Preoperative Tumor Volume Research Articles

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.

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.

Correlation between tumor volume and serum prolactin and its effect on surgical outcomes in a cohort of 219 prolactinoma patients.

Prolactinoma is the most common pituitary adenoma and can be managed medically or surgically. The authors assessed the correlation between tumor volume and prolactin level and its effect on surgical outcomes. The authors reviewed 219 patients who underwent transsphenoidal prolactinoma resection at a single institution from 2012 to 2019. Outcomes were compared between patients with and without biochemical remission. Tumor volumes were quantified with BrainLab Smartbrush. Correlation analysis and linear regression were used to examine the association between tumor volume and serum prolactin level. Volume-adjusted prolactin level was defined as serum prolactin level divided by tumor volume. The authors utilized receiver operating characteristic (ROC) curve analysis to determine the thresholds for predicting biochemical remission status. The mean tumor volume was 5.66 cm3, and the mean preoperative prolactin level was 752.3 µg/L. Men had larger prolactinomas than women (mean volume 11.32 vs 2.54 cm3; p < 0.001), and women had a greater volume-adjusted prolactin level (mean 412.5 vs 175.9 µg/L/cm3, p < 0.001). In total, 66.7% of surgical patients achieved biochemical remission 6 weeks after surgery, whereas a similar cohort of medically treated patients during the same time frame demonstrated a 69.4% remission rate. Pearson correlation and linear regression analysis revealed a strong association between preoperative tumor volume and prolactin levels, with an increase in serum prolactin level of 101.31 µg/L per 1-cm3 increase in tumor volume (p < 0.001). This held true for men (R = 0.601, p < 0.001) and women (R = 0.935, p < 0.001), with women demonstrating a greater increase in prolactin level per 1-cm3 increase in volume (185.70 vs 79.77 µg/L, p < 0.001). Patients who achieved remission exhibited a 66.08-µg/L increase in preoperative prolactin level per 1 cm3 of preoperative tumor volume (p < 0.001), which was less than the 111.46-µg/L increase per 1 cm3 in patients without remission (p < 0.001). Patients who failed to achieve remission had residual tumors with a 77.77-µg/L increase in prolactin per 1 cm3 of remaining tumor volume after resection (p < 0.001). ROC curve analysis revealed significant thresholds that optimally predicted lack of postoperative remission on the basis of preoperative prolactin and tumor volume. These thresholds were rendered nonsignificant in patients with documented Knosp grade ≥ 3. Although the authors found a correlation between prolactinoma volume and serum prolactin level, patients without remission had a greater increase in serum prolactin level per increase in preoperative tumor volume than those who achieved remission, suggesting unique tumor composition. The authors also identified prolactin and tumor volume thresholds that optimally predicted biochemical remission status. The authors hope that their results can be used to identify prolactinomas for which surgery could achieve remission as an alternative to medical management.

Adaptive Hybrid Surgery Experiences in Benign Skull Base Tumors.

Background: The treatment of benign skull base tumors remains challenging. These tumors are often located in close relationship to critical structures. Therefore, radical resection of these tumors can be associated with high morbidity. Multimodal treatment concepts, including controlled partial tumor resection followed by radiosurgery, should be considered. Methods: Adaptive hybrid surgery analysis (AHSA) is an intraoperative tool that has been introduced for the automatic assessment of tumor properties, and virtual real-time radiosurgical treatment simulation and continuous feasibility analysis of adjuvant radiosurgery. The AHSA method (Brainlab®, Munich, Germany) was applied to five patients who underwent partial resection of a benign skull base tumor. Tumor volumetry was obtained on pre- and postoperative MR scans. Organs at risk were, preoperative, automatically delineated with atlas mapping software (Elements® Segmentation Cranial), and adaptations were made if necessary. Results: Five patients with benign skull base lesions underwent planned partial tumor resection in a multimodal therapeutic surgery followed by radiosurgery. The preoperative tumor volumes ranged between 8.52 and 25.2 cm3. The intraoperative residual tumor volume measured with the AHSA® software ranged between 2.13–12.17 cm3 (25–52% of the preoperative tumor volume). The intraoperative automatic AHSA plans of the remaining tumor volume suggested, in all five patients, that safe hypofractionated radiation was feasible. Patients were followed for 69.6 ± 1.04 months, and no complications occurred after the patients were treated with radiation. Conclusions: Intraoperative SRS planning based on volumetric assessments during resection of skull base tumors using AHSA® is feasible and safe. The AHSA method allows the neurosurgeon to continuously evaluate the feasibility of adjuvant radiosurgery while planning and performing a surgical resection. This method supports the treatment strategy of a complementary approach during surgical resection of complex skull base tumors and might contribute to preventing surgical and radiosurgical complications.

