Extent Of Glioma Resection Research Articles

Efficacy and safety of intraoperative MRI in glioma surgery: a systematic review and meta-analysis of prospective randomized controlled trials.

Maximum extent of resection in glioma yields enhanced survival outcomes. The contemporary literature presents contradictory results regarding the benefit of intraoperative MRI (iMRI). This meta-analysis aimed to investigate the efficacy and safety of iMRI-guided surgery. The authors searched the PubMed, Embase, and Cochrane Reviews databases for eligible prospective randomized controlled trials through the end of February 2024. Endpoints were extent of resection, progression-free survival (PFS), overall survival, neurological functioning, and surgical complications. Individual patient data regarding PFS were reconstructed using the R package IPDfromKM. From 1923 identified results, 3 randomized controlled trials with 384 patients met the inclusion criteria. Extended resections after iMRI were performed in 29.2% of the iMRI cases. Intraoperative MRI-guided glioma surgery (OR 5.40, 95% CI 3.25-8.98; p < 0.00001) outperformed conventional navigation-guided surgery in attaining gross-total resection (GTR). In patients in whom a GTR was achieved, the median time to progression was 16.0 months (95% CI 12.3-19.7 months), while the median PFS in patients with a subtotal resection was 9.7 months (95% CI 6.9-12.5 months) (p < 0.001). Despite increased GTR rates, postoperative neurological deterioration was equal among the iMRI and control groups (OR 1.0, 95% CI 0.6-1.7; p = 0.91, I2 = 0%). Intraoperative MRI use prolongs surgery by 42 minutes on average (95% CI 3.3-80.7 minutes; p = 0.03, I2 = 56%). The risk of postoperative intracranial hemorrhage (OR 1.9, 95% CI 0.2-16.9; p = 0.55, I2 = 0%) was not increased, while in one study significantly increased infections were observed in the iMRI arm. Intraoperative MRI outperforms conventional surgery in achieving complete glioma resections of all contrast-enhancing tumor portions, enhancing PFS without added risk. Intraoperative MRI is a tool that facilitates these aims without reducing safety in terms of neurological deficits and surgical complications.

SURG-57. FLUORESCENCE LIFETIME IMAGING (FLIM) PROVIDES HIGHLY ACCURATE, DYE-FREE TUMOR MARGIN DETECTION DURING GLIOMA RESECTIONS

Abstract INTRODUCTION Fluorescence guided tumor margin detection is an important tool to enhance the extent of resection for gliomas. Existing dyes, such as 5-ALA, require planned administration, surgical resection in dark conditions, and are only effective for high-grade tumors. We have developed a novel laser scanning probe to assess tissue autofluorescence decay (lifetime) which allows tumor margin detection without exogenous dyes and under normal room light conditions. This technology has been optimized for margin detection in low-grade and high-grade gliomas. METHODS Patients undergoing craniotomy for resection of gliomas were enrolled. During resection of the final tumor margin, multiple 1x1 mm regions were scanned with FLIm and biopsied for evaluation by a neuropathologist. FLIm data and ground truth pathology were processed by a machine-learning algorithm to develop classifiers for the FLIm data. Classifiers were then applied to the full data set to determine the accuracy of FLIm predictions. RESULTS 12 patients with non-enhancing (LGG) and 25 patients with enhancing (HGG) tumors were enrolled, with a total of 228 biopsies obtained. For LGG, sensitivity of FLIm for detection of residual tumor was 0.89 (95% CI 0.8-0.98) with a specificity of 0.92 (95% CI 0.86-0.97), resulting in a positive predictive value of 0.76 and negative predictive value of 0.96 with an overall accuracy of 0.91. For HGG, sensitivity of FLIm for detection of residual tumor was 0.92 (95% CI 0.84-1.0) with a specificity of 0.95 (95% CI 0.91-0.99), resulting in a positive predictive value of 0.90 and negative predictive value of 0.96 with an overall accuracy of 0.94, exceeding reported values for 5-ALA. CONCLUSION FLIm can distinguish between residual low and high-grade glioma and normal brain at resection margins with very high sensitivity and specificity. This quantitative technology does not require administration of exogenous dyes and can be used under normal room light illumination.

