Impact of extent of resection of glioblastoma multiforme (GBM) in the era of chemoradiation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13029-e13029
Author(s):  
B. J. Slotman ◽  
W. S. Eppinga ◽  
J. C. Reijneveld ◽  
D. P. Noske ◽  
J. Buter ◽  
...  

e13029 Background: Controversy remains regarding the impact of the extent of resection (EOR) on survival in patients with GBM (Sanai 2008). The main reason for this is the fact that most studies were based on the surgeon's estimate of the EOR, which is known to be unreliable, rather than early postoperative MRI scans (po-MRI). Data for the current standard of postoperative chemo-radiotherapy (CTRT) have recently been reported, but suffer from the same limitation (Gorlia 2008). We studied the prognostic impact of the EOR using early (<72 hours) po-MRI scans in a cohort of GBM patients treated with CTRT in a single center. Methods: The results of 48 consecutive patients (35 male, 13 female; age 18–73 yrs) treated with surgery, followed by concurrent CTRT (60 Gy plus temozolomide) and adjuvant temozolomide were assessed with respect to survival and relapse patterns. EOR was determined by both the surgeon's estimation and early po-MRI scans that were available in all but two patients. EOR was categorized as biopsy (N = 3), partial resection (N = 24), major resection (N = 11; i.e., total resection according to the surgeon's report, but residual tumor on po-MRI), and total resection (N = 10; i.e. no residual tumor on po-MRI). Results: Median overall survival of the entire cohort was 18.9 months, and EOR was the only significant prognostic factor (p = 0.02) on multivariate analysis, which also included age, gender, performance, and radiotherapy target volume. 2-year survival rates improved significantly with increasing EOR, with 0%, 18.9%, 68.6%, and 100% for biopsy, partial-, major-, and total resection, respectively. In-field progression was the predominant pattern of failure in 27 out of 30 patients (90%) with a recurrence. Time to neurological progression (TNP) was significantly correlated with EOR (p < 0.001). Median TNP was 3.0 months for biopsy, 7.0 months for partial resection, 20.5 months for major resection, and was not reached for total resection. Conclusions: With the use of more effective local therapy in the form of surgery and CTRT, the prognostic impact of the EOR on survival appears to be higher than previously reported. This should be accounted for in future trials. No significant financial relationships to disclose.

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv19-iv19
Author(s):  
Theodore Hirst ◽  
Patrick McAleavey ◽  
Tom Flannery

Abstract Aims The impact on extent of resection (EOR) in glioblastoma has been well documented. It is clear that gross-total resection (GTR) confers best overall survival (OS), however the minimum EOR required to confer a survival benefit over biopsy is debated. Recent studies favour partial resection (PR) over biopsy for IDH-wildtype, MGMT-unmethylated tumours. We describe our experiences locally with these principles in mind. Method Retrospective evaluation of a single surgeon cohort. All patients over 18 years old, undergoing a surgical treatment for histologically confirmed GBM in the stated period were included. We collected information on demographics, tumour volume, EOR, complications, adjuvant therapies, molecular profile, and OS. We used log rank tests and Cox Proportional Hazards Models to identify factors associated with OS. Results The patient and tumour characteristics of our cohort were similar to those documented in the literature. The mean age was 56.6 years. 72 patients underwent biopsy and 202 had debulking surgery. Median OS was 11 months. Of those debulked, gross-total resection was achieved in 41 patients (20%); associated median OS was 29 months. Patients receiving partial resection (defined as EOR &lt;80%) had no clear survival benefit over patients undergoing biopsy (median OS 6 vs 5 months) but had a higher rate of post-op neurological deficit (3% vs 12%). Tumour molecular profile appeared to influence survival outcome in a manner comparable to worldwide experience. Conclusion In our experience, partial resection is not a justifiable surgical aim in the typical glioblastoma cohort. The limited benefit that it may confer over biopsy appears to be outweighed by the risk of neurological deficit that affects quality and probably quantity of life. This finding applies to our glioblastoma population in general as well as those specifically with an MGM-unmethylated tumour.


2017 ◽  
Vol 126 (2) ◽  
pp. 418-430 ◽  
Author(s):  
Sivashanmugam Dhandapani ◽  
Harminder Singh ◽  
Hazem M. Negm ◽  
Salomon Cohen ◽  
Mark M. Souweidane ◽  
...  

