Postoperative Tumor Volume Research Articles

Surgical cytoreduction of deep-seated high-grade glioma through tubular retractor.

Maximal safe resection is the goal of surgical treatment for high-grade glioma (HGG). Deep-seated hemispheric gliomas present a surgical challenge due to safety concerns and previously were often considered inoperable. The authors hypothesized that use of tubular retractors would allow resection of deep-seated gliomas with an acceptable safety profile. The purpose of this study was to describe surgical outcomes and survival data after resection of deep-seated HGG with stereotactically placed tubular retractors, as well as to discuss the technical advances that enable such procedures. This is a retrospective review of 20 consecutive patients who underwent 22 resections of deep-seated hemispheric HGG with the Viewsite Brain Access System by a single surgeon. Patient demographics, survival, tumor characteristics, extent of resection (EOR), and neurological outcomes were recorded. Cannulation trajectories and planned resection volumes depended on the relative location of white matter tracts extracted from diffusion tractography. The surgical plans were designed on the Brainlab system and preoperatively visualized on the Surgical Theater virtual reality SNAP platform. Volumetric assessment of EOR was obtained on the Brainlab platform and confirmed by a board-certified neuroradiologist. Twenty adult patients (18 with IDH-wild-type glioblastomas and 2 with IDH-mutant grade IV astrocytomas) and 22 surgeries were included in the study. The cohort included both newly diagnosed (n = 17; 77%) and recurrent (n = 5; 23%) tumors. Most tumors (64%) abutted the ventricular system. The average preoperative and postoperative tumor volumes measured 33.1 ± 5.3 cm3 and 15.2 ± 5.1 cm3, respectively. The median EOR was 93%. Surgical complications included 2 patients (10%) who developed entrapment of the temporal horn, necessitating placement of a ventriculoperitoneal shunt; 1 patient (5%) who suffered a wound infection and pulmonary embolus; and 1 patient (5%) who developed pneumonia. In 2 cases (9%) patients developed new permanent visual field deficits, and in 5 cases (23%) patients experienced worsening of preoperative deficits. Preoperative neurological or cognitive deficits remained the same in 9 cases (41%) and improved in 7 (32%). The median overall survival was 14.4 months in all patients (n = 20) and in the newly diagnosed IDH-wild-type glioblastoma group (n = 16). Deep-seated HGGs, which are surgically challenging and frequently considered inoperable, are amenable to resection through tubular retractors, with an acceptable safety profile. Such cytoreductive surgery may allow these patients to experience an overall survival comparable to those with more superficial tumors.

Role of extent of resection on the survival of glioblastoma multiforme

Background. Glioblastoma Multiforme (GBM) is the most prevalent form of brain cancer. The effect of Extent of Resection (EOR) on GBM survival is controversial. EOR degree, pre- and postoperative tumour volume estimation, and significance to residual tumour volume are still challenged. GBM has a 14-month Overall Survival (OS) rate. There is no evidence of a link between EOR and OS survival. We wish to determine whether GBM tumour removal increases survival. Methods. At the Regional Center for Neurosurgery and Neurology in Uzhhorod, Ukraine, we conducted a retrospective evaluation of 86 consecutive patients diagnosed with glioblastoma who underwent surgery between January 1, 2010, and December 31, 2020, and who are being followed until January 1, 2022. Patients were selected if they met the following criteria: they were at least 18 years old, they had a diagnosis of glioblastoma (primary, secondary, or recurrent), they were either IDH mutants or wild types, they had an MRI within 2 weeks before surgery, and they had another MRI within 72 hours after surgery. Before and after surgery, we did a volumetric analysis of gadolinium-enhanced T1 MRI scans of the tumour to figure out EOR. Partial resection (PR) is <70%, sub-total resection (STR) is 70-90%, near-total resection (NTR) is 91-99%, and gross total resection (GTR) is >99%. By comparing pre- and post-operative volumes with the EOR, the Kaplan-Meier survival curve and Cox's regression analysis determined the impact of the EOR on survival rates. Many researchers considered a p value of 0.05 or below to be significant. Results. A total of 86 patients were included in the analysis after being subjected to the criteria used to narrow the pool of potential participants. The average length of time people lived was 15 months. For PR patients, the median survival time was 3 months, for STR patients it was 10 months, and for NTR patients it was 16 months. Patients receiving GTR, on the other hand, had a considerably better outcome, with a median survival time of 36 months. This data demonstrate a direct correlation between EOR and survival rates. It was discovered that EOR improvement affected post-op survival. High EOR patients have a better prognosis for survival. Adjuvant therapy, pre- and post-operative KPS score, pre- and post-operative tumour volume, and gender also contributed significantly to enhanced survival. Conclusion. Patients with glioblastoma appear to benefit from a more aggressive treatment strategy that combines maximal safe resection with the use of salvage adjuvant therapy. There was a correlation between complete resection (gross total resection) of intracranial GBM and improved survival. Whenever feasible, complete surgical removal of the tumour is recommended.

