Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma.

According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With an average lifespan of about 15 months from diagnosis, glioblastoma has a poor prognosis and presents a significant treatment challenge. Aberrant angiogenesis, which promotes tumor neovascularization and is a prospective target for molecular target treatment, is one of its unique and aggressive characteristics. Recently, the existence of glioma stem cells (GSCs) within the tumor, which are tolerant to chemotherapy and radiation, has been linked to the highly aggressive form of glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations and clinical trials demonstrating encouraging results. This suggests the need to discover new treatment options. Glioblastoma is one of the numerous cancers for which metformin, an anti-hyperglycemic medication belonging to the Biguanides family, is used as first-line therapy for type 2 diabetes mellitus (T2DM), and it has shown both in vitro and in vivo anti-tumoral activity. Based on these findings, the medication has been repurposed, which has shown the inhibition of many oncopromoter mechanisms and, as a result, identified the molecular pathways involved. Metformin inhibits cancer cell growth by blocking the LKB1/AMPK/mTOR/S6K1 pathway, leading to selective cell death in GSCs and inhibiting the proliferation of CD133+ cells. It has minimal impact on differentiated glioblastoma cells and normal human stem cells. The systematic retrieval of information was performed on PubMed. A total of 106 articles were found in a search on metformin for glioblastoma. Out of these six articles were Meta-analyses, Randomized Controlled Trials, clinical trials, and Systematic Reviews. The rest were Literature review articles. These articles were from the years 2011 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on metformin use in the treatment of glioblastoma were searched on clinicaltrials.gov. In this article, we examine and evaluate metformin's possible anti-tumoral effects on glioblastoma, determining whether or not it may appropriately function as an anti-angiogenic substance and be safely added to the treatment and management of glioblastoma patients.

Pituitary germinomas: a multi-institutional study analyzing patient demographics and management patterns.

PURPOSE: Intracranial germinomas are exceedingly rare tumors found in the pineal and suprasellar regions. The extremely low incidence of pituitary germinoma has resulted in a significant gap in knowledge regarding its demographics, management, and treatment outcomes. We present the largest multicenter analysis of pituitary germinomas to date, focused on analyzing demographic and management patterns. METHODS: This study utilizes the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (2004-2016) to study patients with a primary intracranial germinoma of the pituitary gland. We analyzed demographic information and management strategies among adult and pediatric populations and conducted a 20-year overall survival analysis using Kaplan-Meier curve for a descriptive evaluation of survival outcomes between age groups and treatment groups. RESULTS: 92 patients were included in the study, consisting of 58% pediatric patients and 42% adults, with overall 60% males. 82% patients received radiation as part of the treatment, with no significant difference between pediatric and adult groups. Chemotherapy was used significantly more in pediatrics (p = 0.0002) while surgery was significantly more common in adults (p = 0.0117). The most common treatment in pediatrics was radiation + chemotherapy (47%), while the most common treatment in adults was radiation + gross total resection + chemotherapy (23%) followed by radiation + gross total resection (19%). Younger age, radiotherapy, and chemotherapy were associated with increased 20-year survival on Kaplan-Meier curves. CONCLUSIONS: There exist significant differences in the management of pediatric and adult populations with pituitary germinomas. The low incidence of these tumors makes them challenging to study, but also highlights the importance of national cancer registries in amassing sufficient patient data from which to draw evidence-based conclusions.

Surgical Complications in Intradural Extramedullary Spinal Cord Tumors - An ACS-NSQIP Analysis of Spinal Cord Level and Malignancy.

BACKGROUND: Intradural extramedullary (IDEM) spinal cord tumors account for two-thirds of all intraspinal neoplasms. Surgery for IDEM tumors carries risks for many different complications, which to date have been poorly described and quantified. In this study, we better characterize risk factors and complications for IDEM tumors, stratifying patients by spinal cord level and malignancy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to determine 30-day outcomes following surgery for IDEM tumors between 2005 and 2016. Patients with cervical, thoracic, and lumbar tumors were compared in terms of demographics, comorbidities, and postoperative complications. A similar analysis was performed comparing patients with benign and malignant tumors. RESULTS: A total of 991 patients with IDEM tumors were identified in the cohort. The majority of tumors were thoracic (44.3%), followed by lumbar (35.4%) and cervical (20.3%). Only 6.3% of patients were readmitted within 30 days, 4.2% returned to the operating room, and 1.0% died. Significant associations were noted between spinal cord level and patient sex, age, functional status, American Society of Anesthesiologists (ASA) classification, prevalence of diabetes and hypertension, and risk of developing pneumonia. Benign and malignant tumors differed by patient sex, baseline ASA class, risk of return to the operating room, mortality, and likelihood of transfusion. CONCLUSIONS: IDEM tumors are common and carry surgical risks, with different complication profiles for tumors at different spinal levels and degrees of malignancy. With definitive risk factors and outcomes, the ACS-NSQIP cohort provides a snapshot of national neurosurgery trends and outcomes in contemporary IDEM surgery.

Preoperative steroids do not improve outcomes for intramedullary spinal tumors: a NSQIP analysis of 30-day reoperation and readmission rates.

BACKGROUND: Intramedullary spinal cord tumors (IMSCTs) account for 8-10% of all spinal cord tumors and affect patients of all ages. Although uncommon, IMSCTs carry risk of neurological morbidity and mortality, with 5-year survival rates ranging from 50% to 80%. In this study, we utilize the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to determine the effect of steroid administration on 30-day outcomes following surgery for IMSCTs. METHODS: ACS-NSQIP data for patients undergoing surgery for intramedullary tumors from 2005 to 2015 was reviewed. Patients were selected based on current procedural terminology (CPT) codes 63285 (Laminectomy, intradural, intramedullary, cervical), 63286 (Laminectomy, intradural, intramedullary, thoracic), and 63287 (Laminectomy, intradural, intramedullary, thoracolumbar). ICD-9 and ICD-10 codes were chosen based on the diagnosis of a tumor. The 30-day clinical outcome data, including reoperations and readmission rates, were collected and compared. RESULTS: A total of 259 patients were reviewed. One hundred eighty-one patients had benign intramedullary tumors and 78 had malignant intramedullary tumors. The majority of IMSCTs were at the thoracic level (n=100), followed by the cervical (n=99), and thoracolumbar (n=39) levels. Thirty-one patients were on corticosteroid therapy prior to surgery. Patients with preoperative steroid administration had no significant difference in reoperation and readmission rates. No significant differences were noted between steroid vs. non-steroid therapy for discharge destination, length of hospital stay, or other postoperative complications. CONCLUSIONS: Contrary to previous reports, corticosteroid use prior to surgery for IMSCTs does not have a significant impact on 30-day risk of readmission, reoperation, and risk of postoperative complications.