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Pöhlmann J, Weller M, Marcellusi A, Grabe-Heyne K, Krott-Coi L, Rabar S, Pollock RF. High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma. Front Oncol 2024; 14:1368606. [PMID: 38571509 PMCID: PMC10987841 DOI: 10.3389/fonc.2024.1368606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 02/28/2024] [Indexed: 04/05/2024] Open
Abstract
Gliomas are a group of heterogeneous tumors that account for substantial morbidity, mortality, and costs to patients and healthcare systems globally. Survival varies considerably by grade, histology, biomarkers, and genetic alterations such as IDH mutations and MGMT promoter methylation, and treatment, but is poor for some grades and histologies, with many patients with glioblastoma surviving less than a year from diagnosis. The present review provides an introduction to glioma, including its classification, epidemiology, economic and humanistic burden, as well as treatment options. Another focus is on treatment recommendations for IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, and glioblastoma, which were synthesized from recent guidelines. While recommendations are nuanced and reflect the complexity of the disease, maximum safe resection is typically the first step in treatment, followed by radiotherapy and/or chemotherapy using temozolomide or procarbazine, lomustine, and vincristine. Immunotherapies and targeted therapies currently have only a limited role due to disappointing clinical trial results, including in recurrent glioblastoma, for which the nitrosourea lomustine remains the de facto standard of care. The lack of treatment options is compounded by frequently suboptimal clinical practice, in which patients do not receive adequate therapy after resection, including delayed, shortened, or discontinued radiotherapy and chemotherapy courses due to treatment side effects. These unmet needs will require significant efforts to address, including a continued search for novel treatment options, increased awareness of clinical guidelines, improved toxicity management for chemotherapy, and the generation of additional and more robust clinical and health economic evidence.
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Affiliation(s)
| | - Michael Weller
- Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
| | - Andrea Marcellusi
- Economic Evaluation and HTA (EEHTA)-Centre for Economic and International Studies (CEIS), Faculty of Economics, University of Rome “Tor Vergata”, Rome, Italy
| | | | | | - Silvia Rabar
- Covalence Research Ltd, Harpenden, United Kingdom
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Mohamed AA, Alshaibi R, Faragalla S, Mohamed Y, Lucke-Wold B. Updates on management of gliomas in the molecular age. World J Clin Oncol 2024; 15:178-194. [PMID: 38455131 PMCID: PMC10915945 DOI: 10.5306/wjco.v15.i2.178] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/06/2024] [Accepted: 01/25/2024] [Indexed: 02/20/2024] Open
Abstract
Gliomas are primary brain tumors derived from glial cells of the central nervous system, afflicting both adults and children with distinct characteristics and therapeutic challenges. Recent developments have ushered in novel clinical and molecular prognostic factors, reshaping treatment paradigms based on classification and grading, determined by histological attributes and cellular lineage. This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023. For adults, the therapeutic triad typically consists of surgical resection, chemotherapy, and radiotherapy. In contrast, pediatric gliomas, due to their diversity, require a more tailored approach. Although complete tumor excision can be curative based on the location and grade of the glioma, certain non-resectable cases demand a chemotherapy approach usually involving, vincristine and carboplatin. Additionally, if surgery or chemotherapy strategies are unsuccessful, Vinblastine can be used. Despite recent advancements in treatment methodologies, there remains a need of exploration in the literature, particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts. This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.
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Affiliation(s)
- Ali Ahmed Mohamed
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Rakan Alshaibi
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, United States
| | - Steven Faragalla
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Youssef Mohamed
- College of Osteopathic Medicine, Kansas City University, Joplin, MO 64804, United States
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32611, United States
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Willman M, Willman J, Figg J, Dioso E, Sriram S, Olowofela B, Chacko K, Hernandez J, Lucke-Wold B. Update for astrocytomas: medical and surgical management considerations. EXPLORATION OF NEUROSCIENCE 2023; 2:1-26. [PMID: 36935776 PMCID: PMC10019464 DOI: 10.37349/en.2023.00009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 12/10/2022] [Indexed: 02/25/2023]
Abstract
Astrocytomas include a wide range of tumors with unique mutations and varying grades of malignancy. These tumors all originate from the astrocyte, a star-shaped glial cell that plays a major role in supporting functions of the central nervous system (CNS), including blood-brain barrier (BBB) development and maintenance, water and ion regulation, influencing neuronal synaptogenesis, and stimulating the immunological response. In terms of epidemiology, glioblastoma (GB), the most common and malignant astrocytoma, generally occur with higher rates in Australia, Western Europe, and Canada, with the lowest rates in Southeast Asia. Additionally, significantly higher rates of GB are observed in males and non-Hispanic whites. It has been suggested that higher levels of testosterone observed in biological males may account for the increased rates of GB. Hereditary syndromes such as Cowden, Lynch, Turcot, Li-Fraumeni, and neurofibromatosis type 1 have been linked to increased rates of astrocytoma development. While there are a number of specific gene mutations that may influence malignancy or be targeted in astrocytoma treatment, O 6-methylguanine-DNA methyltransferase (MGMT) gene function is an important predictor of astrocytoma response to chemotherapeutic agent temozolomide (TMZ). TMZ for primary and bevacizumab in the setting of recurrent tumor formation are two of the main chemotherapeutic agents currently approved in the treatment of astrocytomas. While stereotactic radiosurgery (SRS) has debatable implications for increased survival in comparison to whole-brain radiotherapy (WBRT), SRS demonstrates increased precision with reduced radiation toxicity. When considering surgical resection of astrocytoma, the extent of resection (EoR) is taken into consideration. Subtotal resection (STR) spares the margins of the T1 enhanced magnetic resonance imaging (MRI) region, gross total resection (GTR) includes the margins, and supramaximal resection (SMR) extends beyond the margin of the T1 and into the T2 region. Surgical resection, radiation, and chemotherapy are integral components of astrocytoma treatment.
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Affiliation(s)
- Matthew Willman
- College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Jonathan Willman
- College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - John Figg
- College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Emma Dioso
- School of Medicine, University of Utah, Salt Lake City, UT 84132, USA
| | - Sai Sriram
- College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Bankole Olowofela
- College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Kevin Chacko
- College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Jairo Hernandez
- College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32608, USA
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Lin Q, Bao JH, Xue F, Qin JJ, Chen Z, Chen ZR, Li C, Yan YX, Fu J, Shen ZL, Chen XZ. The Risk of Heart Disease-Related Death Among Anaplastic Astrocytoma Patients After Chemotherapy: A SEER Population-Based Analysis. Front Oncol 2022; 12:870843. [PMID: 35795052 PMCID: PMC9251342 DOI: 10.3389/fonc.2022.870843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 05/12/2022] [Indexed: 11/13/2022] Open
Abstract
Background Despite improved overall survival outcomes, chemotherapy has brought concerns for heart disease–related death (HDRD) among cancer patients. The effect of chemotherapy on the risk of HDRD in anaplastic astrocytoma (AA) patients remains unclear. Methods We obtained 7,129 AA patients from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Kaplan–Meier and Cox regression analysis were conducted to evaluate the effect of chemotherapy on the HDRD risk. Based on the competing risk model, we calculated the cumulative incidences of HDRD and non-HDRD and performed univariate and multivariate regression analyses. Then, a 1:1 propensity score matching (PSM) was used to improve the comparability between AA patients with and without chemotherapy. Landmark analysis at 216 and 314 months was employed to minimize immortal time bias. Results AA patients with chemotherapy were at a lower HDRD risk compared to those patients without chemotherapy (adjusted HR=0.782, 95%CI=0.736–0.83, P<0.001). For competing risk regression analysis, the cumulative incidence of HDRD in non-chemotherapy exceeded HDRD in the chemotherapy group (P<0.001) and multivariable analysis showed a lower HDRD risk in AA patients with chemotherapy (adjusted SHR=0.574, 95%CI=0.331–0.991, P=0.046). In the PSM-after cohort, there were no significant association between chemotherapy and the increased HDRD risk (adjusted SHR=0.595, 95%CI=0.316−1.122, P=0.11). Landmark analysis showed that AA patients who received chemotherapy had better heart disease–specific survival than those in the non-chemotherapy group (P=0.007) at the follow-up time points of 216 months. No difference was found when the follow-up time was more than 216 months. Conclusion AA patients with chemotherapy are associated with a lower risk of HDRD compared with those without chemotherapy. Our findings may help clinicians make a decision about the management of AA patients and provide new and important evidence for applying chemotherapy in AA patients as the first-line treatment. However, more research is needed to confirm these findings and investigate the correlation of the risk of HDRD with different chemotherapy drugs and doses.
