Atypical teratoid/rhabdoid tumor

Atypical teratoid/rhabdoid tumor

A malignant WHO grade IV embryonal tumor of the CNS comprised of poorly differentiated elements and rhabdoid cells and, by definition, includes inactivation of SMARCB1 (INI1) or (extremely rarely) SMARCA4 (BRG1). Histologically similar tumors lacking these molecular genetics should be classified as CNS embryonal tumors with rhabdoid features.

Many of these tumors were probably previously misdiagnosed as MDBs. Occurs primarily in infants and children (> 90% are < 5 years of age, with most age < 2 years). A minority are associated with primary renal rhabdoid tumor. The ratio of supratentorial to infratentorial AT/RTs is 4:3. Posterior fossa AT/RTs may occur in the cerebellar hemispheres, cerebellopontine angle (CPA) and brainstem. 33% have CSF spread at presentation. Althogh the prognosis is poor, not all AT/RTs have the same behavior, and at least 2 different molecular classes have been identified.


Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly malignant, true rhabdoid tumor in the central nervous system predominantly presenting in young children.

It was originally described a histological variant of Wilm’s tumor in 1978.


Atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In a study, Torchia et al., analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets.

They found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, they discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype 1).

Classification

AT/RT can occur anywhere in the central nervous system (CNS) including the spinal cord. About 60% will be in the posterior cranial fossa (particularly the cerebellum). One review estimated 52% posterior fossa, 39% sPNET (supratentorial primitive neuroectodermal tumors), 5% pineal, 2% spinal, and 2% multi-focal.

In the United States, three children per 1,000,000 or around 30 new AT/RT cases are diagnosed each year. AT/RT represents around 3% of pediatric cancers of the CNS.

Around 17% of all pediatric cancers involve the CNS; it is the most common childhood solid tumor.

see Adult sellar atypical teratoid rhabdoid tumor.

see Cerebellopontine angle atypical teratoid rhabdoid tumor.

Atypical Teratoid Rhabdoid Tumor of the Cauda Equina.

Atypical Teratoid Rhabdoid Tumor of the Conus Medullaris.

Pathology

Typically shows rhabdoid cells which can also be seen in other tumors, but it is differentiated from other tumors by the specific genetic alteration involving the SMARCB1 gene. Only a few cases of AT/RT arising in low-grade glioma have been reported. A 13-year-old girl presented with headache, dizziness, nausea and vomiting.A 4.7 cm cerebellar mass was found on MRI.The mass was totally removed. Histologically, the tumor revealed two distinct morphologic appearances: central areas of AT/RT containing rhabdoid cells and sarcomatous component in the background of pleomorphic xanthoastrocytoma(PXA). Immunohistochemically, PXA areas retained nuclear expression of INI-1 and low Ki-67 proliferation index, whereas AT/RT component showed loss of INI-1 nuclear expression and markedly elevated Ki-67 proliferation index. Epithelial membrane antigen (EMA), smooth muscle actin (SMA), and p53 protein were positive only in AT/RT. BRAF V600E mutation was identified in PXA by real-time polymerase chain reaction.We report a rare case of AT/RT arising in PXA which is supposed to progress by inactivation of INI-1 in a pre-existing PXA 2).

Treatment

Atypical teratoid rhabdoid tumor treatment.

Outcome

Patient age at the time of diagnosis, supratentorial location of the mass and fewer complications with adjuvant treatments seem to be factors yielding good prognosis for AT/RT tumors. In agreement with the latest international protocols, multidisciplinary treatment is the ideal treatment, consisting of radiotherapy and chemotherapy after complete tumor resection 3).

Case series

Twenty-eight pediatric patients with CNS AT/RT who were treated with radiation therapy (RT) as part of multimodality treatment regimens at a single institution (1996-2015) were reviewed. Survival outcomes were analyzed in relation to possible prognostic factors.

