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Zeng L, Yang H, Li H, Chen R, Chen J, Yu J. Risk Factors for and Molecular Pathology Characteristics of Systemic Metastasis of Adult Cerebral Glioblastoma: A Pooled Individual Patient Data Analysis and Systematic Review. J Neurol Surg A Cent Eur Neurosurg 2025. [PMID: 39572244 DOI: 10.1055/a-2479-9978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2025]
Abstract
OBJECTIVE The risk factors for and molecular mechanisms of systemic metastasis of cerebral glioblastoma (GBM) remain to be evaluated. PATIENTS AND METHODS Literature about adult GBM patients with systemic metastasis published before December 31, 2022, was searched in "PubMed" and "Web of Science," and the patient's clinical data were collected and compared with those of patients without metastasis to evaluate the risk factors. The molecular pathology results were summarized to evaluate the mechanism. RESULTS One hundred and forty-seven patients with metastasis in 113 papers published from 1928 to 2022 were included. Two hundred and forty-nine patients without metastasis who underwent surgery in our department in 2017 were included. Comparison of the two groups showed that age ≤40 years was significantly correlated with metastasis (hazard ratio [HR]: 2.086, 95% CI: 1.124-3.871, p = 0.020) and better overall survival (HR: 1.493, 95% CI: 1.067-2.083, p = 0.019). Molecular pathology results were reported in 39 cases (39/147, 26.5%). The genetic results showed obvious heterogeneity. According to the frequency and positive ratio, IDH-wild type (positive rate 27/30), TERT promoter mutation (11/13), PTEN mutation (10/11), TP53 mutation (10/13), and RB1 mutation (8/9) were common gene changes. CONCLUSION In young adult GBM patients, especially those ≤40 years of age with long survival, attention should be given to the development of systemic metastases. Metastasis can be the result of multiclonal gene mutations, in which proliferation- and invasion-related gene changes, such as oncogene or tumor suppressor gene mutations and epithelial-mesenchymal transition-related genes, may play an important role in metastasis.
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Affiliation(s)
- Lingcheng Zeng
- Department of Neurosurgery, Huazhong University of Science and Technology Tongji Medical College Tongji Hospital, Wuhan, Hubei, People's Republic of China
| | - Hongkuan Yang
- Department of Neurosurgery, Huazhong University of Science and Technology Tongji Medical College Tongji Hospital, Wuhan, Hubei, People's Republic of China
| | - Hua Li
- Department of Neurosurgery, Huazhong University of Science and Technology Tongji Medical College Tongji Hospital, Wuhan, Hubei, People's Republic of China
| | - Rudong Chen
- Department of Neurosurgery, Huazhong University of Science and Technology Tongji Medical College Tongji Hospital, Wuhan, Hubei, People's Republic of China
| | - Jian Chen
- Department of Neurosurgery, Huazhong University of Science and Technology Tongji Medical College Tongji Hospital, Wuhan, Hubei, People's Republic of China
| | - Jiasheng Yu
- Department of Neurosurgery, Huazhong University of Science and Technology Tongji Medical College Tongji Hospital, Wuhan, Hubei, People's Republic of China
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Basem JI, Seidman R, Franceschi D, Dashti R. Extraneural metastases of glioblastoma: A case report and literature review. Surg Neurol Int 2025; 16:102. [PMID: 40206754 PMCID: PMC11980742 DOI: 10.25259/sni_969_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 01/24/2025] [Indexed: 04/11/2025] Open
Abstract
Background Glioblastoma (isocitrate dehydrogenase [IDH]-wildtype, WHO Grade 4) is known to have a high recurrence rate with poor management of morbidity and mortality. Metastatic spread of glioblastomas is rare with extraneural osseous spread having been reported in under 100 cases. In this report, a case of glioblastoma with widespread extraneural metastatic lesions, including distal extremities, is presented. Case Description A 70-year-old female presented with progressive word-finding difficulty and confusion. Brain magnetic resonance imaging (MRI) revealed a 5 × 7 cm left temporal solid and cystic mass with heterogenous contrast enhancement and significant surrounding edema. She underwent near-total tumor resection, and the pathological diagnosis was glioblastoma, (IDH-wildtype, WHO grade 4), with sarcomatous and primitive neuronal components. She received radiation therapy and temozolomide over 4 months. At 5 months postoperative, she presented with new bilateral lower extremity weakness and left facial droop. MRI and positron emission tomography scans revealed local recurrence and metastatic lesions to vertebrae, extremities, and lymph nodes. Conclusion Previous research into rare glioblastoma bone metastases supports the theories of spread through hematogenous routes, surgical disruption, glymphatic system, and potential genetic susceptibility. However, no literature to date can adequately explain the distal limb metastases presented in this case, which shows the necessity for further understanding of this pathology.
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Affiliation(s)
- Jade I. Basem
- Department of Neurological Surgery, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
| | - Roberta Seidman
- Department of Pathology, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
| | - Dinko Franceschi
- Department of Radiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
| | - Reza Dashti
- Department of Neurological Surgery, Renaissance School of Medicine at Stony Brook University, Stony Brook, United States
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Yuen CA, Pekmezci M, Bao S, Kong XT. Metastatic glioblastoma to the lungs: a case report and literature review. CNS Oncol 2024; 13:2351789. [PMID: 38864820 PMCID: PMC11172249 DOI: 10.1080/20450907.2024.2351789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 05/02/2024] [Indexed: 06/13/2024] Open
Abstract
Glioblastoma is the most common malignant primary brain tumor. Despite its infiltrative nature, extra-cranial glioblastoma metastases are rare. We present a case of a 63-year-old woman with metastatic glioblastoma in the lungs. Sarcomatous histology, a reported risk factor for disseminated disease, was found. Genomic alterations of TP53 mutation, TERT mutation, PTEN mutation, and +7/-10 were also uncovered. Early evidence suggests these molecular aberrations are common in metastatic glioblastoma. Treatment with third-line lenvatinib resulted in a mixed response. This case contributes to the growing body of evidence for the role of genomic alterations in predictive risk in metastatic glioblastoma. There remains an unmet need for treatment of metastatic glioblastoma.
