Atypical meningioma (AM)
In atypical meningiomas bone involvement and large meningioma peritumoral edema are associated with increased tumor progression.
Spinal atypical meningiomas
In a study, Sun et al. review the English-language literature on the management and clinical outcomes using the WHO 2000/2007 grading criteria. Twenty-two studies for AMs were examined in detail. The authors examined clinical decision points using the literature and concepts from evidence-based medicine. Acknowledging the retrospective nature of the studies, the authors did find evidence for the following clinical strategies:
1) maximal safe resection
2) active surveillance after gross-total resection
3) adjuvant radiation therapy after subtotal resection of AM, especially in the absence of putative radio resistant features 1).
The efficacies of adjuvant stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after subtotal resection (STR) remain unclear.
Conformal, high dose radiotherapy resulted in significant improvement of local control for atypical and malignant meningiomas. Increased local control resulted also in improved rates of survival for patients with malignant meningioma 2).
Role of necrosis
Necrosis may be a negative predictor of radiation response regardless of radiation timing or modality 4).
Retrospective series supports the observation that postoperative radiotherapy likely results in lower recurrence rates of gross totally resected atypical meningiomas.
Patients older than 55 years and those with mitoses noted during pathological examination had a significant risk of recurrence after GTR; for these patients, postoperative radiotherapy is recommended 5).
After GTR without postoperative radiation, AMs have a high recurrence rate. Most recurrences occurred within 5 years after resection. Recurrences caused numerous reoperations per patient and shortened survival 6).
A multicenter prospective trial will ultimately be needed to fully define the role of radiotherapy in managing gross totally resected atypical meningiomas 7).
Study limitations, including inadequate statistical power, may underlie the studies’ inability to demonstrate a statistically significant benefit for adjuvant radiotherapy in AM. Because these tumors preferentially recur within 5 years of surgical resection, future studies should define whether early adjuvant therapy should become part of the standard treatment paradigm for completely excised tumors 8).
Brain invasion and high mitotic rates may predict recurrence. After gross total resection (GTR) of AMs, EBRT appears not to affect progression free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR 9).
The most important prognostic factor in determining recurrence was Simpson grading. There was no statistically significant impact of adjuvant radiotherapy on the recurrence of atypical meningiomas. Metaanalysis for the existing literature is needed 10).
GTR is associated with improved OS compared with STR. In the subgroup analysis, adjuvant RT in patients who underwent STR demonstrated significant association with improved OS compared with no adjuvant RT (adjusted hazard ratio [AHR] 0.590, P = .045); however, adjuvant RT is not associated with improved OS in patients who underwent GTR (AHR 1.093, P = .737).
Despite the lack of consensus on whether adjuvant RT reduces recurrence after surgical resection of AM, our study observed significantly improved OS with adjuvant RT compared with no adjuvant RT after STR 11).
The uni- and multivariate analysis showed no statistically significant differences between recurrent and non-recurrent subgroups of patients undergoing complete resection. It is noted in the results that for each year of age above 50 years, the risk of recurrence is decreased by 5.8%.
Although current prognostic factors may show an increased risk of recurrence once patients are stratified by the two most important factors (pathology and extent of resection), those factors are insufficient to predict the ultimate outcome of patients affected by this pathology 12)
Endo et al., reviewed 45 patients with atypical meningioma who underwent surgical intervention between January 2000 and December 2013. The mean age of the patients and mean follow-up period was 58.7 years and 81.0 months, respectively. Analyses included factors such as patient age, gender, location and size of tumor, extent of surgical resection (Simpson Grading System), and MIB-1 index (LI). Univariate analysis was used to detect prognostic factors associated with recurrence and survival.
The 5-year recurrence-free rate for all 45 patients was 58.4 %; 5- and 10-year survival rates were 83.2 % and 79.9 %, respectively. In univariate analyses, age >60 years, and MIB-1 LI correlated with disease recurrence, whereas age >60 years, subtotal surgical resection, MIB-1 LI, and indication for radiotherapy correlated with death. MIB-1 LI levels higher than 12.8 % and 19.7 % predicted recurrence and death, respectively. In our cohort, 26 patients received postoperative radiotherapy including conventional radiation (n = 21) or gamma knife radiosurgery (n = 5). Postoperative radiotherapy did not decrease recurrence rates in our cohort (p = 0.63). Six and two patients who died during the study period underwent conventional radiation and radiosurgery, respectively.
