Does the routine use of intraoperative MRI prolong progression free survival in low-grade glioma surgery? A retrospective study

2015 ◽  
Vol 3 (3-4) ◽  
Author(s):  
Andrej Pala ◽  
Ralph König ◽  
Michal Hlavac ◽  
Christian Rainer Wirtz ◽  
Jan Coburger
Keyword(s):  
Retrospective Study ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Low Grade Glioma ◽  
World Health ◽  
Low Grade ◽  
Free Survival ◽  
Historical Group

AbstractAvailable data imply that extent of resection (EOR) improves progression free survival (PFS) in patients harboring a low-grade glioma (LGG). Intraoperative high-field magnetic resonance imaging (iMRI) is an established diagnostic tool that can detect residual tumors in LGG surgery. We conducted a retrospective study to evaluate the extent of resection, clinical outcome and PFS in conventional and iMRI-based LGG resection.A total of 69 patients was assessed. Only World Health Organization (WHO) grade II LGGs were evaluated. Thirty-three patients had surgery using iMRI (2008–2013). Thirty-six patients underwent surgery before introduction of iMRI at our center (2000–2008). Demographic data, extent of resection (EOR), complication rate, overall time of surgery and progression free survival were evaluated.The majority of patients were treated for a diffuse astrocytoma in both cohorts (iMRI: 46.9%, historical (hist.): 61.1%). Extent of resection was a positive prognostic factor for longer PFS according to Cox regression multivariate analysis controlled by eloquent location, tumor recurrence and histological subtype [P<0.001, hazard ratio (HR) 0.247]. Additionally, the Cox regression showed the advantage and longer PFS of iMRI-assisted resections using the same settings (P=0.038, HR=0.378). Permanent neurological deficits (PND) after surgery were found in 12.5% (n=4) of the iMRI group and in 22.2% (n=8) of the historical group. Duration of surgery was significantly higher in the iMRI group (iMRI: 6.3 h, hist.: 4.3 h, P<0.036). However, there was no significant increase of postoperative surgical complications. Gross total resection (GTR) was achieved in 63.6% (n=21) of iMRI patients and 27.8% (n=10, P<0.0069) in the historical control, respectively. Binary logistic regression showed that iMRI has a significant impact on tumor remnants (P<0.001).In our study we have confirmed EOR to be an important positive prognostic factor for PFS. At our center, compared to a historical group, the routine use of iMRI increases EOR and was associated with a decrease in complications. Due to a selection bias no final conclusion can be drawn as to whether the use of iMRI increases PFS.

scholarly journals Contemporary assessment of extent of resection in molecularly defined categories of diffuse low-grade glioma: a volumetric analysis

2020 ◽  
Vol 133 (5) ◽  
pp. 1291-1301 ◽  
Author(s):  
Vasileios K. Kavouridis ◽  
Alessandro Boaro ◽  
Jeffrey Dorr ◽  
Elise Y. Cho ◽  
J. Bryan Iorgulescu ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Cox Regression ◽  
Molecular Subtypes ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival

OBJECTIVEWhile the effect of increased extent of resection (EOR) on survival in diffuse infiltrating low-grade glioma (LGG) patients is well established, there is still uncertainty about the influence of the new WHO molecular subtypes. The authors designed a retrospective analysis to assess the interplay between EOR and molecular classes.METHODSThe authors retrospectively reviewed the records of 326 patients treated surgically for hemispheric WHO grade II LGG at Brigham and Women’s Hospital and Massachusetts General Hospital (2000–2017). EOR was calculated volumetrically and Cox proportional hazards models were built to assess for predictive factors of overall survival (OS), progression-free survival (PFS), and malignant progression–free survival (MPFS).RESULTSThere were 43 deaths (13.2%; median follow-up 5.4 years) among 326 LGG patients. Median preoperative tumor volume was 31.2 cm3 (IQR 12.9–66.0), and median postoperative residual tumor volume was 5.8 cm3 (IQR 1.1–20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm3; 95% CI 1.00–1.03; p = 0.016), PFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.001), and MPFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.035). This result was more pronounced in the worse prognosis subtypes of IDH-mutant and IDH-wildtype astrocytoma, for which differences in survival manifested in cases with residual tumor volume of only 1 cm3. In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm3. Other significant predictors of OS were age at diagnosis, IDH-mutant and IDH-wildtype astrocytoma classes, adjuvant radiotherapy, and increasing preoperative volume.CONCLUSIONSThe results corroborate the role of EOR in survival and malignant transformation across all molecular subtypes of diffuse LGG. IDH-mutant and IDH-wildtype astrocytomas are affected even by minimal postoperative residuals and patients could potentially benefit from a more aggressive surgical approach.

