Stereotactic radiosurgery for glioblastoma considering tumor genetic profiles: an international multicenter study

2021 ◽  
pp. 1-9
Author(s):  
Adomas Bunevicius ◽  
Stylianos Pikis ◽  
Douglas Kondziolka ◽  
Dev N. Patel ◽  
Kenneth Bernstein ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Methylation Status ◽  
Idh Mutation ◽  
Mgmt Methylation ◽  
Wild Type ◽  
Total Resection ◽  
Treatment Volume ◽  
Prescription Dose ◽  
Molecular Profiles

OBJECTIVE Molecular profiles, such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) methylation status, have important prognostic roles for glioblastoma patients. The authors studied the efficacy and safety of stereotactic radiosurgery (SRS) for glioblastoma patients with consideration of molecular tumor profiles. METHODS For this retrospective observational multiinstitutional study, the authors pooled consecutive patients who were treated using SRS for glioblastoma at eight institutions participating in the International Radiosurgery Research Foundation. They evaluated predictors of overall and progression-free survival with consideration of IDH mutation and MGMT methylation status. RESULTS Ninety-six patients (median age 56 years) underwent SRS (median dose 15 Gy and median treatment volume 5.53 cm3) at 147 tumor sites (range 1 to 7). The majority of patients underwent prior fractionated radiation therapy (92%) and temozolomide chemotherapy (98%). Most patients were treated at recurrence (85%), and boost SRS was used for 12% of patients. The majority of patients harbored IDH wild-type (82%) and MGMT-methylated (62%) tumors. Molecular data were unavailable for 33 patients. Median survival durations after SRS were similar between patients harboring IDH wild-type tumors and those with IDH mutant tumors (9.0 months vs 11 months, respectively), as well as between those with MGMT-methylated tumors and those with MGMT-unmethylated tumors (9.8 vs. 9.0 months, respectively). Prescription dose > 15 Gy (OR 0.367, 95% CI 0.190–0.709, p = 0.003) and treatment volume > 5 cm3 (OR 1.036, 95% CI 1.007–1.065, p = 0.014) predicted overall survival after controlling for age and IDH status. Treatment volume > 5 cm3 (OR 2.215, 95% CI 1.159–4.234, p = 0.02) and absence of gross-total resection (OR 0.403, 95% CI 0.208–0.781, p = 0.007) were associated with inferior local control of SRS-treated lesions in multivariate models. Nine patients experienced adverse radiation events after SRS, and 7 patients developed radiation necrosis at 59 to 395 days after SRS. CONCLUSIONS Post-SRS survival was similar as a function of IDH mutation and MGMT promoter methylation status, suggesting that molecular profiles of glioblastoma should be considered when selecting candidates for SRS. SRS prescription dose > 15 Gy and treatment volume ≤ 5 cm3 were associated with longer survival, independent of age and IDH status. Prior gross-total resection and smaller treatment volume were associated with superior local control.

Preliminary results of linear accelerator radiosurgery for acoustic schwannomas

1996 ◽  
Vol 85 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
William M. Mendenhall ◽  
William A. Friedman ◽  
John M. Buatti ◽  
Francis J. Bova
Keyword(s):  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Linear Accelerator ◽  
Local Control Rate ◽  
Magnetic Resonance Images ◽  
High Rate ◽  
Content Type ◽  
Treatment Volume ◽  
Fine Print

✓ In this paper the authors evaluate the results of linear accelerator (LINAC)—based stereotactic radiosurgery for acoustic schwannomas. Fifty-six patients underwent LINAC-based stereotactic radiosurgery for acoustic schwannomas at the University of Florida between July 1988 and November 1994. Each patient was followed for a minimum of 1 year or until death; no patient was lost to follow up. One or more follow-up magnetic resonance images or computerized tomography scans were obtained in 52 of the 56 patients. Doses ranged between 10 and 22.5 Gy with 69.6% of patients receiving 12.5 to 15 Gy. Thirty-eight patients (68%) were treated with one isocenter and the dose was specified to the 80% isodose line in 71% of patients. Fifty-five patients (98%) achieved local control after treatment. The 5-year actuarial local control rate was 95%. At the time of analysis, 48 patients were alive and free of disease, seven had died of intercurrent disease, and one was alive with disease. Complications developed in 13 patients (23%). The likelihood of complications was related to the dose and treatment volume: 10 to 12.5 Gy to all volumes, three (13%) of 23 patients; 15 to 17.5 Gy to 5.5 cm3 or less, two (9%) of 23 patients; 15 to 17.5 Gy to more than 5.5 cm3, five (71%) of seven patients; and 20 to 22.5 Gy to all volumes, three (100%) of three patients. Linear accelerator—based stereotactic radiosurgery results in a high rate of local control at 5 years. The risk of complications is related to the dose and treatment volume.

