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Caccese M, Busato F, Guerriero A, Padovan M, Cerretti G, Gardiman MP, Zagonel V, Lombardi G. The role of radiation therapy and systemic treatments in meningioma: The present and the future. Cancer Med 2023; 12:16041-16053. [PMID: 37366279 PMCID: PMC10469847 DOI: 10.1002/cam4.6254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 05/19/2023] [Accepted: 06/05/2023] [Indexed: 06/28/2023] Open
Abstract
Meningiomas are the most prevalent tumors of the central nervous system. Their standard treatment is surgery, which can be curative. Adjuvant radiotherapy treatment is reserved for newly diagnosed cases of grade II and grade III meningiomas in cases of recurrent disease or when surgery is not radical or feasible. However, around 20% of these patients cannot undergo further surgical and/or radiotherapy treatment. Systemic oncological therapy can find its place in this setting. Several tyrosine kinase inhibitors have been tested (gefitinib, erlotinib, sunitinib) with unsatisfactory or negative results. Bevacizumab has shown encouraging results in these settings of patients. Immunotherapy with immune checkpoint inhibitors has reported interesting results with modest objective response rates. Several ongoing studies are assessing different target therapies and multimodal therapies; the results are to be disclosed. Not only a better understanding of the molecular characteristics in meningiomas has allowed the gathering of more information regarding pathogenesis and prognosis, but in addition, the availability of new target therapy, immunotherapy, and biological drugs has widened the scope of potentially effective treatments in this patient population. The aim of this review was to explore the radiotherapy and systemic treatments of meningioma with an analysis of ongoing trials and future therapeutic perspectives.
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Affiliation(s)
- Mario Caccese
- Department of Oncology, Oncology Unit 1Veneto Institute of Oncology IOV‐IRCCSPaduaItaly
| | - Fabio Busato
- Department of Radiation OncologyAbano Terme HospitalPaduaItaly
| | - Angela Guerriero
- General Pathology and Cytopathology Unit, Department of Medicine‐DMEDUniversity of PaduaPaduaItaly
| | - Marta Padovan
- Department of Oncology, Oncology Unit 1Veneto Institute of Oncology IOV‐IRCCSPaduaItaly
| | - Giulia Cerretti
- Department of Oncology, Oncology Unit 1Veneto Institute of Oncology IOV‐IRCCSPaduaItaly
| | - Marina Paola Gardiman
- General Pathology and Cytopathology Unit, Department of Medicine‐DMEDUniversity of PaduaPaduaItaly
| | - Vittorina Zagonel
- Department of Oncology, Oncology Unit 1Veneto Institute of Oncology IOV‐IRCCSPaduaItaly
| | - Giuseppe Lombardi
- Department of Oncology, Oncology Unit 1Veneto Institute of Oncology IOV‐IRCCSPaduaItaly
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Azab MA, Cole K, Earl E, Cutler C, Mendez J, Karsy M. Medical Management of Meningiomas. Neurosurg Clin N Am 2023; 34:319-333. [PMID: 37210123 DOI: 10.1016/j.nec.2023.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
Meningiomas represent the most common type of benign tumor of the extra-axial compartment. Although most meningiomas are benign World Health Organization (WHO) grade 1 lesions, the increasingly prevalent of WHO grade 2 lesion and occasional grade 3 lesions show worsened recurrence rates and morbidity. Multiple medical treatments have been evaluated but show limited efficacy. We review the status of medical management in meningiomas, highlighting successes and failures of various treatment options. We also explore newer studies evaluating the use of immunotherapy in management.
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Affiliation(s)
- Mohammed A Azab
- Biomolecular Sciences Graduate Program, Boise State University, 1910 University Drive, Boise, ID 83725, USA
| | - Kyril Cole
- School of Medicine, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132, USA
| | - Emma Earl
- School of Medicine, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132, USA
| | - Chris Cutler
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 N Green Bay Rd., North Chicago, IL 60064, USA
| | - Joe Mendez
- Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr., Salt Lake City, UT 84112, USA
| | - Michael Karsy
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 North Medical Drive East, Salt Lake City, UT 84132, USA.
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3
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Li S, Wang C, Chen J, Lan Y, Zhang W, Kang Z, Zheng Y, Zhang R, Yu J, Li W. Signaling pathways in brain tumors and therapeutic interventions. Signal Transduct Target Ther 2023; 8:8. [PMID: 36596785 PMCID: PMC9810702 DOI: 10.1038/s41392-022-01260-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/16/2022] [Accepted: 11/21/2022] [Indexed: 01/05/2023] Open
Abstract
Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. Although there are few therapeutic options for brain tumors, enhanced biological understanding and unexampled innovations in targeted therapies and immunotherapies have considerably improved patients' prognoses. Nonetheless, the reduced response rates and unavoidable drug resistance of currently available treatment approaches have become a barrier to further improvement in brain tumor (glioma, meningioma, CNS germ cell tumors, and CNS lymphoma) treatment. Previous literature data revealed that several different signaling pathways are dysregulated in brain tumor. Importantly, a better understanding of targeting signaling pathways that influences malignant behavior of brain tumor cells might open the way for the development of novel targeted therapies. Thus, there is an urgent need for a more comprehensive understanding of the pathogenesis of these brain tumors, which might result in greater progress in therapeutic approaches. This paper began with a brief description of the epidemiology, incidence, risk factors, as well as survival of brain tumors. Next, the major signaling pathways underlying these brain tumors' pathogenesis and current progress in therapies, including clinical trials, targeted therapies, immunotherapies, and system therapies, have been systemically reviewed and discussed. Finally, future perspective and challenges of development of novel therapeutic strategies in brain tumor were emphasized.
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Affiliation(s)
- Shenglan Li
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Can Wang
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jinyi Chen
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lan
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Weichunbai Zhang
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Zhuang Kang
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yi Zheng
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Rong Zhang
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jianyu Yu
- grid.24696.3f0000 0004 0369 153XDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wenbin Li
- Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
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The role of bevacizumab for treatment-refractory intracranial meningiomas: a single institution's experience and a systematic review of the literature. Acta Neurochir (Wien) 2022; 164:3011-3023. [PMID: 36117185 DOI: 10.1007/s00701-022-05348-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/17/2022] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Meningiomas account for over 30% of all primary brain tumors. While surgery can be curative for these tumors, several factors may lead to a higher likelihood of recurrence. For recurrent meningiomas, bevacizumab may be considered as a therapeutic agent, but literature regarding its efficacy is sparse. Thus, we present a systematic review of the literature and case series of patients from our institution with treatment-refractory meningiomas who received bevacizumab. METHODS Patients at our institution who were diagnosed with recurrent meningioma between January 2000 and September 2020 and received bevacizumab monotherapy were included in this study. Bevacizumab duration and dosages were noted, as well as progression-free survival (PFS) after the first bevacizumab injection. A systematic review of the literature was also performed. RESULTS Twenty-three patients at our institution with a median age of 55 years at initial diagnosis qualified for this study. When bevacizumab was administered, 2 patients had WHO grade I meningiomas, 10 patients had WHO grade II meningiomas, and 11 patients had WHO grade III meningiomas. Median PFS after the first bevacizumab injection was 7 months. Progression-free survival rate at 6 months was 57%. Two patients stopped bevacizumab due to hypertension and aphasia. Systematic review of the literature showed limited ability for bevacizumab to control tumor growth. CONCLUSION Bevacizumab is administered to patients with treatment-refractory meningiomas and, though its effectiveness is limited, outperforms other systemic therapies reported in the literature. Further studies are required to identify a successful patient profile for utilization of bevacizumab.
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Pellerino A, Bruno F, Palmiero R, Pronello E, Bertero L, Soffietti R, Rudà R. Clinical Significance of Molecular Alterations and Systemic Therapy for Meningiomas: Where Do We Stand? Cancers (Basel) 2022; 14:2256. [PMID: 35565385 PMCID: PMC9100910 DOI: 10.3390/cancers14092256] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 04/28/2022] [Accepted: 04/29/2022] [Indexed: 12/25/2022] Open
Abstract
Meningiomas are common intracranial tumors that can be treated successfully in most cases with surgical resection and/or adjuvant radiotherapy. However, approximately 20% of patients show an aggressive clinical course with tumor recurrence or progressive disease, resulting in significant morbidity and increased mortality. Despite several studies that have investigated different cytotoxic agents in aggressive meningiomas in the past several years, limited evidence of efficacy and clinical benefit has been reported thus far. Novel molecular alterations have been linked to a particular clinicopathological phenotype and have been correlated with grading, location, and prognosis of meningiomas. In this regard, SMO, AKT, and PIK3CA mutations are typical of anterior skull base meningiomas, whereas KLF4 mutations are specific for secretory histology, and BAP1 alterations are common in progressive rhabdoid meningiomas. Alterations in TERT, DMD, and BAP1 correlate with poor outcomes. Moreover, some actionable mutations, including SMO, AKT1, and PIK3CA, regulate meningioma growth and are under investigation in clinical trials. PD-L1 and/or M2 macrophage expression in the microenvironment provides evidence for the investigation of immunotherapy in progressive meningiomas.