The Knosp Criteria Revisited: 3-Dimensional Volumetric Analysis as a Predictive Tool for Extent of Resection in Complex Endoscopic Pituitary Surgery.

The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery. To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas. Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined. One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P < .05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P > .05, area under the curve 0.46). Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods.

Magnetic Resonance Imaging–Guided Laser Interstitial Therapy for In-Field Recurrence After Stereotactic Radiosurgery: Is Complete Ablation Required for Local Control?

Magnetic resonance imaging-guided laser interstitial therapy (MrLITT) presents a new valuable treatment alternative when the in-field recurrence (IFR) of metastatic brain tumors is difficult to safely access with open surgery or maximum radiation therapy has already been completed. To examine the effects of MrLITT on longevity outcomes based on volume of ablation. A retrospective study was carried out of 35 patients treated with MrLITT for IFR after radiosurgery for metastatic brain tumors at a single institution from 2010 to 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed with Kaplan-Meier and Cox regression analyses according to ablation volume. Univariate and multivariate analyses further assessed risk factors based on ablation volume. Kaplan-Meier analyses showed no significant differences between total and subtotal ablation groups in OS (61.1 vs. 49.7 weeks) and PFS (45.1 and 42.7 weeks), respectively (P > 0.05). In the subtotal ablation group, independent risk factors included preoperative tumor volume (hazard ratio [HR], 1.24; P= 0.05) for OS and residual tumor volume (HR, 2.62; P= 0.01) for PFS. Multivariate Cox regressions suggested no significant differences in OS (HR, 1.03; P= 0.19) and PFS (HR, 1.02; P= 0.24) between total and subtotal ablation groups, whereas preoperative tumor volume remained a risk factor for decreased OS (HR, 1.23; P= 0.004). MrLITT is an effective treatment option for IFR after radiosurgery for metastatic brain tumors. The benefits of more aggressive gross total ablations of deep targets near eloquent cortices are limited compared with effective subtotal ablations, but the amount of residual tumor volume left must be appropriately balanced.

Selecting lymph node-positive patients for adjuvant therapy after radical prostatectomy and extended pelvic lymphadenectomy: An outcome analysis of 100 node-positive patients managed without adjuvant therapy.

The aim of the study is to evaluate the effect of deferred androgen deprivation therapy on biochemical recurrence (BCR) and other survival parameters in node-positive prostate cancer patients after robot-assisted radical prostatectomy with bilateral extended pelvic lymph node dissection (RARP + EPLND). Of the 453 consecutive RARP procedures performed from 2011 to 2018, 100 patients with no prior use of androgen deprivation therapy were found to be lymph node (LN) positive and were observed, with initiation of salvage treatment at the time of BCR only. Patients were divided into 1 or 2 LNs (67)-and more than 2 LNs (33)-positive groups to assess survival outcomes. At a median follow-up of 21 months (1-70 months), the LN group (p < 0.000), preoperative prostate-specific antigen (PSA, p = 0.013), tumor volume (TV, p = 0.031), and LND (p = 0.004) were significantly associated with BCR. In multivariate analysis, only the LN group (p = 0.035) and PSA level (p = 0.026) were statistically significant. The estimated BCR-free survival rates in the 1/2 LN group were 37.6% (27%-52.2%), 26.5% (16.8%-41.7%), and 19.9% (9.6%-41.0%) at 1, 3, and 5 years, respectively, with a hazard of developing BCR of 0.462 (0.225-0.948) compared with the more than 2 LN-positive group. Estimated 5-year overall survival, cancer-specific, metastasis-free, and local recurrence-free survival rates were 88.4% (73.1%-100%), 89.5% (74%-100%), 65.1% (46.0%-92.1%), and 94.8% (87.2%-100.0%), respectively, for which none of the factors were significant. Based on cutoff values for PSA, TV, and LND of 30 ng/mL, 30%, and 10%, respectively, the 1/2 LN group was substratified, wherein the median BCR-free survival for the low- and intermediate-risk groups was 40 and 12 months, respectively. Nearly one fourth and one fifth of 1/2 node-positive patients were BCR-free at 3 and 5 years after RARP + EPLND. Further substratification using PSA, TV, and LN density may help in providing individualized care regarding the initiation of adjuvant therapy.

