognosis is very good. A poor prognosis results from leptomeningeal spreading and bleeding, both of which are extremely uncommon in Pilocytic Astrocytoma patients. Case presentation We report the case of a 43-year-old male that presented with a 4 days’ history of right sided frontal headache, non-radiating and mostly felt in the morning. Not associated with vomiting and fever. In addition, there was a sudden decline in level of consciousness with no associated stool or urine incontinence. The patient also developed three episodes of tonic clonic convulsions, lasting less than 3 minutes associated with urine incontinence and frothing from the mouth. Two days later, there was a sudden onset of left sided weakness involving upper and lower limbs. However, there is no history of trauma or hypertension. He was identified as having a hemorrhagic right frontal-parietal PA evidence on MRI associated with essential hypertension. The patient had an intervention combination of medical treatment and craniotomy via fronto-temporal approach plus excision of lesion. Histopathological examination of specimen determined that it was PA WHO grade I. He was treated with oral anti-epileptic therapy (Phenytoin 300 mg once a day), folic acid supplementation (400 mcg once a day), anti-hypertensive therapy (Amlodipine 10 mg and Losartan 50 mg once daily) and he showed marked improvement and was discharged home after 1 month and followed up by primary neurosurgeon, oncologist and physician. CONCLUSION: This case report raises awareness of Pilocytic Astrocytoma among adults and emphasizes the value of early diagnosis and management of patients with Pilocytic Astrocytoma associated with essential hypertension can prevent complications, reduce morbidity and mortality.
SURG-21. THE PROGNOSTIC ROLE OF RE-RESECTION FOR RECURRENT GLIOBLASTOMA: A REPORT OF THE RANO RESECT GROUP USING A NOVEL CLASSIFICATION FOR EXTENT OF RESECTION
Authors: Karschnia Philipp , Dono Antonio , Young Jacob , Juenger Stephanie T , Häni Levin , Teske Nico , Sciortino Tommaso , Mau Christine Y , Bruno Francesco , Nunez Luis , Morshed Ramin , Haddad Alexander F , Weller Michael , van den Bent Martin , Beck Juergen , Hervey-Jumper Shawn , Molinaro Annette , Tandon Nitin , Rudà Roberta , Vogelbaum Michael A , Bello Lorenzo , Schnell Oliver , Grau Stefan J , Chang Susan , Berger Mitchel , Esquenazi Yoshua , Tonn Joerg-Christian 
Published: November 2023

Abstract

BACKGROUND
The role of re-resection in recurrent glioblastoma remains controversial since leaving certain tumor volumes deliberately behind cannot be ethically justified. We aimed to (I) analyze the prognostic value of re-resection using the novel RANO resect classification for quantification of residual tumor, and (II) explore factors that favorably consolidate the effects of re-resection on outcome.

METHODS
The RANO resect group retrospectively accumulated a global, eight-center cohort of patients with first recurrence from a previously resected glioblastoma. The associations of re-resection and clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to mimic randomized clinical trials comparing different residual tumor volumes.

RESULTS
We analyzed 681 patients with first recurrence of IDH-wildtype glioblastoma, including 310 patients who underwent re-resection at first recurrence. The use of re-resection was associated with prolonged survival also when stratifying for molecular and clinical confounders (HR:0.65, CI:0.5-0.8; p = 0.001). Smaller post-operative contrast-enhancing (CE) tumor volumes were favorably associated with outcome of re-resected patients (HR per cm3:1.04, CI:1.0-1.1; p = 0.009), and ≤ 1 cm3 residual CE tumor translated into improved survival compared to non-surgical management. Accordingly, ‘maximal resection’ (class 2) had superior survival compared to ‘submaximal resection’ (class 3) (mOS after recurrence: 12 vs. 9 months; p = 0.003). Adjuvant chemotherapy further augmented the beneficial effects of lower residual CE tumor. Conversely, ‘supramaximal resection’ of non-CE tumor (class 1) was not associated with prolonged survival but frequently accompanied by post-operative deficits, hampering further treatment. The prognostic role of residual CE tumor was confirmed in propensity score analyses.

