Diagnosis Of WHO Grade Research Articles

Gliomatosis Cerebri Growth Pattern: Association of Differential First-Line Treatment with Overall Survival in WHO Grade II and III Gliomas

Introduction: Gliomatosis cerebri (GC) is defined by diffuse, widespread glial tumor growth affecting three or more cerebral lobes. Previous studies in gliomas found no distinct histological or molecular GC subtype, yet the presence of GC is associated with worse median overall survival (OS). Here, we explored whether differing therapeutic strategies in first-line treatment could account for this. Methods: From our University Cancer Center database, 47 patients with histological diagnosis of WHO grade II or III glioma and GC imaging pattern were identified. GC criteria were confirmed by independent review. Patients with WHO grade II or III glioma with non-GC pattern served as control cohort (n = 343). Results: Within the GC patient cohort, lower WHO grade, mutated isocitrate dehydrogenase 1 (IDH1) status, and absence of contrast enhancement were associated with better OS. Compared to the control cohort, patients with GC had significantly shorter OS independent of histological diagnosis or IDH1 mutation status. Patients with GC preferentially received chemotherapy alone (62 vs. 18%), and less frequently radiochemotherapy (21 vs. 27%). OS was significantly shorter in the GC cohort compared to the non-GC cohort both for chemotherapy (3.9 vs. 7.6 years, p = 0.0085) and for combined radiochemotherapy (1.1 vs. 8.4 years, p < 0.0001). However, when only patients who received biopsy plus chemotherapy were analyzed, the differences lost statistical significance (3.5 vs. 6.6 years, p = 0.196). Conclusion: We found major differences in the selection of first-line therapies of GC versus non-GC patients. Our results suggest that these differences may partly account for the worse prognosis of GC patients.

NCOG-18. IS THE RANO CRITERIA FOR LOW-GRADE GLIOMA RELIABLE IN THE CLINICAL SETTING? – A RELIABILITY STUDY

Abstract INTRODUCTION Magnetic resonance imaging (MRI) is a fundamental component of longitudinal neuro-oncology evaluation and decision-making. The Response Assessment in Neuro-Oncology criteria for low-grade gliomas (RANOLGG) was designed as an outcome measure for clinical trials. Thus, this project intends to study the reliability of RANOLGG in the clinic setting. METHODS 21 pairs of brain MRIs, that averaged three years apart, were selected from 21 patients with tissue diagnosis of WHO grade 2 gliomas. Two neuro-oncologists and two neuro-radiologists reviewed and independently scored the MRI pairs according to RANOLGG categories of progressive disease, stable disease, minor response, partial response, and complete response. Kappa-Fleiss (KF) was used to evaluate agreement among reviewers. RESULTS Reviewers awarded identical scores in only 33% of MRI pairs and there was a complete disagreement in one MRI pair. Overall reliability of the criteria in the clinical setting is moderate (KF = 0.44). Agreement between neuroradiologists (KF = 0.51) and between neuro-oncologists (KF = 0.48) were similar. Interpretation of post-contrast T1-weighted images had a better agreement (KF = 0.31) than T2/FLAIR-weighted images which had a poor agreement (KF = -0.02). Classification of progression versus non-progression had only a moderate agreement (KF= 0.49). History of radiation therapy or chemotherapy did not influence the criteria reliability (fisher exact text, p = 0.58, p =0.27, respectively). CONCLUSION RANOLGG reliability in the clinical setting is moderate, therefore it should be used cautiously for clinical decision-making. Other tools that can support the neuro-oncologist in the follow-up of patients with low-grade glioma are additional MRI sequences other than T2/FLAIR and contrast – weighted images, computer-aided diagnosis such as volumetrics, spectroscopy, positron emission tomography, and multidisciplinary tumor boards. Likewise, when image criteria for low-grade gliomas are designed, T2/FLAIR should be used guardedly, due to low interpretation agreement.

AdultDiffuse Low-Grade Gliomas: 35-Year Experience at the Nancy France Neurooncology Unit.

