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2. Outcomes and Pattern of Care for Spinal Myxopapillary Ependymoma in the Modern Era—A Population-Based Observational Study

Author

Wang, Chenyang, primary, Rooney, Michael K., additional, Alvarez-Breckenridge, Christopher, additional, Beckham, Thomas H., additional, Chung, Caroline, additional, De, Brian S., additional, Ghia, Amol J., additional, Grosshans, David, additional, Majd, Nazanin K., additional, McAleer, Mary F., additional, McGovern, Susan L., additional, North, Robert Y., additional, Paulino, Arnold C., additional, Perni, Subha, additional, Reddy, Jay P., additional, Rhines, Laurence D., additional, Swanson, Todd A., additional, Tatsui, Claudio E., additional, Tom, Martin C., additional, Yeboa, Debra N., additional, and Li, Jing, additional

Published
2024
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3. Accelerated tumor progression after COVID-19 infection in patients with glioblastoma: a retrospective case-control study

Author

Gregory, Timothy A, primary, Knight, Stephanie R, additional, Aaroe, Ashley E, additional, Highsmith, Kaitlin N, additional, Janatpour, Zachary C, additional, O’Brien, Barbara J, additional, Majd, Nazanin K, additional, Loghin, Monica E, additional, Patel, Chirag B, additional, Weathers, Shiao-Pei, additional, Puduvalli, Vinay K, additional, and Kamiya-Matsuoka, Carlos, additional

Published
2024
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8. Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience

Author

Gregory, Timothy A, primary, Mastall, Maximilian, additional, Lin, Heather, additional, Hess, Kenneth R, additional, Yuan, Ying, additional, Martin-Bejarano Garcia, Manuela, additional, Fuller, Gregory N, additional, Alfaro, Kristin D, additional, Gule-Monroe, Maria K, additional, Huse, Jason T, additional, Khatua, Soumen, additional, Rao, Ganesh, additional, Sandberg, David I, additional, Wefel, Jeffrey S, additional, Yeboa, Debra N, additional, Paulino, Arnold C, additional, McGovern, Susan L, additional, Zaky, Wafik, additional, Mahajan, Anita, additional, Suki, Dima, additional, Weathers, Shiao-Pei, additional, Harrison, Rebecca A, additional, de Groot, John F, additional, Puduvalli, Vinay K, additional, Penas-Prado, Marta, additional, and Majd, Nazanin K, additional

Published
2023
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9. Molecular, Histological, and Clinical Characteristics of Oligodendrogliomas: A Multi-Institutional Retrospective Study

Author

Dono, Antonio, Alfaro-Munoz, Kristin, Yan, Yuanqing, Lopez-Garcia, Carlos A., Soomro, Zaid, Williford, Garret, Takayasu, Takeshi, Robell, Lindsay, Majd, Nazanin K., de Groot, John, Esquenazi, Yoshua, Kamiya-Matsuoka, Carlos, and Ballester, Leomar Y.

Subjects
Adult, Male, Craniotomy: Brain Tumor, Brain Neoplasms, Class I Phosphatidylinositol 3-Kinases, Oligodendroglioma, Temozolomide, Humans, Female, Surgery, Neurology (clinical), Retrospective Studies
Abstract

Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined. OBJECTIVE: To evaluate the role of PIK3CA mutations in mODGs. METHODS: One hundred seven mODGs (2008-2019) diagnosed at 2 institutions were included. A retrospective review of clinical characteristics, molecular alterations, treatments, and outcomes was performed. RESULTS: The median age was 37 years, and 61 patients (57%) were male. There were 64 (60%) World Health Organization (WHO) grade 2 and 43 (40%) WHO grade 3 tumors. Eighty-two patients (77%) were stratified as high risk (age 40 years or older and/or subtotal resection per Radiation Treatment Oncology Group-9802). Gross-total resection was achieved in 47 patients (45%). Treatment strategies included observation (n = 15), TMZ (n = 11), radiation (n = 13), radiation/TMZ (n = 62), and others (n = 6). Our results show a benefit of TMZ vs observation in progression-free survival (PFS). No difference in PFS or overall survival (OS) was observed between radiation and radiation/TMZ. PIK3CA mutations were detected in 15 (14%) mODG, and shorter OS was observed in PIK3CA-mutant compared with PIK3CA wild-type mODGs (10.7 years vs 15.1 years, P = .009). WHO grade 3 tumors showed a shorter PFS, but no significant difference in OS was observed between WHO grades. CONCLUSION: Our findings suggest that mODGs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS with TMZ treatment, adjuvant TMZ, radiation, or a combination of the two showed no significant improvement in OS.