WP1-18 Risk factors and patterns of recurrence of low grade glioma: a systematic review

2019 ◽  
Vol 90 (3) ◽  
pp. e6.3-e6
Author(s):  
V Narbad ◽  
JP Lavrador ◽  
A Elhag ◽  
S Acharya ◽  
J Hanrahan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Tp53 Mutation ◽  
Methylation Status ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Diffuse Glioma ◽  
Idh Mutation ◽  
Mgmt Methylation ◽  
Inclusion Criteria

ObjectivesTo review the risk factors and patterns of progression/recurrence of low grade glioma (LGG).DesignSystematic review of the published literature.SubjectsInclusion criteria were peer reviewed publications of cohort studies of recurrent/progressive LGG. Studies of wider populations were included if relevant LGG data could be analysed separately.MethodsMedline and Cochrane databases were searched using MeSH and non-MeSH terms, including ‘glioma’, ‘astrocytoma’, ‘oligoastrocytoma’, ‘diffuse glioma’, ‘oligodendroglioma’, ‘low grade’ and ‘disease recurrence’ by two independent reviewers.ResultsOverall, 917 studies were screened, of which 57 studies met the inclusion criteria. The most frequently described risk factor for recurrent LGG was suboptimal extent of resection (EOR) of the initial tumour (in 20 studies); recurrence was also associated with the patient’s age (2), tumour location (4), neurological status (3), tumour volume (6), bihemispherical tumour (3) and astrocytic histology (6). IDH mutation was associated with recurrence in 1 out of 3 studies, but TP53 mutation (2 of 4) and MGMT methylation status (4) were not. Malignant transformation was associated with TP53 mutations (3), IDH mutation (1) and EOR (1). Favourable progression free survival (PFS) and/or overall survival (OS) were associated with greater EOR (16), oligodendroglioma histology (2 of 4), initial KPS (3) and the use of adjuvant therapies (9 of 14). IDH mutation was associated with improved PFS and OS (3 of 4). TP53 mutation improved PFS in 1 of 3 studies. MGMT methylation and 1 p/19q codeletion may predict treatment response but their effects on survival are unclear.ConclusionsAstrocytoma histology, IDH and TP53 mutation statuses and surgical treatment (EOR) are essential in determining the time to recurrence or progression in LGG.

scholarly journals The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

2020 ◽  
Author(s):  
Huy Gia Vuong ◽  
Thu Quynh Nguyen ◽  
Tam N.M Ngo ◽  
Hoang Cong Nguyen ◽  
Kar-Ming Fung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Web Of Science ◽  
Meta Analysis ◽  
Methylation Status ◽  
Mgmt Methylation ◽  
Wild Type ◽  
Promoter Mutation ◽  
Prognostic Implication ◽  
Kaplan Meier ◽  
The Individual

Abstract Background There are controversial results concerning the prognostic implication of TERT promoter mutation in glioma patients concerning MGMT status. In this meta-analysis, we investigated whether there are any interactions of these two genetic markers on the overall survival (OS) of glioma patients. Methods Electronic databases including PubMed and Web of Science were searched for relevant studies. Hazard ratio (HR) and its 95% confidence interval (CI) for OS adjusted for selected covariates were calculated from the individual patient data (IPD), Kaplan-Meier curve (KMC), or directly obtained from the included studies. Results A total of nine studies comprising 2819 glioma patients were included for meta-analysis. Our results showed that TERT promoter mutation was associated with a superior outcome in MGMT-methylated gliomas (HR = 0.73; 95% CI = 0.55-0.98; p-value = 0.04), whereas this mutation was associated with poorer survival in gliomas without MGMT methylation (HR = 1.86; 95% CI = 1.54-2.26; p-value < 0.001). TERT-mutated glioblastoma (GBM) patients with MGMT methylation benefited from temozolomide (TMZ) treatment (HR = 0.33; 95% CI = 0.23-0.47; p-value < 0.001). MGMT methylation was not related with any improvement in OS in TERT-wild type GBMs (HR = 0.80; 95% CI = 0.56-1.15; p-value = 0.23).ConclusionsThe prognostic value of TERT promoter mutation may be modulated by MGMT methylation status. Not all MGMT-methylated GBM patients may benefit from TMZ; it is possible that only TERT-mutated GBM with MGMT methylation, in particular, may respond.

scholarly journals An independently validated nomogram for isocitrate dehydrogenase-wild-type glioblastoma patient survival

