Resection Of Glioblastoma Research Articles

Interstitial photodynamic therapy for newly diagnosed glioblastoma

PurposeInnovative, efficient treatments are desperately needed for people with glioblastoma (GBM).MethodsSixteen patients (median age 65.8 years) with newly diagnosed, small-sized, not safely resectable supratentorial GBM underwent interstitial photodynamic therapy (iPDT) as upfront eradicating local therapy followed by standard chemoradiation. 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX was used as the photosensitizer. The tumors were irradiated with light at 635 nm wavelength via stereotactically implanted cylindrical diffuser fibers. Outcome after iPDT was retrospectively compared with a positively-selected in-house patient cohort (n = 110) who underwent complete tumor resection followed by chemoradiation.ResultsMedian progression-free survival (PFS) was 16.4 months, and median overall survival (OS) was 28.0 months. Seven patients (43.8%) experienced long-term PFS > 24 months. Median follow-up was 113.9 months for the survivors. Univariate regression revealed MGMT-promoter methylation but not age as a prognostic factor for both OS (p = 0.04 and p = 0.07) and PFS (p = 0.04 and p = 0.67). Permanent iPDT-associated morbidity was seen in one iPDT patient (6.3%). Patients treated with iPDT experienced superior PFS and OS compared to patients who underwent complete tumor removal (p < 0.01 and p = 0.01, respectively). The rate of long-term PFS was higher in iPDT-treated patients (43.8% vs. 8.9%, p < 0.01).ConclusioniPDT is a feasible treatment concept and might be associated with long-term PFS in a subgroup of GBM patients, potentially via induction of so far unknown immunological tumor-controlling processes.

Evaluation of the Efficiency of Neuronavigation in Patients with Glioblastoma

Objective: To investigate the effect of neuronavigation use on mortality in patients with glioblastoma. Methods: For each of the 26 patients that underwent neuronavigation-assisted supratotal resection for glioblastoma between 2018 and 2020, one patient that underwent supratotal resection without navigation was selected. Results: Radiographic radicality was observed in 35% of the cases in the neuronavigation-assisted surgery group and 29% of those in the conventional surgery group. Absolute and relative residual tumor volumes were significantly lower in the neuronavigation-assisted surgery group. Radical tumor resection was associated with a very significant increase in survival. There was no significant difference in the survival rates between the patients that underwent surgery with and without neuronavigation. This was attributed to the small number of participants and supratotal resection being performed in all statistically determined patients The low median survival period of glioblastoma may have also contributed to this finding. Conclusions: Surgery plays an important role in the treatment of glioblastoma. A combination of techniques including intraoperative magnetic resonance imaging, neuronavigation, ultrasound, and fluorescence guidance allows for safe and maximum surgical resection, leading to better outcomes in terms of survival and postoperative functional recovery. However, despite maximal surgical resection and adjuvant chemotherapy-radiotherapy, most cases develop tumor recurrence within 10 months, which is considered to be due to established cancer stem cells. Therefore, there is an urgent need to develop more effective treatment strategies for glioblastoma.

Supratotal Resection of Glioblastoma: Better Survival Outcome than Gross Total Resection

Supratotal resection (SupTR) of glioblastoma allows for a superior long-term disease control and increases overall survival. On the other hand, aggressive conventional approaches, including gross total resections (GTR), are limited by the impairment risk of adjacent eloquent areas, which may cause severe postoperative functional morbidity. This study aimed to analyze institutional cases with respect to the potential survival benefits of additional resection, including lobectomy, as a paradigm for SupTR in patients of glioblastoma. Between 2014 and 2018, 15 patients with glioblastoma underwent SupTR (GTR and additional lobectomy) at the authors' institution. The postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS) were analyzed for the patients. Patients with SupTR showed significantly prolonged PFS and OS. The median PFS and OS values for the entire study group were 33.5 months (95% confidence intervals (CI): 18.5-57.3 months) and 49.1 months (95% CI: 24.7-86.6 months), respectively. Multivariate analysis revealed that the O6-DNA-methylguanine methyltransferase (MGMT) promoter methylation status was the only predictor for both superior PFS (p = 0.03, OR 5.7, 95% CI 1.0-49.8) and OS (p = 0.04, OR 6.5, 95% CI 1.1-40.2). There was no significant difference between the pre- and postoperative KPS scores. Our results suggest that SupTR with lobectomy allows for a superior PFS and OS without negatively affecting patient performance. However, due to the small number of patients, further studies that include more patients are needed.