Combined use of intraoperative MRI and awake tailored microsurgical resection to respect functional neural networks: preliminary experience.

The combined use of intraoperative MRI and awake surgery is a tailored microsurgical resection to respect functional neural networks (mainly the language and motor ones). Intraoperative MRI has been classically considered to increase the extent of resection for gliomas, thereby reducing neurological deficits. Herein, we evaluated the combined technique of awake microsurgical resection and intraoperative MRI for primary brain tumours (gliomas, metastasis) and epilepsy (cortical dysplasia, non-lesional, cavernomas). Eighteen patients were treated with the commonly used "asleep awake asleep" (AAA) approach at Lille University Hospital, France, from November 2016 until May 2020. The exact anatomical location was insular with various extensions, frontal, temporal or fronto-temporal in 8 (44.4%), parietal in 3 (16.7%), fronto-opercular in 4 (22.2%), Rolandic in two (11.1%), and the supplementary motor area (SMA) in one (5.6%). The patients had a mean age of 38.4 years (median 37.1, range 20.8-66.9). The mean surgical duration was 4.1 hours (median 4.2, range 2.6-6.4) with a mean duration of intraoperative MRI of 28.8 minutes (median 25, range 13-55). Overall, 61% (11/18) of patients underwent further resection, while 39% had no additional resection after intraoperative MRI. The mean preoperative and postoperative tumour volumes of the primary brain tumours were 34.7 cc (median 10.7, range 0.534-130.25) and 3.5 cc (median 0.5, range 0-17.4), respectively. Moreover, the proportion of the initially resected tumour volume at the time of intraoperative MRI (expressed as 100% from preoperative volume) and the final resected tumour volume were statistically significant (p= 0.01, Mann-Whitney test). The tumour remnants were commonly found posterior (5/9) or anterior (2/9) insular and in proximity with the motor strip (1/9) or language areas (e.g. Broca, 1/9). Further resection was not required in seven patients because there were no remnants (3/7), cortical stimulation approaching eloquent areas (3/7) and non-lesional epilepsy (1/7). The mean overall follow-up period was 15.8 months (median 12, range 3-36). The intraoperative MRI and awake microsurgical resection approach is feasible with extensive planning and multidisciplinary collaboration, as these methods are complementary and synergic rather than competitive to improve patient oncological outcomes and quality of life.

The Extent of Resection in Gliomas—Evidence-Based Recommendations on Methodological Aspects of Research Design

Modern neurosurgery has established maximal safe resection as a cornerstone in the management of diffuse gliomas. Evaluation of the extent of resection (EOR), and its association with certain outcomes or interventions, heavily depends on an adequate methodology to draw strong conclusions. We aim to identify weaknesses and limitations that may threaten the internal validity and generalizability of studies involving the EOR in patients with glioma and to suggest methodological recommendations that may help mitigate these threats. A systematic search was performed by querying PubMed, Web of Science, and Scopus since inception to April 30, 2021 using PICOS/PRISMA guidelines. Articles were then screened to identify high-impact studies evaluating the EOR in patients diagnosed with diffuse gliomas in accordance with predefined criteria. We identify common weakness and limitations during the evaluation of the EOR in the selected studies and then delineate potential methodological recommendations for future endeavors dealing with the EOR. We identified 31 high-impact studies and found several research design issues including inconsistencies regarding EOR terminology, measurement, data collection, analysis, and reporting. Although some of these issues were related to now outdated reporting standards, many were still present in recent publications and deserve attention in contemporary and future research. There is a current need to focus more attention to the methodological aspects of glioma research. Methodological inconsistencies may introduce weaknesses into the internal validity of the studies and hamper comparative analysis of cohorts from different institutions. We hope our recommendations will eventually help develop stronger methodological designs in future research endeavors.

