Radiation-induced Meningiomas Research Articles

Genetic characterization and mutational profiling of foramen magnum meningiomas: a multi-institutional study.

Foramen magnum (FM) meningiomas pose significant surgical challenges and have high morbidity and mortality rates. This study aimed to investigate the distribution of clinically actionable mutations in FM meningiomas and identify clinical characteristics associated with specific mutational profiles. The authors conducted targeted next-generation sequencing of 62 FM meningiomas from three international institutions, covering all relevant meningioma genes (AKT1, KLF4, NF2, POLR2A, PIK3CA, SMO, TERT promoter, and TRAF7). Patients with a radiation-induced meningioma or neurofibromatosis type 2 (NF2) were excluded from the study. Additionally, patient and tumor characteristics, including age, sex, radiological features, and tumor location, were retrospectively collected and evaluated. The study cohort consisted of 46 female and 16 male patients. Clinically significant driver mutations were detected in 58 patients (93.5%). The most commonly observed alteration was TRAF7 mutations (26, 41.9%), followed by AKT1E17K mutations (19, 30.6%). Both mutations were significantly associated with an anterolateral tumor location relative to the brainstem (p = 0.0078). NF2 mutations were present in 11 cases (17.7%) and were associated with posterior tumor location, in contrast to tumors with TRAF7 and AKT1E17K mutations. Other common mutations in FM meningiomas included POLR2A mutations (8, 12.9%; 6 POLR2AQ403K and 2 POLR2AH439_L440del), KLF4K409Q mutations (7, 11.3%), and PIK3CA mutations (4, 6.5%; 2 PIK3CAH1047R and 2 PIK3CAE545K). POLR2A and KLF4 mutations exclusively occurred in female patients and showed no significant association with specific tumor locations. All tumors harboring AKT1E17K and POLR2A mutations displayed meningothelial histology. Ten tumors exhibited intratumoral calcification, which was significantly more frequent in NF2-mutant compared with AKT1-mutant FM meningiomas (p = 0.047). These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.

Favourable outcomes with an initial active surveillance strategy for asymptomatic radiation-induced meningiomas in long-term survivors of paediatric and young adult malignancies

PurposeRadiation-induced meningiomas (RIM) are the most common secondary neoplasm post cranial radiotherapy, yet optimal surveillance and treatment strategies remain contentious. Herein, we report the clinical outcomes and radiological growth rate of RIM, diagnosed in a cohort of survivors undergoing MRI screening, with the objective of informing clinical guidelines and practice. Materials and methodsLong-term survivors of paediatric or young-adult malignancies, diagnosed with RIM between 1990 and 2015, were identified. Absolute (AGR) and relative (RGR) volumetric growth rates were calculated. Rapid growth was defined as AGR > 2 cm3/year or AGR > 1 cm3/year and RGR ≥ 30% ResultsFifty-two patients (87 RIM) were included. Median age at first RIM diagnosis was 33.9 (range,13.8–54.1) years. Seventy-seven (88%) RIM were asymptomatic at detection. Median follow-up time from first RIM detection was 11 (range, 0.6–28) years. Median absolute and relative volumetric growth rates were 0.05 (IQR 0.01–0.11) cm3 and 26 (IQR 7–79) % per year, respectively. Two (3.3%) RIM demonstrated rapid growth. Active surveillance was adopted for 67 (77%) RIM in 40 patients. Neurological sequelae due to RIM progression were reported in 5% of patients on active surveillance. Surgery was performed for 33 RIM (30 patients): 18 (54.5%) at diagnosis and 15 (45.5%) after active surveillance. Histopathology was WHO Grade 1 (85.2%), 2 (11.1%), 3 (3.7%). Following resection, 10-year local recurrence rate was 12%. During follow-up, 19 (37%) survivors developed multiple RIM. ConclusionsAsymptomatic RIM are typically low-grade tumours which exhibit slow growth. Active surveillance appears to be a safe initial strategy for asymptomatic RIM, associated with a low rate of neurological morbidity.