CONCLUSION
Residual CE tumor is highly prognostic in recurrent glioblastoma and the RANO resect classification serves to stratify patients accordingly. Chemotherapy may favorably contribute to the prognostic associations of re-resection. When pursuing re-resection of non-CE tumor, intraoperative mapping strategies to minimize the risk of post-operative deficits are recommended.
SURG-24. FACTORS PREDICTING REMISSION AND RECURRENCE AFTER SURGICAL TREATMENT OF ACTH SECRETING PITUITARY ADENOMAS - CUSHING’S DISEASE
Authors: Suri Ashish , Khadgawat Rajesh , Sharma M C , Garg Ajay 
Published: November 2023

Abstract
Despite recent advances in management, disease persistence and recurrences are common in patients with ACTH secreting pituitary adenomas-Cushing’s disease (CD). The study aims to determine clinical, biochemical, radiological, histological factors that correlate with persistence and recurrence in patients with CD, and also aims to understand the clinico-pathological significance of EGFR-MAPK, NF-kB, SHH pathway activation. Clinical data of 167 patients who underwent surgical treatment (n = 174 surgeries) for CD was ambispectively analysed with median follow-up of 8.1years(1-13.29 years). Among the 174 surgeries performed, 140 were primary, 22 were redo, 24 were for paediatric patients and 12 surgeries were performed in Nelson syndrome. In the primary surgery cohort, 74.3% were females and the average age was 28.73years(SD = 10.15). 75% of patients experienced remission after primary surgery compared to 47.4% in redo surgery. The remission rate in paediatric patients was 55.5%. Post-operative day-1 plasma cortisol (p &lt; 0.001;AUC = 0.8894[0.8087-0.9701]) and ACTH (p &lt; 0.001;AUC 0.9[0.7386-1]) levels were seen to be strong independent predictors of remission in primary surgery cohort. Remission rates after endoscopic trans-sphenoidal surgery- TSS were more than those after microscopic TSS, in patients undergoing primary surgery (81.08%vs57.14%;p = 0.008). Presence of adenoma on histopathological examination(HPE) was also strong predictor of disease remission (p = 0.020). On categorising based on surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of non-remission (OR 38.1;95%CI-4.2-348.3) compared to endoscopically operated patients with adenoma on HPE. Lower immune reactivity score (IRS) of NR4A1 was found to correlate with higher remission rates (p = 0.074). However, none of the molecular markers studied - NR4A1, c-Fos, c-Jun, GLI1, pMEK, p44 showed a significant correlation with the preoperative cortisol values. Post-operative day-1 serum cortisol and ACTH are reliable predictors of remission. Additionally, endoscopic approach and histopathological evidence of adenoma are associated with higher remission rate, with both features together raising the odds significantly.
SURG-33. LATERAL VERSUS MIDLINE APPROACHES TO RESECTION OF SKULL BASE CHORDOMAS: A META-ANALYSIS
Authors: Brown Nolan , Kuo Cathleen , Nguyen Oanh , Gendreau Julian 
Published: November 2023

Abstract

INTRODUCTION
Though it remains a rare and devastating tumor, great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. With respect to surgical techniques, lateral transcranial (TC) approaches have traditionally been used, however endoscopic endonasal approaches (EEA) have been advocated for midline lesions. However, due to the rarity of this tumor (0.2% of all intracranial neoplasms), investigations within the literature remain limited to small retrospective series.

METHODS
Accordingly, we performed a systematic review and meta-analysis in order to profile surgical outcomes for midline versus lateral approaches to resection of skull base chordoma. Meta-analysis of pooled mortality rates and sub-analyses of operative margin and surgical complications were used to compare midline versus lateral approaches via the Mantel-Haenszel method. We considered all p-values &lt; 0.05 to be statistically significant.

RESULTS
Fifty studies published between 1993-2022 reporting data for 2252 patients remained eligible for analysis. Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. The relative risk for mortality (Figure 2) in patients undergoing surgical intervention was -0.93 [-1.03,-0.97], I^2=95%, (p &lt; 0.001), indicating low surgery-related mortality rates. From the seven studies eligible for formal meta-analysis, we found that there was no statistically significant difference between midline and lateral approaches with respect to rates of GTR or recurrence. Nor was there a significant difference between rates of postoperative cranial nerve dysfunction, although the result trended toward favoring midline approaches. Finally, midline approaches exhibited a lower odds for peri- and post-operative complications, including CSF leak (OR 0.59 [0.35, 0.97], I^2 = 0%, p = 0.04).

CONCLUSION
Ultimately, there are no striking differences between midline versus lateral approaches to resection of skull base chordoma, particularly as they relate to operative margins, recurrence, or rates of cranial nerve palsy.
SURG-38. SAFETY AND EFFICACY OF COMBINATORIAL IMMUNE CHECKPOINT BLOCKADE AND LASER INTERSTITIAL THERMAL THERAPY
Authors: Haskell-Mendoza Aden , Wachsmuth Lucas , Srinivasan Ethan , Jackson Joshua , Zaidi Saif , Gonzalez Ariel , Reason Elle , Lerner Emily , Fecci Peter 
Published: November 2023

Abstract

INTRODUCTION
Treatment of intracranial lesions with laser interstitial thermal therapy (LITT) allows for simultaneous cytoreduction and the potential to generate an anti-tumor immune response. The safety and efficacy of combination immune checkpoint blockade (ICB) and LITT has not been determined.