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Affiliation(s)
- Carlen A Yuen
- Department of Neurology, Division of Neuro-Oncology, University of California, Irvine, CA92868, USA
| | - Melike Pekmezci
- Department of Pathology, University of California, San Francisco, CA94143, USA
| | - Silin Bao
- Department of Internal Medicine, Division of Neurosciences, Community Regional Medical Center, Fresno, CA93721, USA
| | - Xiao-Tang Kong
- Department of Neurology, Division of Neuro-Oncology, University of California, Irvine, CA92868, USA
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De Martino L, Picariello S, Russo C, Errico ME, Spennato P, Papa MR, Normanno N, Scimone G, Colafati GS, Cacchione A, Mastronuzzi A, Massimino M, Cinalli G, Quaglietta L. Extra-neural metastases in pediatric diffuse midline gliomas, H3 K27-altered: presentation of two cases and literature review. Front Mol Neurosci 2023; 16:1152430. [PMID: 37547920 PMCID: PMC10398382 DOI: 10.3389/fnmol.2023.1152430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 06/26/2023] [Indexed: 08/08/2023] Open
Abstract
Introduction Pediatric diffuse midline gliomas (DMG), H3 K27- altered, are the most aggressive pediatric central nervous system (CNS) malignancies. Disease outcome is dismal with a median survival of less than one year. Extra-neural metastases are an unusual occurrence in DMG and have been rarely described. Methods and results Here, we report on two pediatric patients affected by DMG with extra-neural dissemination. Their clinical, imaging, and molecular characteristics are reported here. An 11-year-old male 5 months after the diagnosis of diffuse intrinsic pontine glioma (DIPG) developed metastatic osseous lesions confirmed with computed tomography (CT) guided biopsy of the left iliac bone. The patient died one month after the evidence of metastatic progression. Another 11-year-old female was diagnosed with a cerebellar H3K27- altered DMG. After six months, she developed diffuse sclerotic osseous lesions. A CT-guided biopsy of the right iliac bone was non-diagnostic. She further developed multifocal chest and abdominal lymphadenopathy and pleural effusions. Droplet digital polymerase chain reaction (ddPCR) on pleural effusion revealed the presence of H3.3A mutation (c.83A>T, p.K28M). The patient died 24 months after the diagnosis of DMG and 3 months after the evidence of metastatic pleural effusion. Discussion Extra-neural metastasis of DMG is a rare event and no standard therapy exists. An accurate and early diagnosis is necessary in order to develop a personalized plan of treatment. Further research is needed to gain further insights into the molecular pathology of DMG, H3K27- altered and improve the quality of life and the final outcome of patients with this deadly disease.
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Affiliation(s)
- Lucia De Martino
- Neurooncology Unit, Department of Pediatric Oncology, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Stefania Picariello
- Neurooncology Unit, Department of Pediatric Oncology, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Carmela Russo
- Neuroradiology Unit, Department of Neurosciences, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Maria Elena Errico
- Patology Unit, Department of Pathology, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Pietro Spennato
- Pediatric Neurosurgery Unit, Department of Pediatric Neurosciences, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Maria Rosaria Papa
- Department of Paediatric Haematology/Oncology, Cell Therapy, A.O.R.N. Santobono-Pausilipon, Naples, Italy
| | - Nicola Normanno
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS "Fondazione G. Pascale", Naples, Italy
| | - Giuseppe Scimone
- Radiotherapy Unit, AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy
| | - Giovanna Stefania Colafati
- Oncological Neuroradiology Unit, Department of Imaging, Istituto di Ricovero e Cura a Carattere Scientifico, Bambino Gesù Children's Hospital, Rome, Italy
| | - Antonella Cacchione
- Neurooncology Unit, Department of Paediatric Haematology/Oncology, Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico, Bambino Gesù Children's Hospital, Rome, Italy
| | - Angela Mastronuzzi
- Neurooncology Unit, Department of Paediatric Haematology/Oncology, Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico, Bambino Gesù Children's Hospital, Rome, Italy
| | - Maura Massimino
- Pediatric Oncology, Fondazione IRCCS-Istituto Nazionale dei Tumori, Milan, Italy
| | - Giuseppe Cinalli
- Pediatric Neurosurgery Unit, Department of Pediatric Neurosciences, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Lucia Quaglietta
- Neurooncology Unit, Department of Pediatric Oncology, Santobono-Pausilipon Children's Hospital, Naples, Italy
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5
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Lessi F, Morelli M, Franceschi S, Aretini P, Menicagli M, Marranci A, Pasqualetti F, Gambacciani C, Pieri F, Grimod G, Zucchi V, Cupini S, Di Stefano AL, Santonocito OS, Mazzanti CM. Innovative Approach to Isolate and Characterize Glioblastoma Circulating Tumor Cells and Correlation with Tumor Mutational Status. Int J Mol Sci 2023; 24:10147. [PMID: 37373295 DOI: 10.3390/ijms241210147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/08/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
Circulating tumor cells (CTCs) are one of the most important causes of tumor recurrence and distant metastases. Glioblastoma (GBM) has been considered restricted to the brain for many years. Nevertheless, in the past years, several pieces of evidence indicate that hematogenous dissemination is a reality, and this is also in the caseof GBM. Our aim was to optimize CTCs' detection in GBM and define the genetic background of single CTCs compared to the primary GBM tumor and its recurrence to demonstrate that CTCs are indeed derived from the parental tumor. We collected blood samples from a recurrent IDH wt GBM patient. We genotyped the parental recurrent tumor tissue and the respective primary GBM tissue. CTCs were analyzed using the DEPArray system. CTCs Copy Number Alterations (CNAs) and sequencing analyses were performed to compare CTCs' genetic background with the same patient's primary and recurrent GBM tissues. We identified 210 common mutations in the primary and recurrent tumors. Among these, three somatic high-frequency mutations (in PRKCB, TBX1, and COG5 genes) were selected to investigate their presence in CTCs. Almost all sorted CTCs (9/13) had at least one of the mutations tested. The presence of TERT promoter mutations was also investigated and C228T variation was found in parental tumors and CTCs (C228T heterozygous and homozygous, respectively). We were able to isolate and genotype CTCs from a patient with GBM. We found common mutations but also exclusive molecular characteristics.