Benefits of combined use of 68−Ga Dotatoc and 5-ALA fluorescence for recurrent atypical skull-base meningioma after previous microsurgery and Gamma Knife radiosurgery: a case report

BackgroundStudies of novel microsurgical adjuncts, such as 5-aminolevulinic acid (5-ALA) fluorescence have shown various fluorescence patterns within meningiomas, opening new avenues for complete microsurgical resection. Here, we present a recurrent, radiation-induced meningioma, previously operated on two occasions (initial gross total resection and subtotal 12 years later) and also irradiated by Gamma Knife radiosurgery (GKR, 6 years after the first surgery). We thought to assess the usefulness of 68−Ga Dotatoc in surgical target planning and of 5-ALA as an adjunct for maximal microsurgical excision.Case reportWe report on a 43 years-old Caucasian male diagnosed with atypical, radiation induced WHO II meningioma, with left basal temporal bone implantation. Hodgkin lymphoma treated with cranial and mediastinal radiation during infancy marked his personal history. He underwent a first gross total microsurgical resection, followed 6 and 12 years later by Gamma Knife radiosurgery (GKR) and second subtotal microsurgical resection, respectively. Magnetic resonance imaging (MRI) displayed new recurrence 13 years after initial diagnosis. He was clinically asymptomatic but routine Magnetic resonance imaging showed constant progression. There was strong 68−Ga Dotatoc uptake. We used 5-ALA guided microsurgical resection. Intraoperative views confirmed strong fluorescence, in concordance with both preoperative Magnetic resonance imaging enhancement and 68−Ga Dotatoc. The tumor was completely removed, with meningeal and bone resection.ConclusionThe authors conclude that fluorescence-guided resection using 5-ALA is useful for recurrent atypical, radiation-induced meningioma even despite previous irradiation and multiple recurrences.

Severe course of radiation-induced meningioma — a new insight in screening for patients after radiotherapy?

Severe course of radiation-induced meningioma — a new insight in screening for patients after radiotherapy?

Radiation-induced meningiomas (RIM) in adults: A single-centre retrospective experience

IntroductionRadiotherapy of central nervous system (CNS) is treatment against many paediatric cancers, even if it is a well-recognized risk factor for meningioma formation. An increased risk of developing secondary brain tumors like radiation-induced meningiomas (RIM) is related to irradiated patients. Research questionThis retrospective study aims to present RIM cases treated in a single tertiary-hospital in Greece and compare the results with international literature and cases of sporadic meningiomas. Materials and methodsA single-centre retrospective study of all patients diagnosed between January 2012 and September 2022 with RIM after having been irradiated in CNS for paediatric cancer was undertaken through hospital’s electronic record and clinical notes, identifying baseline demographics and latency period. ResultsThirteen patients were identified with RIM diagnosis after receiving irradiation for Acute Lymphoblastic Leukaemia (69.2%), Premature Neuro-Ectodermal Tumour (23.1%), and Astrocytoma (7.7%). Median age at irradiation was 5 years old and 32 years old at RIM’s presentation. The latent period from irradiation to meningioma diagnosis was 26.23 ​± ​5.96 years. After surgical excision, histopathologic results showed grade I meningiomas in 12 out of thirteen cases, while only one atypical meningioma was diagnosed. ConclusionPatients who underwent CNS-radiotherapy in childhood for any condition have an increased risk of developing secondary brain tumors such as radiation-induced meningiomas. RIMs resemble sporadic meningiomas in symptomatology, location, treatment, and histologic grade. However, long-term follow-up and regular check-ups are recommended in irradiated patients due to short latency period from irradiation to RIM development, which means younger age patients than those with sporadic meningiomas cases.

Radiation-Induced Meningiomas.

