WHO grade II meningioma: a retrospective study for outcome and prognostic factor assessment

To analyse the outcome of patients with WHO grade II meningioma and identify factors that may influence recurrence and survival. Between January 2007 and September 2015, a retrospective search identified 194 WHO grade II meningiomas at the National Hospital for Neurology and Neurosurgery, London. Survival methods were implemented. 31 patients (16?%) had a previous history of grade I meningioma. The patients underwent a total of 344 surgical resections and 43.3?% received radiotherapy. 55 patients (28.4?%) had been re-operated on for a WHO grade II meningioma relapse. Median follow-up was 4.4 years. At the end of the study, 75 patients (40.1?%) had no residual tumour on the last scan. Surgical recurrence free survival at 5 years was 71.6, 95?% CI [63.5, 80.8]. Secondary grade II meningioma (HR?=?2.29, p?=?0.010), and, Simpson resection grade 1, 2 and 3 vs. 4 and 5 (HR?=?0.57, p?=?0.050) were associated with the surgical recurrence-free survival. 32 died from meningioma (16.5?%). Overall survival probability at 5 years was 83.2, 95?% CI [76.6, 90.4]. Age at diagnosis (HR?=?0.22, p?p?=?0.001), tumour location (HR?=?0.19, p?p?=?0.010) were independently associated with the overall survival. Patients who received radiotherapy demonstrated neither a reduced risk of recurrence nor a longer overall survival (p?=?0.310). In our series shorter survival correlated with older age, increased mitoses, progression from grade I to II and location. We were not able to demonstrate a significant improvement in any of the clinical outcomes after radiotherapy.     

Intracranial meningiomas of atypical (WHO grade II) histology

Atypical (WHO grade II) meningiomas occupy an intermediate risk group between benign (WHO grade I) and anaplastic (WHO grade III) meningiomas. Although grade II meningiomas have traditionally been recognized in only about 5% of cases, after changes in diagnostic criteria with the current 2007 WHO standards, they now comprise approximately 20–35% of all meningiomas. Given the magnitude of this change, much work is now needed to solidify the adoption of these standards, to render inter-observer and inter-institutional comparisons more uniform, and to more carefully define the incidence of grade II histology. However, it is clear that they carry a several-fold increased risk of recurrence, as well as an increased rate of mortality. We will discuss the definition, diagnosis, and treatment of patients with atypical meningioma; review the current phase II cooperative trials; and draw attention to some questions timely for pre-clinical and clinical research.     

Stereotactic radiosurgery for WHO grade I meningiomas

Meningiomas represent a common intracranial tumor in the adult population. Although extirpation to achieve a gross total resection or at least decrease mass effect has been the mainstay of treatment, stereotactic radiosurgery has come to play an increasingly important role in the management of patients with meningiomas. Radiosurgery utilizes highly focused, beams of ionizing radiation to inactivate tumor cells. Image guidance and a steep dose fall off are critical features of this approach. The radiobiology of radiosurgery differs in certain advantageous ways from conventional radiotherapy. Radiosurgery initially was utilized to treat recurrent or residual skull base meningiomas. As success was observed in this setting, radiosurgery has gradually expanded its role so as to treat convexity meningiomas; it is also used as an upfront treatment for patients for whom clinical and neuro-imaging findings are consistent with a meningioma. Most large series demonstrate tumor control rates for patients with grade I meningiomas in excess of 85%. Neurological function is generally preserved or improved for patients with meningiomas. However, complications can occur. Longitudinal follow-up including neurologic and radiologic assessment is required. Single and multisession stereotactic radiosurgery will likely play an expanded role in the treatment of patients with meningiomas.     

Recursive partitioning analysis of prognostic factors in WHO grade III glioma patients treated with radiotherapy or radiotherapy plus chemotherapy

Background  

We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for WHO grade III gliomas.     

Adult intracranial WHO grade II ependymomas: long-term outcome and prognostic factor analysis in a series of 114 patients