METHODS
All patients who received LITT for neuro-oncologic indications at a single NCI-designated cancer center from 2015 – 2022 were included. Simultaneous ICB was defined as receipt of therapy within 6 weeks of LITT. Demographic, clinical, and survival data were collected. Immune-related and intracranial adverse events (iRAEs and IAEs) were graded according to Common Terminology Criteria.

RESULTS
Twenty-four patients received simultaneous LITT and ICB. Median age was 62 (range 40 - 78) and 12 (48%) were female. Median KPS was 80 (50 – 100). Use of ICB increased during the study period (r = 0.69). The most common pathology was non-small cell lung cancer (15 patients, 62.5%), followed by melanoma in 3 (12.5%) and 2 (8.3%) patients each with renal cell carcinoma or high-grade glioma. Twenty-three (96%) patients received single agent ICB, with pembrolizumab most common (12, 50%), followed by nivolumab (6, 25%). The median interval between LITT and ICB was 2.56 (0.85 – 4.98) weeks. The most common iRAE was hypothyroidism in 4 (16.6%) patients, with grade 3 pneumonitis in one patient. The most common IAE was seizures in 4 (16.6%) patients. Local progression was seen in 4 patients (16.6%), with a post-LITT overall survival of 20.6 (1.0 – 36.1) months for the cohort.

CONCLUSIONS
Combination LITT and ICB appears safe and effective, with iRAEs commensurate with trials of checkpoint inhibition. High-grade intracranial toxicity was rare. Prospective studies of combinatorial LITT + ICB are needed to establish biomarkers and optimal timing.
SURG-40. AWAKE CRANIOTOMY IN A MIDDLE-INCOME COUNTRY. CHALLENGES AND TECHNICAL NUANCES
Authors: De Leon Alvino , Wong Eduardo , Villarreal Maria Antonia 
Published: November 2023

Abstract

OBJECTIVES
Describe the first experience in this technically challenging procedure

RESULTS
on morbidity

INTRODUCTION
Awake craniotomy allows for maximal safe resection and lower incidence of adverse events. Nonetheless, it represents a technical challenge.

METHODS
We enroll forty patients, 18 women, and 22 men. Due to the lack of a navigation system, craniometrics points became paramount to craniotomy planning. Ultrasound is used to compensate for brain shift and confirm the tumor's exact location. We engaged in cortical and subcortical mapping and clinical evaluation of motor and sensory functions. Linguistic tests were applied. The first 24 hours are in the ICU, and an MRI is obtained.

RESULTS
The mean age was 51, and the mean Karfnosky scale was 80. The median size was 12 cm3. Locations were: Thirteen precentral gyri. Ten insular cortex. Eight cingulate gyri. Six supplementary motor gyri Two Supramarginal gyri. One paracentral lobe tumor. Four patients had obese morbidity, three had depression, and two had a midline displacement treated with steroids. Intraoperative, we encountered three seizures managed with cold saline, two speech arrest, and one transient hand motor deficit. Post-op adverse events were one central facial paralysis, one upper limb, and one lower limb paresthesias; all improved after 72 hours. The median length of stay is 48 hours. The median extent of resection is 93%. The mean KPS was 80 at discharge. We undertook a median of 18 months follow-up. 38 Glioblastomas(GMB) and 2 Low-Grade Gliomas(LGG) were found. The standard oncology treatment was Temozolomide and stereotaxic radiosurgery(SRS). The median time from surgery to SRS was 4.3 months. The median SRS marginal and maximal dose were 15Gy and 26Gy. The median overall survival(OS) was sixteen months, and the Progression-free survival(PFS) was ten months.