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Affiliation(s)
- Francesca Lessi
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Mariangela Morelli
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Sara Franceschi
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Paolo Aretini
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Michele Menicagli
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Andrea Marranci
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
| | - Francesco Pasqualetti
- Department of Radiation Oncology, Azienda Ospedaliera Universitaria Pisana, University of Pisa, 56122 Pisa, Italy
| | - Carlo Gambacciani
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Francesco Pieri
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Gianluca Grimod
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Vanna Zucchi
- Division of Pathology, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Samanta Cupini
- Division of Oncology, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Anna Luisa Di Stefano
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
- Neurology Department, Foch Hospital, 92150 Suresnes, France
| | - Orazio Santo Santonocito
- Division of Neurosurgery, Spedali Riuniti di Livorno-USL Toscana Nord-Ovest, 57124 Livorno, Italy
| | - Chiara Maria Mazzanti
- Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, Italy
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6
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Ammendola S, Barresi V, Bariani E, Girolami I, D’Errico A, Brunelli M, Cardillo M, Lombardini L, Carraro A, Boggi U, Cain O, Neil D, Eccher A. Risk factors of extraneural spreading in astrocytomas and oligodendrogliomas in donors with gliomas: A systematic review. World J Transplant 2022; 12:131-141. [PMID: 35979537 PMCID: PMC9258267 DOI: 10.5500/wjt.v12.i6.131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/25/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria. The risk assessment of tumor transmission via organ transplant in primary brain tumors is primarily based on the assessment of tumor histotype and grade. Previous surgeries, chemo-/radiotherapy, and ventriculo-peritoneal shunt placement can lead to a disruption of the blood-brain barrier, concurring to an increase in the transmission risk. AIM To investigate the role of tumor transmission risk factors in donors with oligodendrogliomas and astrocytomas. METHODS We searched PubMed and EMBASE databases for studies reporting extraneural spreading of oligodendrogliomas and astrocytomas and extracted clinical-pathological data on the primary tumor histotype and grade, the elapsed time from the diagnosis to the onset of metastases, sites and number of metastases, prior surgeries, prior radiotherapy and/or chemotherapy, ventriculo-atrial or ventriculo-peritoneal shunt placement, and the presence of isocitrate dehydrogenase 1/2 mutation and 1p/19q codeletion. Statistical analysis was performed using R software. Statistical correlation between chemotherapy or radiotherapy and the presence of multiple extra-central nervous system metastases was analyzed using χ 2 and Fischer exact test. The Kaplan-Meier method was used to evaluate the presence of a correlation between the metastasis-free time and: (1) Localization of metastases; (2) The occurrence of intracranial recurrences; and (3) The occurrence of multiple metastases. RESULTS Data on a total of 157 patients were retrieved. The time from the initial diagnosis to metastatic spread ranged from 0 to 325 mo in patients with oligodendrogliomas and 0 to 267 mo in those with astrocytomas. Respectively, 19% and 39% of patients with oligodendroglioma and astrocytoma did not receive any adjuvant therapy. The most frequent metastatic sites were bone, bone marrow, and lymph nodes. The lungs and the liver were the most commonly involved visceral sites. There was no significant correlation between the occurrence of multiple metastases and the administration of adjuvant chemo-/radiotherapy. Patients who developed intracranial recurrences/metastases had a significantly longer extraneural metastasis-free time compared to those who developed extraneural metastases in the absence of any intra- central nervous system spread. CONCLUSION A long follow-up time does not exclude the presence of extraneural metastases. Therefore, targeted imaging of bones and cervical lymph nodes may improve safety in the management of these donors.