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Affiliation(s)
- Alessia Pellerino
- Division of Neuro-Oncology, Department Neuroscience, University and City of Health and Science Hospital, 10126 Turin, Italy; (A.P.); (F.B.); (R.P.); (R.R.)
| | - Francesco Bruno
- Division of Neuro-Oncology, Department Neuroscience, University and City of Health and Science Hospital, 10126 Turin, Italy; (A.P.); (F.B.); (R.P.); (R.R.)
| | - Rosa Palmiero
- Division of Neuro-Oncology, Department Neuroscience, University and City of Health and Science Hospital, 10126 Turin, Italy; (A.P.); (F.B.); (R.P.); (R.R.)
| | - Edoardo Pronello
- Department of Neurology Unit, Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy;
| | - Luca Bertero
- Pathology Unit, Department of Medical Sciences, University and City of Health and Science Hospital, 10126 Turin, Italy;
| | - Riccardo Soffietti
- Division of Neuro-Oncology, Department Neuroscience, University and City of Health and Science Hospital, 10126 Turin, Italy; (A.P.); (F.B.); (R.P.); (R.R.)
| | - Roberta Rudà
- Division of Neuro-Oncology, Department Neuroscience, University and City of Health and Science Hospital, 10126 Turin, Italy; (A.P.); (F.B.); (R.P.); (R.R.)
- Department of Neurology, Castelfranco Veneto and Treviso Hospital, 31100 Treviso, Italy
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Graillon T, Tabouret E, Chinot O. Chemotherapy and targeted therapies for meningiomas: what is the evidence? Curr Opin Neurol 2021; 34:857-867. [PMID: 34629433 DOI: 10.1097/wco.0000000000001002] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE OF REVIEW Although most meningiomas are slow growing tumors mainly controlled by surgery with or without radiotherapy, aggressive meningiomas that fail these conventional treatments constitute a rare situation, a therapeutic challenge and an unmet need in neuro-oncology. RECENT FINDING Mutational landscape in recurrent high-grade meningiomas includes mainly NF2 mutation or 22q chromosomal deletion, whereas telomerase reverse transcriptase promoter, BAP-1 and CDK2NA mutations were also found in aggressive meningiomas. Pi3K-Akt-mTOR pathway is currently the most relevant intracellular signaling pathway target in meningiomas with preliminary clinical activity observed. Assessment of drug activity with progression free survival rate at 6 months is challenging in regard to meningioma growth rate heterogeneity, so that 3-dimensional growth rate before and during treatment could be considered in the future to selected new active drugs. SUMMARY Despite a low evidence level, some systemic therapies may be considered for patients with recurrent meningioma not amenable to further surgery or radiotherapy. In recurrent high-grade meningioma, everolimus-octreotide combination, bevacizumab, sunitinib and peptide receptor radionuclide therapy exhibit a signal of activity that may justify their clinical use. Despite a lack of clear signal of activity to date, immunotherapy may offer new perspectives in the treatment of these refractory tumors.
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Affiliation(s)
- Thomas Graillon
- Aix Marseille Univ, APHM, INSERM, MMG, UMR1251, La Timone Hospital, neurosurgery department Marseille, France
| | - Emeline Tabouret
- Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, La Timone Hospital, Neurooncology Department, Marseille, France
| | - Olivier Chinot
- Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, La Timone Hospital, Neurooncology Department, Marseille, France
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Maggio I, Franceschi E, Di Nunno V, Gatto L, Tosoni A, Angelini D, Bartolini S, Lodi R, Brandes AA. Discovering the Molecular Landscape of Meningioma: The Struggle to Find New Therapeutic Targets. Diagnostics (Basel) 2021; 11:1852. [PMID: 34679551 PMCID: PMC8534341 DOI: 10.3390/diagnostics11101852] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 09/27/2021] [Accepted: 10/04/2021] [Indexed: 02/06/2023] Open
Abstract
Meningiomas are the most common primary CNS tumors. They are usually benign but can present aggressive behavior in about 20% of cases. The genetic landscape of meningioma is characterized by the presence (in about 60% of cases) or absence of NF2 mutation. Low-grade meningiomas can also present other genetic alterations, particularly affecting SMO, TRAF7, KLF4 AKT1 and PI3KCA. In higher grade meningiomas, mutations of TERT promoter and deletion of CDKN2A/B seem to have a prognostic value. Furthermore, other genetic alterations have been identified, such as BAP1, DMD and PBRM1. Different subgroups of DNA methylation appear to be correlated with prognosis. In this review, we explored the genetic landscape of meningiomas and the possible therapeutic implications.
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Affiliation(s)
- Ilaria Maggio
- Medical Oncology Department, Azienda USL, Via Altura n. 3, 40139 Bologna, Italy; (I.M.); (V.D.N.); (L.G.)
| | - Enrico Franceschi
- Nervous System Medical Oncology Department, IRCSS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy; (A.T.); (D.A.); (S.B.); (A.A.B.)
| | - Vincenzo Di Nunno
- Medical Oncology Department, Azienda USL, Via Altura n. 3, 40139 Bologna, Italy; (I.M.); (V.D.N.); (L.G.)
- Nervous System Medical Oncology Department, IRCSS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy; (A.T.); (D.A.); (S.B.); (A.A.B.)
| | - Lidia Gatto
- Medical Oncology Department, Azienda USL, Via Altura n. 3, 40139 Bologna, Italy; (I.M.); (V.D.N.); (L.G.)
- Nervous System Medical Oncology Department, IRCSS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy; (A.T.); (D.A.); (S.B.); (A.A.B.)
| | - Alicia Tosoni
- Nervous System Medical Oncology Department, IRCSS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy; (A.T.); (D.A.); (S.B.); (A.A.B.)
| | - Daniele Angelini
- Nervous System Medical Oncology Department, IRCSS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy; (A.T.); (D.A.); (S.B.); (A.A.B.)
| | - Stefania Bartolini
- Nervous System Medical Oncology Department, IRCSS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy; (A.T.); (D.A.); (S.B.); (A.A.B.)
| | - Raffaele Lodi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy; or
| | - Alba Ariela Brandes
- Nervous System Medical Oncology Department, IRCSS Istituto di Scienze Neurologiche di Bologna, 40139 Bologna, Italy; (A.T.); (D.A.); (S.B.); (A.A.B.)
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Maggio I, Franceschi E, Tosoni A, Nunno VD, Gatto L, Lodi R, Brandes AA. Meningioma: not always a benign tumor. A review of advances in the treatment of meningiomas. CNS Oncol 2021; 10:CNS72. [PMID: 34015955 PMCID: PMC8162186 DOI: 10.2217/cns-2021-0003] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 03/30/2021] [Indexed: 11/21/2022] Open
Abstract
Meningiomas are the most common primary intracranial tumors. The majority of meningiomas are benign, but they can present different grades of dedifferentiation from grade I to grade III (anaplastic/malignant) that are associated with different outcomes. Radiological surveillance is a valid option for low-grade asymptomatic meningiomas. In other cases, the treatment is usually surgical, aimed at achieving a complete resection. The use of adjuvant radiotherapy is the gold standard for grade III, is debated for grade II and is not generally indicated for radically resected grade I meningiomas. The use of systemic treatments is not standardized. Here we report a review of the literature on the clinical, radiological and molecular characteristics of meningiomas, available treatment strategies and ongoing clinical trials.