P11.55.B Postoperative MRI is able to detect an unexpected residual tumor after surgery of brain metastases: experience from 5 specialized centers

Abstract Background Brain metastases (BM) constitute the most common central nervous system tumors. The treatment options of BM consist of surgery, radiotherapy, radiosurgery, chemotherapy, and immunotherapy. Regarding surgery in BM, the extent of resection (EOR) represents a crucial factor for patient prognosis. However, first studies using postoperative MRI demonstrated that an unexpected residual tumor after surgery of BM is not uncommon despite these tumors were considered to be well-demarcated. The aim of this study was thus to investigate in a large cohort including multiple neurosurgical centers the EOR following BM resection, potential risk factors for incomplete resection and postsurgical follow-up data. Material and Methods In the current retrospective study conducted at 5 specialized neurosurgical centers in Austria, we included patients with BM resection and available postoperative MRI. The EOR following BM resection was determined by postoperative MRI (complete vs incomplete resection). Additionally, the data on the intraoperative judgement of the EOR of the performing neurosurgeon were collected. Moreover, potential factors for incomplete resection including tumor localization, tumor volume, primary tumor, pattern of contrast media enhancement on imaging and tumor eloquence were investigated. Finally, the rate of local progression of BM after initial surgery was analyzed in the follow-up period and overall survival data were collected. Results Altogether, 548 patients with 649 surgically treated BM were included. According to postoperative MRI, complete resection was achieved in 407 (66%) of 649 BM and incomplete resection in 176 (29%) of 649 BM. Misjudgment of the EOR by the neurosurgeon was found in 25% of cases and resulted in an unexpected residual tumor which was evident on postoperative MRI in 122 (22%) BM. Preoperative tumor volume was significantly larger in incompletely resected BM. Moreover, local progression was significantly more common in cases with incompletely resected BM and was also associated with shorter overall survival. Conclusion Our data of this study including multiple centers indicate that postoperative MRI is capable to detect a relatively high rate of unexpected residual tumors following resection of BM. Since local progression was more common in BM with residual tumors and this was associated with shorter survival, special attention should be paid to achieve a complete tumor resection.

OS07.6.A Extent of resection in glioblastoma: refinement and prognostic validation of a classification system from the RANOresectgroup

Abstract Background Extent of resection in glioblastoma is inconsistently described across clinical trials. Based upon the absolute residual contrast-enhancing (CE) tumor (in cm3) and the relative reduction of CE tumor (in percentage) on postoperative MRI, a surgical classification system for glioblastoma was previously proposed. In this context, class 0 was defined as ‘supramaximal CE resection’ (also including removal of non-CE tumor), class 1 as ‘maximal CE resection’, class 2 as ‘submaximal CE resection’, and class 3 as ‘biopsy’. We herein aimed to (I) analyze the prognostic value of the proposed classification system, and (II) explore how much non-CE tumor needs to be resected in order to provide a survival benefit. Material and Methods An international Response Assessment in Neuro-Oncology (RANO) group was formed, entitled RANO resect. The RANO resectinvestigators retrospectively searched the databases from seven neuro-oncological centers in the USA and Europe for individuals with newly diagnosed glioblastoma. Demographics, clinical information and volumetrics from pre- and postoperative MRI were collected. Kaplan-Meier survival analysis and log-rank test were utilized to calculate survival, and Cox’s proportional hazard regression model was used to adjust for multiple variables. The significance level was set at p ≤ 0.05. Results We identified 1021 individuals with newly diagnosed glioblastoma, including 1008 IDHwt patients. Among those, 744 IDHwt patients were postoperatively treated with radiochemotherapy per EORTC 26981/22981 (TMZ/RT→TMZ). Within this homogenously treated cohort, higher extent of resection was favorably associated with outcome: individuals with ‘maximal CE resection’ (class 1) had superior outcome compared to patients with ‘submaximal CE resection’ (class 2) or ‘biopsy’ (class 3) (median OS: 20 versus 16 versus 10 months; p = 0.001). Similar findings were made when assessing progression (median PFS: 9 versus 8 versus 5 months; p = 0.001). Extensive resection of non-CE tumor (≥60% of non-CE tumor removed and ≤5 cm3 residual non-CE tumor) provided an additional survival benefit in patients with complete CE resection (class 1), thus defining class 0 (‘supramaximal CE resection’) (median OS: 29 versus 20 months; p = 0.003). The favourable prognostic effect of CE resection was retained in a multivariate analysis when stratifying for clinical and molecular characteristics including pre-operative tumor volume and MGMT promotor status (p = 0.001). Conclusion The proposed classification system to describe extent of glioblastoma removal is highly prognostic, and thus may serve for stratification of clinical trials. Resection of non-CE tumor beyond the CE tumor borders provides an additional survival benefit in glioblastomas, highlighting the need to explicitly denominate such a ‘supramaximal CE resection’.