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Affiliation(s)
- Serena Ammendola
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona 37134, Italy
| | - Valeria Barresi
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona 37134, Italy
| | - Elena Bariani
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona 37134, Italy
| | - Ilaria Girolami
- Division of Pathology, Central Hospital, Bolzano 39100, Italy
| | - Antonia D’Errico
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna 40138, Italy
| | - Matteo Brunelli
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona 37134, Italy
| | - Massimo Cardillo
- National Transplant Center, Istituto Superiore di Sanità, Rome 00161, Italy
| | - Letizia Lombardini
- National Transplant Center, Istituto Superiore di Sanità, Rome 00161, Italy
| | - Amedeo Carraro
- General Surgery and Liver Transplant Unit, Verona University Hospital, Verona 37126, Italy
| | - Ugo Boggi
- Division of General and Transplant Surgery, Pisa University Hospital, Pisa 56126, Italy
| | - Owen Cain
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Desley Neil
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Albino Eccher
- Department of Pathology and Diagnostics, Verona University Hospital, Verona 37126, Italy
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7
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Preoperative Thrombocytosis is Not Associated with Overall Survival in 309 Glioblastoma Patients. J Neurol Surg A Cent Eur Neurosurg 2021; 83:548-554. [PMID: 34897615 DOI: 10.1055/s-0041-1739501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND In recent years, a correlation of thrombocytosis and a worse prognosis was shown for many solid cancers, including glioblastoma multiforme (GBM). METHODS A retrospective review was performed for all patients with a histologically proven and first-diagnosed GBM between 2005 and 2015 in our department. Clinical and paraclinical parameters were acquired from patient documentation and structured for subsequent data analysis. The association of potential risk factors with overall survival was assessed using the Kaplan-Meier survival analysis and Cox regression. RESULTS The present study includes 309 patients first diagnosed with primary GBM. Our analyses validate well-known risk factors of a decreased overall survival such as higher patient age, a larger preoperative tumor volume, Karnofsky performance status, extent of resection, tumor localization, and adjuvant treatment. However, no correlation was observed between a preoperative thrombocytosis, the mean platelet volume, leucocyte count, activated partial thromboplastin time (apTT), fibrinogen level, and acetylsalicylic acid 100 co-medication. Patients with preoperative hemoglobin below 7.5 mmol/L had decreased overall survival. CONCLUSION The present study, enrolling the largest numbers of patients assessing this topic to date, did not find any association between a preoperative thrombocytosis and overall survival in 309 patients with GBM.
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8
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Zhang X, Katsakhyan L, LiVolsi VA, Roth JJ, Rassekh CH, Bagley SJ, Nasrallah MP. TP53 Mutation and Extraneural Metastasis of Glioblastoma: Insights From an Institutional Experience and Comprehensive Literature Review. Am J Surg Pathol 2021; 45:1516-1526. [PMID: 34366423 DOI: 10.1097/pas.0000000000001762] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Extraneural metastases of glioblastoma (GBM), although rare, are becoming an increasingly recognized occurrence. Currently, the biological mechanism underlying this rare occurrence is not understood. To explore the potential genomic drivers of extraneural metastasis in GBM, we present the molecular features of 4 extraneural metastatic GBMs, along with a comprehensive review and analysis of previously reported cases that had available molecular characterization. In addition to our 4 cases, 42 patients from 35 publications are reviewed. To compare the molecular profiles between GBM cases with extraneural metastasis and the general GBM population, genomic data from GBM samples in The Cancer Genome Atlas (TCGA) database were also analyzed. We found that 64.5% (20/31) of the cases with extraneural metastasis that were tested for TP53 changes had at least 1 TP53 pathogenic variant detected in either 1 or both primary and metastatic tumors. In contrast, TP53 mutation was significantly less frequent in the unselected GBM from TCGA (22.6%, 56/248) (P=0.000). In addition, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was more common in unselected TCGA GBM cases (48.6%, 170/350) than in cases with extraneural metastasis (31.8%, 7/22), although not statistically significant. Although isocitrate dehydrogenase (IDH) mutation is a rare occurrence in high-grade astrocytomas, IDH-mutant grade 4 astrocytomas are at least as likely to metastasize as IDH wild-type GBMs; 3 metastatic cases definitively harbored an IDH1 (p.R132H) mutation in our analysis. Our findings not only provide potential biomarkers for earlier screening of extraneural metastasis, but could also suggest clues to understanding biological mechanisms underlying GBM metastasis, and for the development of therapeutic modalities.
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Affiliation(s)
| | | | | | | | | | - Stephen J Bagley
- Hematology Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
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9
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Zhu M, Bian Y, Jiang J, Lei T, Shu K. Rapid screening for safety of donation from donors with central nervous system malignancies. Medicine (Baltimore) 2020; 99:e22808. [PMID: 33285676 PMCID: PMC7717844 DOI: 10.1097/md.0000000000022808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
With the increasing demand on organ transplants, it has become a common practice to include patients with primary central nervous system (CNS) malignancies as donors given the suggested low probability metastatic spread outside of the CNS. However, an extra-CNS spread of the disease cannot be excluded raising potential risks of cancer transmission from those donors. In order to balance between the risk of donor-derived disease transmission and the curative benefit for the recipient, a careful donor and organ selection is important. We performed a literature research and summarized all reported studies of organ transplants from donors suffered from primary CNS malignancies and determined the risk of tumor transmission to recipients. There were 22 cases of transplant-transmitted CNS tumors onto recipients since 1976. The association risks of cancer transmission were attributed to donor tumor histology, disruption of the blood-brain barrier, cerebrospinal fluid extra-CNS, and false diagnosis of primary intracranial tumor as well as the molecular properties of the primary tumor such as the existence of EGFR-amplification. The association risks and features of CNS tumors transmission recipients indicated that we need to reassess our thresholds for the potential fatal consequences of these donors.
