WP1-17 Risk factors and patterns of progression in a surgical cohort of low grade glioma patients

2019 ◽  
Vol 90 (3) ◽  
pp. e6.2-e6
Author(s):  
S Acharya ◽  
J Lavrador ◽  
R Visagan ◽  
V Narbad ◽  
J Jung ◽  
...  

ObjectivesTo understand the risk factors for and patterns of progression of low grade glioma (LGG).DesignSingle centre retrospective cohort study.SubjectsPatients undergoing at least two neurosurgical procedures for LGG, the first being for diffuse LGG (WHO 2). 22 patients included (14M; 8F); mean age at time of first operation 37.7±2.7 years. 20 patients had a Performance Status (PS) 0–1 and 2 patients had a PS 2.MethodsAll patients with LGG diagnosed in between 2009–2018 were retrospectively evaluated. Variables of interest included demographics, staging, performance status, time to re-operation (TTR), extent of resection, molecular genetics (1p19q co-deletion, IDH status). Tumour volumes were estimated from MRI images by the validated ABC/2 equation. Statistical analyses were performed by Stata13.0.ResultsThe tumour progressed in WHO grade in 18 patients (WHO grade 3 (n=15); WHO grade 4 (n=3). Mean time to re-operation after the first surgery was 7.0±1.2 years following gross total resection (GTR) and 3.2±0.7 years following subtotal resection (STR). Non-adjusted analysis of risk factors for time to re-operation (TTR) showed absence of 1p19q co-deletion as a risk factor (p=0.021). Adjusted analysis revealed that GTR, 1p19q mutation, PS 0 at 1 st surgery and tumour volumetric change decrease the risk for re-intervention (p<0.05). Chemo-radiotherapy was not associated with TTR.ConclusionsIn our cohort, TTR in LGG was influenced by the amount of initial resection, 1p19q deletion, PS and post-operative volumetric change.

2017 ◽  
Vol 5 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Yahya Ghazwani ◽  
Ibrahim Qaddoumi ◽  
Johnnie K Bass ◽  
Shengjie Wu ◽  
Jason Chiang ◽  
...  

Abstract Background Hearing loss may occur in patients with posterior fossa low-grade glioma who undergo surgery. Methods We retrospectively reviewed 217 patients with posterior fossa low-grade glioma, including 115 for whom results of hearing tests performed after surgery and before chemotherapy or radiation therapy were available. We explored the association of UHL with age at diagnosis, sex, race, tumor location, extent of resection, posterior fossa syndrome, ventriculoperitoneal shunt placement, and histology. Results Of the 115 patients, 15 (13.0%: 11 male, 6 black, 8 white, 1 multiracial; median age 7 years [range, 1.3–17.2 years]) had profound UHL after surgery alone or before receiving ototoxic therapy. Median age at tumor diagnosis was 6.8 years (range, 0.7–14.1 years), and median age at surgery was 6.8 years (range, 0.7–14.1 years). Patients with UHL had pathology characteristic of pilocytic astrocytoma (n = 10), ganglioglioma (n = 4), or low-grade astrocytoma (n = 1). Of these 15 patients, 4 underwent biopsy, 1 underwent gross total resection, 1 underwent near-total resection, and 9 underwent subtotal resection. UHL was more frequent in black patients than in white patients (OR 7.3, P = .007) and less frequent in patients who underwent gross total resection or near-total resection than in those who underwent subtotal resection (OR 0.11, P = .02). Conclusions Children undergoing surgery for posterior fossa low-grade glioma are at risk for UHL, which may be related to race or extent of resection. These patients should receive postoperative audiologic testing, as earlier intervention may improve outcomes.


2013 ◽  
Vol 119 (2) ◽  
pp. 318-323 ◽  
Author(s):  
Philippe Schucht ◽  
Fadi Ghareeb ◽  
Hugues Duffau

Object A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient's functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life. Methods Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution. Results For the central cohort, the median extent of resection was 92% (range 80%–97%), and for the frontal cohort, the median extent of resection was 93% (range 83%–98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001). Conclusions Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.