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Affiliation(s)
- Qi Lin
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jia-Hao Bao
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
| | - Fei Xue
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jia-Jun Qin
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhen Chen
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhong-Rong Chen
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chao Li
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yi-Xuan Yan
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
| | - Jin Fu
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- *Correspondence: Xian-Zhen Chen, ; Zhao-Li Shen, ; Jin Fu,
| | - Zhao-Li Shen
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- *Correspondence: Xian-Zhen Chen, ; Zhao-Li Shen, ; Jin Fu,
| | - Xian-Zhen Chen
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- *Correspondence: Xian-Zhen Chen, ; Zhao-Li Shen, ; Jin Fu,
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Detti B, Scoccianti S, Teriaca MA, Maragna V, Lorenzetti V, Lucidi S, Bellini C, Greto D, Desideri I, Livi L. Bevacizumab in recurrent high-grade glioma: a single institution retrospective analysis on 92 patients. Radiol Med 2021; 126:1249-1254. [PMID: 34081269 PMCID: PMC8370943 DOI: 10.1007/s11547-021-01381-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 05/20/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND High-grade gliomas are among the most aggressive central nervous system primary tumors, with a high risk of recurrence and a poor prognosis. Re-operation, re-irradiation, chemotherapy are options in this setting. No-best therapy has been established. Bevacizumab was approved on the basis of two Phase 2 trials that evaluated its efficacy in patients with recurrent glioblastoma. MATERIALS AND METHODS We have retrospectively review data of patients with high-grade glioma treated at our institution that undergone radiological or histological progression after at least one systemic treatment for recurrent disease. Bevacizumab was administered alone or in combination with chemotherapy until disease progression or unacceptable toxicity. Bevacizumab regimen was analyzed to assess PFS and OS. Histological, molecular and clinical features of the entire cohort were collected. RESULTS We reviewed data from 92 patients, treated from April 2009 to November 2019, with histologically confirmed diagnosis of high-grade gliomas and recurrent disease. A PFS of 55.2%, 22.9% and 9.6% was observed at 6, 12 and 24 months, respectively. Performance status, age at diagnosis (< 65 or > 65 ys.) and use of corticosteroids during bevacizumab therapy were strongly associated with PFS. The OS was 74.9% at 6 months, 31.7% at 12 months, 10.1% at 24 months. In our cohort, 51.1% were long-term responders (PFS > 6 months). Globally, bevacizumab treatment was well tolerated. CONCLUSION Our analysis confirms the efficacy of bevacizumab in recurrent high-grade glioma patients with an acceptable toxicity profile, in keeping with its known safety in the literature.
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Affiliation(s)
- Beatrice Detti
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Silvia Scoccianti
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Maria Ausilia Teriaca
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy.
| | - Virginia Maragna
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Victoria Lorenzetti
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Sara Lucidi
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Chiara Bellini
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Daniela Greto
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Isacco Desideri
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
| | - Lorenzo Livi
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 1, 50134, Florence, Italy
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An efficient and novel treatment regimen including temozolomide for medulloblastoma: a case study. JOURNAL OF RADIOTHERAPY IN PRACTICE 2021. [DOI: 10.1017/s1460396921000340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Abstract
Background:
The central nervous system (CNS) embryonal tumour is a rare malignancy reported in adults and more commonly in children. The most available treatments may cause neurological dysfunctions requiring clinical attention.
Case presented:
A 29-year-old male was referred with ataxia and diplopia, and brain imaging revealed a posterior fossa lesion suggesting medulloblastoma. The tumour and related symptoms were notably alleviated following treatment with dexamethasone. Following the recurrence of tumour, a biopsy and pathology report, the diagnosis of desmoplastic/nodular medulloblastoma was confirmed. The patient underwent 18 fractions of 180 cGy spine and whole-brain radiation therapy (RT). In addition, 5400 cGy irradiation in 12 fractions was given to the posterior fossa together with 2 mg/m2 intravenous vincristine (VCR) weekly over 6 weeks. Following a 3-week break, the patient was scheduled to receive 150 mg/m2/day temozolomide for 5 days, 2 mg VCR and 65 mg/m2/day cisplatin every 3 weeks for 8 cycles.
Conclusion:
The patient gained survival benefit to date (60 months since diagnosis) with favourable life quality. The promising response in this one exemplary case study proposes that a combined chemotherapy regimen including temozolomide, vincristine and cisplatin is an effective treatment choice for CNS embryonal tumours following RT; however, the further evaluation and a randomised clinical trial are needed.
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Hypoxia and Microvascular Alterations Are Early Predictors of IDH-Mutated Anaplastic Glioma Recurrence. Cancers (Basel) 2021; 13:cancers13081797. [PMID: 33918764 PMCID: PMC8068871 DOI: 10.3390/cancers13081797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/31/2021] [Accepted: 04/06/2021] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Anaplastic gliomas (AGs) are considered the most common and aggressive primary brain tumors of young adults with inevitable recurrence and treatment failure. The aim of this study was to investigate whether the imaging biomarkers of hypoxia, microvascular architecture and neovascularization activity can be of assistance to detect pathophysiological changes in the early developmental stages of isocitrate-dehydrogenase (IDH) mutated AG recurrence. We evaluated 142 physiological magnetic resonance imaging follow-up examinations as a part of the conventional magnetic resonance imaging (MRI) protocol in 60 AG patients after standard therapy. Physiological MRI biomarkers showed intensifying local tissue hypoxia 250 days prior to radiological recurrence with following upregulation of neovascularization activity 50 to 70 days later. Integration of physiological MRI in the monitoring of AG patients may be of clinical significance to make personalized decision of early tumor recurrence without an additional delay for multimodal therapy. Abstract Anaplastic gliomas (AG) represents aggressive brain tumors that often affect young adults. Although isocitrate-dehydrogenase (IDH) gene mutation has been identified as a more favorable prognostic factor, most IDH-mutated AG patients are confronted with tumor recurrence. Hence, increased knowledge about pathophysiological precursors of AG recurrence is urgently needed in order to develop precise diagnostic monitoring and tailored therapeutic approaches. In this study, 142 physiological magnetic resonance imaging (phyMRI) follow-up examinations in 60 AG patients after standard therapy were evaluated and magnetic resonance imaging (MRI) biomarker maps for microvascular architecture and perfusion, neovascularization activity, oxygen metabolism, and hypoxia calculated. From these 60 patients, 34 patients developed recurrence of the AG, and 26 patients showed no signs for AG recurrence during the study period. The time courses of MRI biomarker changes were analyzed regarding early pathophysiological alterations over a one-year period before radiological AG recurrence or a one-year period of stable disease for patients without recurrence, respectively. We detected intensifying local tissue hypoxia 250 days prior to radiological recurrence which initiated upregulation of neovascularization activity 50 to 70 days later. These changes were associated with a switch from an avascular infiltrative to a vascularized proliferative phenotype of the tumor cells another 30 days later. The dynamic changes of blood perfusion, microvessel density, neovascularization activity, and oxygen metabolism showed a close physiological interplay in the one-year period prior to radiological recurrence of IDH-mutated AG. These findings may path the wave for implementing both new MR-based imaging modalities for routine follow-up monitoring of AG patients after standard therapy and furthermore may support the development of novel, tailored therapy options in recurrent AG.
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Esteyrie V, Dehais C, Martin E, Carpentier C, Uro-Coste E, Figarella-Branger D, Bronniman C, Pouessel D, Ciron DL, Ducray F, Moyal ECJ, Network P. Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort. Oncologist 2021; 26:e838-e846. [PMID: 33524191 DOI: 10.1002/onco.13701] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 01/22/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear. METHODS In a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity. RESULTS The 4-year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38-0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41-0.97; p = .0348) in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30-1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001). CONCLUSION RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated. IMPLICATIONS FOR PRACTICE In the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH-mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH-mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression-free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH-mutant AA.