The 28 patients analyzed were followed up for a median 48-month period. Median progression-free survival (PFS) was 11 months, and overall survival (OS) was 57 months. Patients < 3 years old had RT delayed for a longer period after surgery (p = 0.04), and the mean RT dose to tumor bed was lower (p < 0.01) than in patients ≥ 3 years old. In multivariate analysis, a higher primary tumor bed RT dose was identified as a favorable prognostic factor for both PFS (hazard ratio [HR] = 0.85 per gray, p < 0.01) and OS (HR = 0.92 per gray, p = 0.02). In addition, an interval between surgery and RT initiation > 2 months, with disease progression observed before RT, as compared with an interval ≤ 2 months without disease progression prior to RT, was associated with worse PFS (HR = 8.50, p < 0.01) and OS (HR = 5.27, p < 0.01).

Early and aggressive RT after surgery is critical for successful disease control in AT/RT patients. Conversely, a delay in RT until disease progression is observed that leads to unfavorable outcomes 4).


In a study, Torchia et al. analyzed 191 primary Atypical teratoid rhabdoid tumor ATRTs and 10 ATRT cell lines to define the genomics and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. They found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, they discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype 5).

References

1) , 5)

Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M, Yu M, Gendoo DM, Dzamba M, Barszczyk M, Medina T, Riemenschneider AN, Morrissy AS, Ra YS, Ramaswamy V, Remke M, Dunham CP, Yip S, Ng HK, Lu JQ, Mehta V, Albrecht S, Pimentel J, Chan JA, Somers GR, Faria CC, Roque L, Fouladi M, Hoffman LM, Moore AS, Wang Y, Choi SA, Hansford JR, Catchpoole D, Birks DK, Foreman NK, Strother D, Klekner A, Bognár L, Garami M, Hauser P, Hortobágyi T, Wilson B, Hukin J, Carret AS, Van Meter TE, Hwang EI, Gajjar A, Chiou SH, Nakamura H, Toledano H, Fried I, Fults D, Wataya T, Fryer C, Eisenstat DD, Scheinemann K, Fleming AJ, Johnston DL, Michaud J, Zelcer S, Hammond R, Afzal S, Ramsay DA, Sirachainan N, Hongeng S, Larbcharoensub N, Grundy RG, Lulla RR, Fangusaro JR, Druker H, Bartels U, Grant R, Malkin D, McGlade CJ, Nicolaides T, Tihan T, Phillips J, Majewski J, Montpetit A, Bourque G, Bader GD, Reddy AT, Gillespie GY, Warmuth-Metz M, Rutkowski S, Tabori U, Lupien M, Brudno M, Schüller U, Pietsch T, Judkins AR, Hawkins CE, Bouffet E, Kim SK, Dirks PB, Taylor MD, Erdreich-Epstein A, Arrowsmith CH, De Carvalho DD, Rutka JT, Jabado N, Huang A. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. Cancer Cell. 2016 Dec 12;30(6):891-908. doi: 10.1016/j.ccell.2016.11.003. PubMed PMID: 27960086.
2)

Jeong JY, Suh YL, Hong SW. Atypical teratoid/rhabdoid tumor arising in pleomorphic xanthoastrocytoma: a case report. Neuropathology. 2014 Aug;34(4):398-405. PubMed PMID: 25268025.
3)

Valencia-Moya A, González-García L, Ros-López B, Acha-García T, Weil-Lara B, Obando-Pacheco P, Arráez-Sánchez MÁ. Prognosis of atypical teratoid rhabdoid tumors (AT/RT) treated with multimodal therapy protocols. Report of our series. Neurocirugia (Astur). 2015 Apr 17. pii: S1130-1473(15)00020-2. doi: 10.1016/j.neucir.2015.01.003. [Epub ahead of print] PubMed PMID: 25900785.
4)

Yang WC, Yen HJ, Liang ML, Chen HH, Lee YY, Wong TT, Hu YW, Chen YW. Role of early and aggressive post-operative radiation therapy in improving outcome for pediatric central nervous system atypical teratoid/rhabdoid tumor. Childs Nerv Syst. 2019 Apr 13. doi: 10.1007/s00381-019-04126-y. [Epub ahead of print] PubMed PMID: 30982172.