Ependymomas account for 2% of all intracranial tumors in adults. Considerable controversy continues to exist with regard to their prognostic factors and therapeutic management due to the rarity and the heterogeneity of series reported so far. The authors report a retrospective study of a homogenous population of 114 adult patients harboring WHO grade II intracranial ependymomas from 32 French Neurosurgical Centers between 1990 and 2004. All clinico-radiological and follow-up data were analyzed, and a central pathologic review was performed by two confirmed neuropathologists. The 5- and 10-year overall survival (OS) rates were 86.1% and 81.0%, respectively; the 5- and 10-year progression-free survival (PFS) rates were 74.6% and 58.9%, respectively. On multivariate analysis, the OS rates were associated with preoperative KPS score (P = .027), extent of surgery (P = .008), and tumor location (supratentorial vs infratentorial, P = .012). The multivariate analysis also revealed that the risk of recurrence was associated with incomplete resection (P = .001) and supratentotrial location (P = .038). Moreover, adjuvant radiotherapy (RT) for patients with incompletely resected tumors is responsible for a significant improvement of both overall (P = .005) and progression-free (P = .002) survival. This study clearly supports the major prognostic impact of the extent of surgery in WHO grade II. Interestingly, tumor location also seems to have an actual impact on both OS and PFS. Finally, the prognostic impact of RT was found to be beneficial for incompletely resected tumors.     

No prognostic value of IDH1 mutations in a series of 100 WHO grade II astrocytomas

Mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) have been identified in approximately 70-80 % of astrocytomas and oligodendrogliomas of WHO grades II and III, and in secondary glioblastomas. In addition, a low incidence of IDH2 mutations has been detected in these tumors, and the occurence of IDH1 and IDH2 mutations is mutually exclusive. For patients with anaplastic gliomas and glioblastomas with IDH1 mutations, overall survival was significantly longer than for patients with wild-type tumours. However, the prognostic value of IDH1 in low-grade gliomas remains ambiguous. IDH1 codon 132 and IDH2 codon 172 mutation status were determined by direct sequencing for a retrospective series of 100 patients with histologically diagnosed Astrocytomas WHO Grad II (A II), and investigated for association with patient outcome. For the patient cohort analysed, median progression-free survival (PFS) was 44.6 months (95 %-CI 1.0-267.0), time to progression (median time to malignant progression (TtMP) was 74.9 months (95 %-CI 1.6-236.2), and median overall survival (OS) was 81.4 months (95 %-CI 5.5-274.8). IDH1 mutations were identified in 79 % of the patients. IDH2 mutations were not observed. Univariate and multivariate analysis revealed no association between IDH1 mutation status and PFS, TtMP, and OS. Furthermore, there were no significant differences regarding PFS, TtMP, and OS between patients with and without IDH1 mutations who did not receive adjuvant treatment. The prognostic value of IDH1 mutations in low-grade astrocytomas is rather low compared with that in high-grade gliomas.     

Multisession radiosurgery for grade 2 (WHO), high risk meningiomas. A phase II clinical trial

Journal of Neuro-Oncology - Patients suffering from recurrent and residual grade 2 (WHO) meningiomas after subtotal excision should be considered as high-risk groups with an uncertain prognosis....     

Outcomes of salvage radiation for recurrent world health organization grade II meningiomas: a retrospective cohort study

Journal of Neuro-Oncology -     

Temozolomide during and after radiation therapy for WHO grade III gliomas: preliminary report of a prospective multicenter study

This prospective study was performed to determine the efficacy, safety, and tolerability of concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy with temozolomide (TMZ) in the treatment of patients with WHO grade III gliomas. Thirty-three adult patients with WHO grade III glioma and aged >17 years were enrolled from three institutions between 2003 and 2008. The median age was 41 years (range, 17?C60 years). The pathological diagnoses were anaplastic astrocytomas in 21 patients and anaplastic oligodendrogliomas in 12 patients. The preoperative Karnofsky performance scale score was >60 for all patients. The patients received fractionated focal irradiation in daily fractions of 2 Gy administered five days per week for six weeks, for a total of 60 Gy, in combination with continuous daily TMZ, followed by six cycles of adjuvant TMZ. The median dose of radiotherapy was 59.4 Gy (range, 28.8?C61.2 Gy) and the duration of CCRT was 7.0 weeks (range, 3.1?C8.3 weeks). A median of 6.2 cycles (range, 2?C12 cycles) of TMZ chemotherapy were performed during the period of adjuvant chemotherapy. The response rate was 61% and the tumor-control rate was 82%. Mean progression-free survival (PFS) was 48.7 months (95% CI, 36.0?C61.4) and the 12, 24, and 36-month PFS was 74%, 60%, and 50%, respectively. Mean overall survival (OS) was 66.4 months (95% CI, 56.4?C76.4) and the 12 and 24-month OS was 97% and 77%, respectively. The extent of surgical resection was a significant prognostic factor for PFS and OS (hazard ratio, 0.24; 95% CI, 0.02?C0.73; and hazard ratio, 0.12; 95% CI, 0.01?C0.88, respectively; P < 0.001). However, there was no significant difference in the PFS and OS of patients regarding loss of heterozygosity in chromosomes 1p and 19q and methylation of O ⁶-methylguanine-DNA methyltransferase promoter, because of the small number of patients available. Only five cases (15%) receiving CCRT with TMZ and three cases (9%) receiving adjuvant chemotherapy had hematological toxicity greater than grade 3. All these patients, however, tolerated the therapy well enough to continue treatment. No opportunistic infections were noted. This protocol for WHO grade III gliomas was relatively safe and tolerable. It showed the possibility of achieving favorable results compared with those of historical controls. A randomized controlled study with a long-term follow-up may be mandatory to evaluate its efficacy.     