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Affiliation(s)
- Vincent Esteyrie
- Department of Radiotherapy, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France
| | - Caroline Dehais
- Department of Neurology 2-Mazarin, Public Assistance-Paris Hospitals (APHP), University Hospital Pitié Salpêtrière-Charles Foix, Paris, France
| | - Elodie Martin
- Department of Biostatistics, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France
| | - Catherine Carpentier
- Department of Neurology 2-Mazarin, Public Assistance-Paris Hospitals (APHP), University Hospital Pitié Salpêtrière-Charles Foix, Paris, France.,Brain and Spinal Cord Institute, Sorbonne University and University Hospital Pitié Salpêtrière-Charles Foix, National Institute of Health and Medical Research (INSERM), Centre National de la Recherche Scientifique (CNRS), Paris, France
| | - Emmanuelle Uro-Coste
- Department of Pathology and Histology-Cytology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France
| | - Dominique Figarella-Branger
- Department of Pathology and Neuropathology, Timone Hospital, Public Assistance-Marseille Hospitals (APHM), Marseille, France
| | - Charlotte Bronniman
- Department of Oncology, Saint-André Hospital, Centre Hospitalier Universitaire de Bordeaux 1, Bordeaux, France
| | - Damien Pouessel
- Department of Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France
| | - Delphine Larrieu Ciron
- Department of Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France
| | - François Ducray
- Department of Neuro-Oncology, Civil Hospices of Lyon, Pierre Wertheimer Hospital, Lyon, France
| | - Elizabeth Cohen-Jonathan Moyal
- Department of Radiotherapy, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France.,Université Paul Sabatier, Toulouse III, Toulouse, France
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Valiyaveettil D, Malik M, Joseph D, Ahmed SF, Kothwal SA. Prognostic factors and outcomes in anaplastic gliomas: An institutional experience. South Asian J Cancer 2020; 7:1-4. [PMID: 29600221 PMCID: PMC5865085 DOI: 10.4103/sajc.sajc_55_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Background: There is lack of clear evidence and treatment guidelines for anaplastic gliomas (AGs) with very few studies focusing exclusively on these patients. The aim of the study was to analyze the clinical profile and survival in these patients. Materials and Methods: Patients of AGs treated with radiation and concurrent ± adjuvant chemotherapy from January 2010 to December 2015 were analyzed. Statistical analysis was done using SPSS version 20 software. Results: A total of 100 patients were included in the study. The median age was 35 years (range 6–68 years). Eighty-four patients had follow-up details and were included for survival analysis. The 5-year overall survival (OS) was 58%. Age, presentation with seizures, and focal neurological deficit were not found to significantly influence survival. The 5-year survival for oligodendroglioma and astrocytoma was 69% and 52%, respectively. Patients with Karnofsky Performance Score (KPS) of ≥70 had a significantly better 5-year OS (65%) as compared to those with KPS <70 (33%) (P = 0.000). The use of adjuvant temozolomide (TMZ) showed longer 5-year OS of 67.7% compared to 36% in patients who did not receive adjuvant chemotherapy (P = 0.018). Patients receiving both concurrent and adjuvant TMZ showed longer 5-year OS (68.5% vs. 40%, P = 0.010). Twenty-two patients had recurrence with average time to recurrence being 37 months. Fourteen patients underwent salvage surgery and two patients received reirradiation. Conclusions: OS significantly correlated with KPS and receipt of concurrent and adjuvant chemotherapy with TMZ. Therefore, adjuvant radiation with concurrent and adjuvant TMZ should be the standard of care for AGs.
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Affiliation(s)
- Deepthi Valiyaveettil
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Monica Malik
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Deepa Joseph
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Syed Fayaz Ahmed
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Syed Akram Kothwal
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
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Nabors LB, Portnow J, Ahluwalia M, Baehring J, Brem H, Brem S, Butowski N, Campian JL, Clark SW, Fabiano AJ, Forsyth P, Hattangadi-Gluth J, Holdhoff M, Horbinski C, Junck L, Kaley T, Kumthekar P, Loeffler JS, Mrugala MM, Nagpal S, Pandey M, Parney I, Peters K, Puduvalli VK, Robins I, Rockhill J, Rusthoven C, Shonka N, Shrieve DC, Swinnen LJ, Weiss S, Wen PY, Willmarth NE, Bergman MA, Darlow SD. Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020; 18:1537-1570. [PMID: 33152694 DOI: 10.6004/jnccn.2020.0052] [Citation(s) in RCA: 279] [Impact Index Per Article: 55.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.
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Affiliation(s)
| | | | - Manmeet Ahluwalia
- 3Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Henry Brem
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | - Steven Brem
- 6Abramson Cancer Center at the University of Pennsylvania
| | | | - Jian L Campian
- 8Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | | | | | | | - Craig Horbinski
- 13Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | - Larry Junck
- 14University of Michigan Rogel Cancer Center
| | | | - Priya Kumthekar
- 13Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Manjari Pandey
- 19St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | | | | | - Vinay K Puduvalli
- 21The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Ian Robins
- 22University of Wisconsin Carbone Cancer Center
| | - Jason Rockhill
- 23Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | | | - Lode J Swinnen
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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11
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Abstract
PURPOSE OF REVIEW Low-grade gliomas (LGG) are a group of primary brain tumors that arise from supporting glial cells. They are characterized by a mutation in the isocitrate dehydrogenase (IDH) enzyme and include astrocytomas and oligodendrogliomas. They usually affect young adults, and their main treatment consists of surgical resection, followed by radiation and chemotherapy in selected patients. This article reviews recent research on the clinical and molecular aspects of the disease and innovative therapeutic modalities in the process. RECENT FINDINGS Newly identified clinical and molecular features are currently used in the classification of LGG and applied in treatment-planning decisions. Advanced studies on the cellular level have an advanced understanding of the metabolic effects induced by IDH mutations, offering opportunities for specific targeted therapies that may improve patient outcomes. Such findings may lead to a paradigm shift in the treatment of these tumors. Although LGG are sensitive to radiation and chemotherapy, these therapies are not curative, and patient survival remains limited, raising the need for more creative and effective interventions.
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Affiliation(s)
- Gilbert Youssef
- Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
| | - Julie J Miller
- Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
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McDuff SGR, Dietrich J, Atkins KM, Oh KS, Loeffler JS, Shih HA. Radiation and chemotherapy for high-risk lower grade gliomas: Choosing between temozolomide and PCV. Cancer Med 2019; 9:3-11. [PMID: 31701682 PMCID: PMC6943166 DOI: 10.1002/cam4.2686] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 10/06/2019] [Accepted: 10/07/2019] [Indexed: 11/07/2022] Open
Abstract
Purpose The majority of patients with high‐risk lower grade gliomas (LGG) are treated with single‐agent temozolomide (TMZ) and radiotherapy despite three randomized trials showing a striking overall survival benefit with adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy and radiotherapy. This article aims to evaluate the evidence and rationale for the widespread use of TMZ instead of PCV for high‐risk LGG. Methods and Materials We conducted a literature search utilizing PubMed for articles investigating the combination of radiotherapy and chemotherapy for high‐risk LGG and analyzed the results of these studies. Results For patients with IDH mutant 1p/19q codeleted LGG tumors, there is limited evidence to support the use of TMZ. In medically fit patients with codeleted disease, existing data demonstrate a large survival benefit for PCV as compared to adjuvant radiation therapy alone. For patients with non‐1p/19q codeleted LGG, early data from the CATNON study supports inclusion of adjuvant TMZ for 12 months. Subset analyses of the RTOG 9402 and EORTC 26951 do not demonstrate a survival benefit for adjuvant PCV for non‐1p/19q codeleted gliomas, however secondary analyses of RTOG 9802 and RTOG 9402 demonstrated survival benefit in any IDH mutant lower grade gliomas, regardless of 1p/19q codeletion status. Conclusions At present, we conclude that current evidence does not support the widespread use of TMZ over PCV for all patients with high‐risk LGG, and we instead recommend tailoring chemotherapy recommendation based on IDH status, favoring adjuvant PCV for patients with any IDH mutant tumors, both those that harbor 1p/19q codeletion and those non‐1p/19q codeleted. Given the critical role radiation plays in the treatment of LGG, radiation oncologists should be actively involved in discussions regarding chemotherapy choice in order to optimize treatment for their patients.