Update: Atypical meningioma

Atypical meningioma (AM)

Atypical (WHO Grade IImeningiomas comprise a heterogeneous group of tumors, with histopathology delineated under the guidance of the WHO and a spectrum of clinical outcomes.
In atypical meningiomas bone involvement and large meningioma peritumoral edema are associated with increased tumor progression.

Classification

Intracranial atypical meningiomas
Spinal atypical meningiomas

Epidemiology

Approximately 15-20% of meningiomas are atypical, meaning that the tumor cells do not appear typical or normal. Atypical meningiomas are neither malignant (cancerous) nor benign, but may become malignant.

Treatment

The treatment of atypical meningioma remains controversial and under-investigated in prospective studies. The roles of surgery, radiation therapy, radiosurgery, and chemotherapy have been incompletely delineated. This has left physicians to decipher how they should treat patients on a case-by-case basis.
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).

Postoperative radiotherapy

Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection despite data that suggests that close observation remains reasonable in the setting of aggressive microsurgical resection.
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
Adjuvant radiation therapy or external beam radiation therapy (EBRT) improved local control after stereotactic radiosurgery STR but only for tumors without spontaneous necrosis. Spontaneous necrosis may aid in decisions to administer adjuvant SRS or EBRT after STR of AMs 3).
Necrosis may be a negative predictor of radiation response regardless of radiation timing or modality 4).

Recurrence

Grade II atypical meningiomas tend to recur and grow faster.
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).

Outcome

The rarity and the inconsistent criteria for defining atypical meningioma prior to the WHO 2007 classification made its management and prognostic factors poorly understood. Only few articles have addressed the survival rates of WHO-classified atypical meningiomas. The small number or the disproportionate representation of irradiated patients was a weakness for these articles.
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).

Case series

2017

The National Cancer Database was used to identify 2515 patients who were diagnosed with AM between 2009 and 2012 and underwent STR or GTR with or without adjuvant RT. Propensity score matching was first applied to balance covariates including age, year of diagnosis, sex, race, histology, and tumor size in STR or GTR cohorts stratified by adjuvant RT status. Multivariate regression according to the Cox proportional hazards model and Kaplan-Meier survival plots with log-rank test were then used to evaluate OS difference associated with adjuvant RT.
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).

2016

Real-Peña et al published 27 patients with pathological diagnosis of atypical meningioma, and who had a minimum follow-up time of 6 months after diagnosis. Later prognostic factors (age <50years, male gender, bone involvement, peri-lesional swelling, tumour volume, location, Ki67/MIB-1) were evaluated after the stratification of patients undergoing complete resection in recurrencies and non-recurrencies. Univariate analysis was performed using Mann-Whitney test, χ(2) homogeneity test/Fisher exact test. Finally, multivariate analysis was performed using binary logistic regression to obtain the values for R(2) Nagelkerke and the Hosmer-Lemeshow to evaluate the goodness of fit.
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).

2015

Twenty-eight patients with skull base atypical meningiomas underwent microsurgical resection between June 2001 and November 2009. The clinical characteristics of the patients and meningiomas, the extent of surgical resection, and complications after treatment were retrospectively analyzed.
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).

Case reports

Only two prior cases of benign dendritic melanocytes colonizing a meningioma have been reported.
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).

References

1)

Sun SQ, Hawasli AH, Huang J, Chicoine MR, Kim AH. An evidence-based treatment algorithm for the management of WHO Grade II and III meningiomas. Neurosurg Focus. 2015 Mar;38(3):E3. doi: 10.3171/2015.1.FOCUS14757. PubMed PMID: 25727225.
2)

Hug EB, Devries A, Thornton AF, Munzenride JE, Pardo FS, Hedley-Whyte ET, Bussiere MR, Ojemann R. Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy. J Neurooncol. 2000 Jun;48(2):151-60. PubMed PMID: 11083080.
3)

Sun SQ, Cai C, Murphy RK, DeWees T, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Leonard JR, Evans J, Simpson JR, Robinson CG, Perrin RJ, Huang J, Chicoine MR, Kim AH. Management of atypical cranial meningiomas, part 2: predictors of progression and the role of adjuvant radiation after subtotal resection. Neurosurgery. 2014 Oct;75(4):356-63. doi: 10.1227/NEU.0000000000000462. PubMed PMID: 24932708.
4)