OBJECTIVE Craniopharyngiomas can be difficult to remove completely based on their intimate relationship with surrounding visual and endocrine structures. Reoperations are not uncommon but have been associated with higher rates of complications and lower extents of resection. So radiation is often offered as an alternative to reoperation. The endonasal endoscopic transsphenoidal approach has been used in recent years for craniopharyngiomas previously removed with craniotomy. The impact of this approach on reoperations has not been widely investigated. METHODS The authors reviewed a prospectively acquired database of endonasal endoscopic resections of craniopharyngiomas over 11 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, performed by the senior authors. Reoperations were separated from first operations. Pre- and postoperative visual and endocrine function, tumor size, body mass index (BMI), quality of life (QOL), extent of resection (EOR), impact of prior radiation, and complications were compared between groups. EOR was divided into gross-total resection (GTR, 100%), near-total resection (NTR, > 95%), and subtotal resection (STR, < 95%). Univariate and multivariate analyses were performed. RESULTS Of the total 57 endonasal surgical procedures, 22 (39%) were reoperations. First-time operations and reoperations did not differ in tumor volume, radiological configuration, or patients' BMI. Hypopituitarism and diabetes insipidus (DI) were more common before reoperations (82% and 55%, respectively) compared with first operations (60% and 8.6%, respectively; p < 0.001). For the 46 patients in whom GTR was intended, rates of GTR and GTR+NTR were not significantly different between first operations (90% and 97%, respectively) and reoperations (80% and 100%, respectively). For reoperations, prior radiation and larger tumor volume had lower rates of GTR. Vision improved equally in first operations (80%) compared with reoperations (73%). New anterior pituitary deficits were more common in first operations compared with reoperations (51% vs 23%, respectively; p = 0.08), while new DI was more common in reoperations compared with first-time operations (80% vs 47%, respectively; p = 0.08). Nonendocrine complications occurred in 2 (3.6%) first-time operations and no reoperations. Tumor regrowth occurred in 6 patients (11%) over a median follow-up of 46 months and was not different between first versus reoperations, but was associated with STR (33%) compared with GTR+NTR (4%; p = 0.02) and with not receiving radiation after STR (67% vs 22%; p = 0.08). The overall BMI increased significantly from 28.7 to 34.8 kg/m2 over 10 years. Six months after surgery, there was a significant improvement in QOL, which was similar between first-time operations and reoperations, and negatively correlated with STR. CONCLUSIONS Endonasal endoscopic transsphenoidal reoperation results in similar EOR, visual outcome, and improvement in QOL as first-time operations, with no significant increase in complications. EOR is more impacted by tumor volume and prior radiation. Reoperations should be offered to patients with recurrent craniopharyngiomas and may be preferable to radiation in patients in whom GTR or NTR can be achieved.


2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Hieu Trong Le ◽  
Tam N.M. Ngo ◽  
Kar-Ming Fung ◽  
James D. Battiste ◽  
...  

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.


2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii18-ii19
Author(s):  
Takahiro Yamauchi ◽  
Ryuhei Kitai ◽  
Yoshinori Shibaike ◽  
Mizuki Oiwa ◽  
Shintaro Yamada ◽  
...  

Abstract OBJECTIVE To improve resection rate, multiple operative modalities have been essential for glioblastoma (GBM) surgery. Aim of this study is to clarify the impact of intraoperative computed tomography (i-CT) for GBM surgery with 5-aminolevulinic acid photodynamic diagnosis (5-ALA PDD). METHODS Consecutive 24 patients newly diagnosed GBM were analyzed, retrospectively. To exclude 6 patients decided timing for i-CT based on neural monitoring, 18 patients performed i-CT after total resection of 5-ALA positive lesion were included, finally. RESULTS The median age was 58 years old, and average preoperative tumor volume was 47.78 cm3. Tumor locations were frontal lobe 5 (27%), parietal lobe 3 (17%), temporal lobe 9 (50%), and corpus callosum 1 (6%). Seventeen tumors (78%) harbored in eloquent area. After i-CT performed, 7 (39%) were confirmed residual tumor, and additional resections were needed. Subtotal resection (STR) was 5 and partial resection (PR) was 2 on volumetry in i-CT before additional resection. After additional resection, those cases were judged as 2 gross total resection (GTR), 4 STR and 1 PR in postoperative magnetic resonance imaging (MRI). 11 cases without additional resection were judged as 4 GTR, 3 STR and 4 PR in postoperative MRI. In 18 patients confirmed total resection of 5-ALA positive lesion, i-CT and postoperative MRI revealed 14 (78%) residual tumors. I-CT revealed 7 (50%) in all residual tumor. DISCUSSION Hemorrhage, brain edema, air, invasive lesion, and limitation of resolution of CT might make difficult to detect residual tumor. CONCLUSION I-CT may be useful to detect residual tumor even with 5-ALA and improve resection rate.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1525-1525
Author(s):  
Aline Renneville ◽  
Sylvie Castaigne ◽  
Sylvie Chevret ◽  
Laura Llopis ◽  
Nathalie Philippe ◽  
...  