The impact of intra-operative magnetic resonance imaging and 5-ALA in the achievement of gross total resection of gliomas: A systematic literature review and meta-analysis.

In an effort to maximize extent of resection (EOR) regarding gliomas, intraoperative MRI (i-MRI) and 5-aminolevulinic acid (5-ALA) have been developed. Our study aimed to investigate the comparative contribution of 5-aminolevulinic acid and i-MRI in maximizing EOR in gliomas. We searched the PubMed and ScienceDirect services for randomized controlled trials, controlled trials and interrupted time series studies evaluating the effect of i-MRI on gross total resection (GTR) rates and on overall survival in glioma patients. Our primary study endpoint was the definition of the percentage of patients who were offered GTR. Other relevant points of interest included the determination of overall and progression-free survival and subgroup analyses for level of evidence. I-MRI aids in achieving GTR (odds ratio 2.71, p&lt;0.0001). Magnet field strength does not affect significantly either GTR rates (p=0.08). The cost of the procedure is dependent on the workload of the i-MRI system. These data suggest that i-MRI or 5-ALA improves progression-free and overall survival, although there are several restrictions related to their effectiveness and reliability. I-MRI and 5-ALA are considered to be effective adjuncts in the achievement of GTR of gliomas. When these methods are compared, there is no definite conclusion regarding which method is more effective.

Radiomic Features Associated with Extent of Resection in Glioma Surgery.

Radiomics defines a set of techniques for extraction and quantification of digital medical data in an automated and reproducible way. Its goal is to detect features potentially related to a clinical task, like classification, diagnosis, prognosis, and response to treatment, going beyond the intrinsic limits of operator-dependency and qualitative description of conventional radiological evaluation on a mesoscopic scale. In the field of neuro-oncology, researchers have tried to create prognostic models for a better tumor diagnosis, histological and biomolecular classification, prediction of response to treatment, and identification of disease relapse. Concerning glioma surgery, the most significant aid that radiomics can give to surgery is to improve tumor extension detection and identify areas that are more prone to recurrence to increase the extent of tumor resection, thereby ameliorating the patients' prognosis. This chapter aims to review the fundamentals of radiomics models' creation, the latest advance of radiomics in neuro-oncology, and possible radiomic features associated with the extent of resection in the brain gliomas.

Intraoperative imaging technology to maximise extent of resection for glioma: a network meta-analysis.

Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach. To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary. We searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs). RCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI. Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. We identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound. Network meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies. One trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence). Intraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, is needed.

Intraoperative imaging technology to maximise extent of resection for glioma: a network meta-analysis

Background Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach. Objectives To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary. Search methods We searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs). Selection criteria RCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI. Data collection and analysis Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. Main results We identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound. Network meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies. One trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence). Authors' conclusions Intraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, is needed.

Resection versus biopsy in the treatment of multifocal glioblastoma: a weighted survival analysis.

Diffuse tumor invasion in multifocal/multicentric GBM (mGBM) often foreshadows poor survival outcome. The correlation between extent of resection in gliomas and patient outcome is well described. The objective of this study was to assess the effect of gross total resection compared to biopsy for mGBM on patient overall survival and progression free survival. Thirty-four patients with mGBM received either biopsy or resection of their largest enhancing lesion from 2011 to 2019. Relevant demographic, peri-operative, and radiographic data were collected. Tumor burden and extent of resection was assessed through measurement of pre-operative and post-operative contrast-enhancing volume. An adjusted Kaplan-Meier survival analysis was conducted using inverse probability of treatment weighting (IPTW) to account for the covariates of age, number of lesions, satellite tumor volume, total pre-operative tumor volume, degree of spread, and location. Thirty-four patients were identified with sixteen (47.1%) and eighteen (52.9%) patients receiving resection and biopsy respectively. Patients receiving resection exhibited greater median overall survival but not progression free survival compared to biopsy on IPTW analysis (p = 0.026, p = 0.411). Greater than or equal to 85% extent of resection was significantly associated with increased median overall survival (p = 0.016). Overall, our study suggests that resection of the largest contrast-enhancing lesion may provide a survival benefit. Our volumetric analysis suggests that a greater degree of resection results in improved survival. Employing IPTW analysis, we sought to control for selection bias in our retrospective analysis. Thus, aggressive surgical treatment of mGBM may offer improved outcomes. Further clinical trials are needed.