While the majority of meningiomas encountered clinically are sporadic, there is a rare subset that arises due to early life or childhood irradiation. Sources of this radiation exposure may be due to treatment of other cancers such as acute childhood leukemia, other central nervous system tumors such as medulloblastoma, the treatment of tinea capitis(rarely and historically), or environmental exposures, as seen in some of the Hiroshima and Nagasaki atomic bomb survivors. Regardless of their etiology, however, radiation-induced meningiomas (RIMs) tend to be highly biologically aggressive irrespective of WHO grade and are usually refractory to the conventional treatment modalities of surgery and/or radiotherapy. In this chapter, we will discuss these RIMs in their historical context, their clinical presentation, their genomic features and ongoing efforts to better understand these tumors from a biological standpoint in order to develop better, more efficacious therapies for these patients.

Evaluation of the growth rates and related prognostic factors in radiation-induced meningiomas

Literature dedicated to growth patterns and growth rate influencing factors of radiation-induced meningiomas (RIMs) is limited. To deliver new insights into the topic, a volumetric growth analysis of RIMs was performed. This single-center, retrospective cohort study included patients diagnosed with intracranial meningioma who received radiation treatment at least > 5years before the RIM diagnosis. Volumetric analysis of individual RIMs was performed using 3D volumetry at the time of RIM diagnosis and during follow-up. RIM growth was determined by calculating absolute (AGR), and relative (RGR) growth rates. Prognostic factors associated with RIM growth were evaluated. A total of 26 patients with 33 meningiomas were enrolled in the study and radiologically/clinically followed up during a median duration of 5.6years (IQR 3.9-8.8years). Median AGR was 0.19 cm3 per year and the median RGR was 34.5% per year. Surgically managed RIMs were more likely fast-growing compared to observed ones based on the AGR (p < 0.002). The recurrence rate after total resection was 14.3%. Younger age at RIM diagnosis was associated with higher tumor growth (RGR ≥ 30%, p = 0.040). A significant correlation was found between the length of latency period and the RGR (p = 0.005). To diagnose RIM as early as possible comprehensive MRI surveillance is required. Younger patients with shorter latency periods may profit from shortened MRI intervals, with further management being dependent on the growth rate and eventual symptomatology.

Highlights from Recent Cancer Literature.

Highlights from Recent Cancer Literature.

Cranial Irradiation for Childhood Cancers and Adult Risk of Meningioma

Introduction: Following cranial irradiation, there is an increased risk of developing secondary neoplasms, especially meningiomas. Despite childhood cancer survivors who have undergone cranial irradiation having an increased risk of acquiring radiation-induced meningioma (RIM), there is no widely used standard guideline for meningioma screening. Methods: At a single institution, we reviewed three adult survivors of childhood cancer who were treated for RIM between 2010 and 2020. We recorded age at diagnosis for the primary lesion, the radiation dose, age at RIM diagnosis, and tumor characteristics including treatment, pathology, and outcome. Two had had T-cell acute lymphocytic leukemia and one a rhabdomyosarcoma. The age of diagnosis of the RIM ranged from 20 to 40 years, with latencies ranging from 18 to 33 years. All lesions were classified as WHO Grade I meningiomas, and only 1 patient had a subsequent recurrence. A literature search identified articles that address RIM: a total of 684 cases were identified in 36 publications. Results: Mean radiation doses ranged from 1.4 gray to 70 gray. Mean age of diagnosis for secondary meningioma ranged from 8 to 53.4 years old, with latency periods ranging from 2.8 to 44 years. Given variability in the way that investigators have published their results, it is difficult to make a single recommendation for RIM screening. Using our experience and the literature, we devised two different screening protocols and calculated their expense. Conclusions: We recommend that data be standardized in a registry to provide greater insight into the clinical and resource allocation questions, especially as long-term survival of children with pediatric cancer into full adulthood becomes more commonplace worldwide.

Outcomes of radiation-induced meningiomas treated with stereotactic radiosurgery.