2020 ◽  
Vol 133 (5) ◽  
pp. 1291-1301 ◽  
Author(s):  
Vasileios K. Kavouridis ◽  
Alessandro Boaro ◽  
Jeffrey Dorr ◽  
Elise Y. Cho ◽  
J. Bryan Iorgulescu ◽  
...  

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.


2014 ◽  
Vol 32 (6) ◽  
pp. 535-541 ◽  
Author(s):  
Roshan S. Prabhu ◽  
Minhee Won ◽  
Edward G. Shaw ◽  
Chen Hu ◽  
David G. Brachman ◽  
...  

Purpose The addition of PCV (procarbazine, lomustine, and vincristine) chemotherapy to radiotherapy (RT) for patients with WHO grade 2 glioma improves progression-free survival (PFS). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long-term survival. Patients and Methods A total of 251 patients with WHO grade 2 glioma age ≥ 40 years with any extent of resection or age < 40 years with subtotal resection/biopsy were randomly assigned to RT (54 Gy) or RT plus PCV. We observed 111 patients age < 40 years with gross total resection. CF was assessed by Mini–Mental State Examination (MMSE) at baseline and years 1, 2, 3, and 5. Results Overall, few patients experienced significant decline in MMSE score. There were no significant differences in the proportion of patients experiencing MMSE score decline between the randomized study arms at any time point. Both study arms experienced a significant gain in average MMSE score longitudinally over time, with no difference between arms. Conclusion The MMSE is a relatively insensitive tool, and subtle changes in CF may have been missed. However, the addition of PCV to RT did not result in significantly higher rates of MMSE score decline than RT alone through 5 years of follow-up. Patients in both randomly assigned arms experienced a statistically significant average MMSE score increase over time, with no difference between arms. The addition of PCV chemotherapy to RT improves PFS without excessive CF detriment over RT alone for patients with low-grade glioma.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13520-e13520
Author(s):  
Rolando Barjas ◽  
David Eric Piccioni

e13520 Background: Hemangiopericytoma (HPC), or solitary fibrous tumor of the central nervous system (CNS), is a rare mesenchymal tumor that arises from the pericytes of the meningeal capillaries. These tumors account for less than 1% of all CNS tumors and are categorized into low-grade (WHO grade I and II) or high-grade (WHO grade III, anaplastic) neoplasms. The optimal treatment for grade III HPC is unclear. The aim of this study was to evaluate treatment patterns and survival for grade III HPC using the California Cancer Registry (CCR). Methods: Treatment and demographic data were extracted from the CCR for patients with grade III HPC of the CNS, from 1988-2010. Overall Survival (OS) was evaluated as a function of treatment (surgery, radiation or both), as well as extent of resection. Kaplan Meier survival analyses were performed for OS. Bivariate and multivariable analyses were done via cox proportional hazard regression models for all demographic and treatment variables. Results: A total of 94 patients with grade III HPC were identified from the registry. The most prevalent demographics were age > 50 years (59%), female (61%), non-Hispanic White (60%), and married (54%). 54% received radiation, and subtotal resection (STR) (63%) was the most common surgical outcome. However, survival was greatest in patients that received gross total resection (GTR) with radiation (median OS not reached). GTR/radiation (median OS not reached) demonstrated improved OS compared to STR/radiation (median OS 10.3 years; HR = 0.389, 95%CI 0.157-0.960) or GTR alone (median OS 6.6 years; HR = 0.254, 95%CI 0.073-0.880). Age < 50 (median OS 15.7 years), Asian/PI (median OS not reached) and married (median OS 9.9 years) were significant predictors of OS. In the multivariable cox model worse overall survival remained for older age (HR = 3.079, 95%CI 1.428-6.636) and divorced/widowed/separated (HR = 2.027, 95%CI 1.054-3.897) when compared to their younger and married counterparts. Conclusions: Patients that received GTR and radiation demonstrated the best long-term prognosis. Demographic analyses identified additional independent predictors of survival.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii188-ii188
Author(s):  
Warren Rehrer ◽  
Yazmin Odia ◽  
Muni Rubens ◽  
Noah Kalman ◽  
Michael Chuong ◽  
...  