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Affiliation(s)
- Susan G R McDuff
- Department of Radiation Oncology, Duke Cancer Center, Medicine Circle, Durham, NC, USA
| | - Jorg Dietrich
- Department of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Katelyn M Atkins
- Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Kevin S Oh
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Jay S Loeffler
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Helen A Shih
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
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13
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McTyre E, Lucas JT, Helis C, Farris M, Soike M, Mott R, Laxton AW, Tatter SB, Lesser GJ, Strowd RE, Lo HW, Debinski W, Chan MD. Outcomes for Anaplastic Glioma Treated With Radiation Therapy With or Without Concurrent Temozolomide. Am J Clin Oncol 2018; 41:813-819. [PMID: 28301347 PMCID: PMC11668142 DOI: 10.1097/coc.0000000000000380] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVES Postoperative management of anaplastic glioma remains without a clear standard of care-in this study we report outcomes for patients treated with radiotherapy (RT) with and without temozolomide (TMZ). MATERIALS AND METHODS We identified 71 consecutive patients with World Health Organization grade III glioma treated with either RT alone or with concurrent TMZ (RT+TMZ), between 2000 and 2013. Tumor histology was anaplastic astrocytoma in 42 patients, anaplastic oligodendroglioma in 25 patients, and anaplastic oligoastrocytoma in 4 patients. In total, 26 patients received RT and 45 received RT+TMZ. Adjuvant TMZ was administered to 12/26 (46.1%) patients who received RT and 42/45 (93.3%) patients who received RT+TMZ. Time-to-event endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS Kaplan-Meier estimates revealed that patients receiving RT+TMZ followed by adjuvant TMZ had improved PFS (P=0.04) and OS (P=0.02) as compared with those receiving RT followed by adjuvant TMZ. Cox proportional hazards multivariate analysis revealed improved PFS and OS with RT+TMZ for all patients (PFS: hazard ratio [HR]=0.42, P=0.02; OS: HR=0.41, P=0.03) and for anaplastic astrocytoma patients (PFS: HR=0.35, P=0.03; OS: HR=0.26, P=0.01), regardless of whether patients received further adjuvant TMZ. CONCLUSIONS These findings support the use of RT+TMZ in the postoperative management of grade III glioma, and suggest that there is a benefit to concurrent RT+TMZ that is independent of adjuvant monthly TMZ. Further investigation is warranted, both to prospectively validate the benefit of RT+TMZ, as well as to determine if an additional benefit truly exists for adjuvant TMZ following concurrent RT+TMZ.
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Affiliation(s)
- Emory McTyre
- Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC
| | - John T. Lucas
- Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Corbin Helis
- Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Michael Farris
- Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Michael Soike
- Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Ryan Mott
- Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
| | - Adrian W. Laxton
- Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
| | - Stephen B. Tatter
- Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
| | - Glenn J. Lesser
- Department of Internal Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
| | - Roy E. Strowd
- Department of Internal Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
| | - Hui-Wen Lo
- Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
| | - Waldemar Debinski
- Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
| | - Michael D. Chan
- Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC
- Department of Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC
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14
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Reduced expression of DNA repair genes and chemosensitivity in 1p19q codeleted lower-grade gliomas. J Neurooncol 2018; 139:563-571. [PMID: 29923053 DOI: 10.1007/s11060-018-2915-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 05/27/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Lower-grade gliomas (LGGs, defined as WHO grades II and III) with 1p19q codeletion have increased chemosensitivity when compared to LGGs without 1p19q codeletion, but the mechanism is currently unknown. METHODS RNAseq data from 515 LGG patients in the Cancer Genome Atlas (TCGA) were analyzed to compare the effect of expression of the 9 DNA repair genes located on chromosome arms 1p and 19q on progression free survival (PFS) and overall survival (OS) between patients who received chemotherapy and those who did not. Chemosensitivity of cells with DNA repair genes knocked down was tested using MTS cell proliferation assay in HS683 cell line and U251 cell line. RESULTS The expression of 9 DNA repair genes on 1p and 19q was significantly lower in 1p19q-codeleted tumors (n = 175) than in tumors without the codeletion (n = 337) (p < 0.001). In LGG patients who received chemotherapy, lower expression of LIG1, POLD1, PNKP, RAD54L and MUTYH was associated with longer PFS and OS. This difference between chemotherapy and non-chemotherapy groups in the association of gene expression with survival was not observed in non-DNA repair genes located on chromosome arms 1p and 19q. MTS assays showed that knockdown of DNA repair genes LIG1, POLD1, PNKP, RAD54L and MUTYH significantly inhibited recovery in response to temozolomide when compared with control group (p < 0.001). CONCLUSIONS Our results suggest that reduced expression of DNA repair genes on chromosome arms 1p and 19q may account for the increased chemosensitivity of LGGs with 1p19q codeletion.
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15
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Using Smaller-Than-Standard Radiation Treatment Margins Does Not Change Survival Outcomes in Patients with High-Grade Gliomas. Pract Radiat Oncol 2018; 9:16-23. [PMID: 30195927 DOI: 10.1016/j.prro.2018.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 04/10/2018] [Accepted: 06/04/2018] [Indexed: 01/16/2023]
Abstract
PURPOSE The number of studies that evaluate treatment margins for high grade gliomas (HGG) are limited. We hypothesize that patients with HGG who are treated with a gross tumor volume (GTV) to planning tumor volume (PTV) expansion of ≤1 cm will have progression-free survival (PFS) and overall survival (OS) rates similar to those treated in accordance with standard protocols by the Radiation Therapy Oncology Group or European Organisation for Research and Treatment of Cancer. Furthermore, the PFS and OS of subgroups within the study population will have equivalent survival outcomes with GTV1-to-PTV1 margins of 1.0 cm and 0.4 cm. METHODS AND MATERIALS Treatment plans and outcomes for patients with pathologically confirmed HGG were analyzed (n = 267). Survival (PFS and OS) was calculated from the time of the first radiation treatment and a χ2 test or Fisher exact test was used to calculate the associations between margin size and patient characteristics. Survival was estimated using Kaplan-Meier and compared using the log-rank test. All analyses were performed on the univariate level. RESULTS The median PFS and OS times were 10.6 and 19.1 months, respectively. By disease, the median PFS and OS times were 8.6 and 16.1 months for glioblastoma and 26.7 and 52.5 months for anaplastic glioma. The median follow-up time was 18.3 months. The treatment margin had no effect on outcome and the 1.0 cm GTV1-PTV1 margin subgroup (n = 212) showed median PFS and OS times of 10.7 and 19.1 months, respectively, and the 0.4 cm margin subgroup (n = 55) 10.2 and 19.3 months, respectively. In comparison with the standard treatment with 2 cm to 3 cm margins, there was not a significant difference in outcomes. CONCLUSIONS There is no apparent difference in survival when utilizing smaller versus larger margins as defined by the guidelines of the Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer. Although there remains no class I evidence that outcomes after treatment with smaller margins are identical to those after treatment with larger margins, this large series with long-term follow up suggests that a reduction of the margins is safe and further investigation is warranted.
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16
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Jhaveri J, Liu Y, Chowdhary M, Buchwald ZS, Gillespie TW, Olson JJ, Voloschin AD, Eaton BR, Shu HKG, Crocker IR, Curran WJ, Patel KR. Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high-risk grade 2 glioma: An analysis of the National Cancer Data Base. Cancer 2017; 124:1169-1178. [PMID: 29205287 DOI: 10.1002/cncr.31158] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 09/28/2017] [Accepted: 10/31/2017] [Indexed: 11/10/2022]
Abstract
BACKGROUND The addition of chemotherapy to adjuvant radiotherapy (chemotherapy and radiation therapy [CRT]) improves overall survival (OS) for patients with high-risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is unknown. This study compares the OS of patients with high-risk grade 2 gliomas treated with CA versus CRT. METHODS Patients with high-risk grade 2 gliomas (subtotal resection or age ≥ 40 years) with oligodendrogliomas, astrocytomas, or mixed tumors were identified with the National Cancer Data Base. Patients were grouped into CA and CRT cohorts. Univariate analyses and multivariate analyses (MVAs) were performed. Propensity score (PS) matching was also implemented. The Kaplan-Meier method was used to analyze OS. RESULTS A total of 1054 patients with high-risk grade 2 gliomas were identified: 496 (47.1%) received CA, and 558 (52.9%) received CRT. Patients treated with CA were more likely (all P values < .05) to have oligodendroglioma histology (65.5% vs 34.2%), exhibit a 1p/19q codeletion (22.8% vs 7.5%), be younger (median age, 47.0 vs 48.0 years), and receive treatment at an academic facility (65.2% vs 50.3%). The treatment type was not a significant predictor for OS (P = .125) according to the MVA; a tumor size > 6 cm, astrocytoma histology, and older age were predictors for worse OS (all P values < .05). After 1:1 PS matching (n = 331 for each cohort), no OS difference was seen (P = .696) between the CA and CRT cohorts at 5 (69.3% vs 67.4%) and 8 years (52.8% vs 56.7%). CONCLUSIONS No long-term OS difference was seen in patients with high-risk grade 2 gliomas treated with CA versus CRT. These findings are hypothesis-generating, and prospective clinical trials comparing these treatment paradigms are warranted. Cancer 2018;124:1169-78. © 2017 American Cancer Society.