BackgroundTo report survival, spontaneous prognostic factors, and treatment efficacy in a French monocentric cohort of diffuse low-grade glioma (DLGG) patients over 35 years of follow-up.MethodsA monocentric retrospective study of 339 patients diagnosed with a new DLGG between 01/01/1982 and 01/01/2017 was created. Inclusion criteria were patient age ≥18 years at diagnosis and histological diagnosis of WHO grade II glioma (according to 1993, 2007, and 2016 WHO classifications). The survival parameters were estimated using the Kaplan-Meier method with a 95% confidence interval. Differences in survival were tested for statistical significance by the log-rank test. Factors were considered significant when p ≤ 0.1 and p ≤ 0.05 in the univariate and multivariate analyses, respectively.ResultsA total of 339 patients were included with a median follow-up of 8.7 years. The Kaplan-Meier median overall survival was 15.7 years. At the time of radiological diagnosis, Karnofsky Performance Status score and initial tumor volume were significant independent prognostic factors. Oncological prognostic factors were the extent of resection for patients who underwent surgery and the timing of radiotherapy for those concerned. In this study, patients who had delayed radiotherapy (provided remaining low grade) did not have worse survival compared with patients who had early radiotherapy. The functional capabilities of the patients were preserved enough so that they could remain independent during at least three quarters of the follow-up.ConclusionThis large monocentric series spread over a long time clarifies the effects of different therapeutic strategies and their combination in the management of DLGG.

Clinical outcomes of resecting scarpa's ganglion during vestibular schwannoma surgery

Vestibular schwannomas are slow-growing tumors arising from the Schwann cells of the vestibular nerve. Scarpa’s ganglion, the vestibular nerve ganglion, is located within the internal auditory meatus. Surgical treatment of vestibular schwannomas carries the potential of resecting Scarpa’s ganglion along with the tumor. No prior studies have evaluated outcomes based on the presence of Scarpa’s ganglion within tumor specimens. The neurosurgery patient records were queried for patients who underwent surgical resection of vestibular schwannomas at the University of Missouri Healthcare between January 1, 2008 and December 31, 2018. Inclusion criteria consisted of minimum age of 18, imaging demonstrating an eighth nerve tumor, surgical resection thereof, and a final pathological diagnosis of WHO grade I schwannoma. Data were collected retrospectively. The histological slides of the tumors were reviewed, and the presence or absence of the ganglion was noted. Outcomes analyzed included postoperative dizziness, hearing, and facial nerve function. Fifty-two patients met inclusion criteria. Ten (19%) resected tumors contained portions of the ganglion. No difference in risk of resection of ganglion occurred based on the surgical approach (p = 0.2454). Mean follow-up duration was 24.6 months ± 26.2 standard deviation. No differences in postoperative hearing or dizziness (p = 0.8483 and p = 0.3190 respectively) were present if Scarpa’s ganglion was resected. House-Brackmann classification of facial nerve function at last follow-up was similar (p = 0.9190). Resection of Scarpa’s ganglion with vestibular schwannomas does not increase risk of post-operative dizziness, facial nerve weakness, or hearing loss.

SURG-14. DOES WAITING MATTER? HOW TIME FROM DIAGNOSTIC MRI TO SURGICAL RESECTION AFFECTS OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA

Abstract Surgical resection is standard of care for patients with lesions concerning for high-grade glioma on MRI scan. There is no consensus on the urgency of the procedure for patients with good clinical performance status. Treatment history and functional outcomes were collected retrospectively from the electronic medical record for 105 consecutive patients with newly diagnosed WHO Grade IV gliomas who underwent surgical resection at the University of California, San Francisco in 2014 and 2015 (41% female, average age = 61.25). Median preoperative KPS score was 80. Median wait time to surgery was 11 days after the initial MRI scan (range: 0–213 days). Mean tumor volume at the time of initial MRI scan was 29.0 cm3 (SD = 26.1 cm3), which did not significantly differ from the mean pre-operative tumor volume of 31.2 cm3 (SD = 27.3 cm3). In this retrospective cohort, patients with larger glioblastomas were taken to surgery more quickly. Patients who presented to the emergency room were more likely to wait less than 7 days (p &amp;lt; 0.001). Patients who waited less than 7 days had a larger initial and pre-operative tumor volume compared to patients who waited between 7–21 days and patients who waited over 21 days (p=&amp;lt; 0.001, p=&amp;lt; 0.001). Tumor growth occurred in 10% of patients who waited one week or less, 26% of patients who waited one to three weeks, and 55% of patients who waited over 3 weeks. Overall survival was not significantly affected by wait time until tumor resection (p=0.52). Additionally, Tumor growth was not associated with postoperative outcomes including postoperative KPS score, postoperative deficits, 3-month follow up KPS score, overall survival, and survival after surgery. In conclusion, longer wait time to surgery does not impact overall survival, pre-, and post-operative KPS, but the tumor is likely to grow in the interim.