Endoscopic endonasal transsphenoidal surgery for pituitary adenomas

Endoscopic endonasal transsphenoidal surgery (EETS) is a widely accepted technique for the surgical resection of pituitary tumours. In this report, we present our single-centre experience with EETS for pituitary adenomas, mainly focusing on its efficacy and postoperative complications. Among 100 patients who underwent EETS, 57 (57%) were female and 43 were (43%) male. The mean age of the patients was 51.55 ± 13.51 years. Nonfunctional adenoma was found in 61 (61%) patients, acromegaly was found in 29 (29%) patients, Cushing’s disease in six (6%), and prolactinoma was found in four (4%) patients. On average, a 75.8% decrease in the postoperative tumour volume was observed in nonfunctional adenomas. Surgical cure was achieved in 51.7% of patients with acromegaly, 50% of those with Cushing’s disease, and 25% of those with prolactinoma. The most common postoperative complication was found to be cerebrospinal fluid fistula.

Fluorescein-guided surgery for high-grade glioma resection: a five-year-long retrospective study at our institute.

This study investigates the extent of resection, duration of surgery, intraoperative blood loss, and postoperative complications in patients with high-grade glioma who received surgery with or without sodium fluorescein guidance. A single-center retrospective cohort study was conducted on 112 patients who visited our department and underwent surgery between July 2017 and June 2022, with 61 in the fluorescein group and 51 in the non-fluorescein group. Baseline characteristics, intraoperative blood loss, surgery duration, resection extent, and postoperative complications were documented. The duration of surgery was significantly shorter in the fluorescein group than in the non-fluorescein group (P = 0.022), especially in patients with tumors in the occipital lobes (P = 0.013). More critically, the gross total resection (GTR) rate was significantly higher in the fluorescein group than in the non-fluorescein group (45.9% vs. 19.6%, P = 0.003). The postoperative residual tumor volume (PRTV) was also significantly lower in the fluorescein group than in the non-fluorescein group (0.40 [0.12-7.11] cm3 vs. 4.76 [0.44-11.00] cm3, P = 0.020). Particularly in patients with tumors located in the temporal and occipital lobes (temporal, GTR 47.1% vs. 8.3%, P = 0.026; PRTV 0.23 [0.12-8.97] cm3 vs. 8.35 [4.05-20.59] cm3, P = 0.027; occipital, GTR 75.0% vs. 0.0%, P = 0.005; PRTV 0.15 [0.13-1.50] cm3 vs. 6.58 [3.70-18.79] cm3, P = 0.005). However, the two groups had no significant difference in intraoperative blood loss (P = 0.407) or postoperative complications (P = 0.481). Fluorescein-guided resection of high-grade gliomas using a special operating microscope is a feasible, safe, and convenient technique that significantly improves GTR rates and reduces postoperative residual tumor volume when compared to conventional white light surgery without fluorescein guidance. This technique is particularly advantageous for patients with tumors located in non-verbal, sensory, motor, and cognitive areas such as the temporal and occipital lobes, and does not increase the incidence of postoperative complications.

Prognostic evaluation of surgical re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection: A report of the RANO resect group.

2010 Background: The clinical effects of re-resection for recurrent glioblastoma remain controversial, and the role of post-operative tumor volume is unclear since leaving certain tumor volumes deliberately behind cannot be ethically justified. A surgical classification system was previously proposed for stratification based upon residual contrast-enhancing (CE) tumor: RANO class 1 was defined as ‘supramaximal CE resection’ (including non-CE tumor removal), class 2 as ‘maximal CE resection’, class 3 as ‘submaximal CE resection’, and class 4 as ‘biopsy’. We aimed to (I) explore the prognostic role of extent of re-resection using this classification and (II) define clinical factors which consolidate the effects of re-resection. Methods: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with first recurrence from a previously resected glioblastoma. The combined associations of re-resection and clinical factors with outcome were analyzed. Kaplan-Meier survival analysis and log-rank test were applied to calculate survival, and Cox’s proportional hazard regression models to adjust for multiple variables (significance level: p ≤ 0.05). A propensity score-matched analysis was constructed to mimic a randomized clinical trial comparing the different RANO classes. Results: We encountered 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 on multivariate analysis including pre-operative tumor volume, MGMT promotor status, and non-surgical therapies (HR: 0.65, CI: 0.5-0.8; p = 0.001); 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) (median OS 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. Conclusions: Extent of resection for recurrent glioblastoma as quantified by residual CE tumor is highly prognostic and the RANO resect classification may serve to stratify patients accordingly. Chemotherapy may favorably contribute to the prognostic associations of re-resection. When pursuing resection of non-CE tumor, intraoperative mapping strategies to minimize the risk of post-operative deficits are recommended.

Brain metastases in the elderly - Impact of residual tumor volume on overall survival.