Data on the efficacy and safety of stereotactic radiosurgery (SRS) for treatment of radiation-induced meningiomas (RIMs) are limited. A single institution database of Cobalt-60 SRS cases from 08/1999 to 10/2020 was reviewed. Radiation-induced meningiomas were identified using Cahan's criteria. Endpoints included overall survival (OS), progression free survival (PFS), local control (LC), treatment failure, and treatment toxicity. Univariate and multivariate analyses were performed using cox proportional hazard models. A total of 29 patients with 86 RIM lesions wereidentified. Median follow-up after SRS was 59months. The median dose prescribed to the 50% isodose line was 14Gy (range 12-20Gy). The actuarial 5-yr OS and PFS were 96% and 68%, respectively. Patients treated for recurrent RIMs had a significantly lower PFS (45% vs 94% at 3yr, p < 0.005) than patients treated in the upfront setting. Patients with presumed or WHO grade I RIMs had a significantly greater PFS (3-year PFS 96% vs 20%) than patients with WHO grade II RIMs (p < 0.005). On a per-lesion basis, local control (LC) at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. On multivariate analysis, female gender was associated with improved LC (p < 0.001), while marginal doses > 14Gy were associated with worse local control (p < 0.001). Grade I-III toxicity following treatment was 9.0%. Stereotactic radiosurgery is a safe and effective treatment option for radiographic RIMs, WHO grade I RIMs, or lesions treated in the upfront setting. WHO grade II lesions and recurrent lesions are at increased risk for disease progression.

Repeat stereotactic radiosurgery for cerebral arteriovenous malformations.

The purpose of this retrospective, single-institution study was to evaluate radiological and clinical outcomes of patients managed with repeat stereotactic radiosurgery (SRS) for residual cerebral arteriovenous malformation (AVM) after prior SRS. The authors evaluated the clinical and radiological outcomes of consecutive patients treated with repeat single-session SRS for a residual brain AVM from 1989 to 2021. In total, 170 patients underwent repeat SRS for AVM (90 [52.9%] females; median [interquartile range] age at the first SRS procedure 28 [21.5] years; median [interquartile range] age at the second SRS procedure 32 [22.5] years). After repeat SRS, the actuarial 3-, 5-, and 10-year AVM obliteration rates were 37.6%, 57.3%, and 80.9%, respectively. Higher obliteration rates were associated with margin dose ≥ 19 Gy (p = 0.001). After the second SRS procedure, hemorrhage occurred in 8.2% of patients and was lethal in 1 patient. The risk factors of intracranial hemorrhage were age < 18 years (p = 0.03) and residual AVM diameter > 20 mm (p = 0.004). Lower obliteration rates were noted in patients with residual AVM diameter > 20 mm (p = 0.04) and those < 18 years of age (p = 0.04). Asymptomatic, symptomatic, and permanent radiation-induced changes (RICs) after the second SRS procedure occurred in 25.9%, 8.8%, and 5.3% of patients, respectively, and were associated with RIC after the first SRS procedure (p = 0.006). There was 1 case of a radiation-induced meningioma 12 years after SRS. Repeat SRS is a reasonable therapeutic option, in particular for patients with residual AVM. Repeat SRS was associated with more favorable outcomes in adult patients and those with residual AVM smaller than 20 mm in maximum diameter. To increase the rate of residual AVM obliteration, a prescription dose ≥ 19 Gy should ideally be used for repeat SRS.

OTHR-31. The molecular profile of secondary meningiomas in survivors of childhood non-central nervous system (CNS) cancers