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Affiliation(s)
- Ilaria Maggio
- Medical Oncology Department, Azienda USL, Via Altura 3, 40139, Bologna, Italy
| | - Enrico Franceschi
- Medical Oncology Department, Azienda USL, Via Altura 3, 40139, Bologna, Italy
| | - Alicia Tosoni
- Medical Oncology Department, Azienda USL, Via Altura 3, 40139, Bologna, Italy
| | - Vincenzo Di Nunno
- Medical Oncology Department, Azienda USL, Via Altura 3, 40139, Bologna, Italy
| | - Lidia Gatto
- Medical Oncology Department, Azienda USL, Via Altura 3, 40139, Bologna, Italy
| | - Raffaele Lodi
- IRCSS Istituto di Scienze Neurologiche di Bologna, Bologna 40139, Italy
| | - Alba A Brandes
- Medical Oncology Department, Azienda USL, Via Altura 3, 40139, Bologna, Italy
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Wilson TA, Huang L, Ramanathan D, Lopez-Gonzalez M, Pillai P, De Los Reyes K, Kumal M, Boling W. Review of Atypical and Anaplastic Meningiomas: Classification, Molecular Biology, and Management. Front Oncol 2020; 10:565582. [PMID: 33330036 PMCID: PMC7714950 DOI: 10.3389/fonc.2020.565582] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 09/17/2020] [Indexed: 12/12/2022] Open
Abstract
Although the majority of meningiomas are slow-growing and benign, atypical and anaplastic meningiomas behave aggressively with a penchant for recurrence. Standard of care includes surgical resection followed by adjuvant radiation in anaplastic and partially resected atypical meningiomas; however, the role of adjuvant radiation for incompletely resected atypical meningiomas remains debated. Despite maximum treatment, atypical, and anaplastic meningiomas have a strong proclivity for recurrence. Accumulating mutations over time, recurrent tumors behave more aggressively and often become refractory or no longer amenable to further surgical resection or radiation. Chemotherapy and other medical therapies are available as salvage treatment once standard options are exhausted; however, efficacy of these agents remains limited. This review discusses the risk factors, classification, and molecular biology of meningiomas as well as the current management strategies, novel therapeutic approaches, and future directions for managing atypical and anaplastic meningiomas.
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Affiliation(s)
| | - Lei Huang
- Loma Linda University, Loma Linda, CA, United States
| | | | | | - Promod Pillai
- Loma Linda University, Loma Linda, CA, United States
| | | | | | - Warren Boling
- Loma Linda University, Loma Linda, CA, United States
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Maiuri F, Mariniello G, Peca C, Guadagno E, Corvino S, d'Avanzo S, Del Basso De Caro M, de Divitiis O. Multicentric and diffuse recurrences of meningiomas. Br J Neurosurg 2020; 34:439-446. [PMID: 32312105 DOI: 10.1080/02688697.2020.1754335] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Background: Meningiomas recur with a rate of 10-32% at 10 years. Several features influence the risk of recurrence.Objective: To define the pathological and surgical features at risk of multicentric-diffuse versus local-peripheral recurrence.Methods: Thirty-three patients operated on for intracranial meningiomas who experienced multicentric-diffuse recurrence were retrospectively analyzed. The data of these patients were compared to those of 50 patients who experienced local-peripheral recurrence. The analyzed factors included age and sex, tumor location and shape, brain-tumor interface, entity of resection, WHO grade, Ki67 MIB1, progesterone receptor (PR) expression, number of reoperations, progression of WHO grade, and outcome.Results: Meningiomas which recurred in multicentric-diffuse pattern showed at initial surgery a significantly higher rate of flat-shaped tumors (p = .0008) and of cases with Ki67 Li ≥ 4% (p = .037) than those which recurred in localized-peripheral pattern, whereas other factors did not significantly differ. Among patients with multicentric-diffuse recurrences, 25 underwent one to three reoperations; 17 among them (66%) are alive with local tumor control or slow progression 2-25 years after the initial surgery versus only 2 out of 8 who did not undergo surgery.Conclusions: Flat-shaped meningiomas and those with Ki67 Li ≥ 4% are at higher risk of multicentric-diffuse recurrence. Multiple reoperations over a period of several years may obtain rather long survivals in selected patients with prevalent intradural, not anaplastic tumors and not too extensive dural infiltration.
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Affiliation(s)
- Francesco Maiuri
- Department of Neurosciences and Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, Naples, Italy
| | - Giuseppe Mariniello
- Department of Neurosciences and Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, Naples, Italy
| | - Carmela Peca
- Department of Neurosciences and Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, Naples, Italy
| | - Elia Guadagno
- Department of Advanced Biomorphological Sciences, "Federico II" University School of Medicine, Naples, Italy
| | - Sergio Corvino
- Department of Neurosciences and Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, Naples, Italy
| | - Stefania d'Avanzo
- Department of Neurosciences and Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, Naples, Italy
| | | | - Oreste de Divitiis
- Department of Neurosciences and Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, Naples, Italy
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11
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Szychot E, Goodden J, Whitfield G, Curry S. Children's Cancer and Leukaemia Group (CCLG): review and guidelines for the management of meningioma in children, teenagers and young adults. Br J Neurosurg 2020; 34:142-153. [PMID: 32116043 DOI: 10.1080/02688697.2020.1726286] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Primary tumours of the meninges are rare accounting for only 0.4-4.6% of all paediatric tumours of the central nervous system. Due to the rarity of these tumours in children, and the consequent absence of collaborative prospective trials, there is no clear consensus on how the unique characteristics of paediatric meningiomas impact clinical status, management approach, and survival. Much of the evidence and treatment recommendations for paediatric meningiomas are extrapolated from adult data. Translating and adapting adult treatment recommendations into paediatric practice can be challenging and might inadvertently lead to inappropriate management. In 2009, Traunecker et al. published guidelines for the management of intracranial meningioma in children and young people on behalf of UK Children's Cancer and Leukaemia Group (CCLG). Ten years later we have developed the updated guidelines following a comprehensive appraisal of the literature. Complete surgical resection is the treatment of choice for symptomatic meningiomas, while radiotherapy remains the only available adjuvant therapy and may be necessary for those tumours that cannot be completely removed. However, significant advances have been made in the identification of the genetic and molecular alterations of meningioma, which has not only a potential value in the development of therapeutic agents but also in surveillance of childhood meningioma survivors. This guideline builds upon the CCLG 2009 guideline. We summarise recommendations for the diagnosis, treatment, surveillance and long-term follow-up of children and adolescents with meningioma.
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Affiliation(s)
- Elwira Szychot
- Paediatric Oncology Cinical Studies, The Institute of Cancer Research, Sutton, London.,The Royal Marsden Hospital, Sutton, London
| | - John Goodden
- Department of Neurosurgery, Leeds General Infirmary, Leeds, UK
| | - Gillian Whitfield
- Department of Clinical Neuro-oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Sarah Curry
- Department of Paediatric Oncology, Southampton Children's Hospital, Southampton, UK
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12
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Abstract
Surgery is curative for most meningiomas, but a minority of these tumors recur and progress after resection. Initial trials of medical therapies for meningioma utilized nonspecific cytotoxic chemotherapies. The presence of hormone receptors on meningioma ushered in trials of hormone-mimicking agents. While these trials expanded clinical understanding of meningioma, they ultimately had limited efficacy in managing aggressive lesions. Subsequent detection of misregulated proteins and genomic aberrancies motivated the study of therapies targeting specific biological disturbances observed in meningioma. These advances led to trials of targeted kinase inhibitors and immunotherapies, as well as combinations of these agents together with chemotherapies. Prospective trials currently recruiting participants are testing a diverse range of medical therapies for meningioma, and some studies now require the presence of a specific protein alteration or genetic mutation as an inclusion criterion. Increasing understanding of the unique and heterogeneous nature of meningiomas will continue to spur the development of novel medical therapies for the arsenal against aggressive tumors.
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13
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Ahsan SA, Chendeb K, Profyris C, Teo C, Sughrue ME. Pharmacotherapeutic options for atypical meningiomas. Expert Opin Pharmacother 2019; 20:1831-1836. [PMID: 31322413 DOI: 10.1080/14656566.2019.1643840] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Introduction: Atypical meningiomas are aggressive tumors associated with high rates of recurrence and mortality. Current therapy is surgical resection followed by radiotherapy which has reasonable success rates. However, there are cases where surgical resection is not possible, and radiotherapy is not advisable. Areas covered: In this short review, the authors have searched the current literature for explorations of adjuvant treatments such as chemotherapy and pharmaceutical agents. Most current chemotherapeutic agents have been unsuccessful in producing radiographic reduction or disease stabilization, although drugs like somatostatin analogs and plant-derived chemotherapeutics have shown some promise. The authors note that most of the studies in this field have been case series with a few randomized trials present. This makes it hard to ascertain the effectiveness of the drugs and so further research is required in the field. Expert opinion: Finding pharmacotherapies to combat atypical meningiomas needs Big data genomic analysis. This will assist in generating drug candidates and a multidrug approach to therapy that will exploit several of the pathological pathways of atypical meningiomas. Using multidrug therapy that affects several pathways also addresses the issue of meningioma heterogeneity and adaptability.