Due to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival. The aim of this study was to analyze the impact of resection and residual tumor volume on clinical outcome and overall survival (OS) in elderly patients suffering from BM. Patients ≥ 75 years who had surgery for BM between April 2007 and January 2020 were retrospectively included. Residual tumor burden (RTB) was determined by segmentation of early postoperative brain MRI (72h). Contrast-enhancing tumor subvolumes were segmented manually. "Postoperative tumor volume" refers to the targeted BMs. Impact of preoperative Karnofsky performance status scale (KPSS), age, sex and RTB on OS was analyzed. Survival analyses were performed using Kaplan-Meier estimates for the univariate analysis and the Cox regression proportional hazards model for the multivariate analysis. One hundred and one patients were included. Median age at surgery was 78 years (IQR 76-81). Sixty-two patients (61%) had a single BM; 16 patients (16%) had two BMs; 13 patients (13%) had three BMs; and 10 patients (10%) had more than three BMs. Median preoperative tumor burden was 10.3 cm3 (IQR 5-25 cm3), and postoperative tumor burden was 0 cm3 (IQR 0-1.1 cm3). Complete cytoreduction (RTB = 0) was achieved in 52 patients (52%). Complete resection of the targeted metastases was achieved in 78 patients (78%). Median OS was 7 months (IQR 2-11). In univariate analysis, high preoperative KPSS (HR 0.986, 95% CI 0.973-0.998, p = 0.026) and small postoperative tumor burden (HR 1.025, 95% CI 1.002-1.047, p = 0.029) were significantly associated with prolonged OS. Patients with RTB = 0 survived significantly longer than those with residual tumor did (12 [IQR 5-19] vs. 5 [IQR 3-7] months, p = 0.007). Furthermore, prolongation of survival was significantly associated with surgery in patients with favorable KPSS, with an adjusted HR of 0.986 (p = 0.026). However, there were no significances regarding age. RTB is a strong predictor for prolonged OS, regardless of age or cancer type. Postoperative MRI should confirm the extent of resection, as intraoperative estimates do not warrant a complete resection. It is crucial to aim for maximal cytoreduction to achieve the best long-term outcomes for these patients, despite the fact the patients are advanced in age.

Volumetric measurement of paranasal sinuses and its clinical significance in pituitary neuroendocrine tumors operated using an endoscopic endonasal approach.

Endoscopic endonasal surgery (EES) for deep intracranial lesions has gained popularity following recent developments in endoscopic technology. The operability of invasive pituitary neuroendocrine tumors (PitNETs) depends on the anatomy of the nasal cavity and paranasal sinus. This study aimed to establish a simple volume reconstruction algorithm of the nasal cavity and paranasal sinus. Additionally, this is the first study to demonstrate the relationship between the segmentation method and the clinical significance in patients with PitNET. Pre-and postoperative tumor volumes were analyzed in 106 patients with primary (new-onset) PitNETs (80 nonfunctioning and 26 functioning) who underwent EES. The efficiency and accuracy of the semiautomatic segmentation with manual adjustments (SSMA) method was compared with other established segmentation methods for volumetric analysis in the nasal cavity and paranasal sinuses. Correlations between the measured nasal cavity and paranasal sinus volumes and the extent of tumor removal were evaluated. The SSMA method yielded accurate and time-saving results following the volumetric analyses of nasal cavity and paranasal sinuses with complex structures. Alternatively, the manual and semiautomatic segmentation methods proved time-consuming and inaccurate, respectively. The sphenoid sinus volume measured by SSMA was significantly correlated with the extent of tumor removal in patients with nonfunctioning Knosp grade 3 and 4 PitNET (r = 0.318; p = 0.015). The volume of sphenoid sinus potentially could predict the extent of resection due to better visualization of the tumor for PitNETs with CS invasion.

Analysis of Imaging Results for Semisitting Compared with Supine Positioning in the Retrosigmoid Approach for Resection of Cerebellopontine Angle Vestibular Schwannomas.

To compare the completeness of resection of vestibular schwannomas using three-dimensional segmented volumetric analysis of pre- and postoperative magnetic resonance imaging (MRI) of patients undergoing supine and semisitting positioning for the retrosigmoid approach. Retrospective chart review. Tertiary medical center. Patients with vestibular schwannomas undergoing surgical resection via the retrosigmoid approach. Tumor resection via the retrosigmoid approach with different patient positioning: standard supine versus semisitting. Preoperative versus postoperative three-dimensional segmented volumetric MRI analysis of vestibular schwannomas. A total of 43 patients (15 supine and 28 semisitting) underwent retrosigmoid craniotomy for resection of vestibular schwannomas. For the conventional supine and semisitting positioning, mean preoperative tumor volumes were 12.65 and 8.73 cm 3 ( p = 0.15), respectively. Postoperative mean tumor volumes for the supine and semisitting positions were 2.09 and 0.48 cm 3 ( p = 0.13), respectively. There were 11 cases of postoperative sigmoid sinus thrombosis, 3 in the conventional supine group and 8 in the semisitting groups, and there were 6 cases of postoperative cerebrospinal fluid leaks, all in the semisitting group. The mean House-Brackmann scores for the supine and semisitting groups were 2.9 and 2.3, respectively. There was no statistically significant difference between groups in the rates of these or any other postoperative complications. The semisitting position for the suboccipital retrosigmoid approach for vestibular schwannoma resection does not compromise the ability to adequately resect the tumor as seen by volumetric MRI results. Further studies are needed to establish the safety of this position compared with the traditional supine approach.