Sun SQ, Cai C, Murphy RK, DeWees T, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Simpson JR, Robinson CG, Chicoine MR, Perrin RJ, Huang J, Kim AH. Radiation Therapy for Residual or Recurrent Atypical Meningioma: The Effects of Modality, Timing, and Tumor Pathology on Long-Term Outcomes. Neurosurgery. 2016 Jul;79(1):23-32. doi: 10.1227/NEU.0000000000001160. PubMed PMID: 26645969.
5)

Lee KD, DePowell JJ, Air EL, Dwivedi AK, Kendler A, McPherson CM. Atypical meningiomas: is postoperative radiotherapy indicated? Neurosurg Focus. 2013 Dec;35(6):E15. doi: 10.3171/2013.9.FOCUS13325. PubMed PMID: 24289123.
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Aghi MK, Carter BS, Cosgrove GR, Ojemann RG, Amin-Hanjani S, Martuza RL, Curry WT Jr, Barker FG 2nd. Long-term recurrence rates of atypical meningiomas after gross total resection with or without postoperative adjuvant radiation. Neurosurgery. 2009 Jan;64(1):56-60; discussion 60. doi: 10.1227/01.NEU.0000330399.55586.63. PubMed PMID: 19145156.
7)

Komotar RJ, Iorgulescu JB, Raper DM, Holland EC, Beal K, Bilsky MH, Brennan CW, Tabar V, Sherman JH, Yamada Y, Gutin PH. The role of radiotherapy following gross-total resection of atypical meningiomas. J Neurosurg. 2012 Oct;117(4):679-86. doi: 10.3171/2012.7.JNS112113. Epub 2012 Aug 24. PubMed PMID: 22920955.
8)

Kaur G, Sayegh ET, Larson A, Bloch O, Madden M, Sun MZ, Barani IJ, James CD, Parsa AT. Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review. Neuro Oncol. 2014 May;16(5):628-36. doi: 10.1093/neuonc/nou025. Epub 2014 Apr 2. PubMed PMID: 24696499; PubMed Central PMCID: PMC3984561.
9)

Sun SQ, Kim AH, Cai C, Murphy RK, DeWees T, Sylvester P, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Leonard JR, Evans J, Simpson JR, Robinson CG, Perrin RJ, Huang J, Chicoine MR. Management of atypical cranial meningiomas, part 1: predictors of recurrence and the role of adjuvant radiation after gross total resection. Neurosurgery. 2014 Oct;75(4):347-55. doi: 10.1227/NEU.0000000000000461. PubMed PMID: 24932707.
10)

Hammouche S, Clark S, Wong AH, Eldridge P, Farah JO. Long-term survival analysis of atypical meningiomas: survival rates, prognostic factors, operative and radiotherapy treatment. Acta Neurochir (Wien). 2014 Aug;156(8):1475-81. doi: 10.1007/s00701-014-2156-z. Epub 2014 Jun 26. PubMed PMID: 24965072.
11)

Wang C, Kaprealian TB, Suh JH, Kubicky CD, Ciporen JN, Chen Y, Jaboin JJ. Overall survival benefit associated with adjuvant radiotherapy in WHO grade II meningioma. Neuro Oncol. 2017 Mar 24. doi: 10.1093/neuonc/nox007. [Epub ahead of print] PubMed PMID: 28371851.
12)

Real-Peña L, Talamantes Escribá F, Quilis-Quesada V, González-Darder JM. [Prognostic variability in atypical meningioma with complete resection. Proposed treatment algorithm]. Neurocirugia (Astur). 2016 Jan-Feb;27(1):15-23. doi: 10.1016/j.neucir.2015.08.003. Spanish. PubMed PMID: 26687847.
13)

