Potential Role of Thymosin-α1 Adjuvant Therapy for Glioblastoma

Glioblastomas are high-grade, malignant CNS neoplasms that are nearly always fatal within 12 months of diagnosis. Immunotherapy using proinflammatory cytokines such as IL-2 or IL-12 may prolong survival with glioblastoma. Thymosin-α1 (Talpha1) is a thymic hormone and immunemodulator that increase IL-2 production and T-cell proliferation. We examined potential therapeutic effects of Talpha1 in experimental in vivo glioblastoma, and characterized Talpha1's anti-tumor effects in vitro. Rar 9L cells (104) were implanted into the right frontal lobe of adult Long Evans rats that were subsequently treated with vehicle, BCNU, Talpha1, or Talpha1+BCNU from postoperative day 6. Talpha1+BCNU significantly lowered tumor burdens, and increased cure rates. In vitro experiments demonstrated that Talpha1 had no direct effect on viability or mitochondrial function, and instead, it increased expression of pro-apoptosis genes, including FasL, FasR and TNFα-R1 (65.89%, 44.08%, and 22.18%, resp.), and increased 9L cell sensitivity to oxidative stress. Moreover, Talpha1 enhanced 9L cell sensitivity to both Granzyme B- and BCNU-mediated killing. The findings suggest that Talpha1 enhances BCNUmediated eradication of glioblastoma in vivo, and that Talpha1 mediates its effects by activating pro-apoptosis mechanisms, rendering neoplastic cells more sensitive to oxidative stress and immune-mediated killing by Granzyme B and chemotherapeutic agents

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

PURPOSE: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach. MATERIALS AND METHODS: Patients with brain metastases treated with SRS from 2001 to 2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky performance status \u3e /=70, and life expectancy \u3e /=3 months. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with \u3e /=1-year WBRT-free survival (N = 104), and those who died or required salvage WBRT within 3 months of SRS (N = 56). Differences between these groups were assessed by univariate and multivariate analyses. RESULTS: Median survival for all patients was 11 months. Among patients with \u3e /=1-year WBRT-free survival, median survival was 33 months (12-107 months) with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p \u3c 0.05) included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden ( \u3c /=5 metastatic lesions). After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival. CONCLUSION: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone

Bilateral trigeminal nerve sheath tumors treated with stereotactic radiosurgery: A case report

Bilateral trigeminal nerve sheath tumors are extremely rare with a paucity of previously disseminated cases. In addition, bilateral nerve sheath tumors are often secondary to genetic conditions such as Neurofibromatosis (NF) 2 and schwannomatosis. Here, we present the case of a 55-year-old male who presents with bilateral trigeminal nerve sheath tumors who was subsequently treated with stereotactic radiosurgery. We also review literature relevant to NF1, NF2, and schwannomatosis diagnosis and discuss previous cases of bilateral trigeminal nerve sheath tumors

Stereotactic radiosurgery for large brain metastases

We evaluated patient outcomes following stereotactic radiosurgery (SRS)-treatment of large brain metastasis (3cm) at our institution. SRS is an established treatment for limited brain metastases. However, large tumors pose a challenge for this approach. For this study, 343 patients with 754 total brain metastases were treated with SRS, of which 93 had large tumors. The tumor size was 3-3.5, 3.5-4, and 4cm in 29%, 32%, and 39% of these patients. Surgical resection was performed prior to SRS in 68% of patients, and 53% achieved a gross total resection. The local control of large metastases was inferior compared to smaller tumors, with 1 year local control of 68 versus 86%, respectively (p \u3c 0.001). Among the patients with large metastases, no correlation between local control and surgical resection (p=0.747), or extent of surgery (gross total versus subtotal resection; p=0.120), was identified. Histology (p=0.939), tumor size (3-4 versus \u3e 4cm; p=0.551), and SRS dose (16 versus \u3e 16Gy; p=0.539) also showed no correlation with local failure. The overall survival at 1, 2, and 5years was 46%, 29% and 5%, respectively. Prolonged survival was seen in patients with age \u3c 65years (p=0.009), primary treatment compared with salvage (p=0.077), and controlled primary tumors (p=0.022). Radiation necrosis developed in 10 patients (11.8%). For patients with large brain metastases, SRS is well tolerated and can achieve local central nervous system disease control in the majority of patients, and extended survival in some, though the local control rate is suboptimal. Further strategies to improve the outcomes in this subgroup of patients are needed

Stereotactic radiosurgery for large brain metastases.