Abstract Introduction: The impact of gene mutations, i.e. poor-prognosis FLT3 internal tandem duplications (ITDs) and good-prognosis NPM1 or CEBPA mutations, has been welldocumented in several recent reports dealing with younger patients with acute myeloid leukemia (AML). As these mutations were associated with cytogenetically normal (CN) AML, most of these reports focused on CN-AML patients. Both FLT3-ITD and NPM1 mutations were also associated with higher WBC. The objective of the present study was to evaluate the incidence, correlations, and prognostic value of these mutations in older patients with the disease. Methods: The French ALFA group has screened a total of 583 patients, including 333 younger patients (15–50 years) treated in the ALFA-9802 trial and 250 older patients (50–70 years) treated in the ALFA-9801 trial. The older ALFA-9801 trial included 468 patients with previously untreated de novo AML and studied the role of idarubicin (IDA) as compared to high-dose daunorubicin (DNR) as well as interleukine-2 as a maintenance therapy (C. Pautas et al. ASH 2007, abstract #162). Comparison between the 250 patients tested for mutations in that trial and the 218 patients not tested showed no differences in age, sex ratio, FAB classification, bone marrow blasts percentage, randomization arm, and performance status at entry in the study. There was, however, a higher rate of patients with intermediate cytogenetics (p=.01) or increased WBC (p=.01) in the former subgroup. Results: Median age of the 250 patients tested was 60 years. Cytogenetics was studied in 232 patients (12 favorable, 174 intermediate, 46 unfavorable). One hundred twenty-two patients (49%) had CN-AML. CR rate was 67.5% and estimated 4-year OS was 26% (95% CI, 20–33). Incidences of FLT3-ITD, NPM1, and CEBPA mutations were 37/250 (15%), 64/249 (26%), and 20/249 (8%), respectively. These incidences were very similar than in the younger ALFA-9802 population [50/329 (15%), 76/321 (24%), and 24/316 (8%), respectively]. In these older AML patients, the correlation between increased WBC and FLT3-ITD (p&lt;.001) or NPM1 mutation (p&lt;.001) was still observed. Conversely, NPM1 mutations only (p&lt;.001), but not FLT3-ITDs (p=.10) or CEBPA mutations (p=.99), were significantly associated with CN-AML. In the whole group of 249 patients with either normal or abnormal karyotype tested for all mutations, 46 were NPM1+/FLT3-ITDwt, 19 FLT3-ITD+/NPM1wt, 18 FLT3-ITD+/NPM1+, and 166 NPM1wt/FLT3-ITDwt. CR rate was 87%, 84%, 56%, and 75% and median OS was 20.5, 18.6, 6.0, and 14.6 months, respectively. In the 20 CEBPA+ patients, CR rate was 80% and median OS was 22.8 months. In the group of 122 CN-AML patients tested for all mutations, 36 were NPM1+/FLT3-ITDwt, 8 FLT3-ITD+/NPM1wt, 15 FLT3-ITD+/NPM1+, and 63 NPM1wt/FLT3- ITDwt. CR rate was 92%, 87.5%, 60%, and 78% and median OS was 20.5, 16.9, 7.0, and 16.8 months, respectively. In the 10 CEBPA+ patients, CR rate was 80% and median OS was not reached. In multivariate analysis including age, WBC, cytogenetics (favorable versus others), and gene mutational status (NPM1+ or CEBPA+ if FLT3-ITDwt versus others), a pejorative effect of age (p=.02) and WBC (p&lt;.001), but a protective effect of mutational status (HR= 0.66, p=.05) and favorable cytogenetics (HR=0.43, p=.06) was observed in the whole patient population. Nevertheless, estimated 4-year OS was only 37% (95% CI, 23–50) in patients with a favorable mutational status. In those with CNAML and a favorable mutational status, estimated 4-year OS reached only 40% (95% CI, 23–56). In this subgroup of patients with CN-AML, WBC was the only significant prognostic factor identified in multivariate analysis (p&lt;.001). Conclusion: This study conducted in a large cohort of patients aged 50 to 70 years and prospectively treated in the same trial showed that gene mutational status still affect the outcome of older patients with AML. Mutation incidences are in the same range than in younger patients. Nevertheless, their impact on OS appeared to be less marked than in younger patients, probably due to the worse general outcome observed in these older patients.