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Affiliation(s)
| | | | - Jipin Jiang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China
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10
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Sistigu A, Musella M, Galassi C, Vitale I, De Maria R. Tuning Cancer Fate: Tumor Microenvironment's Role in Cancer Stem Cell Quiescence and Reawakening. Front Immunol 2020; 11:2166. [PMID: 33193295 PMCID: PMC7609361 DOI: 10.3389/fimmu.2020.02166] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 08/10/2020] [Indexed: 12/12/2022] Open
Abstract
Cancer cell dormancy is a common feature of human tumors and represents a major clinical barrier to the long-term efficacy of anticancer therapies. Dormant cancer cells, either in primary tumors or disseminated in secondary organs, may reawaken and relapse into a more aggressive disease. The mechanisms underpinning dormancy entry and exit strongly resemble those governing cancer cell stemness and include intrinsic and contextual cues. Cellular and molecular components of the tumor microenvironment persistently interact with cancer cells. This dialog is highly dynamic, as it evolves over time and space, strongly cooperates with intrinsic cell nets, and governs cancer cell features (like quiescence and stemness) and fate (survival and outgrowth). Therefore, there is a need for deeper insight into the biology of dormant cancer (stem) cells and the mechanisms regulating the equilibrium quiescence-versus-proliferation are vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. Here, we review and discuss microenvironmental regulations of cancer dormancy and its parallels with cancer stemness, and offer insights into the therapeutic strategies adopted to prevent a lethal recurrence, by either eradicating resident dormant cancer (stem) cells or maintaining them in a dormant state.
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Affiliation(s)
- Antonella Sistigu
- Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy.,Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Martina Musella
- Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Claudia Galassi
- Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Ilio Vitale
- IIGM - Italian Institute for Genomic Medicine, c/o IRCSS Candiolo (TO), Candiolo, Italy.,Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy
| | - Ruggero De Maria
- Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy.,Fondazione Policlinico Universitario "A. Gemelli" - IRCCS, Rome, Italy
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11
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Rodrigues LF, Camacho AHDS, Spohr TCLDSE. Secondary glioblastoma metastasis outside the central nervous system in a young HIV-infected patient. Ther Adv Med Oncol 2020; 12:1758835920923432. [PMID: 32489434 PMCID: PMC7238297 DOI: 10.1177/1758835920923432] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 04/10/2020] [Indexed: 12/17/2022] Open
Abstract
Glioblastoma is the most common adult primary brain tumor that occurs in the
central nervous system and is characterized by rapid growth and diffuse
invasiveness with respect to the adjacent brain parenchyma, which renders
surgical resection inefficient. Although it is a highly infiltrative tumor, it
is rarely disseminated beyond the central nervous system, wherein extracranial
metastasis is a unique but rare manifestation of this kind of tumor. It is very
common for acquired immunodeficiency syndrome (AIDS) patients to be infected
with the human immunodeficiency virus (HIV), which suggests that a possible
association between HIV infection and tumor development exists. In this paper,
we present a new case of a young patient’s HIV-associated glioblastoma, with
glioblastoma metastasis within the T9 vertebral body and lymph nodes in the
anterior neck tissue. Initially, the patient was diagnosed with a grade III
plastic astrocytoma. The patient lived a normal life for a year while being
treated with temozolomide, radiotherapy, and highly active antiretroviral
therapy. However, the tumor quickly evolved into a glioblastoma. We believe that
the drastic progression of the tumor from a grade III anaplastic astrocytoma to
a metastatic glioblastoma is due to the HIV infection that the patient had
acquired, which contributed to a weakened immune system, thus accelerating
progression of the cancer.
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12
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Mohme M, Maire CL, Schliffke S, Joosse SA, Alawi M, Matschke J, Schüller U, Dierlamm J, Martens T, Pantel K, Riethdorf S, Lamszus K, Westphal M. Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape. Acta Neuropathol Commun 2020; 8:28. [PMID: 32151286 PMCID: PMC7063778 DOI: 10.1186/s40478-020-00906-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 02/29/2020] [Indexed: 12/22/2022] Open
Abstract
Peripheral metastases of glioblastoma (GBM) are very rare despite the ability of GBM cells to pass through the blood-brain barrier and be disseminated through the peripheral blood. Here, we describe a detailed genetic and immunological characterization of a GBM metastasis in the skeleton, which occurred during anti-PD-1 immune checkpoint therapy. We performed whole genome sequencing (WGS) and 850 K methylation profiling of the primary and recurrent intracranial GBM as well as one of the bone metastases. Copy number alterations (CNA) and mutational profiles were compared to known genomic alterations in the TCGA data base. In addition, immunophenotyping of the peripheral blood was performed. The patient who was primarily diagnosed with IDH-wildtype GBM. After the resection of the first recurrence, progressive intracranial re-growth was again detected, and chemotherapy was replaced by PD-1 checkpoint inhibition, which led to a complete intracranial remission. Two months later MR-imaging revealed multiple osseous lesions. Biopsy confirmed the GBM origin of the skeleton metastases. Immunophenotyping reflected the effective activation of a peripheral T-cell response, with, however, increase of regulatory T cells during disease progression. WGS sequencing demonstrated distinct genomic alterations of the GBM metastasis, with gains along chromosomes 3 and 9 and losses along chromosome 4, 10, and 11. Mutational analysis showed mutations in potentially immunologically relevant regions. Additionally, we correlated tumour-infiltrating lymphocyte and microglia presence to the occurrence of circulating tumour cells (CTCs) in a larger cohort and found a decreased infiltration of cytotoxic T cells in patients positive for CTCs. This study exemplifies that the tumour microenvironment may dictate the response to immune checkpoint therapy. In addition, our study highlights the fact that despite an effective control of intracranial GBM, certain tumour clones have the ability to evade the tumour-specific T-cell response and cause progression even outside of the CNS.