QOLP-29. MINDFULNESS MEDITATION PRACTICE IN MALIGNANT GLIOMA PATIENTS THROUGHOUT CONCOMITANT RADIATION AND TEMOZOLOMIDE: A FEASIBILITY STUDY

Abstract With a bleak prognosis for malignant glioma, maintaining quality of life (QoL) and decreasing distress of the patient are important in the clinical care of the patient. Mindfulness meditation is a mind-body therapy that has been recently investigated in the oncology field as a non-pharmacological strategy to ameliorate cancer symptoms and to improve QoL. This practice has not been studied in the primary brain tumor population. We initiated a pilot study among newly diagnosed brain tumor patients with the hypothesis that mindfulness meditation practice may benefit the patient by decreasing stress and anxiety and provide a means to cope with their new diagnosis. The specific aim of this pilot study is to determine the feasibility of a mindfulness meditation program to this population during standard of care chemoradiation and to determine whether it merits additional research in a subsequent trial. The intervention consists of six weekly one hour telephone-based mindfulness sessions followed by one in- person mindfulness session consisting of: mindfulness and healing, understanding stress, abiding in kindness, working with difficult emotions, finding peace, going forward and living fully. Subjects are provided with downloadable guided meditations. We plan to enroll fifteen newly diagnosed WHO grade III or IV malignant glioma subjects prior to their 6 week chemoradiation course. We will determine the percentage of subjects approached vs enrolled, number of sessions that each subject attends, completion of study questionnaires and satisfaction of the subjects. QoL surveys include: Functional Assessment of Cancer Therapy- Brain, Functional Assessment of Cancer Therapy- Cognitive Function, Pittsburgh Sleep Quality Index, Functional Assessment of Chronic Illness Therapy-Fatigue and the Five Facet Mindfulness Questionnaire – short form. 13 subjects have been approached and 8 signed consent over a two-month period. We will provide final study results at time of presentation.

ACTR-60. A PHASE 2, HISTORICALLY CONTROLLED STUDY TESTING THE EFFICACY OF TTFIELDS WITH ADJUVANT TEMOZOLOMIDE IN HIGH-RISK WHO GRADE II AND III ASTROCYTOMAS (FORWARD)

Abstract BACKGROUND A long-standing observation in neuro-oncology concerns a group of patients with WHO Grade II and III gliomas expressing isolated hTERT promoter mutations, which exhibit indolent histological features but are highly aggressive and resistant to standard chemoradiation therapy. These patients show an overall survival rate similar to glioblastoma WHO Grade IV, necessitating new treatment options. This represents the first study of its kind testing novel treatment for this rare subgroup of lower grade gliomas with high-risk cytogenetics. METHODS This Phase 2, single arm, multicenter open label study [NCT03906448] will enroll 100 adult patients with newly diagnosed WHO grade II and III astrocytoma without IDH mutations and 1p/19q codeletions and with isolated hTERT promoter mutations who have completed standard radiotherapy with concurrent temozolomide, followed by adjuvant temozolomide for 12 cycles in combination with 24 months of TTFields therapy. The primary endpoint is overall survival compared to historical controls. Secondary endpoints are safety, quality of life, and progression free survival. Correlative studies will examine the effect of TTFields on intratumoral immune microenvironment and the role of electric field distribution on disease control and outcomes. Sample size was based on improvement in median OS versus historical controls (N=59; median survival 22 months). Improvements in median overall survival was based on a one-sided Wald test of the Weibull regression coefficient (H0: beta=0, alpha=0.05). A consortium of 15 institutions across the US will participate, with the first enrollment May 2019. Total accrual of 100 is planned over 36 months. The survival results and the correlative studies are designed to provide new insights for future therapeutic development for these patients.