Published
2022
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10. A first-in-human Phase I trial of the oral p-STAT3 inhibitor WP1066 in patients with recurrent malignant glioma

Author

Groot, John de, primary, Ott, Martina, additional, Wei, Jun, additional, Kassab, Cynthia, additional, Fang, Dexing, additional, Najem, Hinda, additional, O'Brien, Barbara, additional, Weathers, Shiao-Pei, additional, Matsouka, Carlos Kamiya, additional, Majd, Nazanin K, additional, Harrison, Rebecca A, additional, Fuller, Gregory N, additional, Huse, Jason T, additional, Long, James P, additional, Sawaya, Raymond, additional, Rao, Ganesh, additional, MacDonald, Tobey J, additional, Priebe, Waldemar, additional, DeCuypere, Michael, additional, and Heimberger, Amy B, additional

Published
2022
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11. Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells

Author

Khan, Sabbir, primary, Mahalingam, Rajasekaran, additional, Sen, Shayak, additional, Martinez-Ledesma, Emmanuel, additional, Khan, Arshad, additional, Gandy, Kaitlin, additional, Lang, Frederick F., additional, Sulman, Erik P., additional, Alfaro-Munoz, Kristin D., additional, Majd, Nazanin K., additional, Balasubramaniyan, Veerakumar, additional, and de Groot, John F., additional

Published
2021
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12. A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram

Author

Ferguson, Sherise D., Hodges, Tiffany R., Majd, Nazanin K., Alfaro-Munoz, Kristin, Al-Holou, Wajd N., Suki, Dima, de Groot, John F., Fuller, Gregory N., Khasraw, Mustafa, Ferguson, Sherise D., Hodges, Tiffany R., Majd, Nazanin K., Alfaro-Munoz, Kristin, Al-Holou, Wajd N., Suki, Dima, de Groot, John F., Fuller, Gregory N., and Khasraw, Mustafa

Abstract

BackgroundGlioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors.MethodsA retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas.ResultsUnivariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden (P = .0055) and PTEN mutations (P = .0235) negatively impacted survival, whereas IDH1 mutations positively impacted survival (P < .0001). Clinical factors significantly associated with GBM survival included age (P < .0001), preoperative Karnofsky Performance Scale score (P = .0001), sex (P = .0164), and clinical trial participation (P < .0001). Higher preoperative T1-enhancing volume (P = .0497) was associated with shorter survival. The ratio of TI-enhancing to nonenhancing disease (T1/T2 ratio) also significantly impacted survival (P = .0022).ConclusionsOur newly devised long-term survival-predictive nomogram based on clinical and genomic data can be used to advise patients regarding their potential outcomes and account for confounding factors in nonrandomized clinical trials.

Published
2021

15. Clinical characterization of adult medulloblastoma and the effect of first-line therapies on outcome; The MD Anderson Cancer Center experience

Author

Majd, Nazanin K, primary, Mastall, Maximilan, additional, Lin, Heather, additional, Dibaj, Seyede Shiva, additional, Hess, Kenneth R, additional, Yuan, Ying, additional, Garcia, Manuela Martin-Bejarano, additional, Fuller, Gregory N, additional, Alfaro, Kristin D, additional, Gule-Monroe, Maria K, additional, Huse, Jason T, additional, Khatua, Soumen, additional, Rao, Ganesh, additional, Sandberg, David I, additional, Wefel, Jeffrey S, additional, Yeboa, Debra N, additional, Paulino, Arnold C, additional, McGovern, Susan L, additional, Zaky, Wafik, additional, Mahajan, Anita, additional, Suki, Dima, additional, Weathers, Shiao-Pei, additional, Harriso, Rebecca A, additional, De Groo, John F, additional, Puduvalli, Vinay K, additional, and Penas-Prado, Marta, additional

Published
2021
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16. A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram

Author

Ferguson, Sherise D, primary, Hodges, Tiffany R, additional, Majd, Nazanin K, additional, Alfaro-Munoz, Kristin, additional, Al-Holou, Wajd N, additional, Suki, Dima, additional, de Groot, John F, additional, Fuller, Gregory N, additional, Xue, Lee, additional, Li, Miao, additional, Jacobs, Carmen, additional, Rao, Ganesh, additional, Colen, Rivka R, additional, Xiu, Joanne, additional, Verhaak, Roel, additional, Spetzler, David, additional, Khasraw, Mustafa, additional, Sawaya, Raymond, additional, Long, James P, additional, and Heimberger, Amy B, additional

Published
2020
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17. Intrathecal topotecan with systemic checkpoint inhibitor therapy for gastroesophageal cancer with leptomeningeal involvement: two case reports and review of the literature.