OS07.7.A Rate and type of recurrence of lower-grade gliomas submitted to functional neurosurgical approach: the impact of the extent of resection

Abstract Background In the last decade, different published studies enlightened the extent-of-resection (EOR) as an independent factor for progression-free-survival (PFS) in patients with lower-grade gliomas (LGG). Aim of this study was to evaluate the impact of resections extending beyond FLAIR MRI abnormalities (supratotal), and eventual predictive factors and characteristics of recurrences. Material and Methods We retrospectively analysed 460 patients submitted to surgery between 2007 and 2016 with a presumptive diagnosis of LGG, i.e., harbouring a mass lesion with no enhancement on contrast-administered T1-weighted MRI-sequences. All resections were performed according to functional boundaries determined by brain mapping/monitoring technique, without any patient or tumor a priori selection. The EOR was defined by analyzing pre- and post-operative volumetric FLAIR images. Results The median pre-operative tumor volume was 43,7 cm3. A supratotal resection (SPR) was achieved in 31.4%, a gross-total (GTR) in 41.1%, a subtotal (STR) in 27.5%. WHO grade II/III gliomas were diagnosed in 347 cases (319 IDH-mutant, 28 IDH-wildtype). Median follow-up was 60 months. SPR versus other EOR was associated to increased PFS (log rank test, p=.000) and malignant PFS (p=.000). Data were confirmed also after IDH status stratification. Rate of immediate and permanent post-op deficits among different EOR were comparable. Pre-op tumor volume, parietal and insular sites, eloquent location and dominant hemisphere tumors, and astrocytoma histology were associated to recurrence (p&amp;lt;.05). In 95.1% of cases recurrences were peri-cavitary. Lesions invading the corpus callosum presented minor rate of relapse; recurrences were most frequently diffuse and at distant sites. After SPR most common radiological appearance of recurrence was solid, while after GTR and STR percentages of solid and diffuse patterns were similar. Occurrence of distant recurrences, away from the resection cavity, were most associated to SPR. Conclusion Our preliminary data suggests the dramatic impact in LGG of resections extending beyond FLAIR abnormalities on PFS and malignant PFS and on the characteristics of tumor recurrence.

Large Pituitary Adenoma: Strategies to Maximize Volumetric Resection Using Endoscopic Endonasal Approaches and an Analysis of Factors Limiting Resection

Large pituitary adenomas (LPAs), which constitute ∼5%-14% of all pituitary adenomas, are considered challenging tumors owing to their locally aggressive behavior, low gross total resection rate, and high prevalence of visual deficits and hypopituitarism. We evaluated the utility of various extended endoscopic endonasal approaches in maximizing the resection of LPAs and studied the factors affecting the extent of surgical resection. A retrospective study of all LPAs (defined as a minimum diameter >3 cm and tumor volume >10 cm3) treated via an endoscopic endonasal approach between January 2015 and December 2020 was performed. The volumetric extent of resection (3-dimensional volumetric analysis software) was correlated with various demographic, tumor-related, pathologic, and immunohistochemical factors and its effects on the clinical outcomes studied. The present study included 106 patients with LPAs. The mean extent of the resection volume was 79.18 ± 21.75 cm3. The factors that affected the extent of resection included the preoperative tumor volume (P= 0.03) and Knosp grade (P= 0.03). The percentage increase in the extent of resection with the use of 2 endonasal corridors was 10.6% and with 3 corridors was 14%. Visual improvement occurred in 82% of patients, and new-onset persistent hormonal insufficiency occurred in 2.9% of patients. Mortality directly related to surgery occurred in 1.8% of cases. Extended endoscopic endonasal approaches can safely and effectively be used for gross total resection of LPAs. However, we found that the preoperative tumor volume and Knosp grade were significant factors affecting the extent of tumor resection. The use of multiple endoscopic endonasal corridors can increase the volumetric extent of resection for LPAs.