2012 ◽  
Vol 117 (5) ◽  
pp. 851-859 ◽  
Author(s):  
Daniel Orringer ◽  
Darryl Lau ◽  
Sameer Khatri ◽  
Grettel J. Zamora-Berridi ◽  
Kathy Zhang ◽  
...  

Object The extent of resection (EOR) is a known prognostic factor in patients with glioblastoma. However, gross-total resection (GTR) is not always achieved. Understanding the factors that prevent GTR is helpful in surgical planning and when counseling patients. The goal of this study was to identify demographic, tumor-related, and technical factors that influence EOR and to define the relationship between the surgeon's impression of EOR and radiographically determined EOR. Methods The authors performed a retrospective review of the electronic medical records to identify all patients who underwent craniotomy for glioblastoma resection between 2006 and 2009 and who had both preoperative and postoperative MRI studies. Forty-six patients were identified and were included in the study. Image analysis software (FIJI) was used to perform volumetric analysis of tumor size and EOR based on preoperative and postoperative MRI. Using multivariate analysis, the authors assessed factors associated with EOR and residual tumor volume. Perception of resectability was described using bivariate statistics, and survival was described using the log-rank test and Kaplan-Meier curves. Results The EOR was less for tumors in eloquent areas (p = 0.014) and those touching ventricles (p = 0.031). Left parietal tumors had significantly greater residual volume (p = 0.042). The average EOR was 91.0% in this series. There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be safely achieved in 37.0% of patients (17 of 46) in this series. Among patients with safely resectable tumors, radiographically complete resection was achieved in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a significantly greater 1-year survival (76.5%) than an EOR less than 90% (p = 0.005). Conclusions The authors' findings confirm that tumor location affects EOR and suggest that EOR may also be influenced by the surgeon's ability to judge the presence of residual tumor during surgery. The surgeon's ability to judge completeness of resection during surgery is commonly inaccurate. The authors' study confirms the impact of EOR on 1-year survival.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii205-ii205
Author(s):  
Alessia Pellerino ◽  
Francesco Bruno ◽  
Antonio Silvani ◽  
Tamara Ius ◽  
Lorenzo Bello ◽  
...  

Abstract BACKGROUND IDH-wild type diffuse astrocytomas with pTERT mutation have been suggested by cIMPACT-NOW update 3 to share a poor prognosis with glioblastoma (GBM). In a previous series of the Italian Association of Neuro-Oncology, we reported that IDH-wild type grade II astrocytomas benefit from gross total resection. However, the impact of surgery in the pTERT-mutated subgroup has not been addressed so far. Here, we present our preliminary data about the impact of the extent surgery according to pTERT status. MATERIAL AND METHODS We re-analysed a national database of 122 patients with grade II IDH-wild type astrocytoma. P-TERT mutation was evaluated by gene sequencing. Kaplan-Meier curves were used for the analysis of progression-free and overall survival (PFS and OS). RESULTS Median follow-up was 33.0 months. P-TERT status was available in 40 cases and the mutation was found in 27 cases (67.5%). Patients with pTERT mutation had a significantly shorter PFS (9.4 vs 147.7 months, P &lt; 0.001) and OS (NR vs 36.6 months, P = 0.012). Furthermore, the OS of patients with pTERT mutation, who underwent gross total resection, was significantly longer than in patients with subtotal / partial resection (37.0 vs 32.0 months, P = 0.018). Thus far, the OS of patients without pTERT mutation was not reached with either subtotal / partial or gross total resection. CONCLUSIONS IDH-wild type astrocytomas may be stratified into classes with different outcome based on the pTERT mutation. As far as we know, this is the first study that specifically investigated the importance of a gross total resection according to pTERT status in IDH-wild type grade II astrocytomas.


