ASSESSMENT OF THE EFFECT OF DIFFERENT PARAMETERS OF RADIOTHERAPY ON TREATMENT OUTCOMES OF INFILTRATIVE LOW-GRADE GLIOMA (GRADE II)

Abstract PURPOSE Timing of postoperative treatment in low-grade glioma (LGG) remains controversial. We sought to evaluate outcomes between adjuvant versus salvage management among patients with IDH-mutant molecularly-defined LGG. METHODS We analyzed a single-institutional database of adults diagnosed with LGG (grade II) with an IDH-mutation and either 1p19q-codeletion (oligodendroglioma) or 1p19q-intact (astrocytoma). Cox multivariable analysis (MVA) accounting for age, sex, and extent-of-resection, was used to compare adjuvant versus salvage approaches on overall survival (OS), progression free survival (PFS), next-intervention free survival (NIFS, defined as intervention subsequent to either adjuvant or salvage treatment), and malignant-transformation free survival (MTFS). Adjuvant treatment was defined as immediate postoperative treatment with radiotherapy (RT) and/or temozolomide (TMZ) prior to progression. Salvage management was defined as postoperative observation followed by surgery or RT and/or TMZ at progression. RESULTS Of 162 patients with oligodendroglioma, median follow-up was 8.5 years (range, 0.03-25.7). Adjuvant treatment was given to 97 (59.9%) patients, with 65 (40.1%) undergoing a salvage approach. On MVA, adjuvant treatment was not associated with OS, PFS, NIFS, or MTFS (p > 0.05 each). Among 82 patients with astrocytoma, median follow-up was 6.1 years (range, 0.5–25.7), and adjuvant treatment was administered to 41 (50.0%) patients, while 41 (50.0%) received salvage management. On MVA, adjuvant treatment was associated with improved PFS (HR 0.42, 95% CI 0.24-0.73, p < 0.001) and NIFS (HR 0.35, 95% CI 0.18–0.65, p < 0.001), but was not associated with OS or MTFS (p > 0.05 each). CONCLUSIONS Among grade II, IDH-mutant oligodendrogliomas, initial postoperative observation followed by salvage treatment at progression may be appropriate, as immediate adjuvant therapy was not associated improved outcomes. However, a more individualized postoperative management approach is required for grade II, IDH-mutant astrocytomas, as adjuvant treatment was associated with improved PFS and NIFS, but not OS. Further validation and prospective studies are required.

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IT-23 * INDUCTION OF ROBUST TYPE-1 CD8+ T-CELL RESPONSES IN WHO GRADE II LOW-GRADE GLIOMA PATIENTS RECEIVING PEPTIDE-BASED VACCINES IN COMBINATION WITH POLY-ICLC

Neuro-Oncology ◽

10.1093/neuonc/nou258.21 ◽

2014 ◽

Vol 16 (suppl 5) ◽

pp. v114-v114

Author(s):

H. Okada ◽

L. Butterfield ◽

R. Hamilton ◽

B. Ahn ◽

G. Kohanbash ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Cd8 T Cell ◽

Low Grade Glioma ◽

Low Grade ◽

Who Grade ◽

Cell Responses ◽

Grade Ii

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Observation versus radiotherapy with or without temozolomide in postoperative WHO grade II high-risk low-grade glioma: a retrospective cohort study

Neurosurgical Review ◽

10.1007/s10143-020-01326-y ◽

2020 ◽

Author(s):

Jingjing Wang ◽

Lvjun Yan ◽

Ping Ai ◽

Yan He ◽

Hui Guan ◽

...

Keyword(s):

Cohort Study ◽

High Risk ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Low Grade Glioma ◽

Low Grade ◽

Who Grade ◽

Grade Ii

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Psychotropic and anti-epileptic drug use, before and after surgery, among patients with low-grade glioma: a nationwide matched cohort study

BMC Cancer ◽

10.1186/s12885-021-07939-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Isabelle Rydén ◽

Erik Thurin ◽

Louise Carstam ◽

Anja Smits ◽

Sasha Gulati ◽

...