Optimization of novel exoscopic blue light filter during fluorescence-guided resection of Glioblastoma.

Operative guidelines and use optimization for new surgical exoscopes are not well described in the literature. In this study, we evaluated use of the ORBEYE (Olympus) surgical exoscope system during 5-ALA fluorescence-guided resection of GBMs to optimize workflow and exoscope settings. The ORBEYE exoscope system was fitted with a blue light filter for 5-ALA mediated fluorescence-guided surgery (FGS). Intraoperative images were obtained during 5-ALA FGS in 9 patients with primary or recurrent GBM. The exoscope was set up at constant, increasing focal distances from the target tissue, and light source intensity varied. High-resolution 4K images were captured and analyzed. Comparisons of fluorescence to background were then generated for use optimization. Light intensity did not significantly influence tumor fluorescence (P = 0.878). However, focal distance significantly impacted relative fluorescent intensity (P = 0.007). Maximum average fluorescence was seen consistently at a focal length of 220mm and a light intensity of approximately 75% maximum. Decreasing focal distance from 400mm to 220mm significantly increased visualized fluorescence (P = 0.0038). The ORBEYE surgical exoscope system with blue light filter is a powerful imaging tool for 5-ALA FGS in GBM. The ORBEYE blue filter performs optimally at shorter focal distance with moderate light intensity. Similar to microscope systems, decreasing focal distance significantly influences visualized fluorescence.

Repeat resection for recurrent glioblastoma in the temozolomide era: a real-world multi-centre study

Introduction In contrast to standard-of-care treatment of newly diagnosed glioblastoma, there is limited consensus on therapy upon disease progression. The role of resection for recurrent glioblastoma remains unclear. This study aimed to identify factors for overall survival (OS) and post-progression survival (PPS) as well as to validate an existing prediction model. Methods This was a multi-centre retrospective study that reviewed consecutive adult patients from 2006 to 2019 that received a repeat resection for recurrent glioblastoma. The primary endpoint was PPS defined as from the date of second surgery until death. Results 1032 glioblastoma patients were identified and 190 (18%) underwent resection for recurrence. Patients that had second surgery were more likely to be younger (<70 years) (adjusted OR: 0.3; 95% CI: 0.1–0.6), to have non-eloquent region tumours (aOR: 1.7; 95% CI: 1.1–2.6) and received temozolomide chemoradiotherapy (aOR: 0.2; 95% CI: 0.1–0.4). Resection for recurrent tumour was an independent predictor for OS (aOR: 1.5; 95% CI: 1.3–1.7) (mOS: 16.9 months versus 9.8 months). For patients that previously received temozolomide chemoradiotherapy and subsequent repeat resection (137, 13%), the median PPS was 9.0 months (IQR: 5.0–17.5). Independent PPS predictors for this group were a recurrent tumour volume of >50cc (aOR: 0.6; 95% CI: 0.4–0.9), local recurrence (aOR: 1.7; 95% CI: 1.1–3.3) and 5-ALA fluorescence-guided resection during second surgery (aOR: 1.7; 95% CI: 1.1–2.8). A National Institutes of Health Recurrent Glioblastoma Multiforme Scale score of 0 conferred an mPPS of 10.0 months, a score of 1–2, 9.0 months and a score of 3, 4.0 months (log-rank test, p-value < 0.05). Conclusion Surgery for recurrent glioblastoma can be beneficial in selected patients and carries an acceptable morbidity rate. The pattern of recurrence influenced PPS and the NIH Recurrent GBM Scale was a reliable prognostication tool.

A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance

Glioblastoma is among the most lethal cancers, with no known cure. A multitude of therapeutics are being developed or in clinical trials, but currently there are no ways to predict which patient may benefit the most from which drug. Assays that allow prediction of the tumor’s response to anti-cancer drugs may improve clinical decision-making. Here, we present a high-density 3D primary cell culture model for short-term testing from resected glioblastoma tissue that is set up on the day of surgery, established within 7 days and viable for at least 3 weeks. High-density 3D cultures contain tumor and host cells, including microglia, and retain key histopathological characteristics of their parent tumors, including proliferative activity, expression of the marker GFAP, and presence of giant cells. This provides a proof-of-concept that 3D primary cultures may be useful to model tumor heterogeneity. Importantly, we show that high-density 3D cultures can be used to test chemotherapy response within a 2–3-week timeframe and are predictive of patient response to Temozolomide therapy. Thus, primary high-density 3D cultures could be a useful tool for brain cancer research and prediction of therapeutic resistance.