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13
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Mishinov SV, Budnik AY, Stupak VV, Leplina OY, Tyrinova TV, Ostanin AA, Chernykh ER. Autologous and Pooled Tumor Lysates in Combined Immunotherapy of Patients with Glioblastoma. Sovrem Tekhnologii Med 2020; 12:34-41. [PMID: 34513051 PMCID: PMC8353674 DOI: 10.17691/stm2020.12.2.04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Indexed: 11/14/2022] Open
Abstract
Although major progress has been made in the standard treatment for glioblastomas, encompassing the maximal surgical resection, chemotherapy and radiation therapy, it is possible to increase survival rates significantly only in a few patients. Therefore, it is necessary to explore new therapeutic modalities, one of which is immunotherapy. The aim of the study was to evaluate the efficacy of the combined use of autologous and pooled tumor lysates in comprehensive treatment of patients with glioblastoma.
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Affiliation(s)
- S V Mishinov
- Senior Researcher, Novosibirsk Scientific Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan of the Ministry of Health of the Russian Federation, 17 Frunze St., Novosibirsk, 630091, Russia
| | - A Ya Budnik
- Resident, Novosibirsk Scientific Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan of the Ministry of Health of the Russian Federation, 17 Frunze St., Novosibirsk, 630091, Russia
| | - V V Stupak
- Professor, Head of Neurosurgery Research Department, Novosibirsk Scientific Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan of the Ministry of Health of the Russian Federation, 17 Frunze St., Novosibirsk, 630091, Russia
| | - O Yu Leplina
- Leading Researcher, Laboratory of Cellular Immunotherapy, Scientific Research Institute of Fundamental and Clinical Immunology, 14 Yadrintsevskaya St., Novosibirsk, 630099, Russia
| | - T V Tyrinova
- Researcher, Laboratory of Cellular Immunotherapy, Scientific Research Institute of Fundamental and Clinical Immunology, 14 Yadrintsevskaya St., Novosibirsk, 630099, Russia
| | - A A Ostanin
- Professor, Chief Researcher, Laboratory of Cellular Immunotherapy, Scientific Research Institute of Fundamental and Clinical Immunology, 14 Yadrintsevskaya St., Novosibirsk, 630099, Russia
| | - E R Chernykh
- Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Cellular Immunotherapy, Scientific Research Institute of Fundamental and Clinical Immunology, 14 Yadrintsevskaya St., Novosibirsk, 630099, Russia
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14
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Bang-Christensen SR, Pedersen RS, Pereira MA, Clausen TM, Løppke C, Sand NT, Ahrens TD, Jørgensen AM, Lim YC, Goksøyr L, Choudhary S, Gustavsson T, Dagil R, Daugaard M, Sander AF, Torp MH, Søgaard M, Theander TG, Østrup O, Lassen U, Hamerlik P, Salanti A, Agerbæk MØ. Capture and Detection of Circulating Glioma Cells Using the Recombinant VAR2CSA Malaria Protein. Cells 2019; 8:E998. [PMID: 31466397 PMCID: PMC6769911 DOI: 10.3390/cells8090998] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/21/2019] [Accepted: 08/25/2019] [Indexed: 01/04/2023] Open
Abstract
Diffuse gliomas are the most common primary malignant brain tumor. Although extracranial metastases are rarely observed, recent studies have shown the presence of circulating tumor cells (CTCs) in the blood of glioma patients, confirming that a subset of tumor cells are capable of entering the circulation. The isolation and characterization of CTCs could provide a non-invasive method for repeated analysis of the mutational and phenotypic state of the tumor during the course of disease. However, the efficient detection of glioma CTCs has proven to be challenging due to the lack of consistently expressed tumor markers and high inter- and intra-tumor heterogeneity. Thus, for this field to progress, an omnipresent but specific marker of glioma CTCs is required. In this article, we demonstrate how the recombinant malaria VAR2CSA protein (rVAR2) can be used for the capture and detection of glioma cell lines that are spiked into blood through binding to a cancer-specific oncofetal chondroitin sulfate (ofCS). When using rVAR2 pull-down from glioma cells, we identified a panel of proteoglycans, known to be essential for glioma progression. Finally, the clinical feasibility of this work is supported by the rVAR2-based isolation and detection of CTCs from glioma patient blood samples, which highlights ofCS as a potential clinical target for CTC isolation.
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Affiliation(s)
- Sara R Bang-Christensen
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
- VarCT Diagnostics, 2200 Copenhagen, Denmark
| | - Rasmus S Pedersen
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Marina A Pereira
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Thomas M Clausen
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Caroline Løppke
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Nicolai T Sand
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Theresa D Ahrens
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Amalie M Jørgensen
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Yi Chieh Lim
- Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
| | - Louise Goksøyr
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Swati Choudhary
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Tobias Gustavsson
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Robert Dagil
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Mads Daugaard
- Department of Urologic Sciences, University of British Columbia, and Vancouver Prostate Centre, BC V6H 3Z6 Vancouver, Canada
| | - Adam F Sander
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Mathias H Torp
- Centre for Genomic Medicine, Copenhagen University Hospital, 2100 Copenhagen, Denmark
| | - Max Søgaard
- ExpreS2ion Biotechnologies, SCION-DTU Science Park, 2970 Hørsholm, Denmark
| | - Thor G Theander
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
| | - Olga Østrup
- Centre for Genomic Medicine, Copenhagen University Hospital, 2100 Copenhagen, Denmark
| | - Ulrik Lassen
- Department of Oncology, Copenhagen University Hospital, 2100 Copenhagen, Denmark
| | - Petra Hamerlik
- Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
| | - Ali Salanti
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark.
| | - Mette Ø Agerbæk
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark.
