Background For meningiomas, complete resection is recommended as first-line treatment while stereotactic radiosurgery (SRS) is established for meningiomas of smaller size considered inoperable. If the patient´s medical condition or preference excludes surgery, SRS remains a treatment option. We evaluated the efficacy and safety of SRS in a cohort comprising these cases. Methods In this retrospective single-centre analysis we included patients receiving single fraction SRS either by modified LINAC or robotic guidance by Cyberknife for potentially resectable intracranial meningiomas. Treatment-related adverse events as well as local and regional control rates were determined from follow-up imaging and estimated by the Kaplan–Meier method. Results We analyzed 188 patients with 218 meningiomas. The median radiological, and clinical follow-up periods were 51.4 (6.2–289.6) and 55.8 (6.2–300.9) months. The median tumor volume was 4.2 ml (0.1–22), and the mean marginal radiation dose was 13.0 ± 3.1 Gy, with reference to the 80.0 ± 11.2% isodose level. Local recurrence was observed in one case (0.5%) after 239 months. The estimated 2-, 5-, 10- and 15-year regional recurrence rates were 1.5%, 3.0%, 6.6% and 6.6%, respectively. Early adverse events (≤ 6 months after SRS) occurred in 11.2% (CTCEA grade 1–2) and resolved during follow-up in 7.4% of patients, while late adverse events were documented in 14.4% (grade 1–2; one case grade 3). Adverse effects (early and late) were associated with the presence of symptoms or neurological deficits prior to SRS (p < 0.03) and correlated with the treatment volume (p < 0.02). Conclusion In this analysis SRS appears to be an effective treatment for patients with meningiomas eligible for complete resection and provides reliable long-term local tumor control with low rates of mild morbidity.

Background Stereotactic radiosurgery (SRS) is widely accepted as a therapeutic option for meningiomas (M) and vestibular schwannomas (VS). However, data on outcome and toxicity in the elderly population have rarely been reported in detail. Methods All patients aged ≥ 65 years with M or VS who underwent single fraction SRS were included. Patient data were analyzed in terms of clinical tumor control and incidence of early and late treatment related complications, which were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Results We identified 245 patients with benign brain tumors (129 M and 116 VS, median tumor volume 2.9 ml, range 0.1–28). The median age was 71 years (range 65–86) and the mean follow-up times were 42 months (range 2–181). Tumors were irradiated with a median dose of 12.4 Gy. Actuarial clinical and radiological tumor control rates at 2, 5, and 10 years after SRS were 98%, 93%, and 88%, respectively. Recurrent tumors after previous treatment had a higher probability of post-radiosurgical progression (p < 0.001). Permanent toxicity (CTCAE I/II) were noted in 5.7%. No severe adverse events were observed during early and late follow up, although patients > 70 years had a slightly higher risk for toxicity (p = 0.027). The presence and extent of co-morbidities had no significant influence on local tumor control or toxicity. Conclusion SRS provides favorable tumor control with low risk for treatment-related severe complications. Thus, SRS should always be considered as treatment option for benign intracranial tumors (meningiomas, schwannomas), especially in the group of elderly patients.

BACKGROUND: Meningioma is the most common brain tumors in adults. Despite the overall benign nature of meningioma, cranial-base tumors are difficult to achieve complete resection while others exhibit progression and aggressive profiles characterized by high recurrence rates, pleomorphic histology, and resistance to standard treatment. The lack of clinically relevant animal models is blocking the development of novel therapies. Here, we report our establishment of orthotopic xenograft mouse models and in vitro culture systems from surgical specimens of primary and recurrent meningiomas. MATERIAL AND METHODS: 6 primary surgical samples (3 WHO grade I and 3 atypical), and 4 recurrent samples (1 WHO grade I, 2 atypical and 1 anaplastic meningiomas) were obtained from meningioma patients. Tumor tissues were dissociated into single cells and directly implanted into right cranial base of NOD/ SCID mice (1x10 5 cells/mouse). Primary cultures were initiated in serumfree and traditional FBS-based media. Tumor growth was monitored by small animal MRI. Pathologic features of the PDOX models and the matched patient tumors were compared with standard H&E and immunohistochemical staining. Molecular fidelity of PDOX tumor was examined through genomic analysis and comparison with the parental tumors. RESULTS: Three of the 10 tumors were not tumorigenic, and xenograft tumor formation from 5 additional samples is pending. Growth of intracranial (cranial base) xenograft was confirmed in two samples derived from the same patient diagnosed as atypical meningioma (K029MEN) and progressed as anaplastic meningioma at recurrence (K037MEN). These patient derived orthotopic xenografts (PDOX) have since been serially subtransplanted in mouse brains for generation 2 and can be cryopreserved for long-term maintenance of tumorigenicity. The xenograft tumors replicated histopathological features (invasion, high proliferation and increased microvessel density) of their parental tumors. Genomic analysis is being performed to examine the similarities between parental tumors and the corresponding orthotopic xenograft tumors and the discrepancies between the primary and the recurrent tumor-derived models. In vitro growth of K029MEN and K037MEN as neurospheres and monolayer were maintained for 2 months and passage for 10 times. Additionally, cells from K030MEN, a WHO grade I meningioma, has been passaged as monolayer for more than 30 times. CONCLUSION: A novel set of meningioma PDOX models derived from matching primary and recurrent tumor was established. The xenograft tumors replicated the histopathological and key molecular features of the original patient tumors, providing a unique opportunity to understand the biology of malignant meningiomas and to conduct preclinical drug testing.

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