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Affiliation(s)
- Syed Ali Ahsan
- Centre for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital , Sydney , Australia
| | - Kassem Chendeb
- Centre for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital , Sydney , Australia
| | - Christos Profyris
- Centre for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital , Sydney , Australia
| | - Charles Teo
- Centre for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital , Sydney , Australia
| | - Michael E Sughrue
- Centre for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital , Sydney , Australia
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Buerki RA, Horbinski CM, Kruser T, Horowitz PM, James CD, Lukas RV. An overview of meningiomas. Future Oncol 2018; 14:2161-2177. [PMID: 30084265 PMCID: PMC6123887 DOI: 10.2217/fon-2018-0006] [Citation(s) in RCA: 294] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 06/20/2018] [Indexed: 01/19/2023] Open
Abstract
Meningiomas are the most common primary intracranial tumor. Important advances are occurring in meningioma research. These are expected to accelerate, potentially leading to impactful changes on the management of meningiomas in the near and medium term. This review will cover the histo- and molecular pathology of meningiomas, including recent 2016 updates to the WHO classification of CNS tumors. We will discuss clinical and radiographic presentation and therapeutic management. Surgery and radiotherapy, the two longstanding primary therapeutic modalities, will be discussed at length. In addition, data from prior and ongoing investigations of other treatment modalities, including systemic and targeted therapies, will be covered. This review will quickly update the reader on the contemporary management and future directions in meningiomas. [Formula: see text].
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Affiliation(s)
- Robin A Buerki
- Department of Neurological Surgery, University of California San Francisco, 400 Parnassus Ave., San Francisco, CA 94143, USA
| | - Craig M Horbinski
- Department of Pathology, Northwestern University, IL 60611, USA
- Lou & Jean Malnati Brain Tumor Institute at the Lurie Comprehensive Cancer Center, Northwestern University, IL 60611, USA
| | - Timothy Kruser
- Lou & Jean Malnati Brain Tumor Institute at the Lurie Comprehensive Cancer Center, Northwestern University, IL 60611, USA
- Department of Radiation Oncology, Northwestern University, IL 60611, USA
| | - Peleg M Horowitz
- Section of Neurosurgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Charles David James
- Lou & Jean Malnati Brain Tumor Institute at the Lurie Comprehensive Cancer Center, Northwestern University, IL 60611, USA
- Department of Neurosurgery, Northwestern University, IL 60611, USA
| | - Rimas V Lukas
- Lou & Jean Malnati Brain Tumor Institute at the Lurie Comprehensive Cancer Center, Northwestern University, IL 60611, USA
- Department of Neurology, Northwestern University, 710 North Lake Shore Drive, Abbott Hall 1114, Chicago, IL 60611, USA
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16
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Franke AJ, Skelton IV WP, Woody LE, Bregy A, Shah AH, Vakharia K, Komotar RJ. Role of bevacizumab for treatment-refractory meningiomas: A systematic analysis and literature review. Surg Neurol Int 2018; 9:133. [PMID: 30090665 PMCID: PMC6057170 DOI: 10.4103/sni.sni_264_17] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 05/22/2018] [Indexed: 01/17/2023] Open
Abstract
Background Meningiomas are the most prevalent primary tumor of the central nervous system (CNS), and although the majority of these neoplasms are classified as benign, nearly one fourth of the lesions display an aggressive profile characterized by pleomorphic histology, high recurrence rates, and overall resistance to standard treatment. Despite the ubiquitous nature of these tumors, no adjuvant therapeutic regimen has been identified which effectively controls disease recurrence and progression after surgery and radiation, leading to a dismal prognosis in this patient population. The primary focus of this research study is, hence, to assess the recently emerging use of bevacizumab, an anti-angiogenic agent, in the treatment of meningiomas. This systematic literature review analyzes the efficacy and safety of therapeutic bevacizumab for treatment-refractory meningiomas. Methods A systematic PubMed search was conducted according to PRISMA guidelines to identify all relevant reports investigating the anti-angiogenic agent bevacizumab in the treatment of intracranial meningiomas. The reported parameters from pertinent retrospective reviews, prospective studies, and case studies were volumetric reduction, radiographic response, clinical stability, overall survival (OS), and progression free survival (PFS) measured at 6 and 12 months postinitiation of treatment. Complications were cataloged based on the range and severity of the therapy-related toxicities. Results A total of 11 articles, 5 retrospective series, 2 prospective trials, and 4 case reports, reporting on a total of 92 patients, were included in this review. The use of bevacizumab therapy for intracranial meningiomas demonstrated median overall PFS of 16.8 months (range: 6.5-22 months) and PFS-6 of 73% (range: 44%-93%). Conclusions Therapeutic bevacizumab, either alone or with combination chemotherapies, for select patient populations with recurrent or progressive meningiomas, offers a treatment option that confers improved overall progression-free survival. To assess OS parameters, larger randomized controlled trials assessing the use of anti-angiogenic agents for recurrent/progressive meningiomas are warranted.
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Affiliation(s)
- Aaron J. Franke
- Department of Internal Medicine, University of Florida College of Medicine, Gainesville, USA
| | - William Paul Skelton IV
- Department of Internal Medicine, University of Florida College of Medicine, Gainesville, USA
| | | | - Amade Bregy
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Ashish H. Shah
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Kunal Vakharia
- Department of Neurological Surgery, University at Buffalo School of Medicine, Buffalo, New York, USA
| | - Ricardo J. Komotar
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
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Zhang GJ, Zhang YS, Zhang GB, Li D, Zhang LW, Wu Z, Zhang JT. Prognostic factors and the management of anaplastic meningioma. Clin Neurol Neurosurg 2018; 170:13-19. [DOI: 10.1016/j.clineuro.2018.03.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 03/17/2018] [Accepted: 03/26/2018] [Indexed: 10/17/2022]
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Sharma P, Katiyar V, Sharma R, Gurjar HK, Krishnan S. Letter: Role of Tyrosine Kinase Inhibitors in Recurrent Meningiomas: Controversies and Promises. Neurosurgery 2018; 82:E181-E183. [DOI: 10.1093/neuros/nyy055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Visceral and bone metastases of a WHO grade 2 meningioma: A case report and review of the literature. Cancer Radiother 2017; 21:55-59. [DOI: 10.1016/j.canrad.2016.09.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2015] [Revised: 09/11/2016] [Accepted: 09/16/2016] [Indexed: 11/23/2022]
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Gelerstein E, Berger A, Jonas-Kimchi T, Strauss I, Kanner AA, Blumenthal DT, Gottfried M, Margalit N, Ram Z, Shahar T. Regression of intracranial meningioma following treatment with nivolumab: Case report and review of the literature. J Clin Neurosci 2017; 37:51-53. [PMID: 28089420 DOI: 10.1016/j.jocn.2016.11.011] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 11/28/2016] [Indexed: 10/20/2022]
Abstract
The treatment of refractory meningiomas remains a challenge for both neurosurgeons and neuro-oncologists. There have been no clinical reports of the use or effects of anti-PD-1 therapy in patients with meningioma. We describe a patient whose intracranial meningioma decreased significantly in size after treatment with nivolumab, a monoclonal antibody targeting PD-1, for a concomitant advanced lung cancer. This is the first clinical report suggesting that antibodies targeting PD-1 are effective in treating meningioma. It should encourage further research into the use of checkpoint inhibitors in meningioma.
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Affiliation(s)
- Efrat Gelerstein
- Department of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Assaf Berger
- Department of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Tali Jonas-Kimchi
- Imaging Division, Neuroradiology Unit, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Ido Strauss
- Department of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Andrew A Kanner
- Department of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Deborah T Blumenthal
- Neuro-oncology Service, Division of Oncology, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Maya Gottfried
- Oncology Department, Meir Medical Center, Kfar Saba, Israel
| | - Nevo Margalit
- Department of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Zvi Ram
- Department of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Tal Shahar
- Department of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel.