CONCLUSION
An awake craniotomy without the navigation system is possible; however, careful planning is essential.
TMET-17. LEVERAGING METABOLIC VULNERABILITIES INDUCED BY TERT EXPRESSION FOR GLIOBLASTOMA THERAPY IN VIVO
Authors: Udutha Suresh , Taglang Celine , Batsios Georgios , Gillespie Anne Marie , Viswanath Pavithra 
Published: November 2023

Abstract
Telomerase reverse transcriptase (TERT) is essential for telomere maintenance and tumor immortality. Although TERT is an attractive therapeutic target, targeting TERT directly is hampered by toxicity to stem cells that also rely on TERT for proliferation and the lag period before telomere attrition is observed. Targeting metabolic reprogramming associated with TERT is an alternate strategy. Our studies indicate that TERT is essential for redox homeostasis in glioblastoma cells (GBM; GBM6 and U251). Specifically, TERT increases levels of glutathione (GSH) via upregulation of the catalytic subunit of glutamate-cysteine ligase (GCLC), the rate-limiting enzyme in de novo GSH synthesis. Inhibiting GCLC using buthionine sulfoximine (BSO) or siRNA reduces synthesis of 13C-GSH from [U-13C]-glutamine and inhibits viability of GBM6 and U251 cells. However, GCLC inhibition causes a compensatory increase in synthesis of glutamate, aspartate, and pyrimidine nucleotides from [U-13C]-glutamine via upregulation of two key glutamine-utilizing enzymes i.e., glutaminase (GLS), the enzyme that generates glutamate from glutamine, and carbamoyl phosphate synthetase II (CPSII), the enzyme that converts glutamine to carbamoyl phosphate during pyrimidine biosynthesis. We then examined the therapeutic potential of inhibiting GLS and CPSII in combination with GCLC in GBMs. 6-diazo-5-oxy-L-norleucin (DON), a potent inhibitor of glutamine-utilizing enzymes including GLS and CPSII, synergizes with BSO in inhibiting viability of GBM6 and U251 cells. This effect is specific to TERT-expressing GBM cells because the combination of DON and BSO does not affect viability of normal astrocytes or astrocytomas that use the ALT pathway for telomere maintenance. Importantly, in vivo stable isotope tracing confirmed that combined treatment with JHU-083 (a brain-penetrant prodrug of DON) and BSO abrogates synthesis of GSH, aspartate, and pyrimidine nucleotides from [U-13C]-glutamine and induces apoptotic death in mice bearing intracranial GBM6 tumors.Collectively, our studies highlight the therapeutic potential of targeting metabolic vulnerabilities induced by TERT expression in GBMs in vivo.
TMIC-03. TARGETING THE COLLAGEN RECEPTOR DDR1 PROMOTES ANTI-GLIOMA IMMUNITY BY REMODELING COLLAGEN FIBER ARCHITECTURE
Authors: Faisal Syed M , Varela Maria , Comba Andrea , Argento Anna , West Molly , Brumley Emily , Abel II Clifford , Clewner Jarred , Stack Brooklyn , Haase Santiago , Mujeeb Anzar , Banerjee Kaushik , Barissi Marcus , Abbud Grace , Castro Maria , Lowenstein Pedro 
Published: November 2023

Abstract
Glioblastoma (GBM), characterized by its aggressive nature and profound immunosuppression, poses a significant therapeutic challenge with limited treatment options. We previously demonstrated that targeting Col1α1 eradicates oncostreams and improves survival in murine models. However, the underlying mechanisms by which collagen reshapes the glioma tumor microenvironment (TME) remain unknown. Through RNA-seq analysis we identified that DDR1, a collagen receptor, is overexpressed in genetically engineered glioma mouse models (GEMMs) including NPA (NRAS/shp53/shATRX), and NPD (NRAS/shp53/PDGFβ), compared to healthy brain tissue. Pharmacological inhibition of DDR1 enhanced radiosensitivity, disrupted oncostreams in vitro, and ex vivo, imaged with time-lapse confocal microscopy. GEMMs of DDR1 knockdown (NRAS/shp53/shATRX/shDDR1) using the Sleeping Beauty transposase system significantly increased median survival by over 50%. Gene Ontology analysis of differentially expressed genes between wild-type and DDR1 knockdown gliomas revealed enrichment in immune reactivity, cytokine-chemokine activity, and extracellular matrix. Inhibition of DDR1 enhanced intratumoral infiltration of CD45+, CD8+, and CD3+ immune cells, accompanied by a decrease in the abundance of immune-suppressive cells, suggesting that gliomas exploit DDR1-mediated mechanisms to promote immunosuppression and facilitate tumor growth. We hypothesize that DDR1 in glioma impedes immune surveillance by promoting collagen fiber alignment, as evaluated using collagen-specific second-harmonic generation microscopy. Furthermore, analysis of human datasets demonstrated a negative correlation between DDR1 expression and CD8, suggesting DDR1’s role as a key regulator of immune surveillance in gliomas. Interestingly, when DDR1 knockdown gliomas were implanted in immune deficient mouse models, NSG (NOD-scid-IL2Rγnull) or CD8−/− immune-deficient mice, no significant differences in survival were observed, indicating DDR1 expression in glioma cells dampens anti-glioma immunity. In conclusion, we propose that DDR1 within glioma cells induces an immune-inhibitory TME, reprograms cytokine and chemokine profiles, and promotes collagen fiber alignment, thus inhibiting anti-glioma immunity. Our data highlight DDR1 as a promising therapeutic target, providing a novel avenue for GBM treatment with significant potential.
TMIC-10. TGF-Β2 DRIVEN SURVIVAL IN DMG AND GBM
Authors: Trieu Vuong 
Published: November 2023