Abstract PURPOSE In 2016, RTOG 9802 reported an overall survival advantage with the addition of chemotherapy to adjuvant radiotherapy (CRT) in patients with high-risk low grade glioma (LGG). We used the National Cancer Database (NCDB) to measure trends in CRT use in LGG patients from 2010-2016, a period when no Level 1 evidence existed. METHODS The NCDB was queried for WHO Grade II glioma patients treated from 2010-2016 who met the inclusion criteria for RTOG 9802. Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received adjuvant CRT. Relative percent change and average annual percentage change (AAPC) were compared to determine if a change (defined a priori as &lt; 0.01) occurred in the use of adjuvant CRT in LGG patients during this period. RESULTS The analytic cohort consisted of 5,039 patients; 64.3% of patients were 40 years or older and 35.7% were under 40 with subtotal resection. Use of adjuvant CRT increased from 18.9% to 49.7% (p&lt; 0.001) during 2013-2016, with no change observed before 2013. The AAPC in the use of CRT was +39.6% per year (p&lt; 0.001). Corresponding declines in patients treated with surgery alone (p&lt; 0.001) and surgery plus radiotherapy (p&lt; 0.001) were observed during 2013-2016. Logistic regression demonstrated patients who were under 40 years old were significantly less likely to receive adjuvant CRT than patients 40 years or older (Odds Ratio 0.561, 95% CI 0.475-0.663, p&lt; 0.001). Use of adjuvant CRT increased from 12.5% to 45.1% in patients with oligodendroglioma during 2013-2016 (p&lt; 0.001). CONCLUSIONS During 2013-2016, an increasing number of patients with LGG were treated with surgery followed by adjuvant CRT. Future studies may characterize the use of single agent vs. multiagent chemotherapy in this population and the adoption of trimodality therapy by mutation status.


2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i31-i31
Author(s):  
Jessica Hata ◽  
Mustafa Barbour ◽  
Michael Angelo Huang

Abstract Background Pediatric low-grade gliomas (LGG), in particular those not amenable to surgical resection, are a therapeutic challenge owing to their heterogeneity in clinical behavior. Identification of the RAS/MAPK pathway as a universal feature of these tumors has led to an improved understanding and the development of targeted therapeutics. We examined the impact of known biological and novel molecular risk factors on patient outcomes at our institution. Methods We retrospectively reviewed risk factors and clinical outcomes in 38 LGG cases diagnosed by histopathology at Norton Children’s Hospital in Louisville, KY, USA from March 2015 to Jan 2019. Progression free survival (PFS) rates were generated using the Kaplan-Meier method. Log-rank tests and hazard ratios were used to identify prognostic factors by univariable analysis. Results Among previously described biological risk factors, subtotal resection/biopsy only (HR 3.67, p=0.0257), non-WHO Grade I histology (HR 3.34, p=0.0101), and infant age (&lt; 3 years) (HR 4.19, p=0.0031) were associated with shorter PFS. Brainstem location had no significant impact on PFS. (HR 0.86, p=0.8071). H3K27M mutant status was predictably associated with worse PFS (HR 5.86, p=0.0012). BRAF v600e mutant status, however, was not associated with inferior outcomes. On the contrary, in our study population, BRAF v600e mutant status had a suggested protective effect (HR 0.14, p=0.0247). Patients with 2 or more oncogenic driver mutations demonstrated worsened PFS (HR 4.78, p=0.0059). We utilized the following scoring system for risk stratification: 1 point was allocated for each of the above biological and molecular risk factors except for H3K27M, which was allocated 3 points. A score of &lt; 3 was designated low risk. Non-low risk classification was associated with significantly inferior PFS (median PFS 13 vs. 62 mos, HR 4.26, p=0.0012). Conclusion We herein demonstrate the utility of a combined biological and molecular risk classification for pediatric LGG.