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Tuchen M, Wilisch-Neumann A, Daniel EA, Baldauf L, Pachow D, Scholz J, Angenstein F, Stork O, Kirches E, Mawrin C. Receptor tyrosine kinase inhibition by regorafenib/sorafenib inhibits growth and invasion of meningioma cells. Eur J Cancer 2017; 73:9-21. [PMID: 28082204 DOI: 10.1016/j.ejca.2016.12.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 09/28/2016] [Accepted: 12/06/2016] [Indexed: 12/19/2022]
Abstract
Systemic chemotherapeutic treatment for unresectable and/or aggressive meningiomas is still unsatisfying. PDGF receptor (PDGFR)-mediated activation of mitogenic signalling has been shown to be active in meningiomas. Therefore, we evaluate in vitro and in vivo the effects of inhibiting PDGFR using the clinically well-characterised tyrosine kinase inhibitors sorafenib or regorafenib in meningioma models. IOMM-Lee meningioma cells were used to assess cytotoxic effects, inhibition of proliferation, induction of apoptosis, as well as inhibition of migration and motility by sorafenib and regorafenib. Using an orthotopic mouse xenograft model, growth inhibition as monitored by magnetic resonance imaging, and overall survival of sorafenib- or regorafenib-treated mice compared with control animals was determined. Treatment of malignant IOMM-Lee cells resulted in significantly reduced cell survival and induction of apoptosis following regorafenib and sorafenib treatment. Western blots showed that both drugs target phosphorylation of p44/42 ERK via downregulation of the PDGFR. Both drugs additionally showed significant inhibition of cell motility and invasion. In vivo, mice with orthotopic meningioma xenografts showed a reduced volume (n.s.) of signal enhancement in MRI (mainly tumour) following sorafenib and regorafenib treatment. This was translated in a significantly increased overall survival time (p ≤ 0.05) for regorafenib-treated mice. Analyses of in vivo-grown tumours demonstrated again reduced PDGFR expression and expression/phosphorylation of p44/42. Sorafenib and regorafenib show antitumour activity in vitro and in vivo by targeting PDGFR and p44/42 ERK signalling.
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Affiliation(s)
- Marcus Tuchen
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Annette Wilisch-Neumann
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Evelyn A Daniel
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Lisa Baldauf
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Doreen Pachow
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Johannes Scholz
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Frank Angenstein
- DZNE, Department for Genetics & Molecular Neurobiology, Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Oliver Stork
- Institute of Biology, Department for Genetics & Molecular Neurobiology, Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Elmar Kirches
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany
| | - Christian Mawrin
- Department of Neuropathology & Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany.
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Balasubramanian SK, Sharma M, Silva D, Karivedu V, Schmitt P, Stevens GH, Barnett GH, Prayson RA, Elson P, Suh JH, Murphy ES, Chao ST. Longitudinal experience with WHO Grade III (anaplastic) meningiomas at a single institution. J Neurooncol 2016; 131:555-563. [DOI: 10.1007/s11060-016-2321-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Accepted: 11/08/2016] [Indexed: 11/28/2022]
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Abstract
INTRODUCTION Meningioma comprise 20-30% of all primary brain tumors. Notwithstanding surgery and radiotherapy, a subset of patients will manifest recurrent meningioma. Systemic therapy is recommended only when further surgery and radiotherapy are not possible. No prospective study with a high level of evidence is available to inform as to recommendations regarding systemic therapy. AREAS COVERED We aim to summarize systemic therapies for recurrent meningioma. Expert commentary: Hydroxurea, temozolomide, irinotecan, the combination of cyclophosphamide/adriamycine/vincristine, interferon-alpha, somatostatin analogs, mifepristone, megestrol acetate, imatinib, erlotinib and gefitinib are considered as having limited efficacy. Potential activity of VEGF (vascular endothelial growth factor) inhibitors such as sunitinib, valatinib, and bevacizumab is suggested in small non-controlled studies and requires validation in randomized trials. The identification of new prognostic markers such as TERT promoter mutations and potential new therapeutic targets, such as KLF4, AKT1, TRAF7, and SMO mutations hopefully facilitate this endeavor.
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Affiliation(s)
- E Le Rhun
- a Lille University, PRISM Inserm U1191 , Villeneuve d'Ascq , France.,b Neuro-oncology, Department of Neurosurgery , Lille Universisty Hospital , Lille Cedex , France.,c Breast unit, Department of Medical Oncology , Oscar Lambret Center , Lille Cedex , France
| | - S Taillibert
- d Department of Neurology Mazarin , Pitié-Salpétrière Hospital, Assistance Publique des Hôpitaux de Paris , Paris , France.,e Department of Neurology , University Pierre et Marie Curie, Paris VI , Paris , France
| | - M C Chamberlain
- f Department of Neurology and Neurological Surgery , University of Washington , Seattle , WA , USA
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Karsy M, Guan J, Cohen A, Colman H, Jensen RL. Medical Management of Meningiomas: Current Status, Failed Treatments, and Promising Horizons. Neurosurg Clin N Am 2016; 27:249-60. [PMID: 27012389 DOI: 10.1016/j.nec.2015.11.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Meningiomas are benign tumors of the central nervous system, with low recurrence risk for World Health Organization (WHO) grade I lesions but a high risk for WHO grade II and III lesions. Current standard treatments include maximum safe surgical resection when indicated and radiation. Only three systemic therapies alpha-interferon, somatostatin receptor agonists, and vascular endothelial growth factor inhibitors are currently recommended by the National Comprehensive Cancer Network for treatment of recurrent meningioma. This paper aims to review medical approaches in the treatment of meningiomas.
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Affiliation(s)
- Michael Karsy
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132, USA
| | - Jian Guan
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132, USA
| | - Adam Cohen
- Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
| | - Howard Colman
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132, USA; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
| | - Randy L Jensen
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132, USA; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA; Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
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Karsy M, Hoang N, Barth T, Burt L, Dunson W, Gillespie DL, Jensen RL. Combined Hydroxyurea and Verapamil in the Clinical Treatment of Refractory Meningioma: Human and Orthotopic Xenograft Studies. World Neurosurg 2016; 86:210-9. [DOI: 10.1016/j.wneu.2015.09.060] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Revised: 09/16/2015] [Accepted: 09/19/2015] [Indexed: 11/26/2022]
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Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Cancer Chemother Pharmacol 2015; 77:115-20. [PMID: 26659583 DOI: 10.1007/s00280-015-2927-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 11/17/2015] [Indexed: 10/22/2022]
Abstract
PURPOSE Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. METHODS Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). RESULTS Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. CONCLUSION The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.
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Balik V, Sulla I, Park HH, Sarissky M. In vitro testing to a panel of potential chemotherapeutics and current concepts of chemotherapy in benign meningiomas. Surg Oncol 2015; 24:292-9. [DOI: 10.1016/j.suronc.2015.06.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Revised: 04/05/2015] [Accepted: 06/07/2015] [Indexed: 01/02/2023]
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Chamberlain MC. IFN-α for recurrent surgery- and radiation-refractory high-grade meningioma: a retrospective case series. CNS Oncol 2015; 2:227-35. [PMID: 25054463 DOI: 10.2217/cns.13.17] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
AIM Limited literature is available regarding the treatment of recurrent surgery- and radiation-refractory meningioma, and it primarily examines the treatment of low-grade (WHO grade 1) meningioma. Data regarding systemic therapy for recurrent high-grade meningioma are sparse. A retrospective case series of patients with recurrent WHO grade 2/3 meningioma treated with IFN-α following progression after surgery, radiotherapy and hydroxyurea was carried out, with the primary study objective of overall response rate, and median and 6-month progression-free survival (PFS). PATIENTS & METHODS 35 patients (28 women and 17 men; median age 63 years; range: 36-86 years) with recurrent high-grade meningioma (WHO grade 2 [n = 22] or 3 [n = 13]) were treated with IFN-α (10 million units/m(2)) subcutaneously every 2 days; one cycle was operationally defined as 4 weeks of IFN-α. Patients had progressed radiographically after prior therapy with surgery (35 out of 35), radiotherapy (35 out of 35; external-beam radiotherapy: 35 out of 35; and stereotactic radiotherapy: 34 out of 35) and hydroxyurea chemotherapy (35 out of 35). One patient was also treated with a somatostatin analog before initiating IFN-α treatment. RESULTS Patients received one to 13 cycles (median: three) of IFN-α with moderate toxicity (100% of patients manifested grades 1-3 toxicity, of which only 20% were grade 3). There were no radiographic responses, 63% of patients had stable disease and 37% manifested progressive disease at first evaluation. PFS was 17% at 6 months (95% CI: 0.07-0.31; median PFS: 12 weeks; 95% CI: 8-20 weeks; range: 4-52 weeks). Following progression on IFN-α, the majority of patients (60%) were subsequently treated on an alternative therapy. CONCLUSION In this large retrospective series, IFN-α was moderately toxic, but appeared to have limited activity in patients with recurrent high-grade meningiomas.