Isocitrate-dehydrogenase-mutant lower grade glioma in elderly patients: treatment and outcome in a molecularly characterized contemporary cohort

PurposeLower-grade glioma (LGG) is rare among patients above the age of 60 (“elderly”). Previous studies reported poor outcome, likely due to the inclusion of isocitrate dehydrogenase (IDH) wildtype astrocytomas and advocated defensive surgical and adjuvant treatment. This study set out to question this paradigm analyzing a contemporary cohort of patients with IDH mutant astrocytoma and oligodendroglioma WHO grade 2 and 3.MethodsElderly patients treated in our department for a supratentorial, hemispheric LGG between 2009 and 2019 were retrospectively analyzed for patient-, tumor- and treatment-related factors and progression-free survival (PFS) and compared to patients aged under 60. Inclusion required the availability of subtype-defining molecular data and pre- and post-operative tumor volumes.Results207 patients were included, among those 21 elderlies (10%). PFS was comparable between elderly and younger patients (46 vs. 54 months; p = 0.634). Oligodendroglioma was more common in the elderly (76% vs. 46%; p = 0.011). Most patients underwent tumor resection (elderly: 81% vs. younger: 91%; p = 0.246) yielding comparable residual tumor volumes (elderly: 7.8 cm3; younger: 4.1 cm3; p = 0.137). Adjuvant treatment was administered in 76% of elderly and 61% of younger patients (p = 0.163). Uni- and multi-variate survival analyses identified a tumor crossing the midline, surgical strategy, and pre- and post-operative tumor volumes as prognostic factors.ConclusionElderly patients constitute a small fraction of molecularly characterized LGGs. In contrast to previous reports, favorable surgical and survival outcomes were achieved in our series comparable to those of younger patients. Thus, intensified treatment including maximal safe resection should be advocated in elderly patients whenever feasible.

SURG-39. SURGICAL RESULTS AND LONG-TERM OUTCOME IN SUPRATENTORIAL INTRAVENTRICULAR TUMORS

Abstract BACKGROUND Intraventricular tumors (IVTs) are rare lesions of various entities, which pose a surgical challenge. We aimed to elaborate on surgical approaches and outcomes, postoperative morbidity, and elucidate whether preoperative hydrocephalus necessitates shunting despite surgical resection. METHODS We retrospectively searched the institutional database for patients with supratentorial intraventricular tumours that were treated in the Department of Neurosurgery of the Ludwig-Maximilians-University Munich, Germany between 2014 and 2022. RESULTS We identified 59 patients with supratentorial intraventricular tumors comprising over 15 different tumor entities, most often subependymoma (8/59 patients, 14%). Median age at diagnosis was 41.4 years (range 0-86 years) with 31 male patients (53%) and 28 female patients (48%). Microsurgical tumor resection was completed in 46/59 patients (78%) with incomplete tumor resection (≥ 1ml postoperative tumor volume) in 13/46 patients (28%) and complete tumor resection (< 1ml postoperative tumor volume) in 33/46 patients (72%). In cases where neurosurgical tumor resection was not feasible, stereotactic biopsy was provided in 13/59 patients (22%), often combined with stereotactic internal shunt implantation (5/59 patients, 8%). Mean follow-up was 24 months; median overall survival was not reached. Postoperative persistent hydrocephalus necessitating ventriculoperitoneal shunt placement was rare (5/59 patients, 8%). Ventriculocisternostomy was performed in one patient. New postoperative focal neurological deficits – mostly transient – were encountered in 16/59 patients (27%) at discharge with mild to moderate permanent focal neurological deficits at 3 months in 3/59 patients (5%). CONCLUSION Complete resection of IVT can often be achieved and forms the basis for favourable outcome. Permanent neurological deficits are rare, and hydrocephalus can almost always be alleviated which prevents the need for long-term shunting. If microsurgical resection is not feasible, stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms.

SURG-17. PROGNOSIS IN IDH-MUTANT GLIOMA: THE ROLE OF EXTENT-OF-RESECTION, AGE AND TUMOR GRADE

Abstract BACKGROUND Evidence suggests that smaller residual tumor volumes after initial surgery are associated with longer survival in patients with astrocytoma, IDH-mutant, grade II. For IDH-mutant glioma of higher grade but also for oligodendroglioma, IDH-mutant, and 1p/19q codeleted, the impact of residual tumor volume on survival is unclear. This could be related to the limited follow-up of patients with oligodendroglioma that typically have long overall survival. We expanded a previously published series of patients increase the duration of follow-up and the spectrum of tumor grades. METHODS Single center observational cohort study of patients with adult-type diffuse glioma, IDH-mutant, all WHO-2021 grades, from 2003 to 2021 . Molecular characteristics were assessed by next-generation targeted sequencing. Tumor volumes were calculated by semi-automatic 3D segmentation on pre- and postoperative MRI-scans. Associations between prognostic factors and survival were assessed using univariate and multivariate Cox proportional hazards models. RESULTS 384 patients with IDH-mutant glioma (174 oligodendroglioma, 212 astrocytoma) were followed for a median of 7 years. Median age at diagnosis was 41 years (IQR 33 – 55). Significant prognostic factors for survival were Karnofsky performance status, 1p19q-status and post-operative tumor volume. Smaller post-operative tumor volume was associated with better survival, both in astrocytoma and oligodendroglioma. Age, tumor grade and MRI-contrast enhancement were not associated with survival. CONCLUSION Lower residual tumor volume after first surgery is a strong prognostic factor in all IDH-mutant glioma subgroups, even in patients with very small residual tumor. Importantly, age and histological tumor grade were not significantly associated with survival. The data serves as further support for optimal initial resections of tumors suspected for IDH-mutant glioma, also in oligodendroglioma.