Treatment of glioblastoma using MRIdian® A3i BrainTx™: Imaging and treatment workflow demonstration.

For patients with newly diagnosed glioblastoma, the current standard-of-care includes maximal safe resection, followed by concurrent chemoradiotherapy and adjuvant temozolomide, with tumor treating fields. Traditionally, diagnostic imaging is performed pre- and post-resection, without additional dedicated longitudinal imaging to evaluate tumor volumes or other treatment-related changes. However, the recent introduction of MR-guided radiotherapy using the ViewRay MRIdian A3i system includes a dedicated BrainTx package to facilitate the treatment of intracranial tumors and provides daily MR images. We present the first reported case of a glioblastoma imaged and treated using this workflow. In this case, a 67-year-old woman underwent adjuvant chemoradiotherapy after gross total resection of a left frontal glioblastoma. The radiotherapy treatment plan consisted of a traditional two-phase design (46 Gy followed by a sequential boost to a total dose of 60 Gy at 2 Gy/fraction). The treatment planning process, institutional workflow, treatment imaging, treatment timelines, and target volume changes visualized during treatment are presented. This case example using our institutional A3i system workflow successfully allows for imaging and treatment of primary brain tumors and has the potential for margin reduction, detection of early disease progression, or to detect the need for dose adaptation due to interfraction tumor volume changes.

Treatment of unmethylated MGMT-promoter recurrent glioblastoma with cancer stem cell assay-guided chemotherapy and the impact on patients' healthcare costs.

Glioblastoma (GBM) is a lethal disease. At least in part, the recurrence of GBM is caused by cancer stem cells (CSCs), which are resistant to chemotherapy. Personalized anticancer therapy against CSCs can improve treatment outcomes. We present a prospective cohort study of 40 real-world unmethylated Methyl-guanine-methyl-transferase-promoter GBM patients treated utilizing a CSC chemotherapeutics assay-guided report (ChemoID). Eligible patients who underwent surgical resection for recurrent GBM were included in the study. Most effective chemotherapy treatments were chosen based on the ChemoID assay report from a panel of FDA-approved chemotherapies. A retrospective chart review was conducted to determine OS, progression-free survival, and the cost of healthcare costs. The median age of our patient cohort was 53 years (24-76). Patients treated prospectively with high-response ChemoID-directed therapy, had a median overall survival (OS) of 22.4 months (12.0-38.4) with a log-rank P = .011, compared to patients who could be treated with low-response drugs who had instead an OS of 12.5 months (3.0-27.4 months). Patients with recurrent poor-prognosis GBM treated with high-response therapy had a 63% probability to survive at 12 months, compared to 27% of patients who were treated with low-response CSC drugs. We also found that patients treated with high-response drugs on average had an incremental cost-effectiveness ratio (ICER) of $48,893 per life-year saved compared to $53,109 of patients who were treated with low-response CSC drugs. The results presented here suggest that the ChemoID Assay can be used to individualize chemotherapy choices to improve poor-prognosis recurrent GBM patient survival and to decrease the healthcare cost that impacts these patients.

Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival.

Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohistochemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median peripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.

Minimized photobleaching in 5-ALA glioblastoma resection with Olympus Orbeye LED light source

Minimized photobleaching in 5-ALA glioblastoma resection with Olympus Orbeye LED light source

Supraorbital transciliary approach as primary route to fronto-basal high grade glioma resection with 5-Aminolevulinic Acid use: Technical note

BackgroundGliomas are diffuse intra-axial lesions, which can be accessed by multiple surgical corridors for a same location depending on the surgeon's preference. 5-Aminolevulinic Acid use facilitates the extend of resection in case of high-grade gliomas, especially when differentiating normal brain from tumor periphery is challenging. MethodsComplete resection of glioblastoma via a supraorbital transciliary approach with 5-Aminolevulinic Acid use was performed without any complications, as demonstrated on postoperative MRI. ResultsPatient was discharged on the third postoperative day. Wound follow-up shows good cosmetic result. Patient underwent concomitant chemo-radiation (Temozolomide- 60Gy) and adjuvant chemotherapy (Temozolomide). No tumor recurrence was noted at six months follow-up. ConclusionIn selected cases, supraorbital transciliary approach could be proposed as primary approach as it provides the advantage of full control over all the vasculo-nervous structures at skull base without the necessity of protective brain retractor use while the 5-Aminolevulinic Acid use allows a gross total resection.