Abstract
OT-101 is being developed as immunotherapy for a broad range of cancers. Cancers overexpress TGF-β, which suppresses host innate immune response to the cancers. Treatment with OT-101 lifts the TGF-β cloaking effect and allows innate or therapeutic immunity to attack and eliminate the cancers. OT-101 completed phase 2 for pancreatic cancer and melanoma and phase 2 in glioblastoma with robust efficacy and safety. Here we are presenting data and clinical trial design for OT-101 in DMG (Diffuse Midline Glioma). ADME studies were performed on OT-101 demonstrating perfusion of the brain including the midline by either intracerebral or intraventricular administration. The studies allowed us to bridge intraventricular administration to corpus of CED administered OT-101. Safety studies were performed in two species supporting the safety of OT-101 intraventricular administration. Expression analyses of pediatric brainstem cases of the TCGA database yielded highly significant survival benefit across all four quartiles of TGF-β2 expression. This was not observed for either TGF-β1 and less so for TGF-β3. Expression analyses of all gliomas treated with radiation yielded highly significant survival benefit across all four quartiles of TGF-β2 expression. This was not observed for either TGF-β1 nor TGF-β3. In adult gliomas, OT-101 is noninferior to the most active drugs (TMZ, BCNU, or PCV) in both chemo naïve and chemo-resistant patients. In terms of overall survival when compared to standard chemotherapy (TMZ, BCNU, or PCV) in both G004 and G005 as both the hazard ratio, which was 0.9168, and the 90% upper limit of the confidence interval, which was 1.2245, were both less than the initial non-inferiority bound of 1.25. Together the data support the development of OT-101 for DMG. The phase 2 clinical trial design is being presented for OT-101 in DMG administered using Ommaya reservoir following radiation in newly diagnosed DMG
TMIC-18. CYTOMEGALOVIRUS ONCOMODULATION OF THE GLIOBLASTOMA TUMOR MICROENVIRONMENT: A ROLE FOR THE VIRAL-ENCODED GPCR, US28
Authors: Kelly Michael , Wass Amanda , Silver Daniel , Lathia Justin , O'Connor Christine 
Published: November 2023

Abstract
Glioblastoma (GBM) is a prevalent, malignant glioma, and patient prognosis is poor. Even with surgery and aggressive treatment, survival is a dismal 12-15 months. GBM therapeutic resistance is common, often resulting in tumor recurrence, due in part to cancer stem cells (CSCs) that are resistant to chemo- and radio-therapies. This highlights the need for novel treatments, which requires a deeper understanding of the GBM tumor environment. While controversial, emerging data implicate human cytomegalovirus (CMV) in GBM progression, including findings that CMV drives GBM cell proliferation. Our work confirms CMV accelerates GBM cell proliferation in vitro using patient-derived xenograft (PDX) GBM models. Intracranial injection of these infected cells into murine models also results in decreased survival relative to mock-infected cells, suggesting CMV infection influences survival in vivo. Further, we found the CMV-encoded G-protein coupled receptor (GPCR), US28, influences this, as infection of PDX-derived GBM cells in vitro with US28-deletion virus impacts cell proliferation. In murine models, we find wild type infected PDX-derived GBM cells result in a significant decrease in survival compared to mice receiving cells infected with CMV lacking US28, suggesting US28 expression confers improved overall survival in vivo. Additionally, we find expression of US28 is associated with significantly increased survival for female mice, whereas there was no statistical difference between male mice that received CMV-infected or uninfected GBM cells. This indicates CMV infection, and more specifically, US28 expression, adversely impacts survival of female mice. Collectively, our data further illuminate means by which CMV influences the GBM tumor microenvironment and survival. We are currently working to understand: 1) the impact of US28-mediated signaling pathways on the tumor microenvironment; and 2) the influence of US28 interacting partners on GBM progression, including EphA2, a receptor tyrosine kinase whose increased expression in GBM confers increased CSC invasiveness.