Extent of Glioma Resection on Intraoperative Ultrasound Correlates Well with Postoperative MRI Results

Background: Maximal surgical resection is thought to confer survival benefit for both high- and low-grade gliomas. Intraoperative imaging assists with achieving maximal surgical resection. Different intraoperative imaging modalities have been implemented, but intra-operative MRI has a high cost that may limit its uptake in resource scarce healthcare systems. Objectives: This study aims to evaluate intraoperative ultrasound as a surrogate for intra and post-operative MRI for assessing the extent of resection of glioma. Methods: A partially prospective comparative study, which compares a prospective cohort group with a historical control group. We evaluated 74 glioma patients, who all underwent surgery in a regional UK Neurosurgical centre between October 2013 and October 2017. The study population was divided into 2 groups based on the use of ultrasound to guide the resection. We compared the size of the lesion prior and after excision to evaluate the extent of resection and undertook comparison with post-operative MRI. Results: The mean extent of resection on the ultrasound images was 96.1 % and 97.7 % on the postoperative MR. Using Spearman’s correlation; extent of resection on the ultrasound images was strongly correlated with the extent of resection on the postoperative MR images (P=value &lt;0.001). The use of intraoperative ultrasound was associated with a significant increase in the number of patients in whom 95% or greater extent of resection was achieved (Fisher’s exact test P= value 0.033). Conclusion: Intra-operative ultrasonography could provide a reliable and cheaper alternative to intraoperative MRI to improve the extent of resection in glioma surgery.

High-field intraoperative MRI and glioma surgery: results after the first 100 consecutive patients.

High-field intraoperative MRI (IoMRI) is part of the neurosurgical armamentarium to improve the extent of glioma resection (EOR). To report our oncological and functional outcomes using IoMRI for neuronavigated glioma surgery. In this prospective monocentric study, we reported 100 consecutive adult patients operated on for glioma using IoMRI with neuronavigation, under general anesthesia without intraoperative stimulation, from July 2014 to April 2017. The volumetric evaluation was based on the FLAIR hypersignal for non-enhancing tumors after Gadolinium infusion and on the T1 hypersignal after Gadolinium infusion for enhancing tumors. We evaluated the surgical workflow, the EOR and the clinical outcomes (using Karnofsky performance score (KPS)). Sixty-nine patients underwent one IoMRI, and 31 from two IoMRI controls. At first IoMRI, the median tumor residue was higher in the FLAIR group than in the T1G+ group whereas no more difference was reported after the second IoMRI between the 2 groups (p = 0.56). Additional resection was performed 6 times more frequently in the FLAIR group (OR = 5.7, CI (1.9-17)). The median EOR was 100% (IQR, 93.6-100) whatever the tumor type (first surgery or recurrence) and location. Higher residues were reported only in the insula area (p = 0.004). The median KPS was 90 (IQR, 80-100) at discharge, 3, 6 and 12months after surgery, with no statistical difference between low- and high-grade gliomas (p = 0.34). IoMRI neuronavigated surgery provided maximal EOR whatever the type of glioma and location. IoMRI was all the more useful for non- or minimally enhancing tumors. The step by step surgical resection, introducing the concept of "staged volume" surgery, ensured a high security for the surgeon and low permanent morbidity for the patients.