scholarly journals Management of low-grade glioma: a systematic review and meta-analysis

2018 ◽  
Vol 6 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Timothy J Brown ◽  
Daniela A Bota ◽  
Martin J van Den Bent ◽  
Paul D Brown ◽  
Elizabeth Maher ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Low Grade Glioma ◽  
World Health ◽  
Subtotal Resection ◽  
Low Grade ◽  
Evidence Based ◽  
Free Survival ◽  
Low Grade Gliomas

Abstract Background Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma. Methods A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy. Results Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas. Conclusions Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.

scholarly journals A survival analysis of surgically treated incidental low-grade glioma patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lingcheng Zeng ◽  
Qi Mei ◽  
Hua Li ◽  
Changshu Ke ◽  
Jiasheng Yu ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Total Resection ◽  
Surgical Timing ◽  
Asymptomatic Group ◽  
Free Survival ◽  
Symptomatic Group ◽  
Significant Difference ◽  
Asymptomatic Phase

AbstractTo evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P < 0.05), but there was no significant difference in the total resection rate between the two groups. The incidence of postoperative complications (15.4%) and postoperative epilepsy (23.1%) was higher in the symptomatic group than in the asymptomatic group (4.1% and 10.2%, respectively). Multivariate analysis showed that surgical timing, namely, surgery performed before or after symptom occurrence, had no significant effect on PFS, OS or MPFS, while total resection significantly prolonged PFS, OS and MPFS, and the pathology of oligodendroglioma was positively correlated with PFS and OS (P < 0.05). Surgical timing for iLGGs should facilitate total resection. If total resection can be achieved, even after symptom occurrence, patients can achieve comparable survival benefits to those treated with surgery in the asymptomatic phase.

scholarly journals P04.16 TP53 mutations in codon 273 is predictive of overall survival in astrocytoma patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii32-iii32
Author(s):  
H Noor ◽  
R Rapkins ◽  
K McDonald
Keyword(s):  
Overall Survival ◽  
Tp53 Mutation ◽  
Progression Free Survival ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Wild Type ◽  
Mutation Status ◽  
Free Survival ◽  
Tp53 Mutations ◽  
Fresh Frozen

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C>T and c.818 G>A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p<0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p<0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p<0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

Outcomes in Reoperated Low-Grade Gliomas

Neurosurgery ◽  
2015 ◽  
Vol 77 (2) ◽  
pp. 175-184 ◽  
Author(s):  
Rohan Ramakrishna ◽  
Adam Hebb ◽  
Jason Barber ◽  
Robert Rostomily ◽  
Daniel Silbergeld
Keyword(s):  
Scale Score ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Karnofsky Performance Scale ◽  
Low Grade ◽  
Free Survival ◽  
First Recurrence ◽  
Karnofsky Performance Scale Score ◽  
Performance Scale