Herophilus-Galen line as a predictor of extent of resection in the occipital interhemispheric transtentorial approach to pineal tumors in children.

The goals of this study were to evaluate the extent of resection (EOR) obtained with an occipital interhemispheric transtentorial approach (OITA) in a series of pediatric patients with pineal region tumors and to define preoperative radiological factors predictive of the EOR. This is a retrospective cohort study of a series of pediatric patients with pineal tumors who underwent surgery through a microsurgical OITA performed by the senior author during the period from January 2006 to January 2020. The tumor volume was measured preoperatively, and then on sagittal midline cuts the authors identified the most cranial point of the torcular Herophili (defined as the "Herophilus point") and the lowest point of the inferior profile of the vein of Galen (defined as the "Galen point"). The line joining these two points (defined as the "Herophilus-Galen line" [H-G line]) was used to identify the "Herophilus-Galen plane" (H-G plane) perpendicular to the sagittal plane. Tumor volumes located below and above this plane were measured. EOR was evaluated by measuring residual tumor volume visible on T1 volumetric injected sequences of immediate postoperative MRI. Thirty patients were selected for study inclusion. The preoperative mean tumor volume was 15.120 cm3 (range 0.129-104.3 cm3). The mean volumes were 2.717 cm3 (range 0-31 cm3) above the H-G plane and 12.40 cm3 (median 5.27 cm3, range 0.12-72.87 cm3) below the H-G plane. Three patients underwent only biopsy. Of the remaining 27 patients, gross-total resection (GTR; 100% tumor volume) was achieved in 20 patients (74%). In the remaining 7 patients, the mean residual tumor volume was 7.3 cm3 (range 0.26-17.88 cm3). In 3 of these patients, GTR was accomplished after further surgical procedures (1 in 2 patients, 3 in 1 patient) for an overall GTR rate of 85.18%. Larger tumor volume was significantly associated with incomplete resection (p < 0.001). A tumor volume ≤ 2 cm3 above the H-G plane (p = 0.003), linear extension ≤ 1 mm above the H-G line, and pineal histology were predictive of GTR at first OITA procedure (p = 0.001). The H-G line is an intuitive, easy-to-use, and reliable indicator of the superior anatomical limit of visibility during the microsurgical OITA. This anatomical landmark may be useful as a predictor of EOR for pineal tumors performed through this approach. The main limitations of this study are the small number of patients and the exclusively pediatric age of the patient population.

Association of Postoperative Sigmoid Sinus Occlusion and Cerebrospinal Fluid Leak in Translabyrinthine Surgery.

To characterize the incidence of sigmoid sinus occlusion (SSO) following translabyrinthine (TL) surgery for posterior fossa tumor resection and determine the association with cerebrospinal fluid (CSF) leak. Retrospective case series. Tertiary referral center. Patients undergoing TL surgery for vestibular schwannoma from 2012 to 2020 were included. Demographic data, medical history, preoperative tumor length and volume, and postoperative complications including CSF leak were recorded. Neuroradiology review of postoperative magnetic resonance imaging was used to determine the presence or absence of flow through the sigmoid sinus. Of 205 patients undergoing TL, 21 (10.2%) experienced CSF leak postoperatively. Overall 56 (27%) demonstrated SSO on immediate postoperative magnetic resonance imaging. CSF leaks were more likely in those with SSO (19.6%) than those without SSO (6.7%; odds ratio, 3.54 [95% CI, 1.25-10.17]). Tumor volume and body mass index were not significantly associated with CSF leak. In total, 105 (51%) patients had some degree of sigmoid sinus thrombosis, but nonocclusive thrombosis was not associated with CSF leak. SSO after TL approaches is common and appears to be significantly associated with postoperative CSF leak development. Minimizing manipulation of the sigmoid sinus during TL surgery and compression after surgery may have a role in preventing CSF leak.