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Affiliation(s)
- Jaymin Jhaveri
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Yuan Liu
- Biostatistics and Bioinformatics Shared Resource, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Mudit Chowdhary
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia.,Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois
| | - Zachary S Buchwald
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Theresa W Gillespie
- Department of Surgery and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Jeffrey J Olson
- Department of Neurosurgery and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Alfredo D Voloschin
- Department of Hematology and Medical Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Bree R Eaton
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Hui-Kuo G Shu
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Ian R Crocker
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Walter J Curran
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Kirtesh R Patel
- Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia.,Department of Therapeutic Radiology and Smilow Cancer Center, Yale School of Medicine, New Haven, Connecticut
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17
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Sasaki H, Yoshida K. Treatment Recommendations for Adult Patients with Diffuse Gliomas of Grades II and III According to the New WHO Classification in 2016. Neurol Med Chir (Tokyo) 2017; 57:658-666. [PMID: 28845038 PMCID: PMC5735229 DOI: 10.2176/nmc.ra.2017-0071] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
With advanced understanding of molecular background and correlation with therapeutic outcomes, the revised 4th edition of World Health Organization (WHO) classification of central nervous system (CNS) tumors incorporated molecular information into the definition of diffuse gliomas. Indeed, oligodendroglioma and astrocytoma are now defined by molecular signature, with diagnosis of glioblastoma being made by histology. In parallel, numerous clinical trials are underway all over the world, and important findings are being produced every year that have an impact on patient outcomes. Moreover, novel therapies/technologies are also being actively developed; however, there are still many CNS tumors for which no effective therapy has been established except radiotherapy. In this article, the authors review the recent results of major clinical trials and present their treatment recommendations for patients with adult, supratentorial diffuse gliomas of grades II and III stratified according to the new WHO classification.
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Affiliation(s)
- Hikaru Sasaki
- Department of Neurosurgery, Keio University School of Medicine
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18
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Pessina F, Navarria P, Cozzi L, Tomatis S, Clerici E, Ascolese AM, Simonelli M, Perrino M, Riva M, Rossi M, Rudà R, Santoro A, Bello L, Scorsetti M. Outcome evaluation of patients with newly diagnosed anaplastic gliomas treated in a single institution. CNS Oncol 2017; 6:211-219. [PMID: 28718305 PMCID: PMC6009210 DOI: 10.2217/cns-2016-0043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 02/01/2017] [Indexed: 11/21/2022] Open
Abstract
AIM To evaluate the outcome of newly diagnosed anaplastic glioma patients treated in our institution in relation to the 2016 WHO classification suggestions. METHODS This retrospective study included patients who underwent surgery plus adjuvant chemotherapy alone or concomitant and adjuvant chemoradiotherapy. Response was recorded using the Response Assessment in Neuro-Oncology criteria. RESULTS 123 patients were analyzed. The median progression-free survival time and the 2, 3 and 5 years progression-free survival rate were 27 months, 65.5, 21.2 and 21.2%; the 2, 3 and 5 years overall survival rate were 89.7, 83.0 and 58.4%. From the univariate/multivariate analysis, the factors conditioning survival were Karnofsky performance scale, extent of resection, IDH1 mutation status and presence of 1p/19q codeletion. CONCLUSION The choice of adjuvant treatment have to consider molecular assessment and, in our experience, the extent of surgical resection.
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Affiliation(s)
- Federico Pessina
- Neurosurgery Oncology Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Pierina Navarria
- Radiotherapy & Radiosurgery Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Luca Cozzi
- Radiotherapy & Radiosurgery Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
- Oncology & Hematology Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Stefano Tomatis
- Radiotherapy & Radiosurgery Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Elena Clerici
- Radiotherapy & Radiosurgery Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Anna Maria Ascolese
- Radiotherapy & Radiosurgery Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Matteo Simonelli
- Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Matteo Perrino
- Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Marco Riva
- Neurosurgery Oncology Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Marco Rossi
- Neurosurgery Oncology Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Roberta Rudà
- Neurooncological consultant Neurosurgery Oncology Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Lorenzo Bello
- Neurosurgery Oncology Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
| | - Marta Scorsetti
- Radiotherapy & Radiosurgery Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
- Oncology & Hematology Department, Istituto Humanitas Cancer Center & Research Hospital, Rozzano, Italy
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19
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Patterns of care and outcomes of multi-agent versus single-agent chemotherapy as part of multimodal management of low grade glioma. J Neurooncol 2017; 133:369-375. [DOI: 10.1007/s11060-017-2443-7] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 04/14/2017] [Indexed: 11/25/2022]
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20
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Influence of insurance status and income in anaplastic astrocytoma: an analysis of 4325 patients. J Neurooncol 2016; 132:89-98. [PMID: 27864706 DOI: 10.1007/s11060-016-2339-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 11/12/2016] [Indexed: 10/20/2022]
Abstract
To determine the impact of insurance status and income for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base. Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4325 patients with AA diagnosed from 2004 to 2013 were identified. 2781 (64.3%) had private insurance, 925 (21.4%) Medicare, 396 (9.2%) Medicaid, and 223 (5.2%) were uninsured. Those uninsured were more likely to be Black or Hispanic versus White or Asian (p < 0.001), have lower median income (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). 1651 (38.2%) had income ≥$63,000, 1204 (27.8%) $48,000-$62,999, 889 (20.5%) $38,000-$47,999, and 581 (13.4%) had income <$38,000. Those with lower income were more likely to be Black or Hispanic versus White or Asian (p < 0.001), uninsured (p < 0.001), reside in a rural area (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). Those with private insurance had significantly higher overall survival (OS) than those uninsured, on Medicaid, or on Medicare (p < 0.001). Those with income ≥$63,000 had significantly higher OS than those with lower income (p < 0.001). On multivariate analysis, age, insurance status, income, and adjuvant therapy were independent prognostic factors for OS. Being uninsured and having income <$38,000 were independent prognostic factors for worse OS in AA. Further investigations are warranted to help determine ways to ensure adequate medical care for those who may be socially disadvantaged so that outcome can be maximized for all patients regardless of socioeconomic status.
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21
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Shin JY, Diaz AZ. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy. J Neurooncol 2016; 129:557-565. [PMID: 27401155 DOI: 10.1007/s11060-016-2210-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 07/05/2016] [Indexed: 12/23/2022]
Abstract
To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.
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Affiliation(s)
- Jacob Y Shin
- Department of Radiation Oncology, Rush University Medical Center, 500 S. Paulina St., Chicago, IL, 60612, USA.
| | - Aidnag Z Diaz
- Department of Radiation Oncology, Rush University Medical Center, 500 S. Paulina St., Chicago, IL, 60612, USA
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Navarria P, Pessina F, Cozzi L, Ascolese AM, Lobefalo F, Stravato A, D'Agostino G, Franzese C, Caroli M, Bello L, Scorsetti M. Can advanced new radiation therapy technologies improve outcome of high grade glioma (HGG) patients? analysis of 3D-conformal radiotherapy (3DCRT) versus volumetric-modulated arc therapy (VMAT) in patients treated with surgery, concomitant and adjuvant chemo-radiotherapy. BMC Cancer 2016; 16:362. [PMID: 27287048 PMCID: PMC4901414 DOI: 10.1186/s12885-016-2399-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 06/03/2016] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND To assess the impact of volumetric-modulated arc therapy (VMAT) compared with 3D-conformal radiotherapy (3DCRT) in patients with newly diagnosed high grade glioma in terms of toxicity, progression free survival (PFS) and overall survival (OS). METHODS From March 2004 to October 2014, 341 patients underwent surgery followed by concomitant and adjuvant chemo-radiotherapy. From 2003 to 2010, 167 patients were treated using 3DCRT; starting from 2011, 174 patients underwent VMAT. The quantitative evaluation of the treatment plans was performed by means of standard dose volume histogram analysis. Response was recorded using the Response Assessment in Neuro-Oncology (RANO) criteria and toxicities graded according to Common Terminology Criteria for Adverse Event version 4.0. RESULTS Both techniques achieved an adequate dose conformity to the target. The median follow up time was 1.3 years; at the last observation 76 patients (23.4 %) were alive and 249 (76.6 %) dead (16 patients were lot to follow-up). For patients who underwent 3DCRT, the median PFS was 0.99 ± 0.07 years (CI95: 0.9-1.1 years); the 1 and 3 years PFS were, 49.6 ± 4 and 19.1 ± 3.1 %. This shall be compared, respectively, to 1.29 ± 0.13 years (CI95: 1.01-1.5 years), 60.8 ± 3.8, and 29.7 ± 4.6 % for patients who underwent VMAT (p = 0.02). The median OS for 3DCRT patients was 1.21 ± 0.09 years (CI95:1.03-1.3 years); 1 and 5 year OS was, 63.3 ± 3.8 and 21.5 ± 3.3 %. The corresponding results for 3DRCT patients were 1.56 ± 0.09 years (CI95:1.37-1.74 years), 73.4 ± 3.5, 30 ± 4.6 % respectively (p < 0.01). In both groups, prognostic factors conditioning PFS and OS were age, gender, KPS, histology and extent of resection (EOR). CONCLUSIONS VMAT resulted superior to 3DCRT in terms of dosimetric findings and clinical results.
