scholarly journals Survival and Seizure Control have improved for Adult Low-Grade Gliomas over the last eleven years

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv4-iv4
Author(s):  
Matt Solomons ◽  
Rimona Weil ◽  
Zane Jaunmuktan ◽  
Tedani El-Hassan ◽  
Sebastian Brandner ◽  
...  

Abstract Background There has been a trend towards earlier and more aggressive resection for adult Low-Grade Gliomas (LGG) in the last decade. This study set out to compare seizure control and survival of unselected adults with LGG seen in the same neuro-oncology clinic over 11 years and to determine if a change in surgical philosophy has led to a corresponding improvement in outcomes. Methods Retrospective analysis using case-note review of 153 adults with histologically verified or radiologically suspected LGG, collecting data on patient, tumour and seizure characteristics in 2006 and 2017. Results We studied 79 patients in 2006 and 74 patients in 2017. There were no significant differences between the two groups in age at presentation, tumour location or histological or molecular subtype. The numbers of complete or partial resections increased from 21.5 % in 2006 to 60.8% in 2017 (p<0.05). There was a highly significant improvement in 5- and 10-year survival from 81.8% and 51.7% in 2006 to 100% and 95.8% in 2017 (p<0.001); and a similar improvement was seen in progression free survival. The proportion of patients with intractable epilepsy reduced from 72.2% in 2006 to 43.2% in 2017 (p<0.05). The neurosurgical morbidity rate was identical in both groups (11.8% in 2006 vs 11.1% in 2017). Conclusion Increasing use of surgery for LGG over the last eleven years has led to substantial improvements in survival and seizure control but not at the cost of long-term morbidity.

2019 ◽  
Vol 7 (2) ◽  
pp. 196-201
Author(s):  
Matthew R Solomons ◽  
Zane Jaunmuktane ◽  
Rimona S Weil ◽  
Tedani El-Hassan ◽  
Sebastian Brandner ◽  
...  

Abstract Background There has been a trend toward earlier and more aggressive resection for low-grade gliomas (LGGs). This study set out to compare seizure control and survival of adults with LGG seen in the same neuro-oncology clinic over 11 years and to determine whether a change in surgical philosophy has led to a corresponding improvement in outcomes. Methods We conducted a retrospective analysis using case-note review of 153 adults with histologically verified or radiologically suspected LGG, collecting data on patient, tumor, and seizure characteristics between 2006 and 2017. Results We studied 79 patients in 2006 and 74 patients in 2017. There was no significant difference between the 2 groups in age at presentation, tumor location, or integrated pathological diagnosis. The numbers of complete or partial resections increased from 21.5% in 2006 to 60.8% in 2017 (P &lt; .05). Five- and 10-year overall survival increased from 81.8% and 51.7% in 2006 to 100% and 95.8% in 2017 (P &lt; .001); similarly, 5- and 10-year progression-free survival increased from 47.0% and 30.7% in 2006 to 93.1% and 68.7% in 2017. The proportion of patients with intractable epilepsy declined from 72.2% in 2006 to 43.2% in 2017 (P &lt; .05). The neurosurgical morbidity rate was identical in both groups (11.8% in 2006 vs 11.1% in 2017). Conclusion Management of LGG over the last 11 years has led to substantial improvements in survival and seizure control. This is most likely thanks to a change in surgical philosophy, with early resection now favored over watchful waiting where possible.


1995 ◽  
Vol 82 (4) ◽  
pp. 536-547 ◽  
Author(s):  
Ian F. Pollack ◽  
Diana Claassen ◽  
Qasim Al-Shboul ◽  
Janine E. Janosky ◽  
Melvin Deutsch

