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Predictors of recurrence in the management of chordoid meningioma.

ABSTRACT: Management of chordoid meningiomas (CMs) is complicated by high rates of recurrence, particularly following subtotal resection. Optimal management is not established given the paucity of published experience. To identify prognostic factors for recurrence following resection, the authors conducted the largest systematic review of CMs to date. A comprehensive search on MEDLINE (OVID and Pubmed), Scopus, Embase, and Web of Science utilizing the search terms "chordoid" AND "meningioma" was performed to identify all reports of pathologically confirmed intracranial CMs. A total of 221 patients were included, comprising 120 females and 101 males. Mean age, MIB-1/Ki67, and tumor size was 45.5 years, 4.3% (range 0.1-26.6%), and 4.1 cm (range 0.8-10 cm), respectively. 5-, and 10- year progression free survival was 67.5 and 54.4%, respectively. Gross total resection (GTR) and subtotal resection was achieved in 172 and 48 patients, respectively. Adjuvant radiotherapy (RT) was given to 30 patients. Multivariate analysis found GTR was strongly correlated with decreased recurrence rates (HR 0.04, p = <0.0001), while higher MIB-1 labeling index (?5 vs <5%) was associated with increased recurrence (HR 7.08; p = 0.016). Adjuvant RT, age, gender, and tumor location were not associated with recurrence. GTR resection is the strongest predictor of tumor control, and should be the goal to minimize local progression. Additionally, higher MIB-1 labeling was associated with increased rates of tumor recurrence. Tumors that are subtotally resected or demonstrate higher MIB-1 are at greater recurrence and warrant consideration for RT and close long term follow up.

SUBMITTER: Choy W

PROVIDER: S-EPMC4684776 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Predictors of recurrence in the management of chordoid meningioma.

Choy Winward W Ampie Leonel L Lamano Jonathan B JB Kesavabhotla Kartik K Mao Qinwen Q Parsa Andrew T AT Bloch Orin O

Journal of neuro-oncology 20150926 1

Management of chordoid meningiomas (CMs) is complicated by high rates of recurrence, particularly following subtotal resection. Optimal management is not established given the paucity of published experience. To identify prognostic factors for recurrence following resection, the authors conducted the largest systematic review of CMs to date. A comprehensive search on MEDLINE (OVID and Pubmed), Scopus, Embase, and Web of Science utilizing the search terms "chordoid" AND "meningioma" was performed ...[more]

PMID: 26409888

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Project description:Chordoid meningioma is a morphological variant of meningioma designated as WHO grade 2. However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we identified 12 primary chordoid meningiomas from 12 patients. Histologically, all 12 cases had predominant (> 50%) chordoid morphology. Ten were otherwise grade 1, and two were also atypical. We performed DNA global methylation profile, copy number variation analysis, and targeted next-generation sequencing on 11 chordoid meningiomas, and compared to those of 51 non-chordoid, mostly high grade meningiomas. The chordoid meningiomas demonstrated a unique methylation profile in tSNE, UMAP, and hierarchical heatmap clustering analyses of the most differentially methylated CpGs. The most common copy number variation in chordoid meningioma was loss of 1p (7/11, 64%). Three chordoid meningiomas had 2p loss, which was significantly higher than the non-chordoid control cohort (27% vs 7.2%, p = 0.035). 22q loss was only seen in the two cases with additional atypical histological features. Chordoid meningiomas were enriched in mutations in chromatin remodeling genes EP400 (8/11,73%) KMT2C (4/11, 36%) and KMT2D (4/11, 36%), and showed low or absent NF2, TERT, SMO, and AKT1 mutations. Prognosis wise, only one case recurred. This case had atypical histology and high-grade molecular features including truncating NF2 mutation, 1p, 8p, 10, 14, 22q loss, and homozygous deletion of CDKN2A/B. Progression free survival of chordoid, otherwise grade 1 meningioma was comparable to non-chordoid WHO grade 1 meningioma (p = 0.75), and significantly better than chordoid WHO grade 2 meningioma (p = 0.019). Conclusion: the chordoid histology alone may not justify a universal WHO grade 2 designation. Screening for additional atypical histological or molecular genetic features is recommended.