Abstract INTRODUCTION: Secondary meningiomas are a late effect in children who received cranial irradiation, frequently with a long latency. The molecular genetic profile of primary meningiomas is well studied; however, few studies describe the genomic landscape of radiation-induced meningiomas (RIM). METHODS: Patients followed at the Stollery Children’s Hospital (Edmonton, Canada) with a history of non-CNS malignancies who received cranial irradiation and then developed meningiomas between 1971 and 2013 were identified. Whole exome sequencing (WES), RNA sequencing as well as DNA methylation profiling were performed for patients with available tumor tissue and germline DNA. RESULTS: Of 96 patients who received cranial irradiation for non-CNS tumors, 16 (16.7%) developed symptomatic meningiomas. This patient cohort is unique; all 16 patients identified received 2000-2400 cGy of cranial irradiation, suggesting a threshold dose. 9/16 (56%) had WHO Grade 2 meningiomas or greater and 7/16 (44%) of meningiomas infiltrated other tissues. Post-surgical recurrences occurred in 43%. Patients experienced considerable morbidities directly attributable to the meningiomas or their treatment. 14 patients had samples suitable for further analysis. NF2 mutations were identified in 50% (8; 4 DNA,4 fusion). Other meningioma related genes with mutations identified in other cohorts were not identified. Copy number alternations were noted in all 16 patients in chromosomes 1p and 22q. 850k methylation analysis with PCA as well as UMAP and tSNE did not demonstrate clustering. Ongoing additional studies include examining tumor mutation burden and the radiation mutational profile. CONCLUSIONS: This study examined the RIM in a cohort of patients having received similar doses of radiation for their childhood cancer. There is increased risk of radiation-induced meningioma in survivors of non-CNS cancers given ≥ 2000 cGy during childhood. To date, our findings are consistent with previously described primary and RIM mutations. Enhanced knowledge in secondary meningiomas is crucial for accurate patient counselling, prognostication, and treatment.

OC-0760 Active surveillance is safe for asymptomatic radiation-induced meningiomas in cancer survivors

OC-0760 Active surveillance is safe for asymptomatic radiation-induced meningiomas in cancer survivors

Treatment of Radiation-Induced Meningiomas With Non-Invasive Stereotactic Radiosurgery

Radiation-Induced Meningiomas (RIMs) are one of the most common secondary malignancies from prior brain irradiation and are known to be recurrent. While Gamma Knife (GK) radiosurgery is routinely employed for the treatment of sporadic meningiomas, data on its use for RIMs are limited. Here, we assessed whether the use of GK radiosurgery for RIMs can achieve > 80% local control at 1 year.We retrospectively reviewed our institution's GK database from 08/31/99 - 10/08/20. Meningiomas were considered radiation-induced if they met Cahan's criteria: (1) occurred after brain radiation for a previous neoplasm, (2) were within the previous radiation field, and (3) had a distinct histology or radiographic appearance from previously treated neoplasm. Patients with a genetic predisposition for tumor formation were excluded. Endpoints included overall survival (OS), progression free survival (PFS), local failure (within 2cm of GK field), and distant failure. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.A total of 29 patients with 86 RIM lesions were identified from 1999 to 2020 and followed for a median of 59 months. Of these patients, 20 had WHO grade I (n = 4) or presumed grade I (n = 20) RIMs and 5 had WHO grade II RIMs. The median latency time from previous brain irradiation to initial SRS was 26 years. The median dose prescribed to the 50% isodose line was 14 Gy (range 12-20 Gy) with a median lesion volume of 2 cm3. The actuarial 5-yr OS and 5-yr PFS were 95% and 70%, respectively. Patients who were treated for recurrent RIMs after previous surgery had a significantly lower 5-yr OS (88% vs 100%; log-rank, P < 0.0046) and 5-yr PFS (39% vs 81%; log-rank, P < 0.005) than patients who were treated in the upfront setting. On a per-lesion basis, local control at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. Presumed or WHO grade I RIMs had a significantly greater 5-yr local control than WHO grade II RIMs (100% vs 56%, log-rank, P < 0.001). The rate of distant failure at 1-, 3-, and 5-yrs was 3.5%, 18%, and 32%, respectively. At time of progression, 5 patients had distant failures, while 3 patients had local and distant failures. Failures were salvaged through additional GK (n = 8), surgery (n = 2), or chemotherapy (n = 1). The crude incidence of grade 1-3 toxicity from GK was 10% (n = 3). No grade 4 or 5 adverse events were recorded. Only 1 patient developed grade 3 toxicity (cranial nerve neuropathy), which resolved with steroids.This is the largest series of RIM lesions treated with GK radiosurgery. RIMs are associated with a high OS and GK radiosurgery provides satisfactory PFS and local control. Recurrent and WHO grade II lesions are associated with lower PFS and local control after radiosurgery than upfront and WHO grade I lesions. The majority of failures after GK are distant. Treatment using GK radiosurgery has minimal morbidity. It should be considered for patients or tumors that are not candidates for surgical resection.N.Razavian: None. C.A.Helis: None. A.Laxton: None. S.B. Tatter: None. J.Bourland: None. R.T. Mott: None. G.J. Lesser: None. R.Strowd: None. M.D. Chan: None. C.K. Cramer: None.