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Affiliation(s)
- Marc C Chamberlain
- University of Washington, Department of Neurology & Neurological Surgery, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, 825 Eastlake Avenue E, PO Box 19023, MS-G4940, Seattle, WA 98109-1023, USA.
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Abstract
The efficacy of surgery and radiation has been well validated in the treatment of meningiomas, with efficacy depending on tumor pathology, size, symptomatology and rate of progression. The role of medical therapy has the least amount of data but is being increasingly investigated for tumors that are inoperable or those tumors that recur and/or progress despite standard therapy. In this review, current data on the use of chemotherapeutic agents in the management of meningiomas will be reviewed, including cytotoxic, biologic, targeted molecular and hormonal agents.
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Affiliation(s)
- Wendy J Sherman
- Northwestern University Department of Neurology, 710 North Lake Shore Drive, Abbott Hall, Room 1123, Chicago, IL 60611, USA
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Griffin LR, Nolan MW, Selmic LE, Randall E, Custis J, LaRue S. Stereotactic radiation therapy for treatment of canine intracranial meningiomas. Vet Comp Oncol 2014; 14:e158-e170. [PMID: 25524449 DOI: 10.1111/vco.12129] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Revised: 10/17/2014] [Accepted: 10/30/2014] [Indexed: 12/31/2022]
Abstract
The objective of this study is to determine the rate of toxicity, median survival time (MST) and prognostic factors in dogs with presumed intracranial meningiomas that were treated with stereotactic radiation therapy (SRT). Patient demographics, neurological history, details of SRT plans and response to treatment (including toxicity and survival times) were examined for potential prognostic factors. Overall MST (MST) due to death for any cause was 561 days. There was a mild to moderate exacerbation of neurological symptoms 3-16 weeks following SRT treatments in 11/30 (36.7%) of dogs. This presumed adverse event was treated with corticosteroids, and improvement was seen in most of these dogs. Death within 6 months of treatment as a result of worsening neurologic signs was seen in 4/30 (13.3%) of dogs. Volume of normal brain that received full dose at a prescription of 8Gy × 3 fractions was predictive of death due to neurological problems within this 6-month period.
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Affiliation(s)
- L R Griffin
- Department of Environmental and Biological Health Sciences, Colorado State University, Fort Collins, CO, USA
| | - M W Nolan
- Radiation Oncology, North Carolina State University, Raleigh, NC, USA
| | - L E Selmic
- Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA
| | - E Randall
- Diagnostic Imaging, Colorado State University, Fort collins, CO, USA
| | - J Custis
- Environmental Health and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA
| | - S LaRue
- Animal Cancer Center, Colorado State University, Fort Collins, CO, USA
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Preusser M, Berghoff AS, Hottinger AF. High-grade meningiomas: new avenues for drug treatment? Curr Opin Neurol 2014; 26:708-15. [PMID: 24184974 DOI: 10.1097/wco.0000000000000035] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE OF REVIEW For standard first-line treatment of high-grade meningiomas, surgical resection and radiotherapy are regarded as standard of care. In the recurrent setting after exhaustion of all local treatment options, no effective therapies are known and several drugs have failed to show efficacy, but novel compounds may offer hope for better disease control. RECENT FINDINGS Upregulation of proangiogenic molecules and dysregulation of some signaling pathways such as the platelet-derived growth factor and mammalian target of rapamycin are recurrently found in high-grade meningiomas. Furthermore, in-vitro studies and single patient experience indicate that trabectedin may be an effective therapy in this tumor type. Unfortunately, so far there is a lack of conclusive clinical trials to draw definite conclusions of efficacy of these approaches. SUMMARY There remains a significant unmet need for defining the role of medical therapy in recurrent high-grade meningioma, and more basic research and multicentric well designed trials are needed in this rare and devastating tumor type. Potentially promising novel therapeutics include antiangiogenic drugs, molecular inhibitors of signaling cascades, immunotherapeutics or trabectedin. However, more basic research is required to identify more promising drug targets. VIDEO ABSTRACT AVAILABLE See the Video Supplementary Digital Content 1 (http://links.lww.com/CONR/A22).
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Affiliation(s)
- Matthias Preusser
- aDepartment of Medicine I & Comprehensive Cancer Center - CNS Unit, Medical University of Vienna bDepartment of Clinical Neurosciences, CHUV, Lausanne University Medical Center and University of Lausanne, Switzerland
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Kaley T, Barani I, Chamberlain M, McDermott M, Panageas K, Raizer J, Rogers L, Schiff D, Vogelbaum M, Weber D, Wen P. Historical benchmarks for medical therapy trials in surgery- and radiation-refractory meningioma: a RANO review. Neuro Oncol 2014; 16:829-40. [PMID: 24500419 PMCID: PMC4022224 DOI: 10.1093/neuonc/not330] [Citation(s) in RCA: 187] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 12/25/2013] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND The outcomes of patients with surgery- and radiation-refractory meningiomas treated with medical therapies are poorly defined. Published reports are limited by small patient numbers, selection bias, inclusion of mixed histologic grades and stages of illness, and World Health Organization (WHO) criteria changes. This analysis seeks to define outcome benchmarks for future clinical trial design. METHODS A PubMed literature search was performed for all English language publications on medical therapy for meningioma. Reports were tabulated and analyzed for number of patients, histologic grade, prior therapy, overall survival, progression-free survival (PFS), and radiographic response. RESULTS Forty-seven publications were identified and divided by histology and prior therapies, including only those that treated patients who were surgery and radiation refractory for further analysis. This included a variety of agents (hydroxyurea, temozolomide, irinotecan, interferon-α, mifepristone, octreotide analogues, megestrol acetate, bevacizumab, imatinib, erlotinib, and gefitinib) from retrospective, pilot, and phase II studies, exploratory arms of other studies, and a single phase III study. The only outcome extractable from all studies was the PFS 6-month rate, and a weighted average was calculated separately for WHO grade I meningioma and combined WHO grade II/III meningioma. For WHO I meningioma, the weighted average PFS-6 was 29% (95% confidence interval [CI]: 20.3%-37.7%). For WHO II/III meningioma, the weighted average PFS-6 was 26% (95% CI: 19.3%-32.7%). CONCLUSIONS This comprehensive review confirms the poor outcomes of medical therapy for surgery- and radiation-refractory meningioma. We recommend the above PFS-6 benchmarks for future trial design.
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Affiliation(s)
- Thomas Kaley
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Igor Barani
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Marc Chamberlain
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Michael McDermott
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Katherine Panageas
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Jeffrey Raizer
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Leland Rogers
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - David Schiff
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Michael Vogelbaum
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Damien Weber
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
| | - Patrick Wen
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (T.K.); Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (I.B.); Department of Neurology, University of Washington, Seattle, Washington (M.C.); Department of Neurosurgery, University of California, San Francisco, San Francisco, California (M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (K.P.); Department of Neurology, Northwestern University, Chicago, Illinois (J.R.); Department of Radiation Oncology, Gamma West Cancer Services, Salt Lake City, Utah (L.R.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S.); Department of Neuro-Oncology, Cleveland Clinic, Cleveland, Ohio (M.V.); Division of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland (D.W.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachsetts (P.W.)