ACT-15 EFFICACY AND SAFETY OF SUBTOTAL RESECTION, 'FLAIRECTOMY' FOR RECURRENT GLIOBLASTOMA

Abstract Background Aggressive resection of recurrent glioblastoma has been reported to prolong survival and should be considered for resectable recurrences. In recent years, expanded resection for primary glioblastoma, especially removal of the FLAIR hyperintensity region beyond the contrast-enhancing lesion (FLAIRectomy; FR), has been reported, but there are no reports of FR for recurrent glioblastomas. In this study, we examined the efficacy and safety of FR for recurrent glioblastoma. Methods Recurrent glioblastoma operated on at our institution from January 2014 to July 2022 were included. The extent of resection (EOR) of contrast-enhancing lesions and FLAIR hyperintensity lesion was measured. Progression-free survival (PFS), overall survival (OS), surgical morbidity, KPS, and MMSE were analyzed retrospectively. Removal of at least 20% of the FLAIR hyperintensity lesion was defined as FR. Results Thirty-five surgeries in 28 patients (age at surgery 15-81 years; median 54 years, male 20/female 15) were included. The EOR of the contrast-enhancing lesion was 96.6± 7.4%, with GTR in 28 cases and non-GTR in 7. The EOR of the lesion with FLAIR hyperintensity was 33.2±36.5% and FR was achieved in 15 cases (42.9%). The median preoperative KPS was 90 (50-100; mean 83.3 ) in the FR group and 80 (60-100; mean 81) in the non-FR group. Both PFS and OS from surgery at recurrence were significantly prolonged in the FR group (median PFS; 8.1 months vs. 4.6 months, p=0.032, median OS; 36.1 months vs. 15.9 months, p=0.009); there was no difference in PFS or OS between the GTR and non-GTR groups (p=0.33, 0.79). There were significantly fewer patients in the FR group having a decrease in KPS of 20 or more at 30/90 days postoperatively (p=0.037, 0.020). Conclusion In our retrospective analysis, FR prolongs PFS and OS without decreasing KPS for resectable recurrent glioblastoma. Further validation in prospective studies is warranted.

Photodynamic therapy in glioblastoma: Detection of intraoperative inadvertent 5-ALA mediated photodynamic therapeutical effect after gross total resection.

Glioblastoma (GBM) remains the most frequent and lethal primary brain tumor in adults, despite advancements in surgical resection techniques and adjuvant chemo- and radiotherapy. The most frequent recurrence pattern (75-90%) occurs in the form of continuous growth from the border of the surgical cavity, thus emphasizing the need for locoregional tumor control. Fluorescence-guided surgical resection using 5-ALA has been widely implemented in surgical protocols for such tumors. Recent literature also highlights the applicability of 5-ALA-mediated photodynamic therapy to obtain locoregional tumor control further. This study aims to identify if 5-ALA mediated photodynamic therapeutic effect after gross total glioblastoma resection has inadvertently occurred due to the exposition of protoporphyrin IX charged peripheral tumoral cells to operative room light sources. Of 146 patients who were intervened from glioblastoma between 2015 and 2020, 33 were included in the present study. Strict gross total resection (without supralocal resection) had been accomplished, and adjuvant chemoradiotherapy protocol was administered. Two comparison groups were created regarding the location of the recurrence (group A: up to 1 centimeter from the surgical cavity, and group B: beyond 1 centimeter from the surgical cavity). The cutoff point was determined to be 1 centimeter because of the visible light penetrance to the normal brain tissue. In univariate analysis, both groups only differed regarding 5-ALA administration, which was significantly related to a minor relative risk of presenting the recurrence within the first centimeter from the surgical cavity (Relative Risk = 0,655 (95% CI 0,442-0,970), p-value=0,046). Results obtained in univariate analysis were corroborated posteriorly in multivariate analysis (RR=0,730 (95% CI 0,340-0,980), p=0,017). In the present study, a probable inadvertent 5-ALA photodynamic therapeutical effect has been detected in vivo. This finding widely opens the door for further research on this promising theragnostic tool.