Keyword(s):

Index Date ◽

Low Grade Glioma ◽

Low Grade ◽

Rare Type ◽

Who Grade ◽

Patterns Of Use ◽

Anti Epileptic Drug ◽

Before And After ◽

Grade Ii ◽

One Year

Abstract Background Low-grade glioma (LGG) is a relatively rare type of brain tumour. The use of antidepressant, sedative and anti-epileptic drugs can reflect the burden of the disease. While epilepsy is well-described in patients with LGG, less is known about depression and anxiety. Methods We used nationwide registers to study the use (dispense) of antidepressants, sedatives, and anti-epileptic drugs (AEDs) before and after histopathological LGG diagnosis (WHO grade II). A total of 485 adult patients with a first-time diagnosis and a matched control cohort (n = 2412) were included. Patterns of use were analysed from one year prior to until one year following index date (date of surgery). Logistic regression analysis identified predictors for postoperative use. Results At one year before index date, patients were dispensed AEDs 4 times more than controls, while antidepressants and sedatives were similar. Sedatives and AED peaked shortly after index date at 25 and 69%, respectively. AEDs then stabilized while sedatives decreased rapidly. For antidepressants, a delayed increase was seen after index date, stabilizing at 12%. At one year after index date, the use of antidepressants, sedatives, and AEDs among patients was 2, 3, and 26 times higher, respectively, compared to controls. Predictor for use of AEDs and sedatives at one year following index was previous use and/or a related diagnosis. Female sex and later index year were additional predictors for antidepressants. Conclusions Use of antidepressants, sedatives and AEDs is elevated following diagnosis of LGG. Antidepressants were more commonly dispensed to female patients and in recent years.

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ROBUST INDUCTION OF TYPE-1 CD8+ T-CELL RESPONSES IN WHO GRADE II LOW-GRADE GLIOMA PATIENTS RECEIVING PEPTIDE-BASED VACCINES IN COMBINATION WITH POLY-ICLC

Neuro-Oncology ◽

10.1093/neuonc/nou208.62 ◽

2014 ◽

Vol 16 (suppl 3) ◽

pp. iii39-iii39

Author(s):

H. Okada ◽

L. H. Butterfield ◽

R. L. Hamilton ◽

A. Hoji ◽

M. Sakaki ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Cd8 T Cell ◽

Low Grade Glioma ◽

Low Grade ◽

Who Grade ◽

Cell Responses ◽

Grade Ii

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LINC-26. ORAL VINORELBINE IN PROGRESSIVE UNRESECTABLE LOW-GRADE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.460 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii383-iii383

Author(s):

Andréa M Cappellano ◽

Milena R S Oliveira ◽

Sergio Cavalheiro ◽

Patricia Dastoli ◽

Daniela B Almeida ◽

...

Keyword(s):

Objective Response ◽

Vinca Alkaloid ◽

Neurofibromatosis Type ◽

Low Grade Glioma ◽

Optic Pathway Glioma ◽

Low Grade ◽

Visual Evaluation ◽

Oral Vinorelbine ◽

Grade Ii

Abstract BACKGROUND The management of progressive unresectable low-grade glioma (PULGG) remains controversial. Some series suggests that chemotherapy may delay or even avoid radiotherapy and/or surgery in a group of patients. Within this context, we performed at IOP/GRAACC/UNIFESP an institutional protocol with IV vinorelbine, a semi-synthetic vinca alkaloid that showed activity against PULGG. The objective of this study was to evaluate the response as long as the tolerability of oral vinorelbine in PULGG. PATIENTS AND METHODS From April 2013 to Aug 2017, 17 patients with recurrent (n=5) and newly-diagnosed (n=12) optic-pathway glioma (OPG) were treated with oral vinorelbine in a dose of 90 mg/m² days 0, 8 and 22 for 18 cycles. Response criteria used a combination of magnetic resonance imaging, physical and visual evaluation. RESULTS Mean age 8.6 years (4.8–17.9y). Three children with neurofibromatosis type 1. Eleven patients had neurosurgical intervention revealing grade I (n=8) and grade II astrocytoma (n=3). Twelve patients were assessable after 8 cycles of vinorelbine with 2 objective response (OR), 8 stable disease (SD) and 2 progressive disease (PD), one died after surgery and 1 alive in different protocol. After 18 cycles, eight patients were assessable to date for response with 1 OR, 7 SD. The most important toxicity was gastrointestinal observed in 12 patients- six of them switched to IV vinorelbine (3OR, 3SD). None of the patients showed neurotoxicity. CONCLUSION These results suggest that oral vinorelbine, as the IV formulation, may show some activity in OPG. However, gastrointestinal toxicity should be considered.