A new prognostic scoring scale for patients with primary WHO grade III gliomas based on molecular predictors

This study was designed to select molecular markers associated with prognosis, and to propose a prognostic scoring scale for patients with primary WHO grade III gliomas based on these molecular predictors. A series of 83 grade III glioma patients surgically treated and pathologically confirmed in Beijing Tiantan Hospital between May 2009 and December 2010 were retrospectively reviewed in the study. Log-rank analysis was used to identify molecular markers associated with progression-free survival (PFS) and overall survival (OS), which were further assessed using Cox regression analysis. Based on the prognostic molecular markers, a scoring scale was proposed and Kaplan–Meier plots were compared between different scoring levels by Log-rank method. Age <50, 1p/19q co-deletion, IDH1/2 mutation, negative MGMT and EGFR expression were correlated with longer PFS and OS. Cox regression confirmed age <50 and 1p/19q co-deletion as independent prognostic markers. This scoring scale mainly based on prognostic molecular markers stratified patients into four levels with different prognoses. Longer PFS and OS were correlated with higher scores (P < 0.05). This scoring scale based on prognostic molecular markers identified four levels with significantly different prognoses, and could be used to predict the prognosis of patients with primary WHO grade III gliomas.     

Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas.

BACKGROUND: The aim of this study was to assess the efficacy of temozolomide in patients with World Health Organisation (WHO) grade II gliomas treated with surgery alone using imaging and clinical criteria. PATIENTS AND METHODS: Thirty patients with histologically verified WHO grade II gliomas (17 astrocytoma, 11 oligodendroglioma, two mixed oligoastrocytoma) following surgery 2-104 months (median 23 months) after initial diagnosis received temozolomide 200 mg/m(2)/day for 5 days, on a 28-day cycle, for a maximum of 12 cycles or until tumour progression. Median age was 40 years (range 25-68 years). Median follow-up from entry into the study was 3 years [range 23-47 months (for patients alive)]. Objective response was assessed by 3-monthly magnetic resonance imaging and monthly health-related quality of life (HQoL) and clinical assessment. Tumour size was measured as the high signal intensity area on fluid attenuated inversion recovery sequences. Responses were assessed using change in the product of two perpendicular diameters as complete response (CR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). RESULTS: Twenty-nine of 30 patients entered into the study were evaluable for response. Three patients had a PR, 14 MR, 11 SD and one PD. Twenty-four patients received 12 cycles of chemotherapy. Of 29 evaluable patients, three discontinued after four, five and six cycles and two after 10 cycles. Nine patients progressed (three during chemotherapy-one PD and two initial SD-and six after completion of chemotherapy); five had evidence of transformation. The 3-year progression-free survival was 66%. Five patients died; the actuarial 3-year survival was 82%. Ninety-six per cent of patients with impaired HQoL had improvement in at least one HQoL domain. There was improvement in 115 of the 207 domains (56%). Fifteen of 28 patients (54%) with epilepsy had reduction in seizure frequency, of whom six became seizure free. Six patients had transient grade III/IV haematological toxicity (11 episodes; 3.5%). CONCLUSIONS: Temozolomide has single-agent activity in patients with WHO grade II cerebral glioma, with modest improvement in quality of life and improvement in epilepsy control. On present evidence, temozolomide cannot be considered as primary therapy without formal comparison with other treatment modalities.     

Stereotactic radiosurgery of World Health Organization grade II and III intracranial meningiomas: treatment results on the basis of a 22-year experience

BACKGROUND:

A study was undertaken to define the variables associated with tumor control and survival after single‐session stereotactic radiosurgery (SRS) for patients with atypical and malignant intracranial meningiomas.

METHODS:

Fifty patients with World Health Organization (WHO) grade II (n = 37) or grade III (n = 13) meningiomas underwent SRS from 1990 to 2008. Most tumors were located in the falx/parasagittal region or cerebral convexities (n = 35, 70%). Twenty patients (40%) had progressing tumors despite prior external beam radiation therapy (EBRT) (median dose, 54.0 grays [Gy]). The median treatment volume was 14.6 cm³; the median tumor margin dose was 15.0 Gy. Seven patients (14%) received concurrent EBRT (median dose, 50.4 Gy). Follow‐up (median, 38 months) was censored at last evaluation (n = 28) or death (n = 22).