Prognostic validation and refinement of a classification system for extent of resection in glioblastoma: A report of the RANO resect group.

2003 Background: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system for glioblastoma was previously proposed based upon the absolute residual contrast-enhancing (CE) tumor (in cm3) and the relative reduction of CE tumor (in percentage) on postoperative MRI. Class 0 was defined as ‘supramaximal CE resection’ (also including removal of non-CE tumor), class 1 as ‘maximal CE resection’, class 2 as ‘submaximal CE resection’, and class 3 as ‘biopsy’. We aimed to (I) explore the prognostic utility of the proposed classification system and (II) define how much non-CE tumor needs to be removed to translate into a survival benefit. Methods: An international Response Assessment in Neuro-Oncology (RANO) group was formed, entitled RANO resect. The members of the RANO resect group retrospectively searched the databases from seven neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma. Clinical characteristics, volumetric information from pre- and postoperative MRI, and outcome were collected. Kaplan-Meier survival analysis and log-rank test were applied to calculate survival, and Cox’s proportional hazard regression model to adjust for multiple variables. Significance level was set at p ≤ 0.05. Results: We encountered 1021 patients with newly diagnosed glioblastoma, including 1008 IDHwt patients. 744 IDHwt patients were treated with radiochemotherapy per EORTC 26981/22981 following surgery. Among such homogenously treated patients, higher extent of resection was favorably associated with outcome: patients with ‘maximal CE resection’ (class 1) had superior outcome compared to patients with ‘submaximal CE resection’ (class 2) or ‘biopsy’ (class 3) (median OS: 20 versus 16 versus 10 months; p = 0.001). Similar findings were made when assessing progression (median PFS: 9 versus 8 versus 5 months; p = 0.001). Extensive resection of non-CE tumor (≥60% of non-CE tumor removed and ≤5 cm3 residual non-CE tumor) provided an additional survival benefit in patients with complete CE resection (class 1), thus defining class 0 (‘supramaximal CE resection’) (median OS: 29 versus 20 months; p = 0.003). Smaller pre-operative tumor volumes were associated with larger extent of resection. The favorable prognostic effect of CE resection was conserved in a multivariate analysis when stratifying for molecular and clinical markers including pre-operative tumor volume and MGMT promotor status ( p = 0.001). Conclusions: The proposed classification system for extent of surgery in glioblastoma is highly prognostic and may serve for stratification and design of clinical trials. Removal of non-CE tumor beyond the CE tumor borders translates into additional survival benefit in glioblastomas, providing a rationale to explicitly denominate such a 'supramaximal CE resection.'

5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study.

Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

Surgery of Motor Eloquent Glioblastoma Guided by TMS-Informed Tractography: Driving Resection Completeness Towards Prolonged Survival.

BackgroundSurgical treatment of patients with glioblastoma affecting motor eloquent brain regions remains critically discussed given the risk–benefit dilemma of prolonging survival at the cost of motor-functional damage. Tractography informed by navigated transcranial magnetic stimulation (nTMS-informed tractography, TIT) provides a rather robust estimate of the individual location of the corticospinal tract (CST), a highly vulnerable structure with poor functional reorganisation potential. We hypothesised that by a more comprehensive, individualised surgical decision-making using TIT, tumours in close relationship to the CST can be resected with at least equal probability of gross total resection (GTR) than less eloquently located tumours without causing significantly more gross motor function harm. Moreover, we explored whether the completeness of TIT-aided resection translates to longer survival.MethodsA total of 61 patients (median age 63 years, m = 34) with primary glioblastoma neighbouring or involving the CST were operated on between 2010 and 2015. TIT was performed to inform surgical planning in 35 of the patients (group T; vs. 26 control patients). To achieve largely unconfounded group comparisons for each co-primary outcome (i.e., gross-motor functional worsening, GTR, survival), (i) uni- and multivariate regression analyses were performed to identify features of optimal outcome prediction; (ii), optimal propensity score matching (PSM) was applied to balance those features pairwise across groups, followed by (iii) pairwise group comparison.ResultsPatients in group T featured a significantly higher lesion-CST overlap compared to controls (8.7 ± 10.7% vs. 3.8 ± 5.7%; p = 0.022). The frequency of gross motor worsening was higher in group T, albeit non-significant (n = 5/35 vs. n = 0/26; p = 0.108). PSM-based paired-sample comparison, controlling for the confounders of preoperative tumour volume and vicinity to the delicate vasculature of the insula, showed higher GTR rates in group T (77% vs. 69%; p = 0.025), particularly in patients with a priori intended GTR (87% vs. 78%; p = 0.003). This translates into a prolonged PFS in the same PSM subgroup (8.9 vs. 5.8 months; p = 0.03), with GTR representing the strongest predictor of PFS (p = 0.001) and OS (p = 0.0003) overall.ConclusionThe benefit of TIT-aided GTR appears to overcome the drawbacks of potentially elevated motor functional risk in motor eloquent tumour localisation, leading to prolonged survival of patients with primary glioblastoma close to the CST.