Age, male gender, extent of surgical resection, and higher MIB-1 LI influenced the outcome of atypical meningioma. In our cohort, postoperative radiotherapy failed to provide long-term tumor control. Following incomplete surgical resection of atypical meningioma in elderly patients, adjuvant postoperative radiotherapy may not be an ideal treatment option, particularly when MIB-1 LI is higher than 19.7 % 13).
44 WHO Grade II and 9 WHO Grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.
For WHO Grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58% and 36%, respectively. For WHO Grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation naïve and experienced patients were 48% and 0% (p = 0.14), respectively. Overall, 7 of 44 Grade II patients and 8 of 9 Grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for Grade II and III meningioma were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.
SRS for adjuvant and salvage treatment of WHO Grade II meningioma by a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future work should contribute additional study toward the radiation naïve and the local management of malignant meningioma 14).
A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned 15).
Thirteen patients (46.4%) had disease recurrence or progression during follow up time. The median time to disease progression was 64 months. The extent of the surgical resection significantly impacted prognosis. Gross total resection (GTR) of the tumor improved progression free survival (PFS) compared to subtotal resection (STR, p = 0.011). An older patient age at diagnosis also resulted in a worse outcome (p = 0.024). An MIB-1 index <8% also contributed to improved PFS (p = 0.031). None of the patients that underwent GTR and received adjuvant radiotherapy had tumors recur during follow up. STR with adjuvant radiotherapy tended to result in better local tumor control than STR alone (p = 0.074). Three of 28 patients (10.7%) developed complications after microsurgery. The GTR group had a higher rate of complications than those with STR. There were no late adverse effects after adjuvant radiotherapy during follow up.
For patients with skull base atypical meningiomas, GTR is desirable for longer PFS, unless radical excision is expected to lead to severe complications. Adjuvant radiation therapy is advisable to reduce tumor recurrence regardless of the extent of surgical resection. Age of disease onset and the MIB-1 index of the tumor were both independent prognostic factors of clinical outcome 16).
A retrospective analysis of the patients operated at the Clinic of Neurosurgery, Clinical Center of Serbia, Belgrade, between January 1st 1995 and December 31th 2006 was performed. In that period 88 lesions met the histological criteria for atypical (75) and anaplastic (13) meningioma. Postoperative radiotherapy was conducted in 63.6% of patients.
At a median follow-up of 67.4 months in all patients the overall survival was 68 months and five-year survival was about 54.5%. The median survival was 76 months with surgery and adjuvant radiotherapy and 40 months with surgery alone (Log rank=7.4; p=0.006). Recurrent disease occurred in 58 patients (65.9%). Median time between first surgery and tumor recurrence in patients undergoing radiotherapy was 51 months, while in non-irradiated group 24 months (Log rank=17.7; p˂0.001). Multivariate analysis identified as recurrence-predicting factors anaplastic histotype (hazard ratio=2,9; p=0,003) and postoperative radiotherapy (hazard ratio=4,5; p<0,001).
The addition of adjuvant radiotherapy to surgery for atypical and anaplastic meningiomas resulted in a clinically meaningful and statistically significant survival benefit 17).
Dehghan Harati et al. add a third case, describe clinicopathologic features shared by the three, and elucidate the risk factors for this very rare phenomenon. A 29 year-old Hispanic woman presented with headache and hydrocephalus. MRI showed a lobulated enhancing pineal region mass measuring 41 mm in greatest dimension. Subtotal resection of the mass demonstrated an atypical meningioma, WHO grade II, and the patient subsequently underwent radiotherapy. She presented 4 years later with diplopia, and MRI showed an enhancing extra-axial mass measuring 47 mm in greatest dimension and centered on the tentorial incisura. Subtotal resection showed a brain-invasive atypical meningioma with melanocytic colonization. The previous two cases in the literature were atypical meningiomas, one of which was also brain invasive. Atypical meningiomas may be at particular risk for melanocytic colonization as they upregulate molecules known to be chemoattractants for melanocytes. We detected c-Kit expression in a minority of the melanocytes as well as stem cell factor and basic fibroblast growth factor in the meningioma cells, suggesting that mechanisms implicated in normal melanocyte migration may be involved. In some cases, brain invasion with disruption of the leptomeningeal barrier may also facilitate migration from the subarachnoid space into the tumor. Whether there is low-level proliferation of the dendritic melanocytes is unclear. Given that all three patients were non-Caucasian, meningiomas in persons and/or brain regions with increased dendritic melanocytes may predispose to colonization. The age range spanned from 6 years old to 70 years old. All three patients were female. The role of gender and estrogen in the pathogenesis of this entity remains to be clarified. Whether melanocytic colonization may also occur in the more common Grade I meningiomas awaits identification of additional cases 18).