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Minutoli F, Amato E, Sindoni A, Cardile D, Conti A, Herberg A, Baldari S. Peptide receptor radionuclide therapy in patients with inoperable meningiomas: our experience and review of the literature. Cancer Biother Radiopharm 2014; 29:193-9. [PMID: 24811687 DOI: 10.1089/cbr.2013.1599] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
OBJECTIVE Few studies describe peptide receptor radionuclide therapy (PRRT) using (90)Y- or (177)Lu-labeled peptides in patients with recurrent meningiomas. No clinical data about (111)In-Pentetreotide in such patients are available. We report on (111)In-Pentetreotide therapy in patients with inoperable meningiomas and review the literature about PRRT of meningiomas. METHODS We reviewed clinical records of 8 patients with meningioma/meningiomatosis showing high (111)In-Pentetreotide uptake on pretherapy scintigraphy who were treated with at least one cycle of (111)In-Pentetreotide. In 2 patients, a cocktail of (111)In-Pentetreotide and beta-emitting radiolabeled peptides had been administered. RESULTS No patient experienced acute toxicity, neurological or renal function impairment. Mild transient bone marrow toxicity was observed in 4 patients. Objective partial response was observed in 2 patients, stable disease in 5 and disease progression in one. There were no statistically significant correlations between objective response and patient age, tumor WHO grade, baseline Karnofsky performance score, (111)In-Pentetreotide tumoral uptake grade, tumor/nontumor ratio, disease state at baseline, and cumulative dose. CONCLUSIONS In consideration of its efficacy and the lack of significant toxicity, PRRT of meningiomas using (111)In-Pentetreotide could be proposed even nowadays when the use of (177)Lu- or (90)Y-labeled peptides seems unsafe, namely in patients with renal impairment/toxicity.
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Affiliation(s)
- Fabio Minutoli
- 1 Department of Biomedical Sciences and Morphological and Functional Images, University of Messina , Messina, Italy
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Recurrent high-grade meningioma: a phase II trial with somatostatin analogue therapy. Cancer Chemother Pharmacol 2014; 73:919-23. [PMID: 24619496 DOI: 10.1007/s00280-014-2422-z] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2014] [Accepted: 02/19/2014] [Indexed: 10/25/2022]
Abstract
PURPOSE A prospective, two-stage phase II trial with octreotide in patients with recurrent high-grade meningioma was conducted. The radiographic partial response (RPR) was set as the primary study endpoint, whereas progression-free survival at 6 months (PFS6) was defined as the secondary endpoint. METHODS Nine patients (eight men; median age 65) with histological high-grade meningioma (five with grade II and four with grade III) and progression after prior surgery and radiotherapy were included. All had positive brain octreotide SPECT scanning. Octreotide was administered intramuscularly once every 28 days at a dose of 30 mg for the first two cycles and 40 mg for subsequent cycles until progression. Magnetic resonance imaging was performed every 3 months. Progression and RPR were defined as an increase of ≥25 % and as a decrease of ≥50 % in two-dimensional maximum diameters, respectively. RESULTS Patients received a median of three octreotide cycles (range 1-8) without grade ≥2 toxicities. No RPRs were observed. Stable disease was the best response in 33.3 % (n = 3). All patients had progressive disease at 10 months of follow-up. Median time to progression was 4.23 months (range 1-9.4), and the PFS6 was 44.4 % (n = 4). CONCLUSION Our study failed to provide evidence to support the use of monthly long-acting somatostatin analogue schedule in recurrent high-grade meningiomas, as none of our patients demonstrated RPR. The modest median PFS of 4-5 months along with the unknown natural history of recurrent meningiomas render the use of this therapy against these aggressive brain tumors uncertain.
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A phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and surgery refractory meningiomas. J Neurooncol 2014; 117:93-101. [PMID: 24449400 DOI: 10.1007/s11060-014-1358-9] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Accepted: 01/06/2014] [Indexed: 10/25/2022]
Abstract
When surgery and radiation are no longer treatment options, salvage systemic therapy has been used for recurrent meningiomas with little compelling evidence to suggest effectiveness. Patients with surgery and radiation refractory recurrent meningiomas were treated with the oral multifunctional tyrosine kinase inhibitor PTK787/ZK 222584 (PTK787) at a dose of 500 mg twice a day. Each treatment cycle was 4 weeks with MRI done every 8 weeks. Twenty-five patients (14 men; 11 women) with a median age of 59 years and KPS of 80 were treated. Meningioma WHO Grade was I in 2 patients, II in 14 patients and III in 8 patients; 1 patient had a hemangiopericytoma. All patients had prior surgery, external beam radiation therapy or radiosurgery and 11 patients prior systemic chemotherapy. Median number of cycles of PTK 787 administered was 4 (range <1-22). Best response in the 22 evaluable patients was stable disease in 15 (68.2 %). Predominant PTK787 related toxicities included fatigue (60 %), hypertension (24 %) and elevated transaminases (24 %). Grade II patients had a progression free survival (PFS)-6 of 64.3 %, a median PFS of 6.5 months and an overall survival (OS) of 26.0 months; grade III patients had a PFS-6 of 37.5 %, median PFS of 3.6 months and OS 23 months. PTK787 was modestly toxic at the dose of 500 mg administered twice per day. Activity as determined by PFS-6 suggests that targeting PDGF/VEGF pathway warrants further investigation.
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Moazzam AA, Wagle N, Zada G. Recent developments in chemotherapy for meningiomas: a review. Neurosurg Focus 2013; 35:E18. [DOI: 10.3171/2013.10.focus13341] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Object
Currently, few medical options exist for refractory and atypical/anaplastic meningiomas. New developments in chemotherapeutic options for meningiomas have been explored over the past decade. The authors review these recent developments, with an emphasis on emerging avenues for therapy, clinical efficacy, and adverse effects.
Methods
A review of the literature was performed to identify any studies exploring recent medical and chemotherapeutic agents that have been or are currently being tested for meningiomas. Results from included preclinical and human clinical trials were reviewed and summarized.
Results
Current guidelines recommend only 3 drugs that can be used to treat patients with refractory and highgrade meningiomas: hydroxyurea, interferon-α 2B, and Sandostatin long-acting release. Recent developments in the medical treatment of meningiomas have been made across a variety of pharmacological classes, including cytotoxic agents, hormonal agents, immunomodulators, and targeted agents toward a variety of growth factors and their signaling cascades. Promising avenues of therapy that are being evaluated for efficacy and safety include antagonists of platelet-derived growth factor receptor, epidermal growth factor receptor, vascular endothelial growth factor receptor, and mammalian target of rapamycin. Because malignant transformation in meningiomas is likely to be mediated by numerous processes interacting via a complex matrix of signals, combination therapies affecting multiple molecular targets are currently being explored and hold significant promise as adjuvant therapy options.
Conclusions
Improved understanding of the molecular mechanisms driving meningioma tumorigenesis and malignant transformation has resulted in the targeted development of more specific agents for chemotherapeutic intervention in patients with nonresectable, aggressive, and malignant meningiomas.
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Affiliation(s)
| | | | - Gabriel Zada
- 3Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California
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Andersen BM, Pluhar GE, Seiler CE, Goulart MR, SantaCruz KS, Schutten MM, Meints JP, O'Sullivan MG, Bentley RT, Packer RA, Thomovsky SA, Chen AV, Faissler D, Chen W, Hunt MA, Olin MR, Ohlfest JR. Vaccination for invasive canine meningioma induces in situ production of antibodies capable of antibody-dependent cell-mediated cytotoxicity. Cancer Res 2013; 73:2987-97. [PMID: 23471847 PMCID: PMC3655124 DOI: 10.1158/0008-5472.can-12-3366] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. IFN-γ-elaborating T cells were detected in the peripheral blood of 2 cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and HSP60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, showing common antigens across breed and species. Histologic analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in posttreatment compared with pretreatment samples. Tumor-reactive antibodies were capable of inducing antibody-dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data show the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development toward human trials.
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Affiliation(s)
- Brian M Andersen
- Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
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Chamberlain MC. Is there effective systemic therapy for recurrent surgery- and radiation-refractory meningioma? CNS Oncol 2013; 2:1-5. [PMID: 25054350 PMCID: PMC6169456 DOI: 10.2217/cns.12.38] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Marc C Chamberlain
- University of Washington, Department of Neurology & Neurological Surgery, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, 825 Eastlake Avenue E, PO Box 19023, MS-G4940, Seattle, WA 98109-1023, USA.