Consecutively occurring radiation-induced meningiomas with various pathologic diagnoses: a case report

Consecutively occurring radiation-induced meningiomas with various pathologic diagnoses: a case report

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs. From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS. Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS. SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.

Aggressive Radiation-Induced Cavernous Sinus Meningioma: 2-Dimensional Operative Video.

Radiation-induced meningiomas are the most common radiation-induced neoplasms. They exhibit a distinct aggressive clinical behavior as rapid growth, recurrences, multiplicity, and malignant progression are common features.1-4 Atypical histological findings and aberrant cytogenetics are increasingly identified.5-7 Radical resection of aggressive radiation-induced meningiomas is the best treatment option and would offer the best chance for control of the disease. Wide bone and dural margins should be pursued in the resection. Parasellar extension creates significant surgical challenges. Cavernous sinus exploration through the multidirectional axis provided by the cranioorbital zygomatic approach allows radical resection of the tumor, cranial nerve decompression, and carotid artery preservation and control.8-11 This article describes a cavernous sinus radiation-induced meningioma after radiation for Cushing disease. It demonstrates the details of the extra- and intradural exploration and dissection of the neurovascular structures in the cavernous sinus, with proximal and distal control of the carotid artery. However, even after radical resection, recurrence is a common finding in this malignant behavioral radiation-induced tumor. Patient consented for surgery. Image at 9:41 comes from the Science Museum Group, United Kingdom. Refer to the Wellcome blog post (archive). This image is licensed under the CC-BY 4.0 International license.

Predictors of progression in radiation-induced versus nonradiation-induced pediatric meningiomas: a large single-institution surgical experience.

The goal in this study was to outline unique differences between radiation-induced and nonradiation-induced pediatric meningiomas and to identify independent risk factors of tumor recurrence/progression. This is a retrospective cohort study of all pediatric meningiomas diagnosed and surgically treated at the authors' institution between 1993 and 2017. Multivariable Cox regression was applied to identify independent risk factors for tumor recurrence/progression. Thirty-five patients were identified. The primary etiology was nonradiation-induced (n = 24: n = 3 with neurofibromatosis type 2) or radiation-induced (n = 11: acute lymphoblastic leukemia [n = 5], medulloblastoma [n = 4], germ cell tumor [n = 1], and primitive neuroectodermal tumor [n = 1]) meningioma. The mean age at time of diagnosis was 10.7 ± 5.7 years for nonradiation-induced and 17.3 ± 3.5 years for radiation-induced meningiomas. Overall, 8/24 patients with nonradiation-induced meningioma experienced either recurrence or progression of the tumor. Of the 8 patients with tumor recurrence or progression, the pathological diagnosis was clear cell meningioma (n = 3: 2 recurrent and 1 progressive); grade I (n = 2 progressive); grade I with atypical features (n = 2: 1 recurrent and 1 progressive); or atypical meningioma (n = 1 recurrent). None of the patients with radiation-induced meningioma experienced recurrence or progression. Predictors of tumor recurrence/progression by univariate analysis included age at time of diagnosis ≤ 10 years (p = 0.002), histological subtype clear cell meningioma (p = 0.003), and primary etiology nonradiation-induced meningioma (p = 0.04), and there was a notable trend with elevated MIB-1 staining index (SI) (p = 0.09). There was no significant difference between nonradiation-induced and radiation-induced meningiomas (p = 0.258), although there was a trend between recurrent and nonrecurrent meningiomas (p = 0.09). Multivariate Cox regression, adjusted for length of follow-up, identified younger age at diagnosis (p = 0.004) and a higher MIB-1 SI (p = 0.044) as independent risk factors for recurrence. Elevated MIB-1 SI statistically correlated with atypia (p < 0.001). However, there was no significant statistical correlation between tumor recurrence/progression and atypia (p = 0.2). Younger patient age and higher MIB-1 SI are independent risk factors for recurrence. Atypia was not a predictor of recurrence.