Sharpening the Surgeon's Knife: Value of Extent of Resection for Glioma in Molecular Age

Sharpening the Surgeon's Knife: Value of Extent of Resection for Glioma in Molecular Age

High-field intraoperative MRI in glioma surgery: A prospective study with volumetric analysis of extent of resection and functional outcome

BackgroundHigh-field intraoperative MRI (IoMRI) is a useful tool to improve the extent of glioma resection (EOR). ObjectiveTo compare the interest of 1.5T IoMRI in glioma surgery between enhancing and non-enhancing tumors, based on volumetric analysis. MethodsA prospective single-center study included consecutive adult patients undergoing glioma surgery with IoMRI. Volumetric evaluation was based on FLAIR hypersignal after gadolinium injection in non-enhancing tumors and T1 hypersignal after gadolinium injection in enhancing tumors. Endpoints comprised: residual tumor volume (RTV), EOR, workflow and clinical outcome on Karnofsky performance score (KPS). ResultsFifty-three surgeries were performed from July 2014 to January 2016. Thirty-four patients underwent one IoMRI, and 19 two IoMRIs. In non-enhancing tumors, intraoperative RTV on 1st IoMRI T2/FLAIR was higher than in enhancing tumors on T1 sequences (7.25cm3 vs. 0.74cm3, respectively; P=0.008), whereas the RTV on 2nd IoMRIs and final RTV were no longer significantly different. After IoMRI, 72% of patients underwent additional resection. In non-enhancing tumors, EOR increased from 77.3% on 1st IoMRI to 97.4% on last MRI (P<0.001). Taking all tumors together, final RTV values were: median=0cm3, mean=3.9cm3. Mean final EOR was 94%. In 25% of patients, KPS was reduced during early postoperative course; at 3 and 6 months postoperatively, median KPS was 90. ConclusionIntraoperative MRI guidance significantly enhanced the extent of glioma resection, especially for non- or minimally enhancing tumors, while preserving patient autonomy.

Progression of basic research, clinical application of photodynamic therapy and fluorescence-guided surgery in glioma treatment

The prognosis of glioma remains poor because of the infiltrative nature and the high local relapse rate. The current goals for patients with gliomas is maximal safe resection and adjuvant therapy. Tumor-specific photosensitizer, such as hematoporphyrin derivative (HpD) 5-aminolevulinic acid (5-ALA), can be selective up-taken and accumulated in tumor tissue. Light with appropriate wavelength can penetrate tumor tissue and excite the photosensitizer. The excited photosensitizer within glioma cells permits fluorescence visualization of tumor tissue during surgery and has been introduced in treatment of glioma as fluorescence-guided surgery (FGS). On the other hand, the toxicity of singlet oxygen generated by the excited photosensitizer has been used as photodynamic therapy (PDT) in selective destruction of the tumor. Some reports demonstrated the usefulness of adding PDT as an intraoperative adjuvant therapy, but the complexity associated with its implementation and the introduction of TMZ prevented PDT from becoming a routine therapy. However, FGS using 5-ALA in patients with malignant brain tumors has surfaced globally and may become a useful tool in increasing the extent of resection in gliomas.

Intraoperative imaging technology to maximise extent of resection for glioma.