2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv15-iv15
Author(s):  
Shami Acharya ◽  
Priya Sekhon ◽  
Jose Pedro Lavrador ◽  
Ravindran Visagan ◽  
Vijay Narbad ◽  
...  

Abstract Objectives To study clinical features and treatment options between 2007–2018 in a population of diffuse low grade glioma (DLGG) patients (WHO Grade2). Methods Single centre retrospective cohort study. Variables reviewed: demographics, extent of resection (biopsy – Bx, subtotal resection – STR, gross total resection – GTR), molecular genetics and outcome. Results N=104.M=61 F=43, average age, 41.8 yrs. For their first surgery, 40.4% underwent a Bx, 32.7% STR, 26.9% GTR. 50.9% of patients had a second procedure due to clinical progression (13.8% Bx, 38.85% STR, 47.2% GTR). We were more surgically aggressive at the second sitting (p=0.0021). After 2014, we were more aggressive in terms of achieving a resection over a biopsy alone (pre 2013: 26 Bx, 24 resection, post 2013: 15 Bx, 28 resection). 35% had 1p19q co-deletion, 70% had 1DH1 mutation and 44.6% with MGMT methylated. There was no difference in survival and extent of resection in 1p19 co-deletions (HR 0.35), however there was in the IDH 1 group (HR 1.25. Post operatively, 37.9% patients had chemotherapy and 57.3 % radiotherapy. 80.5% (Bx 65,9% alive, resection 95% alive) of patients are still alive (longest survival 11.6 yrs). Amongst those who died, the mean overall survival was 4.0 (range 0–7 - 5 years): Of these 14% had undergone a Bx and 6% STR/GTR. The adjusted analysis revealed that EOR is the only revelant factor for survival in the population when adjusted for IDH, 1p19q, tumour volume, age, gender and surgery year (p=0.44). Conclusion Our data emphasises the importance of achieving maximal resection when possible.


2012 ◽  
Vol 30 (25) ◽  
pp. 3065-3070 ◽  
Author(s):  
Edward G. Shaw ◽  
Meihua Wang ◽  
Stephen W. Coons ◽  
David G. Brachman ◽  
Jan C. Buckner ◽  
...  

PurposeA prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG).Patients and MethodsEligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests.ResultsIn all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02).ConclusionPFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2047-2047
Author(s):  
Roshan Sudhir Prabhu ◽  
Minhee Won ◽  
Edward G. Shaw ◽  
Meihua Wang ◽  
David Brachman ◽  
...  

2047 Background: The addition of PCV chemotherapy to radiotherapy (RT) for patients with WHO grade II glioma improves progression free survival (PFS) and overall survival (OS), for patients surviving at least 2 years (Shaw, J Clin Oncol 26: 2008). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long term survival. Methods: 251patients with WHO grade II glioma and age > 40 with any extent of resection, or age < 40 with subtotal resection/biopsy were randomized to RT (54Gy) or RT + PCV. 111 patients with age < 40 and gross total resection were observed. CF was assessed by mini-mental status exam (MMSE)at baseline and years 1, 3, and 5 for patients without progression. Change in MMSE score from baseline of > 3 points was considered clinically significant. Results: Overall, very few patients experienced significant decline in MMSE score, with a median follow-up time of 9.7 years for alive patients. There were no significant differences in the proportion of patients experiencing MMSE decline between study arms at any time point. The table below summarizes MMSE change from baseline over time. Neither baseline MMSE score nor change in MMSE at year 1 significantly predicted for OS or PFS, but there was a trend towards worse OS for patients with MMSE loss of ≥ 2 points [HR 1.73, 95% CI (0.86, 3.47), p=0.12]. Conclusions: The MMSE is a relatively insensitive tool that has not been validated in patients receiving cranial RT, and subtle changes in CF may have been missed. However, the addition of PCV to RT for low grade glioma did not result in significantly higher rates of MMSE decline than RT alone or observation. There was a trend towards an MMSE decline of ≥ 2 points at year 1 predicting for worse OS.    [Table: see text]


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