48P Phase II trial on vaccination with autologous dendritic cells loaded with autologous tumour homogenate in resected glioblastoma (COMBI-GVAX): Clinical results of the first step

Glioblastoma (GBM) is a poor prognosis malignant grade IV glioma. After surgical resection, standard therapy consists of concomitant radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Multiple phase I/II trials and at least 3 meta-analysis showed improved survival (OS) and progression free survival (PFS) with dendritic cell (DC) vaccination in high-grade gliomas (HGGs) patients (pts). In those developing antitumor immunity, DC vaccine increases the amount of intratumoral activated cytotoxic T lymphocytes and decreases the number of FoxP3 positive regulatory T cells.

Early repeat resection for residual glioblastoma: decision-making among an international cohort of neurosurgeons.

The importance of extent of resection (EOR) in glioblastoma (GBM) has been thoroughly demonstrated. However, few studies have explored the practices and benefits of early repeat resection (ERR) when residual tumor deemed resectable is unintentionally left after an initial resection, and the survival benefit of ERR is still unknown. Herein, the authors aimed to internationally survey current practices regarding ERR and to analyze differences based on geographic location and practice setting. The authors distributed a survey to the American Association of Neurological Surgeons and Congress of Neurological Surgeons Tumor Section, Society of British Neurological Surgeons, European Association of Neurosurgical Society, and Latin American Federation of Neurosurgical Societies. Neurosurgeons responded to questions about their training, practice setting, and current ERR practices. They also reported the EOR threshold below which they would pursue ERR and their likelihood of performing ERR using a Likert scale of 1-5 (5 being the most likely) in two sets of 5 cases, the first set for a patient's initial hospitalization and the second for a referred patient who had undergone resection elsewhere. The resection likelihood index for each respondent was calculated as the mean Likert score across all cases. Overall, 180 neurosurgeons from 25 countries responded to the survey. Neurosurgeons performed ERRs very rarely in their practices (< 1% of all GBM cases), with an EOR threshold of 80.2% (75%-95%). When presented with 10 cases, the case context (initial hospitalization vs referred patient) did not significantly change the surgeon ERR likelihood, although ERR likelihood did vary significantly on the basis of tumor location (p < 0.0001). Latin American neurosurgeons were more likely to pursue ERR in the provided cases. Neurosurgeons were more likely to pursue ERR when the tumor was MGMT methylated versus unmethylated, with a resection likelihood index of 3.78 and 3.21, respectively (p = 0.004); however, there was no significant difference between IDH mutant and IDH wild-type tumors. Results of this survey reveal current practices regarding ERR, but they also demonstrate the variability in how neurosurgeons approach ERR. Standardized guidelines based on future studies incorporating tumor molecular characteristics are needed to guide neurosurgeons in their decision-making on this complicated issue.

Racial disparities in recommendations for surgical resection of primary brain tumours: a registry-based cohort analysis