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Affiliation(s)
- Pierina Navarria
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy. .,Istituto Clinico Humanitas Cancer Center, Via Manzoni 56 20089 Rozzano, Milano, Italy.
| | - Federico Pessina
- Department of Neurooncological surgery, Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano and Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Luca Cozzi
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Anna Maria Ascolese
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Francesca Lobefalo
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Antonella Stravato
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Giuseppe D'Agostino
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Ciro Franzese
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Manuela Caroli
- Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorenzo Bello
- Department of Neurooncological surgery, Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano and Humanitas Cancer Center and Research Hospital, Milan, Italy
| | - Marta Scorsetti
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center and Research Hospital, Milan, Italy
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Pentsova EI, Reiner AS, Panageas KS, DeAngelis LM. Anaplastic astrocytoma and non-1p/19q co-deleted anaplastic oligoastrocytoma: long-term survival, employment, and performance status of survivors. Neurooncol Pract 2016; 3:71-76. [PMID: 31386086 DOI: 10.1093/nop/npv043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Indexed: 11/14/2022] Open
Abstract
Background Despite optimal treatment for patients with anaplastic gliomas, median survival is 2 to 5 years, but some young adults survive longer. We sought to evaluate the functional and employment status of long-term survivors (5 years or more) diagnosed with anaplastic astrocytoma or non-1p/19q co-deleted anaplastic oligoastrocytoma. Methods We retrospectively identified patients with a diagnosis of anaplastic glioma at Memorial Sloan Kettering Cancer Center from 1999 to 2005. We reviewed demographics, pathology, 1p/19q status, survival, and treatment. Overall survival was estimated by the Kaplan-Meier method. Results There were 195 patients; 167 with anaplastic astrocytoma and 28 with anaplastic oligoastrocytoma. All patients were observed either to death or last follow-up. Sixty-four patients (33%) were identified as long-term survivors; 58% of these were men. The median age of the long-term survivors was 39 years and the median Karnofsky Performance Score was 100 at diagnosis. Thirteen patients underwent stereotactic biopsy, 7 had a gross total resection, and 44 a subtotal resection. Fifty-four patients completed radiation therapy as initial treatment; 54 received chemotherapy. Five years following diagnosis, median KPS was 90 and 55% of long-term survivors were employed and remained fully functional. Conclusions One-third of patients with non-co-deleted anaplastic glioma were long-term survivors, and more than one-half of long-term survivors resumed their prior level of employment and activity. However, a significant proportion could not return to normal function. These findings have serious implications for the social and financial status of these predominantly young adult survivors.
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Affiliation(s)
- Elena I Pentsova
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY (E.I.P., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (A.S.R., K.S.P.)
| | - Anne S Reiner
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY (E.I.P., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (A.S.R., K.S.P.)
| | - Katherine S Panageas
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY (E.I.P., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (A.S.R., K.S.P.)
| | - Lisa M DeAngelis
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY (E.I.P., L.M.D.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (A.S.R., K.S.P.)
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Strowd RE, Abuali I, Ye X, Lu Y, Grossman SA. The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide. J Neurooncol 2016; 127:165-71. [PMID: 26729269 DOI: 10.1007/s11060-015-2028-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 12/25/2015] [Indexed: 02/05/2023]
Abstract
Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p < 0.001). Median OS was 32 months (95 % CI 23-43). Survival was longer in the post-2004 cohort (37 mo, 24-64) than pre-2004 (27 mo, 19-40; HR 0.75, 0.53-1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44-0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA.
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Affiliation(s)
- Roy E Strowd
- Department of Neurology, Johns Hopkins School of Medicine, Cancer Research Building II, 1550 Orleans St, Baltimore, MD, 21287, USA.
| | - Inas Abuali
- Department of Internal Medicine, Saint Agnes Hospital, Baltimore, MD, 21287, USA
| | - Xiaobu Ye
- Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA
| | - Yao Lu
- Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA
| | - Stuart A Grossman
- Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA
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Field K, Rosenthal M, Khasraw M, Sawkins K, Nowak A. Evolving management of low grade glioma: No consensus amongst treating clinicians. J Clin Neurosci 2016; 23:81-87. [PMID: 26601811 DOI: 10.1016/j.jocn.2015.05.038] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 05/02/2015] [Indexed: 02/08/2023]
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Takano K, Kinoshita M, Arita H, Okita Y, Chiba Y, Kagawa N, Fujimoto Y, Kishima H, Kanemura Y, Nonaka M, Nakajima S, Shimosegawa E, Hatazawa J, Hashimoto N, Yoshimine T. Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas. AJNR Am J Neuroradiol 2015; 37:44-50. [PMID: 26381556 DOI: 10.3174/ajnr.a4460] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 05/07/2015] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.
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Affiliation(s)
- K Takano
- From the Department of Neurosurgery (K.T., M.K.), Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.)
| | - M Kinoshita
- From the Department of Neurosurgery (K.T., M.K.), Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.)
| | - H Arita
- Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.)
| | - Y Okita
- Department of Neurosurgery (Y.O., Y.K., M.N., S.N.)
| | - Y Chiba
- Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.) Department of Neurosurgery (Y.C.), Kansai Rosai Hospital, Itami, Japan
| | - N Kagawa
- Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.)
| | - Y Fujimoto
- Department of Neurosurgery (Y.F.), Osaka Neurological Institute, Osaka, Japan
| | - H Kishima
- Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.)
| | - Y Kanemura
- Department of Neurosurgery (Y.O., Y.K., M.N., S.N.) Division of Regenerative Medicine (Y.K.), Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan
| | - M Nonaka
- Department of Neurosurgery (Y.O., Y.K., M.N., S.N.) Department of Neurosurgery (M.N.), Kansai Medical University, Osaka, Japan
| | - S Nakajima
- Department of Neurosurgery (Y.O., Y.K., M.N., S.N.)
| | - E Shimosegawa
- Nuclear Medicine and Tracer Kinetics (E.S., J.H.), Osaka University Graduate School of Medicine, Osaka, Japan
| | - J Hatazawa
- Nuclear Medicine and Tracer Kinetics (E.S., J.H.), Osaka University Graduate School of Medicine, Osaka, Japan
| | - N Hashimoto
- Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.)
| | - T Yoshimine
- Departments of Neurosurgery (K.T., M.K., H.A., Y.C., N.K., H.K., N.H., T.Y.)
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Kang HC, Yu T, Lim DH, Kim IH, Chung WK, Suh CO, Choi BO, Cho KH, Cho JH, Kim JH, Nam DH, Park CK, Hong YK, Kim IA. A multicenter study of anaplastic oligodendroglioma: the Korean Radiation Oncology Group Study 13-12. J Neurooncol 2015; 125:207-15. [PMID: 26341368 DOI: 10.1007/s11060-015-1902-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 08/29/2015] [Indexed: 01/19/2023]
Abstract
Although some existing evidence supports the addition of chemotherapy (CT) to radiation therapy (RT) for anaplastic oligodendroglioma treatment, controversy about both the criteria for suitable candidates and the optimal treatment schedule remains. We reviewed data from 376 newly diagnosed anaplastic oliogodendroglial tumor patients from nine Korean institutes were reviewed from 2000 to 2010. Total tumor removal was performed in 146 patients. More than 85% of the entire patients received postoperative RT, and 59% received CT. Approximately 50% (n = 189) received CT in addition to RT and 9% (n = 32) received CT only. A multivariate analysis revealed that younger age, frontal lobe location of the tumor, gross total removal, 1p/19q codeletion, and initial RT were associated with longer progression-free and overall survival rates. No difference was observed in outcomes from the treatment that included either temozolomide or PCV (procarbazine, lomustine, and vincristine) in addition to RT regardless of the 1p/19q deletion status. A clear improvement in progression-free and overall survival was observed for RT and combined CT/RT in compared with CT only. Postoperative RT appears to improve survival for entire group thus total removal and 1p/19q codeletion may not be sufficient criteria to omit RT as a treatment option. These results suggest that RT should continue to be offered as the standard treatment option for patients with anaplastic oligodendroglial tumors.