CNSC-07. MECHANISMS OF GLIOBLASTOMA-INDUCED CORTICAL REMODELING IDENTIFY THERAPEUTIC VULNERABILITIES

Abstract Prior work demonstrated synaptic integration of malignant gliomas into neural circuits induces local hyperexcitability and tumor proliferation. However, prognostication and therapeutic vulnerabilities are lacking from preclinical models. Here, we integrate in vivo and in vitro neurophysiology spatially matched with gene expression programs and protein signaling mechanisms across 66 IDH WT glioblastoma patients to identify thrombospondin-1 (TSP-1) as a molecular driver of glioma-induced network remodeling. Bulk and single cell RNA-sequencing of 11 intratumoral regions maintaining functional connectivity (13,730 cells analyzed) revealed a distinct neurogenic signature enriched for the synaptogenic factor TSP-1. Mechanistic and functional studies validating therapeutic vulnerabilities to TSP-1 silencing by shRNA knockdown and FDA-approved inhibitors (Gabapentin and LSKL) of excitatory synapse formation through the gabapentin a2d-1 receptor was performed in vitro and in vivo. Glioma-neuron co-culture of TSP-1 overexpressing cells demonstrated increased Ki67 proliferation and tumor microtube (TMT) formation when cultured in the presence of neurons. Pharmacological inhibition of TSP-1 using gabapentin or TSP-1 shRNA inhibited the proliferation and TMT-mediated expansion. Hippocampal xenografted mice with TSP-1 over expressing primary patient cultures demonstrated shorter survival and gabapentin treatment of xenografted mice significantly reduced the proliferation of TSP-1 overexpressing cells in vivo. Electrophysiological properties of glioma-neuron co-cultures analyzed using multi-electrode array (MEA) demonstrated increased neuronal spiking activity and network burst synchrony in the presence of TSP-1 over expressing cells. Strikingly, these increases were eliminated in the presence of gabapentin. We modeled survival risk in patients incorporating the effects of glioma intrinsic neuronal activity, molecular, therapeutic, and clinical factors on overall survival by recursive partitioning. Three risk groups were identified based on tumor intrinsic neuronal activity, pre- and post-operative tumor volume with shortest overall survival in patients with glioma intrinsic neuronal activity. These data identify glioma-induced secretion of TSP-1 as a key contributor of tumor proliferation shedding light on new therapies.

RADT-08. DOSIMETRIC FEASIBILITY OF DIRECT POST-OPERATIVE MRI-LINAC-BASED STEREOTACTIC RADIOSURGERY FOR RESECTION CAVITIES OF BRAIN METASTASES

Abstract Background Post-operative stereotactic radiosurgery (SRS) of patients with brain metastases with single resection cavities is typically planned on a post-recovery MRI, 4-6 weeks after resection. However, meanwhile the intracranial metastasis may (re-)grow, and postponing adjuvant systemic treatment increases chance on extracranial progression as well. Anticipating direct post-operative SRS to minimize this interval would enable rapid start of systemic therapy. In this study, we considered treatment with MRI-Linac (MRL) SRS, because of the possibility to execute the post-operative MRI and SRS treatment combined on the MRL instead of on two separate systems, improving logistics and increasing patient comfort. However, it is unclear whether MRL-based SRS may be feasible from a dosimetric perspective. This study aims to shed light on the dosimetric feasibility of MRL-based SRS. METHODS We simulated MRL treatments including thirteen patients with resectable single brain metastases treated with single fraction CT-Linac (CTL) SRS. We therefore contoured direct post-operative gross tumor volumes (GTV) and compared them to post-recovery MRI GTV. Next, we compared a non-coplanar VMAT technique for CTL (ncVMAT) to a coplanar IMRT technique for MRL (cIMRT), creating three plans per patient: a ncVMAT plan and a cIMRT plan for the direct post-operative GTV, and a post-recovery ncVMAT plan as current clinical standard. RESULTSCompared to GTVs defined on direct post-operative MRI, on post-recovery MRI 15.5% of cavities shrunk by > 2cc, and 46% expanded by > 2cc. Although direct post-operative ncVMAT plans had lower median gradient index and higher median V3Gy of the skin, they were clinically acceptable according to clinical guidelines. CONCLUSION Although slightly inferior to non-coplanar CTL plans, direct post-operative MRL-based SRS for resection cavities of brain metastases is dosimetrically acceptable, at the trade-off between increased patient comfort and logistics. Additionally, MRL-based SRS enables substantially earlier start with adjuvant systemic therapies, thereby maximizing tumor control.