✓ Low-grade gliomas constitute the largest group of cerebral hemispheric tumors in the pediatric population. Although complete tumor resection is generally the goal in the management of these lesions, this can prove difficult to achieve because tumor margins may blend into the surrounding brain. This raises several important questions on the long-term behavior of the residual tumor and the role of adjuvant therapy in the management of these lesions. To examine these issues, the authors reviewed their experience in 71 children with low-grade cerebral hemispheric gliomas who were treated at their institution between 1956 and 1991 and assessed the relationship between clinical, radiographic, pathological, and treatment-related factors and outcome. Only seven patients in the series died, one from perioperative complications, five from progressive disease, and one (a child with neurofibromatosis) from a second neoplasm. For the 70 patients who survived the perioperative period, overall actuarial survivals at 5, 10, and 20 years were 95%, 93%, and 85%, respectively; progression-free status was maintained in 88%, 79%, and 76%, respectively. On univariate analysis, the factor that was most strongly associated with both overall and progression-free survival was the extent of tumor resection (p = 0.013 and p = 0.015, respectively). A relationship between extent of resection and progression-free survival was present both in patients with pilocytic astrocytomas (p = 0.041) and those with nonpilocytic tumors (p = 0.037). Histopathological diagnosis was also associated with overall survival on univariate analysis; poorer results were seen in the patients with nonpilocytic astrocytoma compared to those with other low-grade gliomas, such as pilocytic astrocytoma, mixed glioma, and oligodendroglioma (p = 0.021). The use of radiotherapy was not associated with a significant improvement in overall survival (p = 0.6). All three patients who ultimately developed histologically confirmed anaplastic changes in the vicinity of the original tumor had received prior radiotherapy, 20, 46, and 137 months, respectively, before the detection of malignant progression. In addition, children who received radiotherapy had a significantly higher incidence of late cognitive and endocrine dysfunction than the nonirradiated patients (p < 0.01 and 0.05, respectively). The authors conclude that children with low-grade gliomas of the cerebral hemispheres have an excellent overall prognosis. Complete tumor resection provides the best opportunity for long-term progression-free survival. However, even with incomplete tumor excision, long-term progression-free survival is common. The findings in this study do not support the routine use of postoperative radiotherapy after an initial incomplete tumor resection: although irradiation appears to increase the likelihood of long-term progression-free survival, overall survival is not improved significantly, and long-term morbidity may be increased.


1993 ◽  
Vol 79 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Mitchel S. Berger ◽  
Saadi Ghatan ◽  
Michael M. Haglund ◽  
Jill Dobbins ◽  
George A. Ojemann

✓ Adults and children with low-grade gliomas often present with medically refractory epilepsy. Currently, controversy exists regarding the need for intraoperative electrocorticography (ECoG) to identify and, separately, resect seizure foci versus tumor removal alone to yield maximum seizure control in this patient population. Forty-five patients with low-grade gliomas and intractable epilepsy were retrospectively analyzed with respect to preoperative seizure frequency and duration, number of antiepileptic drugs, intraoperative ECoG data (single versus multiple foci), histology of resected seizure foci, and postoperative control of seizures with or without antiepileptic drugs. Multiple versus single seizure foci were more likely to be associated with a longer preoperative duration of epilepsy. Of the 45 patients studied, 24 were no longer taking antiepileptic drugs and were seizure-free (mean follow-up interval 54 months). Seventeen patients, who all had complete control of their seizures, remained on antiepileptic drugs at lower doses (mean follow-up interval 44 months); seven of these patients were seizure-free postoperatively, yet the referring physician was reluctant to taper the antiepileptic drugs. Four patients continued to have seizures while receiving antiepileptic drugs, although at a reduced frequency and severity. In this series 41% of the adults versus 85% of the children were seizure-free while no longer receiving antiepileptic drugs, with mean postoperative follow-up periods of 50 and 56 months, respectively. This difference was statistically significant (p = 0.016). Therefore, based on this experience and in comparison with numerous retrospective studies involving similar patients, ECoG is advocated, especially in children and in any patient with a long-standing seizure disorder, to maximize seizure control while minimizing or abolishing the need for postoperative antiepileptic drugs.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii367-iii367
Author(s):  
Nongnuch Sirachainan ◽  
Attaporn Boongerd ◽  
Samart Pakakasama ◽  
Usanarat Anurathapan ◽  
Ake Hansasuta ◽  
...  