Project description:Background and purposeMeningiomas are very commonly diagnosed intracranial primary neoplasms, of which the chordoid subtype is seldom encountered. Our aim was to retrospectively review preoperative MR imaging of intracranial chordoid meningiomas, a rare WHO grade II variant, in an effort to determine if there exist distinguishing MR imaging characteristics that can aid in differentiating this atypical variety from other meningioma subtypes.Materials and methodsTen cases of WHO grade II chordoid meningioma were diagnosed at our institution over an 11-year span, 8 of which had preoperative MR imaging available for review and were included in our analysis. Chordoid meningioma MR imaging characteristics, including ADC values and normalized ADC ratios, were compared with those of 80 consecutive cases of WHO grade I meningioma, 21 consecutive cases of nonchordoid WHO grade II meningioma, and 1 case of WHO grade III meningioma.ResultsPreoperative MR imaging revealed no significant differences in size, location, signal characteristics, or contrast enhancement between chordoid meningiomas and other meningiomas. There were, however, clear differences in the ADC values and normalized ADC ratios, with a mean absolute ADC value of 1.62 ± 0.33 × 10(-3) mm(2)/s and a mean normalized ADC ratio of 2.22 ± 0.47 × 10(-3) mm(2)/s in chordoid meningiomas compared with mean ADC and normalized ADC values, respectively, of 0.88 ± 0.13 × 10(-3) mm(2)/s and 1.17 ± 0.16 × 10(-3) mm(2)/s in benign WHO grade I meningiomas, 0.84 ± 0.11 × 10(-3) mm(2)/s and 1.11 ± 0.15 × 10(-3) mm(2)/s in nonchordoid WHO grade II meningiomas, and 0.57 × 10(-3) mm(2)/s and 0.75 × 10(-3) mm(2)/s in the 1 WHO grade III meningioma.ConclusionsChordoid meningiomas have statistically significant elevations of ADC and normalized ADC values when compared with all other WHO grade I, II, and III subtypes, which enables reliable preoperative prediction of this atypical histopathologic diagnosis.

Project description:BackgroundWe and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients.MethodsWe analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent of resection, postoperative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan-Meier analyses to compare progression-free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling.ResultsMeningioma molecular subgroups exhibited divergent clinical courses at 2 years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis factor receptor-associated factor 7 [TRAF7]) recurring at an average rate of 22 times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared with other subgroups. Recurrence of NF2 tumors was associated with male sex, high grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence.ConclusionWe describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide postoperative management decisions for meningiomas.

Project description:Meningiomas, the most common adult brain tumors, recur in up to half of cases. This requires timely intervention and therefore accurate risk assessment of recurrence is essential. Our current practice relies heavily on histological grade and extent of surgical excision to predict meningioma recurrence. However, prediction accuracy can be as poor as 50% for low or intermediate grade tumors which constitute the majority of cases. Moreover, attempts to find molecular markers to predict their recurrence have been impeded by low or heterogenous genetic signal. We therefore sought to apply systems-biology approaches to transcriptomic data to better predict meningioma recurrence. We apply gene co-expression networks to a cohort of 252 adult patients from the publicly available genetic repository Gene Expression Omnibus. Resultant gene clusters ("modules") were represented by the first principle component of their expression, and their ability to predict recurrence assessed with a logistic regression model. External validation was done using two independent samples: one merged microarray-based cohort with a total of 108 patients and one RNA-seq-based cohort with 145 patients, using the same modules. We used the bioinformatics database Enrichr to examine the gene ontology associations and driver transcription factors of each module. Using gene co-expression analysis, we were able predict tumor recurrence with high accuracy using a single module which mapped to cell cycle-related processes (AUC of 0.81?±?0.09 and 0.77?±?0.10 in external validation using microarray and RNA-seq data, respectively). This module remained predictive when controlling for WHO grade in all cohorts, and was associated with several cancer-associated transcription factors which may serve as novel therapeutic targets for patients with this disease. With the easy accessibility of gene panels in healthcare diagnostics, our results offer a basis for routine molecular testing in meningioma management and propose potential therapeutic targets for future research.

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Predictors of recurrence in the management of chordoid meningioma.

Publications

Predictors of recurrence in the management of chordoid meningioma.

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