Primary CNS Lymphoma (PCNSL) is an unusual extranodal form of Non-Hodgkin’s Lymphoma with a locally aggressive course but a rare tendency to disseminate systemically. There are various modalities available for the treatment of PCNSL which include chemotherapy, radiotherapy, surgery and immunotherapy. The effectiveness of adding another anti-neoplastic agent to HD-MTX have been optimized in small scale studies yet the “ perfect combination” has yet to be elucidated Objectives: This study aims to 1) compare the response to treatment of monotherapy with high-dose Methotrexate (HD-MTX) versus HD-MTX and an additional anti-neoplastic agent by evaluating complete response, partial response, stable disease and disease progression and 2) to compare the hematologic and non-hematologic side effects among patients subjected to monotherapy vs combination chemotherapy. Methodology: Journals from Medline, EMBASE, Cochrane Central Register of Control Trials (CENTRAL) and other relevant websites (www.clinicaltrials.org) without any restrictions in the year, language and status of publication were searched. Literatures cited by eligible studies and systemic reviews were also checked to identify useful articles. The following Medical Subject Headings (MeSH) were used: ‘primary CNS lymphoma’, ‘treatment’, ‘chemotherapy’ and ‘randomized control trial’. Statistical analysis was performed using the RevMan software version 5.1. Odds ratio (OR) and 95 % confidence interval (95% CI) were used as summary statistics. Results and Conclusion: The use of high-dose methotrexate and another anti-neoplastic agent showed benefit in terms of achieving complete response and delaying disease progression among patients diagnosed with PCNSL. However, the risks of hematologic toxicities such as anemia, neutropenia, thrombocytopenia and infection was higher in patients treated with the combination chemotherapy. Significant non-hematologic side effects such as mucositis was also observed in patients receiving an add-on to high dose methotrexate.

Hemangiopericytomas (HPC) are widely recognized for their aggressive clinical behavior. We report a large multicenter study, through the International Gamma Knife Research Foundation reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly-discovered HPC’s. Methods: Eight centers participated, reviewing a total of 90 patients harboring 133 tumors. Prior treatments included embolization (n = 8), chemotherapy (n=2), and fractionated radiotherapy (n=34). The median tumor volume at the time of SRS was 4.9 ml (range 0.2-42.4 ml). WHO-grade II (typical) HPC’s formed 78.9% (n=71) of the cohort. The median margin and maximal doses delivered were 15 Gy (2.8-24) and 32 Gy (8-51), respectively. The median clinical and radiographic follow-up period was 59 months (6-190) and 59 months (6-183), respectively. Results: At last follow-up, 55% of tumors and 62.2% of patients demonstrated local tumor control. New remote intracranial tumors were found in 27.8%. 24.4% of patients developed extra-cranial metastases. Adverse radiation effects were noted in 6.7%. The overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression free survival was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Margin dose greater than 16 Gy (p=0.037) and tumor histology (p=0.006) were shown to influence PFS. Conclusions: SRS provides a reasonable rate of local tumor control and a low risk of adverse effects

Gamma knife radiosurgery (GKRS) is well-established in the management of inaccessible, recurrent, or residual benign skull base meningiomas. Most series report clinical outcome parameters and complications in the short -intermediate period after radiosurgery. Reports of long-term tumor control and neurological status are still lacking. Objective: We report the presentation, treatment, and long-term outcome of skull base meningiomas after GKRS. Methods: From a prospectively collected IRB approved database, we selected patients with a WHO grade I skull base meningioma treated with a single-session GKRS and a minimum of 60 months follow up. 135 patients, 54.1% males (n=73) form the cohort. Median age was 54 years (19-80). Median tumor volume was 4.7 cm3 (0.5-23). Median margin dose was 15 Gy (7.5-36). Median follow up was 102.5 months (60.1-235.4). Patient and tumor characteristics were assessed to determine predictors of neurological function and tumor progression. Results: At last follow up, tumor volume control was achieved in 88.1% (n=119). Post-GKRS clinical improvement or stability was reported in 61.5%. The 5, 10, and 15 years actuarial progression free survival rates are 100%, 95.4%, and 68.8%, respectively. Favorable outcome (both tumor control and clinical preservation/improvement) was attained in 60.8% (n=79). Pre-GKRS performance status (KPS) was shown to influence tumor progression (p=0.0001) and post-GKRS clinical improvement / preservation (p=0.003). Conclusion: GKRS offers a highly durable rate of tumor control for WHO-I skull base meningiomas, with an acceptably low incidence of neurological deficits. KPS at the time of radiosurgery serves as a reliable long-term predictor of overall outcome.