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Haley Gittleman ◽  
Gino Cioffi ◽  
Pranathi Chunduru ◽  
Annette M Molinaro ◽  
Mitchel S Berger ◽  
...  
Keyword(s):  
San Francisco ◽  
Isocitrate Dehydrogenase ◽  
Dna Methyltransferase ◽  
Karnofsky Performance Status ◽  
Methylation Status ◽  
Age At Diagnosis ◽  
World Health ◽  
Newly Diagnosed ◽  
Mgmt Methylation ◽  
Wild Type

Abstract Background In 2016, the World Health Organization reclassified the definition of glioblastoma (GBM), dividing these tumors into isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant GBM, where the vast majority of GBMs are IDH-wild-type. Nomograms are useful tools for individualized estimation of survival. This study aimed to develop and independently validate a nomogram for IDH-wild-type patients with newly diagnosed GBM. Methods Data were obtained from newly diagnosed GBM patients from the Ohio Brain Tumor Study (OBTS) and the University of California San Francisco (UCSF) for diagnosis years 2007–2017 with the following variables: age at diagnosis, sex, extent of resection, concurrent radiation/temozolomide (TMZ) status, Karnofsky Performance Status (KPS), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and IDH mutation status. Survival was assessed using Cox proportional hazards regression, random survival forests, and recursive partitioning analysis, with adjustment for known prognostic factors. The models were developed using the OBTS data and independently validated using the UCSF data. Models were internally validated using 10-fold cross-validation and externally validated by plotting calibration curves. Results A final nomogram was validated for IDH-wild-type newly diagnosed GBM. Factors that increased the probability of survival included younger age at diagnosis, female sex, having gross total resection, having concurrent radiation/TMZ, having a high KPS, and having MGMT methylation. Conclusions A nomogram that calculates individualized survival probabilities for IDH-wild-type patients with newly diagnosed GBM could be useful to physicians for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free software for implementing this nomogram is provided: https://gcioffi.shinyapps.io/Nomogram_For_IDH_Wildtype_GBM_H_Gittleman/.

scholarly journals RADI-32. INTRACRANIAL CONTROL AND RADIONECROSIS IN MELANOMA PATIENTS WITH BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i28-i28
Author(s):  
Michael Tjong ◽  
Fabio Moraes ◽  
David Shultz
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Brain Mri ◽  
Lesion Size ◽  
Kaplan Meier ◽  
Prescription Dose ◽  
Melanoma Patients ◽  
The Brain

Abstract PURPOSE/OBJECTIVE(S): Melanoma commonly metastasizes to the brain and is radioresistant. Stereotactic radiosurgery (SRS) confers durable local control of brain metastases (BM) while maintaining neurocognitive function. These advantages are increasingly important as survival among these patients improves secondary to advances in systemic therapies. This study investigated the local control (LC), intracranial PFS (iPFS), freedom from radionecrosis (FFRN), and overall survival (OS) among melanoma patients receiving SRS for BM. MATERIALS/METHODS: We retrospectively reviewed clinical outcomes of melanoma patients with brain metastases treated with SRS between October 2008 and January 2017 in a large academic centre. Post-SRS, patients were followed in a multidisciplinary clinic with clinical examination and brain MRI every 3 months. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: In total, 97 patients with 283 brain metastases (including 12 surgical cavities) treated with SRS were identified. Median age was 60.5 (24.4–90.7). Median follow-up was 9.6 (2.2–74.7) months after first SRS. Median prescription dose was 21 (10–24) Gy delivered in a single fraction. Thirty (30.9%) patients had WBRT post-SRS, 36 (37.1%) patients had BRAF-positive disease. Per lesion (N=283), 1-year LC and FFRN were 84.4%, and 90.1%, respectively; medians were not achieved for either LC or FFRN. Radionecrosis (RN) occurred in 20 (7.1%) lesions. Per patient (N=97), median OS and iPFS were 16.0 and 5.3 months, respectively; 1-year OS and iPFS rates were 62.0%, and 30.1%, respectively. CONCLUSION: SRS resulted in excellent rates of LC, with a low risk of RN. However, most patients developed intracranial progression within 1 year. Further analyses to establish correlates (lesion size, SRS dose, and molecular status) to LC, FFRN, OS, and iPFS will be performed prior to the final presentation.