Abstract INTRODUCTION Low grade glioma (LGG) is the most common central nervous system (CNS) tumor in children accounted for 30–50%. Regarding benign characteristic of disease, surgical management remains the mainstay of treatment. However, surgical approach is limited in some conditions such as location at brainstem or infiltrative tumor. Chemotherapy and radiation treatments have been included in order to control tumor progression. The 5-years survival rate is approach 90% especially in patients who receive complete resection. However, the outcome of children with LGG in low to middle income is limited. Therefore, the aim of the study was to determine long-term outcome of children with newly diagnosed LGG. METHODS A retrospective study enrolled children aged &lt;18 years who were newly diagnosed LGG during January 2006- December 2019. Diagnosis of LGG was confirmed by histological findings of grade I and II according to WHO criteria. RESULTS A total of 40 patients, female to male ratio was 1:1.35 and mean (SD) for age was 6.7 (4.0) years. The most common location was optic chiasmatic pathway (42.5%), followed by suprasellar region (25.0%). Sixty percent of patients received at least partial tumor removal. Chemotherapy and radiation had been used in 70% and 10.0% respectively. The 10-year progression free survival was 74.1±11.4% and overall survival was 96.2±3.8%. SUMMARY: Treatment of Pediatric LGG mainly required surgical management, however, chemotherapy and radiation had been used in progressive disease. The outcome was excellent.


Author(s):  
Sanne ten Hoorn ◽  
Dirkje W. Sommeijer ◽  
Faye Elliott ◽  
David Fisher ◽  
Tim R. de Back ◽  
...  

Abstract Background Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location. Methods Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively. Results When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034). Conclusions The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.


1997 ◽  
Vol 2 (3) ◽  
pp. E1
Author(s):  
Roger J. Packer ◽  
Joanne Ater ◽  
Jeffrey Allen ◽  
Peter Phillips ◽  
Russell Geyer ◽  
...  

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.


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 ◽  
...  

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.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi184-vi185
Author(s):  
Liana Nobre ◽  
Michal Zapotocky ◽  
Vijay Ramaswamy ◽  
Scott Ryall ◽  
Julie Bennett ◽  
...  

Abstract BACKGROUND Children with pediatric low grade glioma’s (PLGG) harboring BRAF V600E mutation have poor outcome due to relative resistance to chemo-radiation and higher risk of malignant transformation. However, the role of targeted BRAF inhibition in these tumors is poorly defined. METHODS We assembled an international cohort of children with BRAF V600E mutant gliomas treated with BRAF inhibition, from 29 centers participating in the PLGG taskforce, and collected response, survival and molecular parameters. RESULTS Sixty-seven patients were treated with BRAFi (56 PLGG and 11 high grade gliomas) for a median time of 17.4 months (6 – 61 months), with 13 PLGG treated upfront. Objective responses was observed in 80% of PLGG patients compared to 28% with conventional chemotherapy (p< 0.001). Rapid responses were observed in most PLGG patients (median of 4 months), sustained in 86% of tumors up to 5 years while on therapy. In contrast, only 36% of PHGG responded to BRAFi with all but one tumor progressing within 18 months. Seventeen patients with PLGG discontinued BRAFi and 76.5% (13/17) progressed rapidly after discontinuation (median time 2.3 months). However, upon re-challenge with BRAFi therapy, 90% achieved an objective response. Poor prognostic factors to conventional therapies such as concomitant homozygous deletion of CDKN2A or H3K27M mutation were not associated with lack of response to BRAFi. Overall these responses translated to 2-year progression-free survival of 0.636 (95%CI 0.505–0.802) and 0.43 (95% CI 0.32–0.57) for BRAFi and chemotherapy treated BRAF V600E PLGG respectively (p=0.003). CONCLUSION The use of BRAFi results in objective, robust and durable responses in BRAF V600E PLGG and is associated with favorable survival. Larger prospective studies will be required to determine appropriate regiments, and long-term functional outcomes with BRAFi therapy in childhood gliomas.


2017 ◽  
Vol 35 (25) ◽  
pp. 2934-2941 ◽  
Author(s):  
Alvaro Lassaletta ◽  
Michal Zapotocky ◽  
Matthew Mistry ◽  
Vijay Ramaswamy ◽  
Marion Honnorat ◽  
...  

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy.


2020 ◽  
pp. jclinpath-2020-206868
Author(s):  
Wei Sang ◽  
Jing Xue ◽  
Li-Ping Su ◽  
Abulajiang Gulinar ◽  
Qian Wang ◽  
...  

AimsA growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma.MethodsExpression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson’s X2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson’s or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis.ResultsHigh expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients.ConclusionOur research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.


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