Grade III meningioma: 10 year single centre case series

Abstract Rationale WHO Grade 3 meningiomas are a rare, malignant subtype of meningioma. Few controlled case series detailing its treatment and follow-up are to be found in the literature. Methods Retrospective cohort study of patients treated in a single neuro-oncology centre in the period between September 2008 and March 2019 with an initial diagnosis of WHO Grade 3 meningioma. Demographic and clinical data has been collected from the available medical records. Results 9 patients were included in this series: 2 had convexity, 2 sphenoid wing, 2 parafalcine, 1 parasagittal with a further 3 multiple locations and 1 patient with parietal convexity meningioma. 3 tumours displayed rhabdoid features, whilst 4 displayed papillary features and a further 2 displayed epithelial structures. All patients underwent surgical intervention: 5 patients had a subtotal resection with 3 having total resection. 3/4 of reported Simpson Grading was grade 2, whilst the remaining 1/4 was grade 1. The extent of resection for 1 patient was uncertain. Post surgically, 6 received adjuvant radiotherapy, 2 had no further treatment and 1 received gamma knife therapy. No patient received chemotherapy. 5 patients saw no tumour recurrence at follow up appointments (mean 50 months). Within 2 years of their respective surgical interventions, 4 patients died due to tumour recurrence and associated complications (3 patients). Conclusion To establish a uniform approach to treatment of patients with WHO Grade 3 meningiomas is challenging. Management involves a patient-centred approach based on multidisciplinary meeting decisions. Multicentre registries may allow further conclusions.

P14.96 Gliomatosis cerebri imaging pattern: a treatment-independent marker for worse overall survival in WHO grade II and III gliomas

Abstract BACKGROUND The term gliomatosis cerebri (GC) refers to glial brain tumors with widespread tumor expansion affecting three or more cerebral lobes. Formerly considered a distinct tumor entity, recent studies found no difference in the mutational profile of glial tumors with GC growth pattern compared to non-GC gliomas. Thus, in the new WHO classification of brain tumors, GC is no longer included as a separate diagnosis. While the presence of gliomas with GC growth pattern is associated with worse overall survival (OS), the underlying factors remain to be identified. Here, we asked whether differing therapeutic strategies in first line treatment could account for the worse outcome of patients with GC growth pattern and grade II and III histology. MATERIAL AND METHODS From the patient data bank of the University Cancer Center (UCT) Frankfurt, 47 patients with histological diagnosis of WHO grade II or III glioma, and with record of GC imaging pattern were identified. GC tumor expansion was confirmed by review of MRI scans prior to treatment initiation. Patients with WHO grade II or III glioma without GC growth pattern served as control cohort (n=379). IDH mutational status was available for 75% of GC tumors (IDH R132H mutated 32%; non-mutated 43%) and 69% of non-GC tumors (IDH R132H mutated 57%; non-mutated 12%). RESULTS Within the GC patient cohort, patients with tumors without contrast enhancement, lower WHO grade and mutated IDH status showed better OS. Compared to the control cohort, patients with GC had significantly shorter OS. This was independent of histological diagnosis or IDH mutation status. Patients with GC more frequently underwent radiochemotherapy (17% vs. 9% in the non-GC cohort), and drastically more often received chemotherapy alone (51% vs. 5%). We then analyzed OS in GC and non-GC patients that had received the same first line treatments. For radiochemotherapy in GC versus non-GC patients, OS was 1.1 years vs. 12.7 years (p =0.0075, log-rank test). For upfront chemotherapy alone, OS was significantly shorter in the GC cohort than in the non-GC cohort (3,6 years vs. undefined, p =0.0016, log-rank test). CONCLUSION Differences in first-line treatment cannot account for the worse prognosis of patients with GC imaging pattern. Further studies are needed to pinpoint biological or clinical factors that might influence responsiveness to therapy and prognosis of GC tumors.

PL3.2 Trabectedin for recurrent WHO grade II or III meningioma: a randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)

Abstract BACKGROUND EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis®) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. METHODS Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). RESULTS Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00–2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54–1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. CONCLUSIONS In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting.

Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic 18F-FET PET.

According to the updated WHO classification of gliomas with its emphasis on molecular parameters, tumours with an IDH-wildtype status have a dismal prognosis. To ensure timely adjustment of treatment, demand for non-invasive prediction methods is high. 18F-FET PET has been shown to be an important diagnostic tool for glioma management. The aim of this study was to assess the value of dynamic 18F-FET PET for the non-invasive prediction of the IDH-mutation status. Newly diagnosed WHO grade II-IV glioma patients with MRI and dynamic 18F-FET PET were included. The 18F-FET PET parameters mean and maximal tumour-to-background ratio (TBRmean, TBRmax) and minimal time-to-peak (TTPmin) were evaluated. The diagnostic power for the prediction of the IDH genotype (positive/negative predictive value) was tested in the overall study group and in the subgroup of non-contrast enhancing gliomas. Three hundred forty-one patients were evaluated. Molecular analyses revealed 178 IDH-mutant and 163 IDH-wildtype tumours. Overall, 270/341 gliomas were classified as 18F-FET-positive (TBRmax > 1.6), 90.2% of the IDH-wildtype and 69.1% of IDH-mutant gliomas. Median TBRmax was significantly higher in IDH-wildtype compared with IDH-mutant gliomas (2.9 vs. 2.3, p < 0.001); however, ROC-analyses revealed no reliable cutoff due to a high overlap (range 1.0-7.1 vs. 1.1-7.9). Dynamic analysis revealed a significantly shorter TTPmin in IDH-wildtype gliomas; using TTPmin ≤ 12.5min as indicator for IDH-wildtype gliomas, a positive predictive value of 87% was reached (negative predictive value 72%, AUC = 0.796, p ≤ 0.001). A total of 161/341 gliomas did not show contrast enhancement on MRI; even within this subgroup, TTPmin ≤ 12.5min remained a good predictor of IDH-wildtype glioma (positive predictive value 83%, negative predictive value 90%; AUC = 0.868, p < 0.001). A short TTPmin in dynamic 18F-FET PET serves as good predictor of highly aggressive IDH-wildtype status in gliomas. In particular, a high diagnostic power was observed in the subgroup of non-contrast enhancing gliomas, which helps to identify patients with worse prognosis.

Trabectedin for recurrent WHO grade II or III meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG).

2007 Background: EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. Methods: Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Results: Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00-2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54-1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. Conclusions: In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting. Clinical trial information: NCT02234050.

Male gender is associated with seizure risk in low-grade glioma (LGG) patients.

e13520 Background: Up to 90% of LGG patients present with seizures, but the risk of developing seizure is not known. Our goal was to determine the association between clinical and molecular factors with seizure incidence in LGG patients. Methods: Retrospective study from 2/2002-1/2015 involving 291 patients ≥18 years old, with diagnosis of WHO grade II glioma. Intractable seizure was defined as patients needing ≥2 anti-epileptic drugs. Chi-square tests of association were used to test for associations between factors and outcome measures. Results: Study population was 54% men, median age of 51, with oligodendroglioma (47%), oligoastrocytoma (25%), astrocytoma (21%), NOS (7%). Among patients with molecular testing (87%), 32% had IDH mutation (IDHmt) and 1p/19q co-deletion, 37% IDHmt and 1p/19q intact and 18% IDH wildtype LGG. Sixty-eight percent of patients had seizures prior to LGG diagnosis; 41% intractable seizures. A trend toward higher incidence of pre-operative seizure was observed in IDHmt LGG patients (p = 0.09). On univariate analysis (Table), oligodendroglioma was significantly associated with a higher risk of intractable seizures. Male gender was strongly associated with the risk of seizure at presentation, seizure development after surgery, and intractable seizures. Conclusions: Consistent with historical data, the majority of our patients presented with seizure; oligodendroglioma with higher risk of intractable seizures. Unexpectedly, gross resection did not favorably predict seizure outcome, possibly due to our small study population. Our study only showed a trend towards higher seizure occurrence in IDHmt LGG patients. Our finding of association between male gender and seizure risk in LGG patients mirrors that of Pallud et al (Brain 2014) and warrants further investigation into the possible molecular basis of sex differences in epileptogenesis in LGG.[Table: see text]

Hybrid 11C-MET PET/MRI Combined With "Machine Learning" in Glioma Diagnosis According to the Revised Glioma WHO Classification 2016.