Abstract BACKGROUND: Low-grade gliomas (LGGs) comprise a diverse set of intrinsic brain tumors that correlate strongly with survival. Data on the effect of reoperation are sparse. OBJECTIVE: To evaluate the effect of reoperation on patients with LGG. METHODS: Fifty-two consecutive patients with reoperated LGGs treated at the University of Washington between 1986 and 2004 were identified and evaluated in a retrospective analysis. RESULTS: The average overall survival (OS) for this cohort was 12.95 ± 0.96 years. The overall 10-year survival rate was 57%. The absence of any residual tumor at either the first or second operation was associated with significantly increased OS. Negative prognostic variables for OS included the use of upfront radiation and pathology at recurrence. The average overall progression-free survival to the first recurrence (PFS1) was 6.23 ± 0.51 years. Positive prognostic factors for improved PFS1 included the use of upfront radiation therapy. Variables not associated with differences in PFS1 included the use of upfront chemotherapy, enhancement, pathology, extent of resection, the presence of residual tumor, and Karnofsky Performance Scale score &lt;80. The average overall progression-free survival to the second recurrence was 2.73 ± 0.39 years. Pathology at recurrence was associated with significant differences in progression-free survival to the second recurrence, as was extent of resection at time of first recurrence, and Karnofsky Performance Scale score &lt;80. CONCLUSION: This is among the largest studies to assess variables associated with outcome in patients with reoperated LGG. Reresection appears to provide significant benefit, and extent of resection remains the strongest predictor of OS.

Role of Extent of Resection in the Long-Term Outcome of Low-Grade Hemispheric Gliomas

2008 ◽  
Vol 26 (8) ◽  
pp. 1338-1345 ◽  
Author(s):  
Justin S. Smith ◽  
Edward F. Chang ◽  
Kathleen R. Lamborn ◽  
Susan M. Chang ◽  
Michael D. Prados ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Malignant Progression ◽  
Low Grade ◽  
Karnofsky Performance Score ◽  
Long Term Outcome ◽  
Free Survival

Purpose The prognostic role of extent of resection (EOR) of low-grade gliomas (LGGs) is a major controversy. We designed a retrospective study to assess the influence of EOR on long-term outcomes of LGGs. Patients and Methods The study population (N = 216) included adults undergoing initial resection of hemispheric LGG. Region-of-interest analysis was performed to measure tumor volumes based on fluid-attenuated inversion-recovery (FLAIR) imaging. Results Median preoperative and postoperative tumor volumes and EOR were 36.6 cm3 (range, 0.7 to 246.1 cm3), 3.7 cm3 (range, 0 to 197.8 cm3) and 88.0% (range, 5% to 100%), respectively. There was no operative mortality. New postoperative deficits were noted in 36 patients (17%); however, all but four had complete recovery. There were 34 deaths (16%; median follow-up, 4.4 years). Progression and malignant progression were identified in 95 (44%) and 44 (20%) cases, respectively. Patients with at least 90% EOR had 5- and 8-year overall survival (OS) rates of 97% and 91%, respectively, whereas patients with less than 90% EOR had 5- and 8-year OS rates of 76% and 60%, respectively. After adjusting each measure of tumor burden for age, Karnofsky performance score (KPS), tumor location, and tumor subtype, OS was predicted by EOR (hazard ratio [HR] = 0.972; 95% CI, 0.960 to 0.983; P < .001), log preoperative tumor volume (HR = 4.442; 95% CI, 1.601 to 12.320; P = .004), and postoperative tumor volume (HR = 1.010; 95% CI, 1.001 to 1.019; P = .03), progression-free survival was predicted by log preoperative tumor volume (HR = 2.711; 95% CI, 1.590 to 4.623; P ≤ .001) and postoperative tumor volume (HR = 1.007; 95% CI, 1.001 to 1.014; P = .035), and malignant progression-free survival was predicted by EOR (HR = 0.983; 95% CI, 0.972 to 0.995; P = .005) and log preoperative tumor volume (HR = 3.826; 95% CI, 1.632 to 8.969; P = .002). Conclusion Improved outcome among adult patients with hemispheric LGG is predicted by greater EOR.