Mind the gap—the use of sodium fluoresceine for resection of brain metastases to improve the resection rate

Introduction and purposeBrain metastases appear to be well resectable due to dissectable tumor margins, but postoperative MRI quite often depicts residual tumor with potential influence on tumor control and overall survival. Therefore, we introduced sodium fluoresceine into the routine workflow for brain metastasis resection. The aim of this study was to evaluate whether the use of fluorescence-guided surgery has an impact on postoperative tumor volume and local recurrence.Material and methodsWe retrospectively included patients who underwent surgical resection for intracranial metastases of systemic cancer between 11/2017 and 05/2021 at our institution. Tumor volumes were assessed pre- and postoperatively on T1-CE MRI. Clinical and epidemiological data as well as follow-up were gathered from our prospective database.ResultsSeventy-nine patients (33 male, 46 female) were included in this study. Median preoperative tumor volume amounted to 11.7cm3 and fluoresceine was used in 53 patients (67%). Surgeons reported an estimated gross total resection (GTR) in 95% of the cases, while early postoperative MRI could confirm GTR in 72%. Patients resected using fluoresceine demonstrated significantly lower postoperative residual tumor volumes with a difference of 0.7cm3 (p = 0.044) and lower risk of local tumor recurrence (p = 0.033). The use of fluorescence did not influence the overall survival (OS). Postoperative radiotherapy resulted in a significantly longer OS (p = 0.001).DiscussionWhile GTR rates may be overrated, the use of intraoperative fluorescence may help neurosurgeons to achieve a more radical resection. Fluoresceine seems to facilitate surgical resection and increase the extent of resection thus reducing the risk for local recurrence.

Comparison of sodium fluorescein and intraoperative ultrasonography in brain tumor resection

Various intraoperative neuroimaging modalities are available to the neurosurgeon during brain tumor surgery. There remains no consensus on which modalities are superior. This retrospective, single-center cohort study directly compares sodium fluorescein (SF) and intraoperative ultrasonography (IOUS) as intraoperative imaging modalities in a sample of patients with glioblastoma isocitrate dehydrogenase 1 wildtype (GBM). Adult patients with GBM who underwent surgical resection using SF or IOUS guidance between 2010 and 2020 were included. Primary outcomes included extent of resection (EOR), post-operative residual tumor volume, gross total resection (GTR) rate, false negative assessments, and the incidence of new post-operative neurologic deficits. Additionally, pre-and post-test probabilities were calculated to assess each modality’s ability to identify residual tumor. 98 patients met inclusion criteria (34 SF and 64 IOUS). Mean EOR was significantly higher for SF (94 ± 11 %) when compared to IOUS (87 ± 20 %; p = 0.032). Mean post-operative residual tumor was significantly higher for IOUS (197 ± 358 mm2) when compared to SF (81 ± 161mm2; p = 0.038). GTR was more frequent with SF (62 % vs 46 %, p = 0.12). False negative assessments for residual tumor were more common with IOUS (22 % vs 15 %, p = 0.53). One patient in each group suffered a new neurologic deficit post-operatively (p = 0.58). Sensitivity, specificity, positive predictive value, and negative predictive value were 62 %, 100 %, 100 %, and 81 % for SF and 59 %, 100 %, 100 %, and 67 % for IOUS, respectively. Taken together, SF may be superior to IOUS in maximizing EOR in patients with GBM, however, both modalities appear to have good efficacy.

Timing of Adjuvant Radiotherapy and Survival Analysis for Molecularly Defined Low Grade Glioma

<h3>Purpose/Objective(s)</h3> The optimal treatment for patients with diffuse low-grade glioma (LGG) is controversial. Level I evidence support the use of radiotherapy (RT) for histologic LGG, but incorporation of molecular biomarkers in the WHO classification compels additional investigation to define the optimal treatment and timing of RT. We hypothesized molecularly defined LGG (IDH-mutant astrocytoma [astro] and IDH-mutant, 1p/19q-codeleted oligodendrogliomas [oligo]) have different survival outcomes following early vs delayed RT, knowledge that may guide RT in the context of resection and chemotherapy. <h3>Materials/Methods</h3> We performed a retrospective analysis of adult patients who were newly diagnosed with a WHO Grade 2 IDH-mutant astro or IDH-mutant, 1p/19q-codel oligo and had initial resection at a single institution from Jan 1998 to Nov 2017. Wilcoxon rank sum and Chi-squared tests were used to compare continuous and categorical variables between cohorts, respectively. Survival analysis was performed using the Kaplan-Meier method. Patients without clinical progression or death were censored at last follow-up date. Pre-operative and post-operative tumor volumes were quantified using 3D Slicer and defined as the T2 FLAIR hyperintense lesion to calculate extent of resection (EOR). <h3>Results</h3> 392 patients (202 astro, 190 oligo) were analyzed with a median follow up of 9.3 yr (95% CI: 8.19–10.16). Median overall survival (OS) was 13.0 yr for astro (95% CI: 11.4 – 18.6) and not reached for oligo (95% CI: 19.9 – NA). 168 patients (42.8%) received RT during their treatment course, with the majority (84%) treated at time of first disease progression. Chemotherapy was used in 81.7% of patients who received RT (TMZ in 90.3% of cases). The median RT dose was 54 Gy (range: 40 – 60 Gy). RT was more likely for astro (51.0%) than for oligo (34.2%) (p < 0.001), and a lower median EOR was associated with RT (88% vs 95%; p = 0.017). RT was not associated with increased OS for astro (p = 0.12) or oligo (p = 0.31) for all comers. For patients < 40 yr of age who had subtotal resections of astros (< 85% EOR), RT increased median OS with a trend toward significance when compared to no RT (13.1 yr [95% CI: 7.3 – NA] vs 9.1 yr [95% CI: 5.4 – NA], p = 0.1). RT within 1 yr of diagnosis was associated with improved median PFS compared to patients who received RT after 1 yr for astro (7.0 yr [95% CI: 5.5 – NA] vs 3.6 yr [95% CI: 2.9 – 4.8], p < 0.001), but not for oligo (p = 0.4). RT within 1 yr of diagnosis increased subsequent survival following RT for astro (median 12.9 yr [95% CI: 7.9 – NA] vs 4.4 yr [95% CI: 3.4 – 8.5], p < 0.001), with a trend toward improvement for oligo (p = 0.08). Patients with astro < 40 yr of age exhibited the greatest improvement in subsequent survival following RT, when RT was delivered within 1 yr of diagnosis (0 recorded deaths out of n = 12, p = 0.001). <h3>Conclusion</h3> Retrospective data from a single institution support the use of early RT for patients < 40 yr of age with molecularly-defined astrocytomas. RT may also improve OS in this population after subtotal resection.