With the advent of the revised WHO classification from 2016, molecular features, including isocitrate dehydrogenase (IDH) mutation have become important in glioma subtyping. This pilot trial analyzed the potential for C-methionine (MET) PET/MRI in classifying glioma according to the revised WHO classification using a machine learning model. Patients with newly diagnosed WHO grade II-IV glioma underwent preoperative MET-PET/MRI imaging. Patients were retrospectively divided into four groups: IDH wild-type glioblastoma (GBM), IDH wild-type grade II/III glioma (GII/III-IDHwt), IDH mutant grade II/III glioma with codeletion of 1p19q (GII/III-IDHmut1p19qcod) or without 1p19q-codeletion (GII/III-IDHmut1p19qnc). Within each group, the maximum tumor-to-brain-ratio (TBRmax) of MET-uptake was calculated. To gain generalizable implications from our data, we made use of a machine learning algorithm based on a development and validation subcohort. A support vector machine model was fit to the development subcohort and evaluated on the validation subcohort. Receiver operating characteristic (ROC) analysis served as metric to assess model performance. Of a total of 259 patients, 39 patients met the inclusion criteria. TBRmax was highest in the GBM cohort (TBRmax 3.83 ± 1.30) and significantly higher (P = 0.004) compared to GII/III-IDHmut1p19qnc group, where TBRmax was lowest (TBRmax 2.05 ± 0.94). ROC analysis showed poor AUC for glioma subtyping (AUC 0.62) and high AUC of 0.79 for predicting IDH status. In the GII/III-IDHmut1p19qcod group, TBR values were slightly higher than in the IDHmut1p19qnc group. MET-PET/MRI imaging in pre-operatively classifying glioma entities appears useful for the assessment of IDH status. However, a larger trial is needed prior to translation into the clinical routine.

Impact of facility type and volume on post-surgical outcomes following diagnosis of WHO grade II glioma

ObjectiveLow grade gliomas present unique and challenging scenarios. We aimed to identify if facility type and/or facility volume impact overall survival (OS) following diagnosis of WHO grade II gliomas. We also sought to compare early post-surgical outcomes based on these factors. MethodsThe National Cancer Database was queried for patients with WHO grade II gliomas diagnosed from 2004 to 2013 with known survival. Patients were grouped based on facility type and facility volume. Multivariable analyses were performed to investigate factors associated with OS following diagnosis, and Chi-square tests were used to compare early post-surgical outcomes. Results6428 patients met inclusion criteria. Factors associated with improved OS on multivariable analysis included younger patient age, female gender, race, non-use of radiotherapy (each p < 0.001). Also, on multivariable analysis, OS was improved among patients treated at Academic/Research programs compared to those treated at Non-Academic/Research programs (HR 0.898, p = 0.014), but facility volume did not impact OS (p = 0.760). Thirty-day mortality did not differ by facility type (p = 0.265), but 90-day morality as well as 30-day readmission rates were more favorable in Academic/Research programs (p = 0.008 and <0.001, respectively). ConclusionsThis study suggests that patients treated in Academic/Research programs have increased survival and generally more favorable early-postsurgical outcomes. The extent to which differences in patient populations, socioeconomic factors, and/or provider expertise play into this cause will be areas of future research.