Extent of resection is considered to be a prognostic factor in neuro-oncology. Intraoperative imaging technologies are designed to help achieve this goal. It is not clear whether any of these sometimes very expensive tools (or their combination) should be recommended as standard care for people with brain tumours. We set out to determine if intraoperative imaging technology offers any advantage in terms of extent of resection over standard surgery and if any one technology was more effective than another. To establish the overall effectiveness and safety of intraoperative imaging technology in resection of glioma. To supplement this review of effects, we also wished to identify cost analyses and economic evaluations as part of a Brief Economic Commentary (BEC). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7, 2017), MEDLINE (1946 to June, week 4, 2017), and Embase (1980 to 2017, week 27). We searched the reference lists of all identified studies. We handsearched two journals, the Journal of Neuro-Oncology and Neuro-oncology, from 1991 to 2017, including all conference abstracts. We contacted neuro-oncologists, trial authors, and manufacturers regarding ongoing and unpublished trials. Randomised controlled trials evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included intraoperative MRI (iMRI), fluorescence-guided surgery, ultrasound, and neuronavigation (with or without additional image processing, e.g. tractography). Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. We identified four randomised controlled trials, using different intraoperative imaging technologies: iMRI (2 trials including 58 and 14 participants, respectively); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around autumn 2018. We identified no trials for ultrasound.Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies. All studies included people with high-grade glioma only.Extent of resection was increased in one trial of iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI) 0.02 to 0.96; 1 study, 49 participants; very low-quality evidence) and in the trial of 5-ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study, 270 participants; low-quality evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants, therefore the trial provides very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection.Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-quality evidence). Overall, reported events were low in most trials. There was no clear evidence of improvement in overall survival with 5-ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270 participants; low-quality evidence). Progression-free survival data were not available in an appropriate format for analysis. Data for quality of life were only available for one study and suffered from significant attrition bias (very low-quality evidence). Intra-operative imaging technologies, specifically iMRI and 5-ALA, may be of benefit in maximising extent of resection in participants with high grade glioma. However, this is based on low to very low quality evidence, and is therefore very uncertain. The short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly. Further research, including studies of ultrasound-guided surgery, is needed.

Real Impact of Intraoperative Magnetic Resonance Imaging in Newly Diagnosed Glioblastoma Multiforme Resection: An Observational Analytic Cohort Study From a Single Surgeon Experience

The goal of surgery for brain glioma is to maximize the extent of tumor resection, avoiding postoperative functional impairment. Intraoperative (Io) magnetic resonance imaging (MRI) has emerged as an effective tool to guide a safer glioma resection. The objective of this study is to assess the real impact of Io MRI in O-6-methylguanine-DNA methyltransferase and non-O-6-methylguanine-DNA methyltransferase methylated glioma surgery. A total of 129 patients suffering glioblastoma who underwent craniotomy for tumor resection were retrospectively evaluated between March 2009 and January 2017 at 2 different affiliated hospitals of the same university. We compared a subgroup of 65 patients operated on without Io MRI (group A) with a second subgroup of 64 patients who underwent surgery with the aid of Io MRI (group B). Volumetric analyses of the extent of resection (EOR) were performed using gadolinium-enhanced T1-weighted imaging. All surgical procedures were performed by a single surgeon (the senior author). The average EOR increased from 86.23%±10.51% for group A to 94.01% ± 7.42% in patients included in group B. The secondary end points of this study were progression-free survival (PFS) and overall survival (OS). PFS was found to be 5.38 ± 2.32 months for group A versus 7.89 ± 2.75 months for group B. Regarding OS, the average value was 13.38 ± 4.06 months for group A versus 16.43±3.41 months for group B. We can affirm that 1.5-T Io MRI is a safe and effective technique, and its use optimizes significantly both the extent of glioma resection and the survival of patients.

Surgical oncology for gliomas: the state of the art.

Surgical resection remains the mainstay of treatment for patients with glioma of any grade. Maximal resection of the tumour is central to achieving long-term disease control; however, the relationship between the extent of glioma resection and actual clinical benefit for the patient is predicated on the balance between cytoreduction and neurological morbidity. For the neurosurgical oncologist, the clinical rationale for undertaking increasingly extensive resections has gained traction. In parallel, novel surgical techniques and technologies have been developed that help improve patient outcomes. During the past decade, neurosurgeons have leveraged advanced intraoperative imaging methods, fluorescence-based tumour biomarkers, and real-time mutational analyses to maximize the extent of tumour resection. In addition, approaches to minimizing the risk of perioperative morbidity continue to be improved through the combined use of stimulation-mapping techniques, corticospinal tract imaging, and stereotactic thermal ablation. Taken together, these modern principles of neurosurgical oncology bear little resemblance to historical therapeutic strategies for patients with glioma and have dramatically altered the approach to the treatment of patients with these brain tumours. Herein, we outline the state of the art in surgical oncology for gliomas.