Surgical management of large cerebellopontine angle meningiomas: long-term results of a less aggressive resection strategy.

Cerebellopontine angle (CPA) meningiomas present many surgical challenges depending on their volume, site of dural attachment, and connection to surrounding neurovascular structures. Assuming that systematic radical resection of large CPA meningiomas carries a high risk of permanent morbidity, the authors adopted an alternative strategy of optimal resection followed by radiosurgery or careful observation of the residual tumor and assessed the efficiency and safety of this approach to meningioma treatment management. This single-center retrospective cohort study included 50 consecutive patients who underwent surgery for meningioma between January 2003 and February 2020. The most common main dural attachments of the meningiomas were posterior (42%) and superior (26%) to the internal auditory meatus. The suboccipital retrosigmoid route was the most routinely used (92%). At the last follow-up examination, 93% of the patients with normal preoperative facial nerve (FN) function retained good House-Brackmann (HB) grades of I and II, whereas 3 patients (7%) displayed intermediate HB grade III FN function. Hearing preservation was achieved in 86% of the patients who presented with preoperative serviceable hearing, and recovery after surgery was achieved in 19% of the patients experiencing preoperative hearing loss. In order to preserve all cranial nerve function, gross-total resection was obtained in 26% of patients. Of the 35 patients who had undergone subtotal resection, 20 (57%) had been allocated into a wait-and-rescan treatment approach and 15 (43%) underwent upfront Gamma Knife surgery (GKS). The mean postoperative tumor volume was 1.20 cm3 in the upfront GKS group and 0.73 cm3 in the wait-and-rescan group (p = 0.08). Tumor control was achieved in 87% and 55% of cases (p < 0.001), with a mean follow-up of 85 and 69 months in the GKS and wait-and-rescan groups, respectively. The 1-, 5-, and 7-year tumor progression-free survival rates were 100%, 100%, and 89% in the GKS group and 95%, 59%, and 47% in the wait-and-rescan group, respectively (p < 0.001). Optimal nonradical resection of large CPA meningiomas provides favorable long-term tumor control and functional preservation. Adjuvant GKS does not carry additional morbidity and appears to be an efficient adjuvant treatment.

P07.11.A Impact of awake craniotomy on extent-of-resection and performance in glioma: a retrospective, propensity-score matched cohort study

Abstract Background The goal of awake craniotomy is to safely optimize the extent-of-resection in patients with glioma. Lower postoperative tumor volume is associated with better overall survival, emphasizing the importance of optimal surgical resection. Awake craniotomy causes less postoperative neurological deficits than surgery under general anesthesia, however, it is unclear whether awake craniotomy leads to lower postoperative tumor volume compared with general anesthesia in presumed lower grade glioma. Methods Retrospective, matched cohort study in patients with astrocytoma, IDH-mutant grade 2 and 3, oligodendroglioma, IDH-mutant, and 1p/19q-codeleted grade 2 and 3, and low-grade glioma, IDH-wildtype (now designated glioblastoma, IDH-wildtype), who underwent resection with awake craniotomy or under general anesthesia between 2003 and 2021 at Erasmus MC Brain Tumor Center. Pre- and postoperative tumor volumes were measured by semi-automatic 3D MRI-segmentation. First, we performed a multivariate logistic regression to assess which factors predicted selection for awake craniotomy. Thereafter, matching based on propensity score was attempted. Outcome variables were postoperative tumor volume, resection percentage and Karnofsky Performance Status (KPS) 3 months after surgery. Results We identified 181 awake craniotomy-patients and 135 general anesthesia-patients. Awake craniotomy-patients were younger, in better condition, more often male, with tumors more often in eloquent areas, in the left side of the brain and non-contrast enhancing. When performing matching without replacement, only 68 awake craniotomy-patients could be matched with 68 general anesthesia-patients, underscoring the imbalance in the dataset. Matching with replacement yielded a matched dataset of 181 awake craniotomy-patients with 60 general anesthesia-patients with adequate matching on most baseline variables, except for eloquent area (47% for awake craniotomy and 21.7% for general anesthesia, p &amp;lt; 0.001). In this matched dataset, median postoperative volume in awake craniotomy was 5.8 mL (IQR 0 - 92.8) vs 12.2 mL (IQR 0 - 90.1) in general anesthesia (p-value = 0.114). Resection percentages did not differ between the awake craniotomy- and general anesthesia-groups. KPS scores at 3 months after surgery did not differ between awake craniotomy and general anesthesia (p = 0.15). Conclusion Postoperative tumor volume was not lower in awake craniotomy-patients than in general anesthesia-patients. Neither were resection percentage and KPS scores at 3 months after surgery significantly different between the groups. Adequate matching was only obtainable using replacement, underscoring the risk of bias in unmatched datasets. These data should be interpreted with care, given the retrospective nature, potential residual confounding and potential lack of generalizability due to unmatched normal resection patients.