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LGG-08. TREATMENT OUTCOMES AND TOLERABILITY OF TRAMETINIB IN PROGRESSIVE CIRCUMSCRIBED LOW-GRADE GLIOMAS

Neuro-Oncology ◽

10.1093/neuonc/noab090.132 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i32-i33

Author(s):

Emily Hanzlik ◽

Bridget Archambault ◽

Mays Dairi ◽

Kristin Schroeder ◽

Mallika Patel ◽

...

Keyword(s):

Treatment Outcomes ◽

Mapk Pathway ◽

Low Grade Glioma ◽

Low Grade ◽

Dramatic Improvement ◽

Optic Pathway ◽

Low Grade Gliomas ◽

Radiographic Response ◽

Dermatologic Toxicity ◽

Best Responses

Abstract Circumscribed low-grade gliomas comprise roughly one-third of pediatric CNS tumors. Most of these tumors are caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway. Drugs targeting the MAPK pathway are effective in other cancers and are being utilized in low-grade gliomas. We describe treatment outcomes and toxicities in a series of thirteen low-grade glioma patients treated with trametinib. We performed a retrospective chart review to evaluate response on T2/FLAIR MRI images per updated RANO criteria, visual outcomes, tolerability, and durability of response in progressive low-grade glioma patients treated with trametinib. Thirteen patients age 22 months to 34 years were included. Best radiographic response on therapy included 2/13 partial response, 3/13 minimal response, 5/13 stable disease, and 3/13 progressive disease. Diagnoses included pilocytic astrocytoma (n=6), desmoplastic infantile ganglioglioma (DIG; n=1), and low-grade glial neoplasms (n=2). Molecular drivers included BRAF:KIAA1549 fusion (n=3), V600E mutation (n=1), and somatic NF1 mutation (n=1). Three patients had germline NF1. In patients with partial or minimal response, best response was seen after longer durations of therapy; 4 of 5 best responses occurred after at least 12 months on therapy. Five patients completed prescribed therapy. Three patients remain stable off therapy at 6, 12, and 21 months; two patients recurred at 1 and 10 months off therapy. Skin manifestations were the predominant form of toxicity. This was more severe in older males, and symptoms improved with intermittent dosing. All patients with optic pathway tumors showed at least stable vision throughout treatment, with some patients having dramatic improvement. Trametinib is effective and well-tolerated in patients with low-grade glioma. Dermatologic toxicity can be mitigated by intermittent dosing. Best responses tended to occur later in therapy, sometimes after relatively stable MRIs. Patients with optic pathway lesions showed stable to improved vision even in the absence of significant radiographic response.

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To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment

Journal of Neurosurgery ◽

10.3171/2019.4.jns183395 ◽

2020 ◽

Vol 133 (2) ◽

pp. 273-280 ◽

Cited By ~ 4

Author(s):

Andrej Paľa ◽

Jan Coburger ◽

Moritz Scherer ◽

Hajrullah Ahmeti ◽

Constantin Roder ◽

...

Keyword(s):

High Risk ◽

Adjuvant Therapy ◽

Adjuvant Treatment ◽

Low Grade Glioma ◽

Histopathological Diagnosis ◽

Low Grade ◽

Who Grade ◽

High Risk Patients ◽

Risk Patients ◽

Grade Ii

OBJECTIVEThe level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called “high-risk” patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery.METHODSBased on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma.RESULTSOne hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8–6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance.CONCLUSIONSIn this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.

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The effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: Secondary analysis of RTOG 98-02.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2047 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2047-2047

Author(s):

Roshan Sudhir Prabhu ◽

Minhee Won ◽

Edward G. Shaw ◽

Meihua Wang ◽

David Brachman ◽

...

Keyword(s):

Cognitive Function ◽

Mmse Score ◽

Low Grade Glioma ◽

Subtotal Resection ◽

Low Grade ◽

Who Grade ◽

Term Survival ◽

Who Grade Ii Glioma ◽

Grade Ii ◽

Grade Ii Glioma

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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