Endo T, Narisawa A, Ali HS, Murakami K, Watanabe T, Watanabe M, Jokura H, Endo H, Fujimura M, Sonoda Y, Tominaga T. A study of prognostic factors in 45 cases of atypical meningioma. Acta Neurochir (Wien). 2016 Sep;158(9):1661-7. doi: 10.1007/s00701-016-2900-7. Epub 2016 Jul 28. PubMed PMID: 27468919.
14)

Zhang M, Ho AL, D’Astous M, Pendharkar AV, Choi CY, Thompson PA, Tayag AT, Soltys SG, Gibbs IC, Chang SD. CyberKnife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas. World Neurosurg. 2016 Apr 20. pii: S1878-8750(16)30092-4. doi: 10.1016/j.wneu.2016.04.019. [Epub ahead of print] PubMed PMID: 27108030.
15)

Jenkinson MD, Waqar M, Farah JO, Farrell M, Barbagallo GM, McManus R, Looby S, Hussey D, Fitzpatrick D, Certo F, Javadpour M. Early adjuvant radiotherapy in the treatment of atypical meningioma. J Clin Neurosci. 2016 Jan 8. pii: S0967-5868(15)00663-3. doi: 10.1016/j.jocn.2015.09.021. [Epub ahead of print] PubMed PMID: 26775147.
16)

Wang YC, Chuang CC, Wei KC, Hsu YH, Hsu PW, Lee ST, Wu CT, Tseng CK, Wang CC, Chen YL, Jung SM, Chen PY. Skull base atypical meningioma: long term surgical outcome and prognostic factors. Clin Neurol Neurosurg. 2015 Jan;128:112-6. doi: 10.1016/j.clineuro.2014.11.009. Epub 2014 Nov 24. PubMed PMID: 25486076.
17)

Pisćević I, Villa A, Milićević M, Ilić R, Nikitović M, Cavallo LM, Grujičić D. The influence of adjuvant radiotherapy in atypical and anaplastic meningiomas: a series of 88 patients in a single institution. World Neurosurg. 2015 Mar 10. pii: S1878-8750(15)00128-X. doi: 10.1016/j.wneu.2015.02.021. [Epub ahead of print] PubMed PMID: 25769488.
18)

Dehghan Harati M, Yu A, Magaki SD, Perez-Rosendahl M, Im K, Park YK, Bergsneider M, Yong WH. Clinicopathologic features and pathogenesis of melanocytic colonization in atypical meningioma. Neuropathology. 2017 Aug 18. doi: 10.1111/neup.12409. [Epub ahead of print] PubMed PMID: 28833600.

Radiotherapy versus Observation following surgical resection of Atypical Meningioma (the ROAM trial).

Atypical meningioma

Atypical (WHO Grade IImeningiomas comprise a heterogeneous group of tumors, with histopathology delineated under the guidance of the WHOand a spectrum of clinical outcomes.
Approximately 15-20% of meningiomas are atypical, meaning that the tumor cells do not appear typical or normal. Atypical meningiomas are neither malignant (cancerous) nor benign, but may become malignant. Grade II atypical meningiomas also tend to recur and grow faster.

Treatment

The role of postoperative radiotherapy for patients with atypical meningiomas who have undergone gross-total resection (GTR) remains unclear.
retrospective series supports the observation that postoperative radiotherapy likely results in lower recurrence rates of gross totally resected atypical meningiomas. Although a multicenter prospective trial will ultimately be needed to fully define the role of radiotherapy in managing gross totally resected atypical meningiomas 1)
1) Komotar RJ, Iorgulescu JB, Raper DM, Holland EC, Beal K, Bilsky MH, Brennan CW, Tabar V, Sherman JH, Yamada Y, Gutin PH. The role of radiotherapy following gross-total resection of atypical meningiomas. J Neurosurg. 2012 Oct;117(4):679-86. doi: 10.3171/2012.7.JNS112113. Epub 2012 Aug 24. PubMed PMID: 22920955.

Jenkinson MD, Weber DC, Haylock BJ, Mallucci CL, Zakaria R, Javadpour M.Radiotherapy versus Observation following surgical resection of Atypical Meningioma (the ROAM trial). Neuro Oncol. 2014 Jul 19. pii: nou149. [Epub ahead of print] PubMed PMID: 25038504.

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