RESULTS:

Tumor grade correlated with disease‐specific survival (DSS) (hazard ratio [HR], 3.4; P = .008), local tumor control (HR, 2.4; P = .02), and progression‐free survival (PFS) (HR, 2.6; P = .02) on univariate analysis, but not on multivariate analysis. Multivariate analysis showed that having failed EBRT and tumor volume >14.6 cm³ were negative predictors of DSS and local control (HR, 3.0; P = .02 and HR, 4.4; P = .01; HR, 3.3; P = .001 and HR, 2.3; P = .02;, respectively). Having failed EBRT was a negative predictor of PFS (HR, 3.5; P = .002). Thirteen patients (26%) had radiation‐related complications at a median of 6 months after radiosurgery.

CONCLUSIONS:

Tumor progression despite prior EBRT and larger tumor volume are negative predictors of tumor control and survival for patients having SRS for WHO grade II and III intracranial meningiomas. Cancer 2012;. © 2011 American Cancer Society.     

Correction to: Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016

Journal of Neuro-Oncology - In the initial, online publication, the authors' given names were captured as family names and vice versa. The names are correctly shown here. The original article...     

Longitudinal experience with WHO Grade III (anaplastic) meningiomas at a single institution

To retrospectively analyze and assess the outcomes and prognostic factors in patients with anaplastic meningioma (AM) (WHO Grade III). Clinical data and outcome [overall (OS) and progression-free (PFS) survival] from 18 patients with Grade III meningioma (AM, based on World Health Organization 2016 definition) initially treated between March 2000 and June 2015 were analyzed. Eleven patients (61%) were male, median age at diagnosis was 63 (range 48–86), and 55% (10/18 patients) had good performance status (KPS?≥?80). Eight patients (45%) had lower grade disease (Grade I—n?=?2; Grade II—n?=?6) prior to being upgraded to AM. Ten patients had fractionated radiation after primary surgery, eight patients had salvage fractionated RT, stereotactic radiosurgery (SRS) boost along with primary RT in 1 patient, and salvage SRS to 18 separate areas in 14 patients. Salvage chemotherapy was mainly considered in third or fourth recurrences. 13 (72%) patients recurred and 10 (56%) have died. Median PFS was 14.5 months (95% CI 6.9–22.2). The 5-year survival rate was 40?±?15% and median OS was 55.8 months (95% CI 27.7–80.3). Of all factors examined, only Karnofsky performance status (KPS) affected outcome (PFS p?=?0.0003; OS p?=?0.0003). With median OS of 55 months (4.6 years) our results are consistent with existing reports of the poor outcomes for AM patients. From the available data, surgical resection followed by RT and salvage radiosurgery and/or chemotherapy can lead to extended survival; however the benefit may decrease with successive treatments.     

Osteopontin expression is a valuable marker for prediction of short-term recurrence in WHO grade I benign meningiomas

Prediction of recurrence remains a challenge in histopathological benign/grade I tumors. Osteopontin (OPN) plays important roles in tumorigenesis, invasion, and metastasis of several human cancers. In this study, we investigated OPN protein expression by evaluating the differences between recurrent and non-recurrent histologically benign meningiomas. Thirty-two patients were enrolled, and 23 benign non-recurrent meningiomas and 9 benign recurrent meningiomas were followed for a mean of 34 months after complete surgical resection (Simpson grades I and II). Cytoplasmic OPN staining was evaluated by means of immunohistochemistry (IHC) score and by use of the Allred-8-unit system. We examined clinical biological data, their relationship with tumor recurrence, and the expression of OPN. Our results showed that meningioma recurrence correlated significantly with OPN IHC score (P = 0.001). An OPN Allred score between 0 and 3 was associated with a recurrence-free time of more than 25 months. In comparison, an OPN Allred score from 4 to 8 was indicative of a shorter average recurrence-free time. We concluded that OPN IHC score may play a role in prediction of the recurrence of the grade I meningiomas. Moreover, determination of the OPN Allred score is a reliable, quantitative tool for predicting recurrence-free time in benign meningioma patients.     

Correction to: Incidental intracranial meningiomas: a systematic review and meta-analysis of prognostic factors and outcomes

Journal of Neuro-Oncology - Issues with data analysis have recently been highlighted by a reader of our article. These have been addressed with changes to Tables 2&amp;4, as shown below, and...