Disparities in treatment and outcomes disproportionately affect minority ethnic and racial populations in many surgical fields. Although substantial research in racial disparities has focused on outcomes, little is known about how surgeon recommendations can be influenced by patient race. The aim of this study was to investigate racial and socioeconomic disparities in the surgical management of primary brain tumors. In this registry-based cohort study, we used data from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) and the American College of Surgeons National Cancer Database (NCDB) in the USA for independent analysis. Adults (aged ≥20 years) with a new diagnosis of meningioma, glioblastoma, pituitary adenoma, vestibular schwannoma, astrocytoma, and oligodendroglioma, with information on tumour size and surgical recommendation were included in the analysis. The primary outcome of this study was the odds of a surgeon recommending against surgical resection at diagnosis of primary brain neoplasms. This outcome was determined using multivariable logistic regression with clinical, demographic, and socioeconomic factors. This study included US national data from the SEER (1975-2016) and NCDB (2004-17) databases of adults with a new diagnosis of meningioma (SEER n=63 674; NCDB n=222 673), glioblastoma (n=35 258; n=104 047), pituitary adenoma (n=27 506; n=87 772), vestibular schwannoma (n=11 525; n=30 745), astrocytoma (n=5402; n=10 631), and oligodendroglioma (n=3977; n=9187). Independent of clinical and demographic factors, including insurance status and rural-urban continuum code, Black patients had significantly higher odds of recommendation against surgical resection of meningioma (adjusted odds ratio 1·13, 95% CI 1·06-1·21, p<0·0001), glioblastoma (1·14, 1·01-1·28, p=0·038), pituitary adenoma (1·13, 1·05-1·22, p<0·0001), and vestibular schwannoma (1·48, 1·19-1·84, p<0·0001) when compared with White patients in the SEER dataset. Additionally, patients of unknown race had significantly higher odds of recommendation against surgical resection for pituitary adenoma (1·80, 1·41-2·30, p<0·0001) and vestibular schwannoma (1·49, 1·10-2·04, p=0·011). Performing a validation analysis using the NCDB dataset confirmed these significant results for Black patients with meningioma (1·18, 1·14-1·22, p<0·0001), glioblastoma (1·19, 1·12-1·28, p<0·0001), pituitary adenoma (1·21, 1·16-1·25, p<0·0001), and vestibular schwannoma (1·19, 1·04-1·35, p=0·0085), and indicated and indicated that the findings are independent of patient comorbidities. When further restricted to the most recent decade in SEER, these inequities held true for Black patients, except those with glioblastoma (meningioma [1·18, 1·08-1·28, p<0·0001], pituitary adenoma [1·20, 1·09-1·31, p<0·0001], and vestibular schwannoma [1·54, 1·16-2·04, p=0·0031]). Racial disparities in surgery recommendations in the USA exist for patients with primary brain tumours, independent of potential confounders including clinical, demographic, and select socioeconomic factors. Further studies are needed to understand drivers of this bias and enhance equality in surgical care. None.

Impact of maximal extent of resection on postoperative deficits, patient functioning, and survival within clinically important glioblastoma subgroups.

The impact of extent of resection (EOR), residual tumor volume (RTV), and gross-total resection (GTR) in glioblastoma subgroups is currently unknown. This study aimed to analyze their impact on patient subgroups in relation to neurological and functional outcomes. Patients with tumor resection for eloquent glioblastoma between 2010 and 2020 at 4 tertiary centers were recruited from a cohort of 3919 patients. One thousand and forty-seven (1047) patients were included. Higher EOR and lower RTV were significantly associated with improved overall survival (OS) and progression-free survival (PFS) across all subgroups, but RTV was a stronger prognostic factor. GTR based on RTV improved median OS in the overall cohort (19.0months, P<.0001), and in the subgroups with IDH wildtype tumors (18.5months, P=.00055), MGMT methylated tumors (35.0months, P<.0001), aged <70 (20.0months, P<.0001), NIHSS 0-1 (19.0months, P=.0038), KPS 90-100 (19.5months, P=.0012), and KPS ≤80 (17.0months, P=.036). GTR was significantly associated with improved OS in the overall cohort (HR 0.58, P=.0070) and improved PFS in the NIHSS 0-1 subgroup (HR 0.47, P=.012). GTR combined with preservation of neurological function (OFO 1 grade) yielded the longest survival times (median OS 22.0months, P<.0001), which was significantly more frequently achieved in the awake mapping group (50.0%) than in the asleep group (21.8%) (P<.0001). Maximum resection was especially beneficial in the subgroups aged <70, NIHSS 0-1, and KPS 90-100 without increasing the risk of postoperative NIHSS or KPS worsening. These findings may assist surgical decision making in individual glioblastoma patients.

The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain.

The central nervous system (CNS) antigen-presenting cell (APC) that primes antitumor CD8+ T-cell responses remains undefined. Elsewhere in the body, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain parenchyma cDC1 are extremely rare; cDCs localize to the choroid plexus and dura. Thus, whether the cDC1 play a function in presenting antigen derived from parenchymal sources in the tumor setting remains unknown. Using preclinical glioblastoma (GBM) models and cDC1-deficient mice, we explored the presently unknown role of cDC1 in CNS antitumor immunity. We determined that, in addition to infiltrating the brain tumor parenchyma itself, cDC1 prime neoantigen-specific CD8+ T cells against brain tumors and mediate checkpoint blockade-induced survival benefit. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor antigen. In patient samples, we observed several APC subsets (including the CD141+ cDC1 equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same APC subsets, we identified a tumor-specific fluorescent metabolite of 5-aminolevulinic acid, which fluorescently labeled tumor cells during fluorescence-guided GBM resection. Together, these data elucidate the specialized behavior of cDC1 and suggest that cDC1 play a significant role in CNS antitumor immunity.