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Affiliation(s)
- Hyun-Cheol Kang
- Department of Radiation Oncology, Dongnam Institute of Radiological & Medical Sciences, Busan, Korea
| | - Tosol Yu
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Do Hoon Lim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Il Han Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Woong-Ki Chung
- Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, Korea
| | - Chang-Ok Suh
- Department of Radiation Oncology, Yonsei Cancer Center, College of Medicine, Yonsei University, Seoul, Korea
| | - Byung Ock Choi
- Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kwan Ho Cho
- Proton Therapy Center, Research Institute Hospital, National Cancer Center, Goyang, Korea
| | - Jae Ho Cho
- Department of Radiation Oncology, Gangnam Severance Cancer Hospital, Seoul, Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Do-Hyun Nam
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chul-Kee Park
- Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea
| | - Yong-Kil Hong
- Department of Neurosurgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - In Ah Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea. .,Department of Radiation Oncology, Seoul National University Bundang Hospital, 166 Gumiro Seongnamsi Kyeonggido, Seoul, 463-707, Korea.
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Swaminathan A, Lightner DD, Pittman T, Horbinski C, Villano JL. Refractory anaplastic astrocytoma responsive to PCV in combination with bevacizumab. CASE REPORTS IN CLINICAL PATHOLOGY 2015; 2:17-22. [PMID: 38222924 PMCID: PMC10786628 DOI: 10.5430/crcp.v2n3p17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2024]
Abstract
We present a patient with anaplastic astrocytoma who had recurrent disease after treatment with surgery, radiation, procarbazine, lomustine (CCNU) and vincristine (PCV) over one year followed by poor response to second line treatment with temozolomide, irinotecan with bevacizumab, Novocure TTF therapy successively over a four year period after her initial treatment who then responded to PCV in combination with bevacizumab as third line therapy. This is the first report demonstrating benefit of concurrent PCV and bevacizumab treatment in a highly treatment refractory tumor.
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Affiliation(s)
- Arun Swaminathan
- Department of Neurology, University of Kentucky Chandler Medical Center, Lexington, Kentucky, United States
| | - Donita D. Lightner
- Department of Neurology, University of Kentucky Chandler Medical Center, Lexington, Kentucky, United States
| | - Thomas Pittman
- Department of Neurosurgery, University of Kentucky Chandler Medical Center, Lexington, Kentucky, United States
| | - Craig Horbinski
- Department of Pathology, University of Kentucky Chandler Medical Center, Lexington, Kentucky, United States
| | - John Lee Villano
- Department of Neurology, University of Kentucky Chandler Medical Center, Lexington, Kentucky, United States
- Department of Medicine, University of Kentucky Chandler Medical Center, Lexington, Kentucky, United States
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Ichimura K, Narita Y, Hawkins CE. Diffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers. Acta Neuropathol 2015; 129:789-808. [PMID: 25975377 DOI: 10.1007/s00401-015-1439-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 04/26/2015] [Accepted: 04/30/2015] [Indexed: 11/28/2022]
Abstract
Diffusely infiltrating astrocytomas include diffuse astrocytomas WHO grade II and anaplastic astrocytomas WHO grade III and are classified under astrocytic tumours according to the current WHO Classification. Although the patients generally have longer survival as compared to those with glioblastoma, the timing of inevitable malignant progression ultimately determines the prognosis. Recent advances in molecular genetics have uncovered that histopathologically diagnosed astrocytomas may consist of two genetically different groups of tumours. The majority of diffusely infiltrating astrocytomas regardless of WHO grade have concurrent mutations of IDH1 or IDH2, TP53 and ATRX. Among these astrocytomas, no other genetic markers that may distinguish grade II and grade III tumours have been identified. Those astrocytomas without IDH mutation tend to have a distinct genotype and a poor prognosis comparable to that of glioblastomas. On the other hand, diffuse astrocytomas that arise in children do not harbour IDH/TP53 mutations, but instead display mutations of BRAF or structural alterations involving MYB/MYBL1 or FGFR1. A molecular classification may thus help delineate diffusely infiltrating astrocytomas into distinct pathogenic and prognostic groups, which could aid in determining individualised therapeutic strategies.
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Affiliation(s)
- Koichi Ichimura
- Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan,
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Radiotherapy and temozolomide for anaplastic astrocytic gliomas. J Neurooncol 2015; 123:129-34. [PMID: 25920709 DOI: 10.1007/s11060-015-1771-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Accepted: 04/02/2015] [Indexed: 10/23/2022]
Abstract
We previously reported results of a phase II non-comparative trial that randomized patients with glioblastoma following radiotherapy to one of two different temozolomide schedules, followed by 13-cis-retinoic acid (RA) maintenance. Here we report the results of an exploratory cohort of patients accrued with anaplastic astrocytic tumors. Patients with newly diagnosed anaplastic astrocytoma (AA) or anaplastic oligo-astrocytoma (AOA) were treated with concurrent radiotherapy (60 Gy over 6 weeks) and temozolomide (75 mg/m(2)), and six adjuvant 28-day cycles of either dose-dense (150 mg/m(2), days 1-7, 15-21) or metronomic (50 mg/m(2), days 1-28) temozolomide. Subsequently, maintenance RA (100 mg/m(2), days 1-21/28) was administered until disease progression. All outcome measures were descriptive without intention to compare between treatment arms. Survival was measured by the Kaplan-Meier method. There were 31 patients (21 men, 10 women) with median age 48 years (range 28-74), median KPS 90 (range 60-100). Extent of resection was gross-total in 35%, subtotal 23%, and biopsy 42%. Histology was AA in 90%, and AOA in 10%. MGMT promoter methylation was methylated in 20%, unmethylated in 50%, and uninformative in 30% of 30 tested. Median progression-free survival was 2.1 years (95% CI 0.95-Not Reached), and overall survival 2.9 years (95 % CI 2.0-Not Reached). We report outcomes among a homogeneously treated population with anaplastic astrocytic tumors. Survival was unexpectedly short compared to other reports. These data may be useful as a contemporary historic control for other ongoing or future randomized trials.
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Speirs CK, Simpson JR, Robinson CG, DeWees TA, Tran DD, Linette G, Chicoine MR, Dacey RG, Rich KM, Dowling JL, Leuthardt EC, Zipfel GJ, Kim AH, Huang J. Impact of 1p/19q Codeletion and Histology on Outcomes of Anaplastic Gliomas Treated With Radiation Therapy and Temozolomide. Int J Radiat Oncol Biol Phys 2015; 91:268-76. [DOI: 10.1016/j.ijrobp.2014.10.027] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 09/03/2014] [Accepted: 10/14/2014] [Indexed: 12/25/2022]
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Pattern of care of anaplastic oligodendroglioma and oligoastrocytoma in a Korean population: the Korean Radiation Oncology Group study 13-12. J Neurooncol 2014; 121:531-9. [PMID: 25391968 DOI: 10.1007/s11060-014-1660-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 11/06/2014] [Indexed: 10/24/2022]
Abstract
This study investigated the treatment of anaplastic oligodendroglial tumors across nine Korean institutions. We reviewed the medical records from 381 patients with histologically confirmed anaplastic oligodendroglioma or anaplastic oligoastrocytoma (AOA) from 2000 to 2010. Clinical factors and treatment patterns were analyzed for each year. Post-operative therapy was performed in 354 patients (94.1 %), of which 133 received radiotherapy (RT) alone and 189 received both RT and chemotherapy. RT alone was the preferred treatment toward the end of the study period (29.4 % in 2000-2001 vs. 56.3 % in 2010, P = 0.005). The use of procarbazine, lomustine, and vincristine (PCV) decreased (57.6 % in 2000-2001 vs. 28.6 % in 2010, P = 0.001) and the use of temozolomide (TMZ) increased (0 % in 2000-2001 vs. 61.9 % in 2010, P < 0.001) over the study period. A combination of chemotherapy and RT was used more often than RT alone in young patients (P = 0.036) and patients with a good performance status (P = 0.023). The 1p/19q co-deletion status and O-6-methyguanine-DNA methyltransferase methylation were analyzed since 2004 but were not significant factors for determining whether to administer chemotherapy. Among the patients who received chemotherapy, TMZ was used more often in patients with AOA (P = 0.007) and PCV was used more often in patients with either multiple lesions (P = 0.027) or the 1p/19q co-deletion (P = 0.026). Our results demonstrate that the treatment pattern for oligodendroglial tumors changed significantly across the study period. In particular, TMZ has replaced PCV, and the use of molecular markers as well as RT alone has increased, but a unified protocol remains to be established.