Delayed cerebral ischemia associated with surgery for pituitary macroadenomas that express elevated levels of PACAP

Delayed cerebral ischemia (DCI) and cerebral vasospasm (VS) are rare but serious post-operative complications after surgery for pituitary macroadenomas; the mechanism of which are poorly understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a vasoactive neuropeptide expressed in pituitary adenomas and may play a role in DCI/VS. The aim of this case-control study was to investigate the association between tumor expression of PACAP and DCI/VS following pituitary surgery. Tumor tissue from five patients with DCI/VS following pituitary surgery and nine matched controls were evaluated for PACAP expression by immunohistochemistry. Nuclear PACAP expression was significantly elevated in patients with DCI/VS following pituitary surgery compared to controls (0.396 ± 0.0.16 a.u. vs 0.093 ± 0.04 a.u, p < 0.0001). There was a positive linear relationship between nuclear PACAP expression and pre-operative tumor volume (r2 = 0.41, p < 0.02) with a significant difference in slopes between the DCI/VS group compared to controls (y = x(5.0 × 10−3), r2 = 0.76 vs y = x(7.4 × 10−4), r2 = 0.07, p < 0.05). Elevated levels of tumor PACAP expression is associated with DCI/VS following pituitary surgery and may have a role in tumor growth. PACAP signaling may play a role the development of DCI, but further studies are needed.

MRI-Based Risk Assessment for Incomplete Resection of Brain Metastases.

ObjectRecent studies demonstrated that gross total resection of brain metastases cannot always be achieved. Subtotal resection (STR) can result in an early recurrence and might affect patient survival. We initiated a prospective observational study to establish a MRI-based risk assessment for incomplete resection of brain metastases.MethodsAll patients in whom ≥1 brain metastasis was resected were prospectively included in this study (DRKS ID: DRKS00021224; Nov 2020 – Nov 2021). An interdisciplinary board of neurosurgeons and neuroradiologists evaluated the pre- and postoperative MRI (≤48h after surgery) for residual tumor. Extensive neuroradiological analyses were performed to identify risk factors for an unintended STR which were integrated into a regression tree analysis to determine the patients’ individual risk for a STR.ResultsWe included 150 patients (74 female; mean age: 61 years), in whom 165 brain metastases were resected. A STR was detected in 32 cases (19.4%) (median residual tumor volume: 1.36ml, median EORrel: 93.6%), of which 6 (3.6%) were intended STR (median residual tumor volume: 3.27ml, median EORrel: 67.3%) - mainly due to motor-eloquent location - and 26 (15.8%) were unintended STR (uSTR) (median residual tumor volume: 0.64ml, median EORrel: 94.7%). The following risk factors for an uSTR could be identified: subcortical metastasis ≥5mm distant from cortex, diffuse contrast agent enhancement, proximity to the ventricles, contact to falx/tentorium and non-transcortical approaches. Regression tree analysis revealed that the individual risk for an uSTR was mainly associated to the distance from the cortex (distance ≥5mm vs. <5mm: OR 8.0; 95%CI: 2.7 – 24.4) and the contrast agent patterns (diffuse vs. non-diffuse in those with distance ≥5mm: OR: 4.2; 95%CI: 1.3 – 13.7). The preoperative tumor volume was not substantially associated with the extent of resection.ConclusionsSubcortical metastases ≥5mm distant from cortex with diffuse contrast agent enhancement showed the highest incidence of uSTR. The proposed MRI-based assessment allows estimation of the individual risk for uSTR and can help indicating intraoperative imaging.

Long-term tumor control after endoscopic endonasal resection of craniopharyngiomas: comparison of gross-total resection versus subtotal resection with radiation therapy.