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15
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Goddard ET, Bozic I, Riddell SR, Ghajar CM. Dormant tumour cells, their niches and the influence of immunity. Nat Cell Biol 2018; 20:1240-1249. [PMID: 30361702 DOI: 10.1038/s41556-018-0214-0] [Citation(s) in RCA: 123] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 09/17/2018] [Indexed: 02/07/2023]
Abstract
Despite increased focus on the clinical relevance of dormant metastatic disease, our understanding of dormant niches, mechanisms underlying emergence from dormancy, and the immune system's role in this phenomenon, remains in its infancy. Here, we discuss key work that has shaped our current understanding of these topics. Because tumour dormancy provides a unique therapeutic window to prevent metastatic disease, we discuss on-going clinical trials and weigh the potential for immunotherapy to eradicate dormant disease.
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Affiliation(s)
- Erica T Goddard
- Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Ivana Bozic
- Department of Applied Mathematics, University of Washington, Seattle, WA, USA
| | - Stanley R Riddell
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Cyrus M Ghajar
- Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. .,Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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16
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Arrieta VA, Cacho-Díaz B, Zhao J, Rabadan R, Chen L, Sonabend AM. The possibility of cancer immune editing in gliomas. A critical review. Oncoimmunology 2018; 7:e1445458. [PMID: 29900059 PMCID: PMC5993488 DOI: 10.1080/2162402x.2018.1445458] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 02/20/2018] [Accepted: 02/20/2018] [Indexed: 01/21/2023] Open
Abstract
The relationship between anti-tumoral immunity and cancer progression is complex. Recently, immune editing has emerged as a model to explain the interplay between the immune system and the selection of genetic alterations in cancer. In this model, the immune system selects cancer cells that grow as these are fit to escape immune surveillance during tumor development. Gliomas and glioblastoma, the most aggressive and most common of all primary malignant brain tumors are genetically heterogeneous, are relatively less antigenic, and are less responsive to immunotherapy than other cancers. In this review, we provide an overview of the relationship between glioma´s immune suppressive features, anti-tumoral immunity and cancer genomics. In this context, we provide a critical discussion of evidence suggestive of immune editing in this disease and discuss possible alternative explanations for these findings.
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Affiliation(s)
- Víctor A Arrieta
- PECEM, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Junfei Zhao
- Department of Systems Biology, Herbert Irving Comprehensive Center, Columbia University, New York City, New York, USA
| | - Raul Rabadan
- Department of Systems Biology, Herbert Irving Comprehensive Center, Columbia University, New York City, New York, USA
| | - Li Chen
- Department of Neurosurgery, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
| | - Adam M Sonabend
- Department of Neurosurgery, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
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17
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Frappaz D, Le Rhun E, Dagain A, Averland B, Bauchet L, Faure A, Guillaume C, Zouaoui S, Provot F, Vachiery F, Taillandier L, Hoang-Xuan K. [Recommendations for the organ donation from patients with brain or medullary primitive tumors on behalf of the Association of the Neuro-oncologists of French Expression (ANOCEF) and the Club of Neuro-oncology of the French Society of Neurosurgery]. Bull Cancer 2017; 104:771-788. [PMID: 28549594 DOI: 10.1016/j.bulcan.2017.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 02/24/2017] [Accepted: 02/27/2017] [Indexed: 11/18/2022]
Abstract
Requests of organs to be transplanted increase. As a matter of urgency, it is not always easy to decide if a patient carrier of a brain tumor can be candidate in the donation. After a review of the literature, the members of the Association of the Neuro-oncologists of French Expression (ANOCEF) and the Club of Neuro-oncology of the French Society of Neurosurgery propose consensual recommendations in case of donor carrier of primitive tumor intra-cranial or intra-medullary. A contact with the neuro-oncologist/neurosurgeon will allow to discuss the indication in case of glioma of grade I/II/III, according to the grade, the current status (absence of progressive disease), the number of surgeries and of lines of treatment. The taking is disadvised in case of glioma of grade IV (glioblastoma), of lymphoma or meningioma of grade III. No contraindication for the meningiomas of grade I, and individual discussion for the meningiomas of grade II. It is advisable to remain careful in case of hemangiopericytoma and of meningeal solitary fibrous tumor. The patients in first complete remission of a medulloblastoma or intra-cranial primitive germinoma seem good candidates for the taking of organ if the follow-up is of at least 10 years (3 years for non germinomas). In every case, a multidisciplinary discussion is desirable when it is materially possible.