scholarly journals The Merits of Awake Craniotomy for Glioblastoma in the Left Hemispheric Eloquent Area: One Institution Experience

2020 ◽  
Author(s):  
Ying-Ching Li ◽  
Hsiao-Yean Chiu ◽  
Ya-Jui Lin ◽  
Ko-Ting Chen ◽  
Peng-Wei Hsu ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Extent Of Resection ◽  
Awake Craniotomy ◽  
Treatment Center ◽  
Low Grade ◽  
Karnofsky Performance Score ◽  
Free Survival ◽  
Neurological Outcomes ◽  
Eloquent Cortex ◽  
The Mean

Abstract Background Awake craniotomy (AC) with intraoperative stimulation mapping is the standard treatment for gliomas, especially those on the eloquent cortex. Many studies have reported survival benefits with the use of AC in patients with glioma, however most of these studies have focused on low-grade glioma. The aim of this study was to evaluate the experience of one treatment center over 10 years for resection of left hemispheric eloquent glioblastoma. Methods This retrospective analysis included 48 patients with left hemispheric eloquent glioblastoma who underwent AC and 61 patients who underwent surgery under general anesthesia (GA) between 2008 and 2018. Perioperative risk factors, extent of resection (EOR), preoperative and postoperative Karnofsky Performance Score (KPS), progression-free survival (PFS) and overall survival (OS) were assessed. Results The postoperative KPS was significantly lower in the GA patients compared to the AC patients (p=0.002). The EOR in the GA group was 90.2% compared to 94.9% in the AC group (p=0.003). The mean PFS was 18.9 months in the GA group and 23.2 months in the AC group (p=0.001). The mean OS was 25.5 months in all patients, 23.4 months in the GA group, and 28.1 months in the AC group (p<0.001). In multivariate analysis, the EOR and preoperative KPSindependently predicted better OS. Conclusion The patients with left hemispheric eloquent glioblastoma in this study had better neurological outcomes, maximal tumor removal, and better PFS and OS after AC than surgery under GA. Awake craniotomy should be performed in these patients if the resources are available.

High Response Rate to Cisplatin/Etoposide Regimen in Childhood Low-Grade Glioma

2002 ◽  
Vol 20 (20) ◽  
pp. 4209-4216 ◽  
Author(s):  
Maura Massimino ◽  
Filippo Spreafico ◽  
Graziella Cefalo ◽  
Riccardo Riccardi ◽  
John David Tesoro-Tess ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Objective Response ◽  
Progression Free Survival ◽  
Neurofibromatosis Type ◽  
High Response Rate ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Free Survival

PURPOSE: The aim of this study was to avoid radiotherapy and to induce an objective response in children with low-grade glioma (LGG) using a simple chemotherapy regimen based on cisplatin and etoposide. PATIENTS AND METHODS: Thirty-four children (median age, 45 months) with unresectable LGG were treated with 10 monthly cycles of cisplatin (30 mg/m2/d on days 1 to 3) and etoposide (150 mg/m2/d on days 1 to 3). Tumor originated in the visual pathway in 29 patients, in the temporal lobe in two, in the frontal lobe in two, and in the spine in one. Eight children were affected by neurofibromatosis type 1. Objective tumor response and toxicity were evaluated by magnetic resonance imaging and neurologic and functional tests at 3-month intervals. RESULTS: An objective response was obtained in 24 (70%) of 34 patients, whereas the others had stable disease. None of the children were electively irradiated. In 31 previously untreated children, overall survival was 100% and progression-free survival was 78% at 3 years, with a median follow-up of 44 months. Acute toxicity was unremarkable; 28% patients evaluated for acoustic neurotoxicity revealed a loss of perception of high frequencies. CONCLUSION: Cisplatin and etoposide combined treatment is one of the most active regimens for LGG in children and allows avoidance of radiotherapy in the vast majority of patients.

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