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.

Subependymal giant cell astrocytoma (SEGA) is typically seen in children with tuberous sclerosis (TS), who present with headaches and seizures, and characteristic clinical and cutaneous manifestations of TS. Surgical resection, CSF diversion (for hydrocephalus), radiotherapy, and chemotherapy with a mammalian target of rapamycin (mTOR) inhibitor are treatment options. SEGA can occur in adults without TS, raising diagnostic and therapeutic challenges. A 53 year old man presented with headaches and diplopia. An exophytic, enhancing mass in the left lateral ventricle was resected, confirming SEGA. There was no recurrence on MRI 13 months later. He previously had an “astrocytoma” involving the left frontal horn resected at age 19. Pathology review was SEGA. He had no clinical or cutaneous findings of TS, and no family history of TS. An identical twin was well. A 66 year old man presented with “weakness”, due to diuretic-induced hypokalemia. CT showed a hypodense mass from the right caudate head deforming the frontal horn. MRI showed an exophytic, enhancing mass from the caudate head into the frontal horn. A stereotactic biopsy confirmed SEGA. He had no clinical or cutaneous findings of TS, and negative family history. His mother had a meningioma resected at age 66. Observation is planned. These 2 adult patients had SEGA without clear clinical findings or family history of TS. SEGA should be in the differential diagnosis of tumors involving the lateral ventricle.

Plasmacytomas are solitary tumours characterized by neoplastic proliferation of plasma cells and can be found isolated or in associated with multiple myeloma. Plasmacytomas uncommonly occur intracranially, and dural plasmacytomas without involvement of the calvarium are exceedingly rare. Reported cases indicate durally-based plasmacytomas mimick the appearance of meningioma, lymphoma or sarcoma of the dura. The authors report a case of a 77-year-old male with known multiple myeloma who presented with a 3-week history of confusion, speech impediment, and right sided weakness. A non-contrast CT scan revealed a dense extra-axial mass in the left frontal lobe with initial concerns of an extra-axial hemorrhage. A subsequent MRI demonstrated a contrast enhancing mass with a broad-based dural tail and no underlying calvarial lesion. Differential diagnosis included meningioma or intracranial plasmacytoma. The patient underwent surgical resection and was found to have intratumoural hemorrhage, with pathology confirming plasmacytoma. In the published literature, there are only 20 prior reports of dural plasmacytomas (with and without primary calvarial infiltration), of which only five previous cases reported associated intratumoural hemorrhage. Our case, along with this literature, suggests that new onset of focal neurologic deficits in patients with a history of multiple myeloma merits careful investigation, and that intracranial plasmacytoma should be considered on the differential diagnosis even when imaging reveals masses consistent with hemorrhage or meningioma.

Traditional and advanced magnetic resonance imaging techniques are often unable to differentiate progressive central nervous system neoplasm from post-treatment radiation effect (PTRE). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with delayed imaging has been shown to increase the specificity of PET imaging for cerebral neoplasm in small studies. We sought to further evaluate the potential diagnostic benefits of delayed imaging at 5 hours versus standard imaging at 1 hour to differentiate progressive disease (PD) from PTRE in patients with primary or metastatic brain tumors treated with radiation therapy.

Ten patients with primary (n=4) and metastatic (n=6) brain tumors were identified, with diagnostic confirmation of PD or PTRE provided by pathology or>3 month clinical and radiographic follow-up. Maximum standard uptake values (SUV) were calculated for suspicious areas of abnormal contrast enhancement (lesion) and compared to contralateral normal appearing brain (background) at both early and delayed time points. Seven patients were classified as having PD and 3 as having PTRE based pathology or clinical/radiographic follow up. The average lesion to background ratio (L/B) at the early time point (1.16+0.50) was significantly different than L/B for the later time point (1.72+1.10), p=0.030. The mean L/B for PD was 2.17+1.01 at the later time point compared to 0.65+0.06 for PTRE (p=0.010). For the earlier time point, L/B for PD was 1.40+0.42, compared to the L/B for PTRE which was 0.61+0.10 (p=0.003).L/B ratios at early and delayed time points successfully differentiated between patients with PD and PTRE, with significantly greater L/B ratios seen at delayed time points. These initial results are promising and further investigation is underway to evaluate the contribution of delayed imaging in differentiating PD from PTRE.