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Affiliation(s)
- Didier Frappaz
- Centre Léon-Bérard, 28, rue Laennec, 69673 Lyon, France.
| | - Emilie Le Rhun
- University hospital, department of neurosurgery, neuro-oncology, 59037 Lille, France; Oscar-Lambret center, department of medical oncology, Breast unit, 59037 Lille, France; Lille university, Inserm U-1192, laboratoire de protéomique, réponse inflammatoire, spectrométrie de masse (PRISM), 59037 Lille, France
| | - Arnaud Dagain
- HIA Sainte-Anne, 2, boulevard Sainte-Anne, 83800 Toulon, France
| | - Benoît Averland
- Agence de la biomédecine, 1, avenue du Stade de France, 93210 Saint-Denis, France
| | - Luc Bauchet
- CHRU Gui-de-Chauliac, CHU de Montpellier, 80, avenue Augustin-Fliche, 34000 Montpellier, France
| | | | | | - Sonia Zouaoui
- CHRU Gui-de-Chauliac, CHU de Montpellier, 80, avenue Augustin-Fliche, 34000 Montpellier, France
| | | | - Florence Vachiery
- CHRU Gui-de-Chauliac, CHU de Montpellier, 80, avenue Augustin-Fliche, 34000 Montpellier, France
| | - Luc Taillandier
- CHU de Nancy, 5, rue du Morvan, 54500 Vandoeuvre-lès-Nancy, France
| | - Khê Hoang-Xuan
- APHP, UMPC-Sorbonne universités, hôpital Pitié-Salpêtrière, 75013 Paris, France
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18
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Yang ZZ, Gao W, Liu YJ, Pang N, Qi XR. Delivering siRNA and Chemotherapeutic Molecules Across BBB and BTB for Intracranial Glioblastoma Therapy. Mol Pharm 2017; 14:1012-1022. [DOI: 10.1021/acs.molpharmaceut.6b00819] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Zhen-zhen Yang
- Beijing
Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System,
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Wei Gao
- Beijing
Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System,
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Yu-jie Liu
- Beijing
Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System,
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Ning Pang
- Beijing
Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System,
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Xian-rong Qi
- Beijing
Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System,
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
- State Key Laboratory of Natural and Biomimetic Drugs, 38 Xueyuan Road, Haidian District, Beijing 100191, China
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19
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Friberg S, Nyström A. Cancer Metastases: Early Dissemination and Late Recurrences. CANCER GROWTH AND METASTASIS 2015; 8:43-9. [PMID: 26640389 PMCID: PMC4664198 DOI: 10.4137/cgm.s31244] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 09/01/2015] [Accepted: 09/03/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Metastatic cells from a primary tumor can occur before the primary cancer is detected. Metastatic cells can also remain in the patient for many years after removal of the primary tumor without proliferating. These dormant malignant cells can awaken and cause recurrent disease decades after the primary treatment. The purpose of this article is to review the clinical evidence for early dissemination and late recurrences in human malignant tumors. We used the following definitions: dormancy of cells may be defined as a nonproliferating state or an arrest in the cell cycle that results in a prolonged G0 phase. If one accepts the term "late metastases" to indicate a period exceeding 10 years from the removal of the primary tumor, then the two malignancies in which this occurs most frequently are cutaneous malignant melanoma (CMM) and renal cell carcinoma (RCC). METHODS PubMed, Web of Science, and Scopus were searched with the keywords "metastases," "early dissemination," "late recurrences," "inadvertently transmitted cancer," "tumor growth rate," "dormancy," "circulating tumor cells," and "transplantation of cancer." RESULTS Several case reports of early dissemination and late recurrences of various types of malignancies were found. Analyses of the growth rates of several malignant tumors in the original host indicated that the majority of cancers had metastasized years before they were detected. CMM, RCC, and malignant glioblastoma were the three most common malignancies resulting from an organ transplantation. CMM and RCC were also the two most common malignancies that showed dormancy. In several cases of transplanted CMM and RCC, the donor did not have any known malignancy or had had the malignancy removed so long ago that the donor was regarded as cured. CONCLUSION (1) Metastases can frequently exist prior to the detection of the primary tumor. (2) Metastatic cells may reside in organs in the original host that are not usually the site of detectable secondary tumors, for example, the kidneys and heart. (3) Metastatic cells remain dormant for decades after the primary tumor has been removed. (4) Dormancy might be reversible and lead to late recurrences.
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Affiliation(s)
- Sten Friberg
- Swedish Medical Nanoscience Centre, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Andreas Nyström
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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20
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Awan M, Liu S, Sahgal A, Das S, Chao ST, Chang EL, Knisely JPS, Redmond K, Sohn JW, Machtay M, Sloan AE, Mansur DB, Rogers LR, Lo SS. Extra-CNS metastasis from glioblastoma: a rare clinical entity. Expert Rev Anticancer Ther 2015; 15:545-52. [DOI: 10.1586/14737140.2015.1028374] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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21
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Xie Q, Mittal S, Berens ME. Targeting adaptive glioblastoma: an overview of proliferation and invasion. Neuro Oncol 2014; 16:1575-84. [PMID: 25082799 DOI: 10.1093/neuonc/nou147] [Citation(s) in RCA: 197] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Glioblastoma is one of the most devastating cancers, in which tumor cell infiltration into surrounding normal brain tissue confounds clinical management. This review describes basic and translational research into glioma proliferation and invasion, in particular the phenotypic switch underlying a stochastic "go or grow" model of tumor cell behavior. We include recent progress in system genomics, cancer stem cell theory, and tumor-microenvironment interaction, from which novel therapeutic strategies may emerge for managing this malignant disease. We suggest that an effective therapeutic strategy should target both adaptive glioblastoma cells and the stroma-tumor interaction.
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Affiliation(s)
- Qian Xie
- Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan (Q.X.); Department of Neurosurgery (S.M.); Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (S.M.); Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, Arizona (M.E.B.)
| | - Sandeep Mittal
- Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan (Q.X.); Department of Neurosurgery (S.M.); Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (S.M.); Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, Arizona (M.E.B.)
| | - Michael E Berens
- Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan (Q.X.); Department of Neurosurgery (S.M.); Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (S.M.); Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, Arizona (M.E.B.)
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