RARE-15. THE MOLECULAR PROFILE OF SECONDARY MENINGIOMAS IN SURVIVORS OF CHILDHOOD NON-CENTRAL NERVOUS SYSTEM CANCERS

IntroductionCranial irradiation remains part of childhood cancer therapy and secondary meningiomas are a late effect. Secondary meningiomas are reported in patients who received low and high dose cranial irradiation and arise ~ 20 years post exposure. The molecular and genetic profile of primary meningiomas has been well studied; however, only a few studies describe these in radiation-induced meningiomas (RIM). MethodsWe identified patients followed at the Childhood Cancer Survivor Clinic, Stollery Children’s Hospital who had a history of non-central nervous system malignancies and received cranial irradiation who developed meningiomas between clinic inception in 1971 and June 2013. Whole exome sequencing (WES) as well as DNA methylation profiling were performed for patients where tumor and germline DNA were available. ResultsOf 96 patients who received cranial irradiation, 16 (16.7%) developed symptomatic meningiomas. This patient cohort is unique; all 16 patients received 2000–2400 cGy, suggesting a threshold dose. 9/16 (56%) had WHO Grade 2 meningiomas or greater and 7/16 (44%) were infiltrative. Post-surgical recurrences occurred in 43%. Patients experienced considerable morbidities directly attributable to the meningiomas or their treatment. 14 patients had samples suitable for further analysis. Preliminary results revealed that NF2 mutations were the most common (5). Other meningioma related genes with mutations identified in our patient cohort include TRAF7, AKT3, MSH4 (2), KMT2C (2), TET1 (2), KDM6A, and MLH3. Copy number alternations were noted with increased frequency on chromosomes 1p, 22q, 19q. 850k methylation analysis did not conclusively show any clustering. Ongoing studies include assessment of tumor mutation burden, RNAseq, and the mutational profile. ConclusionsThis study examined RIM in patients who received similar doses of radiation for their childhood cancer. To date, our findings are consistent with previously described primary and RIM mutations. Enhanced knowledge in secondary meningiomas is crucial for accurate patient counseling, prognostication, and treatment.

Short Latency Period of Radiation Induced Meningioma in Adult Patient Following High Dose Irradiation: A Case Report

Introduction: We present a case of adult onset Radiation-Induced Meningioma (RIM) following resection of astrocytoma with short latency period of only 18 months. Case Report: A 44-year old man who had high dose irradiation following astrocytoma resection came to our institution due to the appearance of intracranial tumor in the field of radiation in the follow-up MRI. Observation was done and a head CT scan was done 6 months later, where intracranial tumor was doubled in size. Surgical resection was done and histopathological result of high-grade meningioma confirming the diagnosis of RIM. Most RIM are usually presenting in children receiving high dose radiotherapy with mean latency period of 26.2 ± 9.3 years. Result: Our patient is older at presentation; he underwent astrocytoma resection previously and was receiving high dose irradiation of 46 Gy. Conclusion: In astrocytoma patients receiving adjuvant radiotherapy, physician must be aware of RIM; in addition to the recurrence of the high-grade gliomas.