SURG-19. PROGNOSTIC VALIDATION OF A NEW CLASSIFICATION SYSTEM FOR EXTENT OF RESECTION IN GLIOBLASTOMA: A REPORT OF THE RANO RESECT GROUP

Abstract BACKGROUND Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (I) explore the prognostic utility of the classification system and (II) define how much removed non-CE tumor translates into a survival benefit. METHODS The international RANO resect group retrospectively searched the databases from seven neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and post-operative MRI were collected. RESULTS We collected 1021 patients with newly diagnosed glioblastoma, including 1008 IDHwt patients. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC 26981/22981 (TMZ/RT→TMZ) following surgery. Among such homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with ‘maximal CE resection’ (class 2) had superior outcome compared to patients with ‘submaximal CE resection’ (class 3) or ‘biopsy’ (class 4) (median OS: 19 versus 15 versus 10 months; p=0.001). Extensive resection of non-CE tumor (≤ 5 cm3 residual non-CE tumor) provided an additional survival benefit in patients with complete CE resection, thus defining class 1 (‘supramaximal CE resection’) (median OS: 24 versus 19 months; p=0.008). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers including MGMT promotor status. Relative tumor reduction (in percentage) was not prognostic for outcome on multivariate analysis, and inter-rater agreement for CE and non-CE tumor on post-operative MRI was sufficient. CONCLUSION The proposed “RANO categories for extent of resection in glioblastoma” are highly prognostic and may serve for stratification of clinical trials. Removal of non-CE tumor beyond the CE tumor borders translates into additional survival benefit, providing a rationale to explicitly denominate such a ‘supramaximal CE resection’.

BIOM-44. MAGNETIC RESONANCE IMAGING MAPPING OF BRAIN TUMOR BURDEN TO EVALUATE RESPONSE TO PULSED LOW-DOSE-RATE RADIOTHERAPY FOLLOWING RESECTION OF GLIOBLASTOMA MULTIFORME: A 4-PATIENT CASE SERIES

Abstract BACKGROUND Pulsed low-dose-rate radiotherapy (pLDR) is an accepted reirradiation technique for recurrent glioma, but its upfront use, concurrent with temozolomide (TMZ) following resection of high-grade glioma is currently under investigation. Evaluating the response to upfront radiation can be challenging and there is limited data on expected rates of pseudoprogression with pLDR. Standard magnetic resonance imaging (MRI) has limitations in differentiating pseudoprogression from tumor progression, sometimes necessitating surgery for pathologic confirmation. Advanced MRI can be used to create fractional tumor burden (FTB) maps that spatially distinguish active tumor from treatment-related effect (pseudoprogression), perhaps providing a more reliable imaging biomarker in the absence of additional surgery. METHODS We performed a retrospective chart review to report the responses of four patients with glioblastoma to upfront pLDR and TMZ following resection. Each patient received advanced surveillance MRI and redo surgery. Tumor pathology included IDH-wild type (n = 4) and O6-methylguanine-DNA methyltransferase (MGMT) methylated (n = 1) tumors. RESULTS The median age of patients was 57.5 years (range 55-60 years) and all were male. One patient experienced mortality and another was transitioned to hospice. In all four cases, there were concerns of tumor progression in postcontrast MRI. Pathologic diagnosis revealed either treatment effect (n = 2) or tumor (n = 2). FTB maps were predominantly indicative of lesion volumes being comprised of treatment effect (n = 3) and tumor (n = 1). From the three FTB maps in the former category, the median fraction of the enhancing tumor volume comprised of vascular tumor was 6.4% (range 1.8-6.8%). CONCLUSION This case series provides insight into response to upfront pLDR and TMZ following resection of glioblastoma and demonstrates the capacity for FTB mapping to spatially distinguish tumor progression from treatment effect in this patient population.