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  1. Home
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Browsing by Author "Nwagwu, Chibueze D."

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    LMD-10. The role of immune checkpoint inhibitors in leptomeningeal disease: a systematic review
    (Oxford University Press, 2021-08) Palmisciano, Paolo; Haider, Ali S.; Nwagwu, Chibueze D.; Wahood, Waseem; Sagoo, Navraj S.; Yu, Kenny; Ene, Chibawane I.; O’Brien, Barbara J.; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Neurological Surgery, School of Medicine
    Background: Leptomeningeal disease (LMD) is a devastating complication of advanced malignancy with a poor prognosis and limited therapeutic options. Whether immune checkpoint inhibitors (ICIs) alter disease course is unknown. Methods: We searched PubMed, EMBASE, Scopus, Cochrane, and clinicaltrials.gov according to PRISMA guidelines to analyze the therapeutic role and toxicity profiles of ICIs in the management of LMD. Studies reporting clinical outcome data of patients with LMD treated with ICIs were included. A comprehensive review of clinical characteristics and survival analysis was conducted. Results: We included 14 studies encompassing 61 patients. The median age at LMD diagnosis was 57 years (female=63.9%). Lung cancer (44.3%), breast cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Parenchymal brain metastases occurred in 37 patients, mostly treated with radiotherapy (83.3%). LMD most frequently presented with headache (42.1%) and was diagnosed by MRI findings (leptomeningeal T1-contrast enhancement: 96.7%) and/or positive cerebrospinal fluid cytology (86.5%). Patients received ICIs for a median duration of 7 months (range, 0.5–58.0): pembrolizumab (49.2%), nivolumab (32.8%), and/or ipilimumab (18.0%). The most common concurrent LMD treatments were radiotherapy (54.7%) and steroids (35.7%). Radiological responses at 6-months were complete (33.3%) and partial response (12.5%), stable disease (33.3%), and progression (20.8%). 22 patients developed ICI-related adverse events, mostly mild (100%) and uncommonly severe (15.6%). Median progression-free survival was 5.1 months, median overall survival was 6.3 months, and 12-month survival was 32.1%. Survival was correlated with ICIs (P=0.042), but not with primary tumors (P=0.144). Patients concurrently receiving steroids showed worse survival (P=0.040), with a median overall survival of 1.9 months. Conclusion: ICI therapy shows promise and appears to be well-tolerated in patients with LMD. Concurrent use of steroids is associated with worse survival. The role of ICIs in the multimodal management of LMD and their combination with steroids requires further analysis.
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    Metastases in the Pineal Region: A Systematic Review of Clinical Features, Management Strategies, and Survival Outcomes
    (Elsevier, 2022) Palmisciano, Paolo; Ogasawara, Christian; Nwagwu, Chibueze D.; Bin Alamer, Othman; Gupta, Aditya D.; Giantini-Larsen, Alexandra M.; Scalia, Gianluca; Yu, Kenny; Umana, Giuseppe E.; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Haider, Ali S.; Neurological Surgery, School of Medicine
    Background: Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases. Methods: PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed. Results: We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P < 0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence. Conclusions: Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.
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    Primary Skull Base Chondrosarcomas: A Systematic Review
    (MDPI, 2021-11-26) Palmisciano, Paolo; Haider, Ali S.; Sabahi, Mohammadmahdi; Nwagwu, Chibueze D.; Alamer, Othman Bin; Scalia, Gianluca; Umana, Giuseppe E.; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Yu, Kenny; Pathmanaban, Omar N.; Neurological Surgery, School of Medicine
    Background: Primary skull base chondrosarcomas (SBCs) can severely affect patients' quality of life. Surgical-resection and radiotherapy are feasible but may cause debilitating complications. We systematically reviewed the literature on primary SBCs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with primary SBCs. Clinical characteristics, management strategies, and treatment outcomes were analyzed. Results: We included 33 studies comprising 1307 patients. Primary SBCs mostly involved the middle-fossa (72.7%), infiltrating the cavernous-sinus in 42.4% of patients. Cranial-neuropathies were reported in 810 patients (62%). Surgical-resection (93.3%) was preferred over biopsy (6.6%). The most frequent open surgical approaches were frontotemporal-orbitozygomatic (17.6%) and pterional (11.9%), and 111 patients (21.3%) underwent endoscopic-endonasal resection. Post-surgical cerebrospinal-fluid leaks occurred in 36 patients (6.5%). Radiotherapy was delivered in 1018 patients (77.9%): photon-based (41.4%), proton-based (64.2%), and carbon-based (13.1%). Severe post-radiotherapy complications, mostly hypopituitarism (15.4%) and hearing loss (7.1%) were experienced by 251 patients (30.7%). Post-treatment symptom-improvement (46.7%) and reduced/stable tumor volumes (85.4%) showed no differences based on radiotherapy-protocols (p = 0.165; p = 0.062). Median follow-up was 67-months (range, 0.1-376). SBCs recurrences were reported in 211 cases (16.1%). The 5-year and 10-year progression-free survival rates were 84.3% and 67.4%, and overall survival rates were 94% and 84%. Conclusion: Surgical-resection and radiotherapy are effective treatments in primary SBCs, with acceptable complication rates and favorable local tumor control.
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    The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review
    (International Institute of Anticancer Research, 2021) Palmisciano, Paolo; Haider, Ali S.; Nwagwu, Chibueze D.; Wahood, Waseem; Yu, Kenny; Ene, Chibawanye I.; O'Brien, Barbara J.; Aoun, Salah G.; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Neurological Surgery, School of Medicine
    Background/aim: Leptomeningeal disease (LMD) is a debilitating complication of advanced malignancies. Immune-checkpoint inhibitors (ICIs) may alter disease course. We analyzed the role and toxicity of ICIs in LMD. Materials and methods: We systematically reviewed the literature reporting on outcome data of patients with LMD treated with ICIs. Results: We included 14 studies encompassing 61 patients. Lung-cancer (44.3%), breast-cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Median duration of ICI-treatment was 7-months (range=0.5-58.0): pembrolizumab (49.2%), nivolumab (32.8%), ipilimumab (18.0%). Radiological responses included complete response (33.3%), partial response (12.5%), stable disease (33.3%), progressive disease (20.8%). Twenty-two patients developed ICI-related adverse-events, mild (100%) and/or severe (15.6%). Median progression-free and overall survival were 5.1 and 6.3 months, and 12-month survival was 32.1%. Survival correlated with ICI agents (p=0.042), but not with primary tumors (p=0.144). Patients receiving concurrent steroids showed worse survival (p=0.040). Conclusion: ICI therapy is well-tolerated in patients with LMD, but concurrent steroids may worsen survival.
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