The Role of Radiosurgery to the Tumor Bed After Resection of Brain Metastases

Neurosurgery ◽  
2012 ◽  
Vol 72 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Jared H. Gans ◽  
Daniel M.S. Raper ◽  
Ashish H. Shah ◽  
Amade Bregy ◽  
Deborah Heros ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Total Resection ◽  
Whole Brain Radiation ◽  
Brain Radiation

Abstract BACKGROUND: Optimal postoperative management paradigm for brain metastases remains controversial. OBJECTIVE: To conduct a systematic review of the literature to understand the role of postoperative stereotactic radiosurgery after resection of brain metastases. METHODS: We performed a MEDLINE search of the literature to identify series of patients with brain metastases treated with stereotactic radiosurgery after surgical resection. Outcomes including overall survival, local control, distant intracranial failure, and salvage therapy use were recorded. Patient, tumor, and treatment factors were correlated with outcomes through the use of the Pearson correlation and 2-way Student t test as appropriate. RESULTS: Fourteen studies involving 629 patients were included. Median survival for all studies was 14 months. Local control was correlated with the median volume treated with radiosurgery (r = −0.766, P &lt; .05) and with the rate of gross total resection (r = .728, P &lt; .03). Mean crude local control was 83%; 1-year local control was 85%. Distant intracranial failure occurred in 49% of cases, and salvage whole-brain radiation therapy was required in 29% of cases. Use of a radiosurgical margin did not lead to increased local control or overall survival. CONCLUSION: Our systematic review supports the use of radiosurgery as a safe and effective strategy for adjuvant treatment of brain metastases, particularly when gross total resection has been achieved. With all limitations of comparisons between studies, no increase in local recurrence or decrease in overall survival compared with rates with adjuvant whole-brain radiation therapy was found.

scholarly journals Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T

2018 ◽  
Vol 20 (12) ◽  
pp. 1661-1671 ◽  
Author(s):  
Daniel Paech ◽  
Johannes Windschuh ◽  
Johanna Oberhollenzer ◽  
Constantin Dreher ◽  
Felix Sahm ◽  
...  
Keyword(s):  
Methylation Status ◽  
Idh Mutation ◽  
Mgmt Methylation ◽  
Cest Mri

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study

2021 ◽  
pp. 1-9
Author(s):  
Adomas Bunevicius ◽  
Mohand Suleiman ◽  
Samir Patel ◽  
Roberto Martínez Álvarez ◽  
Nuria E. Martinez Moreno ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Target Volume ◽  
Cranial Irradiation ◽  
Who Grade ◽  
Cranial Radiation ◽  
Treatment Volume ◽  
Radiation Induced ◽  
Prescription Dose

OBJECTIVERadiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs.METHODSFrom 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS.RESULTSFifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4–195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3–45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028–65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS.CONCLUSIONSSRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.

scholarly journals PATH-02. A COMBINATION OF MGMT METHYLATION AND NFKBIA COPY NUMBER ALTERATION REFINES PROGNOSTICATION OF IDH-WT GLIOBLASTOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi143-vi143
Author(s):  
Toru Umehara ◽  
Hideyuki Arita ◽  
Ema Yoshioka ◽  
Tomoko Shofuda ◽  
Manabu Kinoshita ◽  
...  
Keyword(s):  
Copy Number ◽  
Prognostic Value ◽  
Cox Regression ◽  
Methylation Status ◽  
The Cancer Genome Atlas ◽  
Prognostic Impact ◽  
Mgmt Methylation ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Japanese Cohort

Abstract INTRODUCTION Recent studies have reported that NFKBIA deletion (dNFKBIA) was potentially associated with worse prognosis in glioblastoma (GBM) patients. However, no consensus has been reached to its universal prognostic value. Here, we investigated the survival impact of dNFKBIA using two primary IDH wild-type GBM cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). Additionally, prognostic impact of a combination of NFKBIA copy number and MGMT methylation status was evaluated. METHOD The Japanese cohort was collected from cases registered in Kansai Molecular Diagnosis Network for CNS tumors (KNBTG). The survival impact of dNFKBIA and/or unmethylated MGMT (uMGMT) were analyzed for 212 KNBTG cases and 265 TCGA cases. The hazard ratio (HR) and p-value were computed using Cox regression analysis. RESULTS dNFKBIA was less frequently observed in KNBTG (47 cases, 22.2%) than in TCGA (84 cases, 31.7%). dNFKBIA was associated with unfavorable prognosis in KNBTG (HR 1.52, p = 0.031), while this was not validated in TCGA (HR 1.14, p=0.406). uMGMT was a common adverse prognostic factor in KNBGT (HR 1.72, p = 0.001) and TCGA (HR 1.50, p = 0.008) cohort. When stratified by NFKBIA status, uMGMT was also associated with shorter survival in NFKBIA deleted cases both in KNBTG (HR 1.87, p = 0.002) and TCGA (HR 1.59, p = 0.014). On the other hand, MGMT status was not significantly associated with prognosis in NFKBIA intact cases in either KNBTG (HR 1.45, p = 0.279) or TCGA (HR 1.55, p = 0.131). DISCUSSION Although the prognostic value of dNFKBIA in IDH wild-type GBM patients was not validated in TCGA cohort, our results indicated that the prognostication based on MGMT methylation was potentially interacted by NFKBIA status.

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