Surgical management of craniopharyngiomas (CPAs) is challenging. Controversy exists regarding the optimal goals of surgery. The purpose of this study was to compare the long-term outcomes of patients who underwent gross-total resection with the outcomes of those who underwent subtotal resection of their CPA via an endoscopic endonasal approach. From a prospectively maintained database of all endoscopic endonasal approaches performed at Weill Cornell Medicine, only patients with CPAs with > 3 years of follow-up after surgery were included. The primary endpoint was radiographic progression. Data were collected on baseline demographics, imaging, endocrine function, visual function, and extent of resection. A total of 44 patients with a mean follow-up of 5.7 ± 2.6 years were included. Of these patients, 14 (31.8%) had prior surgery. GTR was achieved in 77.3% (34/44) of all patients and 89.5% (34/38) of patients in whom it was the goal of surgery. Preoperative tumor volume < 10 cm3 was highly predictive of GTR (p < 0.001). Radiation therapy was administered within the first 3 months after surgery in 1 (2.9%) of 34 patients with GTR and 7 (70%) of 10 patients with STR (p < 0.001). The 5-year recurrence-free/progression-free survival rate was 75.0% after GTR and 25.0% after STR (45% in subgroup with STR plus radiotherapy; p < 0.001). The time to recurrence after GTR was 30.2 months versus 13 months after STR (5.8 months in subgroup with STR plus radiotherapy; p < 0.001). Patients with GTR had a lower rate of visual deterioration and higher rate of return to work or school compared with those with STR (p = 0.02). Patients with GTR compared to STR had a lower rate of CSF leakage (0.0% vs 30%, p = 0.001) but a higher rate of diabetes insipidus (85.3% vs 50%, p = 0.02). GTR, which is possible to achieve in smaller tumors, resulted in improved tumor control, better visual outcome, and better functional recovery but a higher rate of diabetes insipidus compared with STR, even when the latter was supplemented with postoperative radiation therapy. GTR should be the goal of craniopharyngioma surgery, when achievable with minimal morbidity.

Predicting pituitary adenoma consistency with preoperative magnetic resonance elastography.

Pituitary adenoma is one of the most common primary intracranial neoplasms. Most of these tumors are soft, but up to 17% may have a firmer consistency. Therefore, knowing the tumor consistency in the preoperative setting could be helpful. Multiple imaging methods have been proposed to predict tumor consistency, but the results are controversial. This study aimed to evaluate the efficacy of MR elastography (MRE) in predicting tumor consistency and its potential use in a series of patients with pituitary adenomas. Thirty-eight patients with pituitary adenomas (≥ 2.5 cm) were prospectively evaluated with MRI and MRE before surgery. Absolute MRE stiffness values and relative MRE stiffness ratios, as well as the relative ratio of T1 signal, T2 signal, and diffusion-weighted imaging apparent diffusion coefficient (ADC) values were determined prospectively by calculating the ratio of those values in the tumor to adjacent left temporal white matter. Tumors were classified into three groups according to surgical consistency (soft, intermediate, and firm). Statistical analysis was used to identify the predictive value of the different radiological parameters in determining pituitary adenoma consistency. The authors included 32 (84.21%) nonfunctional and 6 (15.79%) functional adenomas. The mean maximum tumor diameter was 3.7 cm, and the mean preoperative tumor volume was 16.4 cm3. Cavernous sinus invasion was present in 20 patients (52.63%). A gross-total resection was possible in 9 (23.68%) patients. The entire cohort's mean absolute tumor stiffness value was 1.8 kPa (range 1.1-3.7 kPa), whereas the mean tumor stiffness ratio was 0.66 (range 0.37-1.6). Intraoperative tumor consistency was significantly correlated with absolute and relative tumor stiffness (p = 0.0087 and 0.007, respectively). Tumor consistency alone was not a significant factor for predicting gross-total resection. Patients with intermediate and firm tumors had more complications compared to patients with soft tumors (50.00% vs 12.50%, p = 0.02) and also had longer operative times (p = 0.0002). Whereas other MRI sequences have proven to be unreliable in determining tumor consistency, MRE has been shown to be a reliable tool for predicting adenoma consistency. Preoperative knowledge of tumor consistency could be potentially useful for surgical planning, counseling about potential surgical risks, and estimating the length of operative time.