P18.01.A The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term perioperative care in meningioma patients

Abstract Background Risk factors for the prediction of late-onset tumor recurrence in meningioma patients are sparse but needed to estimate duration and control intervals during long-term follow-up in meningioma patients. In this study, we therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis in a large, single-center series. Material and methods Correlations of established clinical (age, sex, tumor location, extent of resection), radiological (postoperative tumor volume) and histopathological variables (WHO grade, brain invasion) with tumor relapse were analyzed separately after 3, 5, and 10 years following microsurgery for primary diagnosed intracranial meningioma between 1991 and 2021 in uni- and multivariate analyses. The prognostic value was compared to findings in the entire cohort. Results Within a median follow-up of 29 months (range: 0-307 months), recurrence was observed in 141 patients (12%) after a median PFS of 36 months. PFS among the entire cohort (n=1218) at 3, 5, 10 and 15 years postoperatively were 90%, 84%, 74% and 70%, respectively. Among all patients included, skull base location (HR: 1.51, 95%CI 1.05-2.16; p=.026), Simpson ≥IV resections (HR: 2.41, 95%CI 1.52-3.84; p&amp;lt;.001), high-grade histology (HR: 3.70, 95%CI 2.50-5.47; p&amp;lt;.001) and male gender (HR: 1.46, 95%CI 1.01-2.11; p=.042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17-3.17; p=.010 and HR: 2.02, 95%CI 1.04-3.95; p=.038) and high-grade histology (HR: 1.87, 95%CI 1.04-3.38; p=.038 and HR: 2.29, 95%CI 1.07-4.01; p=.034) but not subtotal resection (HR: 1.53, 95%CI .68-3.45; p=.303 and HR: 1.75, 95%CI .52-5.96; p=.369) remained independently correlated with recurrence after an event-free PFS of at least three (n=485) and five years (n=346), respectively. Similarly, postoperative tumor volume was related with recurrence in the entire cohort (p&amp;lt;.001) but not beyond a follow-up of ≥ three years (p&amp;gt;.05). In 147 patients with a follow-up of ≥ ten years, ten recurrences occurred, and no correlation was found with any of the analyzed variables. Conclusion Skull base tumor location and high-grade histology but not the extent of resection should be considered when planning follow-up duration and intervals following ≥5 years after meningioma surgery. Tumor relapses following more than ten years after surgery are very rare, and corresponding predictors are lacking.

OS07.8.A Prognosis in IDH-mutant glioma: the role of extent-of-resection, age and tumor grade

Abstract Background Evidence suggests that smaller residual tumor volumes after initial surgery are associated with longer survival in patients with astrocytoma, IDH-mutant, grade II. For IDH-mutant glioma of higher grade but also for oligodendroglioma, IDH-mutant, and 1p/19q codeleted, the impact on survival of more residual tumor is unclear. This could be related to the limited follow-up of patients with oligodendroglioma that typically have long overall survival. We expanded a previously published series of patients increase the duration of follow-up and the spectrum of tumor grades. Material and Methods Single center observational cohort study of patients with adult-type diffuse glioma, IDH-mutant, all WHO-2021 grades, from 2003 to 2021 . Molecular characteristics were assessed by next-generation targeted sequencing. Tumor volumes were calculated by semi-automatic 3D segmentation on pre- and postoperative MRI-scans. Associations between prognostic factors and survival were assessed using univariate and multivariate Cox proportional hazards models. Results 384 patients with IDH-mutant glioma (174 oligodendroglioma, 212 astrocytoma) were followed for a median of 7 years. Median age at diagnosis was 41 years (IQR 33 - 55). Significant prognostic factors for survival were Karnofsky performance status, 1p19q-status and post-operative tumor volume. Smaller post-operative tumor volume was associated with better survival, both in astrocytoma and oligodendroglioma. Age, tumor grade and MRI-contrast enhancement were not associated with survival. Conclusion Lower residual tumor volume after first surgery is a strong prognostic factor in all IDH-mutant glioma subgroups, even in patients with very small residual tumor. Importantly, age and histological tumor grade were not significantly associated with survival. The data serves as further support for optimal initial resections of tumors suspected for IDH-mutant glioma, also in oligodendroglioma.