2006 ◽  
Vol 104 (3) ◽  
pp. 360-368 ◽  
Author(s):  
Peter W. A. Willems ◽  
Martin J. B. Taphoorn ◽  
Huib Burger ◽  
Jan Willem Berkelbach van der Sprenkel ◽  
Cees A. F. Tulleken

Object The goal of this study was to assess the impact of neuronavigation on the cytoreductive treatment of solitary contrast-enhancing intracerebral tumors and outcomes of this treatment in cases in which neuronavigation was preoperatively judged to be redundant. Methods The authors conducted a prospective randomized study in which 45 patients, each harboring a solitary contrast-enhancing intracerebral tumor, were randomized for surgery with or without neuronavigation. Peri- and postoperative parameters under investigation included the following: duration of the procedure; surgeon’s estimate of the usefulness of neuronavigation; quantification of the extent of resection, determined using magnetic resonance imaging; and the postoperative course, as evaluated by neurological examinations, the patient’s quality-of-life self-assessment, application of the Barthel index and the Karnofsky Performance Scale score, and the patient’s time of death. The mean amount of residual tumor tissue was 28.9% for standard surgery (SS) and 13.8% for surgery involving neuronavigation (SN). The corresponding mean amounts of residual contrast-enhancing tumor tissue were 29.2 and 24.4%, respectively. These differences were not significant. Gross-total removal (GTR) was achieved in five patients who underwent SS and in three who underwent SN. Median survival was significantly shorter in the SN group (5.6 months compared with 9 months, unadjusted hazard ratio = 1.6); however, this difference may be attributable to the coincidental early death of three patients in the SN group. No discernible important effect on the patients’ 3-month postoperative course was identified. Conclusions There is no rationale for the routine use of neuronavigation to improve the extent of tumor resection and prognosis in patients harboring a solitary enhancing intracerebral lesion when neuronavigation is not already deemed advantageous because of the size or location of the lesion.


Neurosurgery ◽  
1991 ◽  
Vol 28 (5) ◽  
pp. 659-665 ◽  
Author(s):  
Mark K. Lyons ◽  
Patrick J. Kelly

Abstract Thirty patients with histologically confirmed posterior fossa ependymomas operated on between January 1976 and December 1988 were reviewed. The median age was 44 years (range, 1-69 yr). There were 7 children (aged 5 yr or younger) and 23 adults (aged 16 yr or older). There were 18 female patients and 12 male patients. Headache, nausea and vomiting, and disequilibrium were the most frequent symptoms. The most common findings were ataxia and nystagmus. Gross total resection was performed in 8 patients (27%), subtotal resection in 21 patients (70%), and biopsy in only 1 patient (3%), Tumors were low grade in 73% and high grade in 27%. Twenty-seven patients underwent posterior fossa radiotherapy (median dose, 5400 cGy). Fourteen patients also underwent spinal irradiation (median dose, 3520 cGy). Age was the only significant prognostic factor identified (P &lt;0.01). The 5-year survival rates were 76% for adults and 14% for children. All 14 patients who died had recurrent or residual tumor at the primary site. This review suggests that in patients with primary posterior fossa ependymomas the following is true: 1) the young patient (5 yr old or younger) has a poor prognosis: 2) there was a trend toward a better 5-year survival rate with a gross total resection; 3) if recurrence occurs, it will be at the primary intracranial site; and 4) symptomatic spinal seeding does not occur frequently.


2020 ◽  
Vol 82 (01) ◽  
pp. 075-086
Author(s):  
Victoria Wykes ◽  
Athanasios Zisakis ◽  
Mihaela Irimia ◽  
Ismail Ughratdar ◽  
Vijay Sawlani ◽  
...  

AbstractMaximal safe resection is an essential part of the multidisciplinary care of patients with glioblastoma. A growing body of data shows that gross total resection is an independent prognostic factor associated with improved clinical outcome. The relationship between extent of glioblastoma (GB) resection and clinical benefit depends critically on the balance between cytoreduction and avoiding neurologic morbidity. The definition of the extent of tumor resection, how this is best measured pre- and postoperatively, and its relation to volume of residual tumor is still discussed. We review the literature supporting extent of resection in GB, highlighting the importance of a standardized definition and measurement of extent of resection to allow greater collaboration in research projects and trials. Recent developments in neurosurgical techniques and technologies focused on maximizing extent of resection and safety are discussed.


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