Author

Pabon CM, Yeboa DN, O'Brien BJ, Majd NK, Wang C, and Blum Murphy MA

Abstract

Background: Leptomeningeal metastases (LM) in gastroesophageal (GE) malignancies are exceedingly rare. Historically, treatment for LM has included steroids, radiation, chemotherapy, and intrathecal (IT) chemotherapy. However, the outcomes in GE malignancies with LM remain poor. Unfortunately, clinical trials in GE malignancies have traditionally excluded those with LM, limiting advances in therapeutic strategies. Given that LM poses potentially devastating neurologic and psychologic sequelae, there is an urgent need for more effective treatments., Case Description: Patient 1 is a 44-year-old woman with localized esophageal adenocarcinoma who undergoes neoadjuvant chemoradiation followed by esophagectomy. Seven months following surgery, she develops ataxia, weakness, and nausea/vomiting. Magnetic resonance imaging (MRI) reveals intracranial disease that is subsequently successfully resected and then treated with gamma knife (GK) radiation. Pathology confirms metastases. Three months later she is found to have LM. She receives palliative whole brain radiation therapy as well as focal radiation to the spine. Following this she transitioned to concurrent IT topotecan plus intravenous (IV) ipilumumab/nivolumab with durable response beyond 14 months. Patient 2 is a 71-year-old man with de novo metastatic esophageal adenocarcinoma with durable response to 5-fluorouracil plus irinotecan. Asymptomatic intracranial metastases are detected on surveillance scans 2 years after initial diagnosis for which he receives GK. Follow up MRI identifies new LM. As such, to treat the LM, he was transitioned to IT topotecan and IV pembrolizumab with good response for 6 months until death from a gastrointestinal bleed., Conclusions: We present two cases of LM in patients with GE adenocarcinoma who had longer survival than what has been reported. They were treated with combination IT topotecan and IV checkpoint inhibition. Further studies evaluating the central nervous system tumor immune-microenvironment can help expand our understanding of how this combination has worked well in our patients and how to care for others with similar scenarios., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-70/coif). B.J.O.B. reports that she participates on a data safety monitoring board for Plus Therapeutics. Mariela Murphy reports that she participates in the advisory board for Astrazeneca. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Published
2024
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18. Prolonged complete response to adjuvant tepotinib in a patient with newly diagnosed disseminated glioblastoma harboring mesenchymal-epithelial transition fusion.

Author

Pham LC, Weller L, Gann CN, Schumacher KM, Vlassak S, Swanson T, Highsmith K, O'Brien BJ, Nash S, Aaroe A, de Groot JF, and Majd NK

Abstract

The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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19. Recent Therapeutic Advances in Pituitary Carcinoma.

Author

Robertson IJ, Gregory TA, Waguespack SG, Penas-Prado M, and Majd NK

Abstract

Pituitary carcinoma (PC) is a rare, aggressive malignancy that comprises 0.1-0.2% of all pituitary tumors. PC is defined anatomically as a pituitary tumor that metastasizes outside the primary intrasellar location as noncontiguous lesions in the central nervous system or as metastases to other organs. Similar to pituitary adenoma, PC originates from various cell types of the pituitary gland and can be functioning or nonfunctioning, with the former constituting the majority of the cases. Compression of intricate skull-based structures, excessive hormonal secretion, impaired pituitary function from therapy, and systemic metastases lead to debilitating symptoms and a poor survival outcome in most cases. PC frequently recurs despite multimodality treatments, including surgical resection, radiotherapy, and biochemical and cytotoxic treatments. There is an unmet need to better understand the pathogenesis and molecular characterization of PC to improve therapeutic strategies. As our understanding of the role of signaling pathways in the tumorigenesis of and malignant transformation of PC evolves, efforts have focused on targeted therapy. In addition, recent advances in the use of immune checkpoint inhibitors to treat various solid cancers have led to an interest in exploring the role of immunotherapy for the treatment of aggressive refractory pituitary tumors. Here, we review our current understanding of the pathogenesis, molecular characterization, and treatment of PC. Particular attention is given to emerging treatment options, including targeted therapy, immunotherapy, and peptide receptor radionuclide therapy., Competing Interests: Conflict of Interest: None., (© 2023.)

Published
2022
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