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Kim MS, Yu DW, Jung YJ, Kim SW, Chang CH, Kim OL. Long-term follow-up result of hydroxyurea chemotherapy for recurrent meningiomas. J Korean Neurosurg Soc 2012; 52:517-22. [PMID: 23346322 PMCID: PMC3550418 DOI: 10.3340/jkns.2012.52.6.517] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Revised: 09/15/2012] [Accepted: 12/18/2012] [Indexed: 11/30/2022] Open
Abstract
Objective Meningiomas represent 18-20% of all intracranial tumors and have a 20-50% 10-year recurrence rate, despite aggressive surgery and irradiation. Hydroxyurea, an inhibitor of ribonucleotide reductase, is known to inhibit meningioma cells by induction of apoptosis. We report the long-term follow-up result of hydroxyurea therapy in the patients with recurrent meningiomas. Methods Thirteen patients with recurrent WHO grade I or II meningioma were treated with hydroxyurea (1000 mg/m2/day orally divided twice per day) from June 1998 to February 2012. Nine female and 4 male, ranging in age from 32 to 83 years (median age 61.7 years), were included. Follow-up assessment included physical examination, computed tomography, and magnetic resonance imaging (MRI). Standard neuro-oncological response criteria (Macdonald criteria) were used to evaluate the follow-up MRI scans. The treatment was continued until there was objective disease progression or onset of unmanageable toxicity. Results Ten of the 13 patients (76.9%) showed stable disease after treatment, with time to progression ranging from 8 to 128 months (median 72.4 months; 6 patients still accruing time). However, there was no complete response or partial response in any patients. Three patients had progressive disease after 88, 89, 36 months, respectively. There was no severe (Grade III-IV) blood systemic disorders and no episodes of non-hematological side effects. Conclusion This study showed that hydroxyurea is a modestly active agent against recurrent meningiomas and can induce long-term stabilization of disease in some patients. We think that hydroxyurea treatment is well tolerated and convenient, and could be considered as an alternative treatment option in patients with recurrent meningiomas prior to reoperation or radiotherapy.
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Affiliation(s)
- Min-Su Kim
- Department of Neurosurgery, College of Medicine, Yeungnam University, Daegu, Korea
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The role of chemotherapy and targeted therapy in the treatment of intracranial meningioma. Curr Opin Oncol 2012; 24:666-71. [DOI: 10.1097/cco.0b013e328356364d] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Abstract
While strong evidence exists for the standard therapy for meningiomas, inclusive of surgery and/or radiation therapy, for those tumors which recur, progress or are inoperable, the optimal medical therapies are yet to be elucidated. This article reviews the current literature for chemotherapeutic options for this subset of tumors, including cytotoxic agents, biologic agents, targeted molecular agents and hormonal agents. At this point in time, the most data is with hydroxyurea and somatostatin, although further trials with combination and targeted molecular therapies are still underway.
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Affiliation(s)
- W J Sherman
- Department of Neurology, Northwestern University, 710 North Lake Shore Dr. Abbott Hall, Room 1123, Chicago, IL 60611, USA
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Horak P, Wöhrer A, Hassler M, Hainfellner J, Preusser M, Marosi C. Imatinib mesylate treatment of recurrent meningiomas in preselected patients: a retrospective analysis. J Neurooncol 2012; 109:323-30. [PMID: 22610940 DOI: 10.1007/s11060-012-0896-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2011] [Accepted: 04/30/2012] [Indexed: 12/20/2022]
Abstract
Some unresectable and symptomatic meningiomas recur after conventional radiation therapy or stereotactic radiosurgery and are a therapeutic challenge. Evidence-based data from medical therapy for patients with recurrent meningioma can be deemed insufficient. Because of the prevalent expression of PDGF receptors in meningiomas, the tyrosine kinase imatinib mesylate has attracted interest as a treatment option for this patient group. In this retrospective study we analyzed 18 patients with recurrent meningiomas who were treated at our institution between 1996 and 2008. Nine patients with positive immunohistochemical staining of at least one of the PDGF receptors were given a daily oral dose of 400 mg imatinib mesylate as first, second, or third-line systemic therapy. Immunohistochemical staining was performed on formalin-fixed and paraffin-embedded tumor tissue with antibodies against PDGFR-α and β, c-Kit, Arg, and c-Abl. Imatinib mesylate at a dose of 400-800 mg/day was well tolerated. Of nine patients treated with imatinib, seven had stable disease and two had progressed at the first scan after three months. We observed no complete or partial responses, although prolonged disease stabilization with progression-free survival of 66.7 % at six months was observed. Overall median progression-free survival was 16 months. We conclude that single-agent imatinib mesylate might be a well-tolerated therapeutic option with high achievement of disease stabilization for preselected patients with recurrent meningiomas. Because of the small cohort, non-randomized design, and highly diverse patient population, we propose future prospective studies to validate our results.
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Affiliation(s)
- Peter Horak
- Department of Medicine I, Clinical Division of Oncology, and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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Lou E, Sumrall AL, Turner S, Peters KB, Desjardins A, Vredenburgh JJ, McLendon RE, Herndon JE, McSherry F, Norfleet J, Friedman HS, Reardon DA. Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series. J Neurooncol 2012; 109:63-70. [PMID: 22535433 DOI: 10.1007/s11060-012-0861-0] [Citation(s) in RCA: 142] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2011] [Accepted: 03/28/2012] [Indexed: 01/22/2023]
Abstract
Intracranial meningiomas are often indolent tumors which typically grow over years to decades. Nonetheless, meningiomas that progress after maximum safe resection and radiation therapy pose a significant therapeutic challenge and effective therapies have yet to be identified. Preclinical studies implicate angiogenesis in the pathophysiology of more aggressive meningiomas, suggesting that anti-angiogenic therapies may be of utility in this setting. We performed a retrospective review of fourteen patients with recurrent meningioma treated at Duke University Medical Center with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, administered either alone or in combination with chemotherapy. Most patients were heavily pre-treated. Progression-free survival at 6 months was 86 % and was comparable regardless of meningioma grade and whether bevacizumab was administered as monotherapy or in combination with chemotherapy. Most toxicities were mild however single patients developed CNS hemorrhage (grade 1) and intestinal perforation (grade 4), respectively. Bevacizumab can be administered safely to patients with meningioma and appears to be associated with encouraging anti-tumor effect when administered as either a single agent or in combination with chemotherapy. Phase II trials investigating bevacizumab in patients with progressive/recurrent meningioma are warranted.
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Affiliation(s)
- Emil Lou
- Department of Surgery, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC, 27710, USA
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Chamberlain MC. Hydroxyurea for recurrent surgery and radiation refractory high-grade meningioma. J Neurooncol 2011; 107:315-21. [PMID: 22127733 DOI: 10.1007/s11060-011-0741-z] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Accepted: 10/05/2011] [Indexed: 12/29/2022]
Abstract
Hydroxyurea (HU), an orally administered chemotherapy, has become the de facto standard chemotherapeutic agent in patients with surgically and radiation refractory meningiomas based on a limited literature. A retrospective case series of 35 patients with recurrent WHO Grade 2 (n = 22) or 3 (n = 13) meningioma treated with HU following progression after surgery and radiotherapy was collated with primary study objectives of overall response rate, median and progression free survival (PFS) at 6-months. Thirty-five patients (25 women; 10 men: median age 63 years, range 34-86) with recurrent high-grade meningioma were treated with HU (1,000 mg/m(2) orally divided twice per day; one cycle operationally defined as 4 weeks of daily HU). Patients had progressed radiographically after prior therapy with surgery (35/35) and radiotherapy (35/35: external beam radiotherapy 35/35; stereotactic radiotherapy 35/35). No patient received prior chemotherapy or targeted therapy before instituting HU. Patients received 0.5-7 cycles (median 2.0) of HU with modest toxicity (28.5% all grades and 8.5% grade 3+ anemia or fatigue). There were no radiographic responses, 43% of patients had stable disease and 57% manifested progressive disease at first evaluation. The overall PFS was 3.0% at 6 months (median PFS 2.0 months; 95% CI 1.6-2.4). The majority of patients (80%) following progression on HU were subsequently treated on an investigational trial. In this retrospective series, HU though well tolerated and convenient appeared to have very limited activity, raise questions of what constitutes effective salvage therapy and indicates an unmet need for alternative treatments for recurrent high-grade meningiomas.
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Affiliation(s)
- Marc C Chamberlain
- Division of Neuro-Oncology, Departments of Neurology and Neurological Surgery, University of Washington, Seattle, WA, USA.
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Reardon DA, Norden AD, Desjardins A, Vredenburgh JJ, Herndon JE, Coan A, Sampson JH, Gururangan S, Peters KB, McLendon RE, Norfleet JA, Lipp ES, Drappatz J, Wen PY, Friedman HS. Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma. J Neurooncol 2011; 106:409-15. [PMID: 21938530 DOI: 10.1007/s11060-011-0687-1] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Accepted: 08/03/2011] [Indexed: 01/28/2023]
Abstract
We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥ 10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.
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Affiliation(s)
- David A Reardon
- Duke University Medical Center, Box 3624, Durham, NC 27710, USA.
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