National care among patients with WHO grade I intracranial meningioma

PurposeTo analyze the national treatment trends of patients diagnosed with benign intracranial meningioma. Methods and materialsData was obtained from the National Cancer Database (NCDB) for patients with WHO grade I meningioma tumors between 2004 and 2014 (190,527 patients), diagnosed by either surgical specimen or diagnostic imaging. Univariable and multivariable analyses (binary logistic models) were performed to generate odds ratios (OR) and investigate factors associated with definitive initial treatment compared to initial observation. Initial treatments considered included surgical resection and/or radiation, including either fractionated external beam radiotherapy (EBRT) or stereotactic radiosurgery (SRS). ResultsThe rate of observation increased over time, from 37% in 2004 to 55% in 2014 (p < 0.001). Conjointly, the rate of resection decreased from 50% to 37% from 2004 to 2014 (p < 0.001). The utilization of radiotherapy, including SRS, remained generally stable over time at 6% or less. SRS was more frequently utilized, compared to EBRT, as definitive treatment (4.6% versus 1.7%, respectively, p < 0.001). Compared to Community Cancer programs, patients at Academic/Research programs were more likely to receive definitive initial treatment over observation (OR = 2.909, each p < 0.001). ConclusionsThere is a national trend favoring initial observation for radiographically diagnosed WHO grade I meningioma. However, patients presenting to academic facilities are more likely to receive definitive initial treatment. Further research into differing approaches among treatment facilities for this common tumor may help clarify this trend.

Durable response to bevacizumab in adults with recurrent pilocytic astrocytoma

Background:Adult pilocytic astrocytomas are rare and highly vascular tumors.Aim:We hypothesized that they may be uniquely responsive to bevacizumab (BEV).Patients:We present four adult patients with pathologically diagnosed WHO grade I pilocytic astrocytoma who had robust and durable responses to BEV at time of recurrence. Three patients developed radiographic changes on MRI, consistent with progressive disease based on response assessment in neuro-oncology criteria. Median time to recurrence was 8.5 months.Methods:All patients were treated with six cycles of BEV for recurrence.Results:At the end of treatment, all patients had achieved a clinical and radiographic response. Median follow-up time after BEV is 20.5 months.Conclusion:This suggests that BEV may have true antitumor activity in adult pilocytic astrocytomas and may be important for achieving durable disease control.

Evaluation of DNA ploidy with intraoperative flow cytometry may predict long-term survival of patients with supratentorial low-grade gliomas: Analysis of 102 cases

ObjectiveThe objective of the present study was evaluation of the prognostic significance of DNA ploidy assessed with intraoperative flow cytometry (iFC) during resection of low-grade gliomas (LGG). Patients and methodsRetrospective analysis of 102 consecutive cases of newly diagnosed WHO grade II supratentorial gliomas, surgical removal of which was accompanied by iFC, was done. There were 46 diffuse astrocytomas (DA) and 56 oligodendrogliomas (OD). According to iFC, 68 tumors (67%) were considered non-aneuploid and 34 (33%) aneuploid. Median extent of resection (EOR) was 95% (mean, 89.0 ± 14.5%). Postoperative FRT with or without adjuvant chemotherapy was administered in 24 cases (24%). ResultsWith median follow-up of 29.9 months (range, 9.4–66.9 months), neither median overall survival (OS) nor median progression-free survival (PFS) were reached. The 3-year actuarial OS and PFS rates were 95.8% and 86.3%, respectively. Non-aneuploid DNA histogram type of the tumor was associated with significantly longer OS both in univariate (P = 0.0094) and multivariate (P = 0.0232) analyses, and with longer PFS in univariate analysis (P = 0.0184). Aneuploidy was encountered more frequently in DA, than in OD (43% vs. 25% of cases; P = 0.0488). Tumor progression was noted in 15 DA and 4 patients succumbed to the disease; in this subgroup the main unfavorable prognostic factors for OS and PFS were presence of aneuploidy (P = 0.0510) and MIB-1 index ≧3.9% (P = 0.0141), respectively. Aneuploid DA more frequently progressed to glioblastoma than to anaplastic astrocytoma, but this difference did not reach statistical significance (P = 0.1362). In contrast, only one OD progressed (non-aneuploid neoplasm), and no one patient with such tumor died of the disease. ConclusionsDNA ploidy assessed with iFC may be effectively used as prognostic indicator in cases of LGG, especially of DA. Aneuploid tumors demonstrate more aggressive clinical course translated into shorter OS of patients. Thus, their detection during surgery may be helpful for decision on the optimal EOR, and for choice of the most appropriate postoperative adjuvant therapy.

Stereotactic radiosurgery for WHO grade I posterior fossa meningiomas: long-term outcomes with volumetric evaluation.