Intraoperative imaging technology to maximise extent of resection for glioma

Intraoperative imaging technology to maximise extent of resection for glioma

A case of left frontal high-grade glioma diagnosed during pregnancy

BackgroundAs pregnancy accelerates glioma growth, therapeutic abortion has been recommended prior to tumor resection. Additionally, it has also been suggested that the extent of glioma resection is closely correlated with patient survival.Case presentationA 162-cm, 61.4-kg, 30-year-old, right-handed primigravida was referred to our institution at 21 weeks gestation to obtain a second opinion. At 18 weeks gestation, the patient developed new-onset generalized convulsive seizures (GCSs), which were poorly controlled by anticonvulsant polytherapy, early in the second trimester. A 6-cm lesion located in her left frontal supplementary motor area (SMA) was suspected as a grade III glioma, classified according to the World Health Organization (WHO) guidelines. Due to the limited evidence on the use of adjuvant therapy during pregnancy, tumors causing neurological symptoms and seizures must be treated, in order to stabilize the maternal condition and enable a safe birth. In the case of pregnant patients, awake craniotomy using intraoperative magnetic resonance imaging (iMRI) is considered advantageous, achieving gross total resection with a reduction of direct cortical stimulation, which may induce seizure, and so reducing fetal exposure to anesthetics. The “Asleep-Awake-Asleep” technique was performed at 27 weeks and 2 days gestation. As use of propofol in pregnant patients is prohibited, general anesthesia was maintained through administration of sevoflurane and remifentanil until the first scan of iMRI, and was subsequently re-induced with dexmedetomidine when tumor removal had been accomplished. A supraglottic airway (SGA) was used until the patient’s cranium was opened. There were no complications during either the procedure or the post-operative period. At 35 weeks gestation, the patient delivered a healthy baby of 2317 g. Pathological examination of the patient, revealed an anaplastic astrocytoma, thus radiotherapy and chemotherapy began 2 months post-delivery. There is no evidence of tumor recurrence in the patient and the child did not show any medical or developmental concerns at the point of the 17-month follow-up.ConclusionsSince evidence on the use of adjuvant therapy during pregnancy is limited, extensive resection with functional monitoring is recommended if a brain tumor is presumed to be malignant. Awake craniotomy is considered advantageous to pregnant patients because subjective movement preserves the patient’s motor function and reduces fetal exposure to anesthetics. Therefore, providing multidisciplinary discussion takes place within the decision-making process, as well as careful perioperative preparation, awake craniotomy should be considered, even in the case of pregnant patients.

Extent of Resection in Glioma-A Review of the Cutting Edge.

Modern glioma surgery has evolved from the principal belief that safe, maximal tumor resection improves symptom management, quality of life, progression-free survival, and overall survival in both low-grade and high-grade glioma. However, in the absence of level I data, the overwhelming support for this idea is derived largely from retrospective series. As a result, the influence of increasing extent of resection and reducing tumor burden on the efficacy of postoperative chemotherapy and radiotherapy, and survival, remains inadequately defined. This situation is particularly true because gliomas represent a widely heterogeneous group of tumors with varying behaviors and prognoses rooted in their complex molecular profile. The neurosurgical community has made a large effort to define the clinical benefits of maximizing tumor resection, with particular attention paid to the ever-evolving understanding of glioma molecular heterogeneity. Important new technologies have been developed concurrently to mitigate neurologic risks related to the pursuit of maximizing extent of resection. These advances reflect the modern goal of glioma surgery to find the optimal balance between tumor removal and neurologic compromise. We review the current literature supporting safe, maximal resection for gliomas.