We evaluated patient outcomes following stereotactic radiosurgery (SRS)-treatment of large brain metastasis (⩾3 cm) at our institution. SRS is an established treatment for limited brain metastases. However, large tumors pose a challenge for this approach. For this study, 343 patients with 754 total brain metastases were treated with SRS, of which 93 had large tumors. The tumor size was 3-3.5, 3.5-4, and ⩾4 cm in 29%, 32%, and 39% of these patients. Surgical resection was performed prior to SRS in 68% of patients, and 53% achieved a gross total resection. The local control of large metastases was inferior compared to smaller tumors, with 1 year local control of 68 versus 86%, respectively (p4 cm; p=0.551), and SRS dose (⩽16 versus >16 Gy; p=0.539) also showed no correlation with local failure. The overall survival at 1, 2, and 5 years was 46%, 29% and 5%, respectively. Prolonged survival was seen in patients with age <65 years (p=0.009), primary treatment compared with salvage (p=0.077), and controlled primary tumors (p=0.022). Radiation necrosis developed in 10 patients (11.8%). For patients with large brain metastases, SRS is well tolerated and can achieve local central nervous system disease control in the majority of patients, and extended survival in some, though the local control rate is suboptimal. Further strategies to improve the outcomes in this subgroup of patients are needed

A Transforaminal Endoscopic Surgical Technique for Treating Lumbar Disc Herniation in the Setting of Spina Bifida

Recent literature suggests that adult patients with spina bifida receive surgery for degenerative disc disease at higher rates than the general population. However, sometimes the complex anatomic features of co-occurring spina bifida and lumbar disc herniation can significantly challenge standard surgical techniques. Here, the technical steps are presented for treating a foraminal lumbar 4-5-disc herniation in the setting of a patient with multifaceted degenerative and spina bifida occulta anatomy. Utilized is a minimally invasive approach that does not require general anesthesia or fusion and allows the patient to leave the same day. To the best of our knowledge, this is the first-reported case of endoscopic surgical decompression of a lumbar disc in a patient with spina bifida

Patients with Long-Term Control of Systemic Disease Are a Favorable Prognostic Group for Treatment of Brain Metastases with Stereotactic Radiosurgery Alone

BACKGROUND: Stereotactic radiosurgery (SRS) alone is an attractive option for treatment of brain metastases. SRS avoids whole-brain radiotherapy (WBRT)-associated morbidity, but is limited by regional central nervous system (CNS) failures and short survival in some patients. We evaluated a subgroup of patients with controlled systemic disease that could represent a favorable patient population for SRS alone. METHODS: All patients with brain metastases treated with SRS without WBRT at our institution between 2004 and 2014 were grouped into two cohorts: those with controlled systemic disease (CSD) for 1 year or longer before prior to presentation with brain metastases and those without (i.e., uncontrolled systemic disease [USD]). Rates of local and regional CNS failure, and overall survival were assessed with chi(2) and Student t tests. Cox regression analysis was performed to evaluate independent predictors of regional control and overall survival. RESULTS: Two hundred ninety-four patients underwent SRS to 697 lesions, of which 65 patients had CSD. Median follow-up was 9.7 months. There was no difference in local control between the two cohorts (P = 0.795). Regional CNS control was significantly better for patients with CSD (68% vs. 48%; P = 0.001). Overall survival at 1 and 5 years for CSD were 65% and 13% with USD yielding 41% and 7%, respectively (P \u3c 0.001). Multivariate analysis demonstrated that USD (relative CSD) independently predicts regional failure (hazard ratio [HR], 1.75; P = 0.008) and shorter overall survival (HR, 1.55; P = 0.007). CONCLUSIONS: Patients with brain metastases after 1 year or longer of primary and systemic disease control represent a particularly favorable cohort, with lower regional CNS failure and prolonged survival, for an approach of SRS alone

Repeat Stereotactic Radiosurgery for Locally Recurrent Brain Metastases

PURPOSE/OBJECTIVES: The outcomes of repeat stereotactic radiosurgery (SRS) after failure of previous SRS are not well established. We report our overall experience using SRS for the retreatment of locally recurrent brain metastases. METHODS: Patients with brain metastases diagnosed between 2003 and 2015 who underwent repeat SRS for local tumor progression following prior SRS were identified. Rates of local control, radiation necrosis, and overall survival were analyzed. Factors affecting local failure and radiation necrosis were assessed by chi-square test. RESULTS: Twenty-four lesions in 22 patients underwent repeat SRS in a single fraction. Median age was 59 years. The median SRS-1 dose was 18 Gy, and the median SRS-2 dose was 15.5 Gy. The median SRS-1 target volume was 2.25 cm(3), and the median SRS-2 target volume was 3.30 cm(3). The median follow-up from SRS-2 was 8.8 months. The actuarial local controls for SRS-2 were 94.1% and 61.1% at 6 and 12 months, respectively. The incidences of actuarial radiation necrosis were 9.2% and 9.2% at 6 and 12 months, respectively. Volume of tumor \u3e 4 cm(3) correlated with increased risk of local failure (P = 0.006) with no local failures recorded with volumes \u3c /=4 cm(3). SRS-2 dose, cumulative SRS dose, receipt of whole brain radiotherapy, and use of SRS-2 as boost after surgery did not correlate with local failure or radiation necrosis. Median overall survival after SRS-2 was 8.78 months. CONCLUSION: Repeat SRS is feasible for select patients, particularly for those with tumor volume \u3c /=4 cm(3). Further evaluation is needed to establish the most appropriate treatment doses and volumes for this approach