OBJECTIVEResearch over the past 2 decades has been characterizing the role of stereotactic radiosurgery (SRS) in the treatment of benign intracranial tumors, including meningiomas. However, few studies have examined the long-term outcomes of SRS treatment for posterior fossa meningiomas (PFMs). Furthermore, previous studies have typically used single diameter measurements when reporting outcomes, which can yield misleading results. The authors describe the use of SRS in the treatment of benign WHO grade I PFMs and correlate volumetric analysis with long-term outcomes.METHODSThis study is a retrospective analysis of a prospectively maintained IRB-approved database. Inclusion criteria were a diagnosis of WHO grade I PFM with subsequent treatment via single-session SRS and a minimum of 3 follow-up MRI studies available. Volumetric analysis was performed on the radiosurgical scan and each subsequently available follow-up scan by using slice-by-slice area calculations of the meningioma and numerical integration with the trapezoid rule.RESULTSThe final cohort consisted of 120 patients, 76.6% (92) of whom were female, with a median age of 61 years (12-88 years). Stereotactic radiosurgery was the primary treatment for 65% (78) of the patients, whereas 28.3% (34) had 1 resection before SRS treatment and 6.7% (8) had 2 or more resections before SRS. One patient had prior radiotherapy. Tumor characteristics included a median volume of 4.0 cm3 (0.4-40.9 cm3) at treatment with a median margin dose of 15 Gy (8-20 Gy). The median clinical and imaging follow-ups were 79.5 (15-224) and 72 (6-213) months, respectively. For patients treated with a margin dose ≥ 16 Gy, actuarial progression-free survival rates during the period 2-10 years post-SRS were 100%. In patients treated with a margin dose of 13-15 Gy, the actuarial progression-free survival rates at 2, 4, 6, 8, and 10 years were 97.5%, 97.5%, 93.4%, 93.4%, and 93.4%, respectively. Those who were treated with ≤ 12 Gy had actuarial progression-free survival rates of 95.8%, 82.9%, 73.2%, 56.9%, and 56.9% at 2, 4, 6, 8, and 10 years, respectively. The overall tumor control rate was 89.2% (107 patients). Post-SRS improvement in neurological symptoms occurred in 23.3% (28 patients), whereas symptoms were stable in 70.8% (85 patients) and worsened in 5.8% (7 patients). Volumetric analysis demonstrated that a change in tumor volume at 3 years after SRS reliably predicted a volumetric change and tumor control at 5 years (R2 = 0.756) with a p < 0.001 and at 10 years (R2 = 0.421) with a p = 0.001. The authors also noted that the 1- to 5-year tumor response is predictive of the 5- to 10-year tumor response (R2 = 0.636, p < 0.001).CONCLUSIONSStereotactic radiosurgery, as an either upfront or adjuvant treatment, is a durable therapeutic option for WHO grade I PFMs, with high tumor control and a low incidence of post-SRS neurological deficits compared with those obtained using alternate treatment modalities. Lesion volumetric response at the short-term follow-up of 3 years is predictive of the long-term response at 5 and 10 years.

Diffusion tensor image features predict IDH genotype in newly diagnosed WHO grade II/III gliomas

We hypothesized that machine learning analysis based on texture information from the preoperative MRI can predict IDH mutational status in newly diagnosed WHO grade II and III gliomas. This retrospective study included in total 79 consecutive patients with a newly diagnosed WHO grade II or III glioma. Local binary pattern texture features were generated from preoperative B0 and fractional anisotropy (FA) diffusion tensor imaging. Using a training set of 59 patients, a single hidden layer neural network was then trained on the texture features to predict IDH status. The model was validated based on the prediction accuracy calculated in a previously unseen set of 20 gliomas. Prediction accuracy of the generated model was 92% (54/59 cases; AUC = 0.921) in the training and 95% (19/20; AUC = 0.952) in the validation cohort. The ten most important features were comprised of tumor size and both B0 and FA texture information, underlining the joint contribution of imaging data to classification. Machine learning analysis of DTI texture information and tumor size reliably predicts IDH status in preoperative MRI of gliomas. Such information may increasingly support individualized surgical strategies, supplement pathological analysis and highlight the potential of radiogenomics.