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Thon N, Kunz M, Lemke L, Jansen NL, Eigenbrod S, Kreth S, Lutz J, Egensperger R, Giese A, Herms J, Weller M, Kretzschmar H, Tonn JC, la Fougère C, Kreth FW. Dynamic 18F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses. Int J Cancer 2014; 136:2132-45. [PMID: 25311315 DOI: 10.1002/ijc.29259] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2014] [Accepted: 09/03/2014] [Indexed: 11/08/2022]
Abstract
In suspected grade II gliomas, three distinct patterns of time-activity curves (TAC) on O-(2-[(18)F]fluoroethyl)-1-tyrosine ((18)F-FET) positron emission tomography (PET) have been delineated (i) increasing TAC homogeneously throughout the tumor, and decreasing TAC, (ii) either homogeneously throughout the tumor or (iii) only focally within otherwise increasing TAC patterns. Increasing TAC was associated with low-grade histology and decreasing TAC with high-grade histology. This prospective study analyzed whether these patterns correlate with distinct biological tumor subtypes and differential outcome. (18)F-FET PET-guided biopsies were used for stepwise histopathological evaluation. Molecular-genetic evaluation included O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase (IDH1/2) mutational and 1p/19q codeletion status. Progression-free survival (PFS) was estimated with the Kaplan-Meier method. Prognostic factors were obtained from multivariate regression models. 98 adult patients were included. Homogeneous increasing, focal decreasing and homogeneous decreasing TAC were seen in 51, 19 and 28 patients. The corresponding 1-year (2-years) PFS were 92% (85%), 89% (51%) and 50% (28%; p = 0.002). IDH1/2 mutations were more frequent in tumors with homogeneous increasing (90%) and focal decreasing (79%) TAC, but were rare in those exhibiting homogeneous decreasing TAC (25%; p < 0.001). Overall, TAC patterns, IDH1/2 mutational and 1p/19q codeletion status were powerful and independent prognostic factors. Dynamic (18)F-FET PET might be an important and independent imaging biomarker for patients with suspected WHO grade II gliomas and offers perspectives for stratified diagnostic and therapeutic strategies. Tumors with focal decreasing TAC need highly targeted surgical interventions to avoid undergrading and undertreatment.
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Affiliation(s)
- Niklas Thon
- Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Germany
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Kizilbash SH, Giannini C, Voss JS, Decker PA, Jenkins RB, Hardie J, Laack NN, Parney IF, Uhm JH, Buckner JC. The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma. J Neurooncol 2014; 120:85-93. [PMID: 24993250 DOI: 10.1007/s11060-014-1520-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 06/23/2014] [Indexed: 01/24/2023]
Abstract
This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3%, p = 0.02) and IDH mutation (78.9 vs. 22.0%, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.
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Affiliation(s)
- Sani H Kizilbash
- Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA,
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Anaplastic astrocytomas: survival and prognostic factors in a surgical series. Acta Neurochir (Wien) 2014; 156:1053-61. [PMID: 24682619 DOI: 10.1007/s00701-014-2053-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Accepted: 02/26/2014] [Indexed: 01/13/2023]
Abstract
BACKGROUND To study patient characteristics, prognostic factors and overall survival (OS) in a consecutive, surgical series of WHO grade III anaplastic astrocytomas (AA). METHODS Patients were identified from a prospective tumor database at Oslo University Hospital, Norway, and patients undergoing surgery for an AA from 2005-2012 were included. Patients' medical charts were retrospectively reviewed for data collection. RESULTS A total of 99 adult patients with histologically verified AA were included. Median age was 52 years (20-81). Biopsy was conducted in 33 % and resection in 67 %. Adjuvant treatment with radiation therapy + temozolomide or radiation therapy only was given in 63 % and 26 %, respectively. The thirty-day mortality rate was 3 %. Median OS was 19 months (95 % CI 11-27 months). Age ≥ 65 years, KPS < 70, biopsy as opposed to resection, and no adjuvant treatment were confirmed negative prognostic factors in multivariate analysis. For patients undergoing resection, presence of postoperative contrast-enhanced tumor, not volume of residual tumor, had significant impact on OS in adjusted analysis. CONCLUSIONS Median OS following surgery was 19 months, though much variable outcome was observed among subgroups of AA (95 % CI 11-27 months). Age ≥65 years, KPS < 70, biopsy as opposed to resection, and no adjuvant treatment were confirmed negative prognostic factors for OS.
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Chamberlain MC, Chowdhary SA, Glantz MJ. Anaplastic astrocytomas: biology and treatment. Expert Rev Neurother 2014; 8:575-86. [DOI: 10.1586/14737175.8.4.575] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Rahman M, Hoh B, Kohler N, Dunbar EM, Murad GJA. The future of glioma treatment: stem cells, nanotechnology and personalized medicine. Future Oncol 2013; 8:1149-56. [PMID: 23030489 DOI: 10.2217/fon.12.111] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
The development of novel therapies, imaging techniques and insights into the processes that drive growth of CNS tumors have allowed growing enthusiasm for the treatment of CNS malignancies. Despite this energized effort to investigate and treat brain cancer, clinical outcomes for most patients continue to be dismal. Recognition of diverse tumor subtypes, behaviors and outcomes has led to an interest in personalized medicine for the treatment of brain tumors. This new paradigm requires evaluation of the tumor phenotype at the time of diagnosis so that therapy can be specifically tailored to each individual patient. Investigating novel therapies involving stem cells, nanotechnology and molecular medicine will allow diversity of therapeutic options for patients with brain cancer. These exciting new therapeutic strategies for brain tumors are reviewed in this article.
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Affiliation(s)
- Maryam Rahman
- Department of Neurosurgery, University of Florida, Box 100265, Gainesville, FL 32610, USA.
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Berrocal A, Gil M, Gallego Ó, Balaña C, Pérez Segura P, García-Mata J, Reynes G. SEOM guideline for the treatment of malignant glioma. Clin Transl Oncol 2012; 14:545-50. [PMID: 22721801 DOI: 10.1007/s12094-012-0839-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
High-grade gliomas are an infrequent disease diagnosed usually in the fifth or sixth decade. Careful histopathological diagnosis is essential because tumour grade and type condition the treatment. Magnetic resonance with gadolinium is considered the standard radiologic exploration and should be followed by tissue sampling. Treatment of these patients should be decided in a multidisciplinary committee. Surgery, radiotherapy and chemotherapy are the basis of patients' treatment, with the best results obtained when the three of them can be used.
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Affiliation(s)
- Alfonso Berrocal
- Medical Oncology Service, Hospital General Universitario, Valencia, Spain.
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Kim JH, Li L, Quang TS, Emrich JG, Yaeger TE, Jenrette JM, Cohen SC, Black P, Brady LW. Phase II trial of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of anaplastic astrocytoma. ACTA ACUST UNITED AC 2012. [DOI: 10.1007/s13566-012-0071-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Masui K, Cloughesy TF, Mischel PS. Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. Neuropathol Appl Neurobiol 2012; 38:271-91. [PMID: 22098029 PMCID: PMC4104813 DOI: 10.1111/j.1365-2990.2011.01238.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The classification of malignant gliomas is moving from a morphology-based guide to a system built on molecular criteria. The development of a genomic landscape for gliomas and a better understanding of its functional consequences have led to the development of internally consistent molecular classifiers. However, development of a biologically insightful classification to guide therapy is still a work in progress. Response to targeted treatments is based not only on the presence of drugable targets, but rather on the molecular circuitry of the cells. Further, tumours are heterogeneous and change and adapt in response to drugs. Therefore, the challenge of developing molecular classifiers that provide meaningful ways to stratify patients for therapy remains a major challenge for the field. In this review, we examine the potential role of MGMT methylation, IDH1/2 mutations, 1p/19q deletions, aberrant epidermal growth factor receptor and PI3K pathways, abnormal p53/Rb pathways, cancer stem-cell markers and microRNAs as prognostic and predictive molecular markers in the setting of adult high-grade gliomas and we outline the clinically relevant subtypes of glioblastoma with genomic, transcriptomic and proteomic integrated analyses. Furthermore, we describe how these advances, especially in epidermal growth factor receptor/PI3K/mTOR signalling pathway, affect our approaches towards targeted therapy, raising new challenges and identifying new leads.
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Affiliation(s)
- K Masui
- Department of Pathology and Laboratory Medicine, David Geffen University of California at Los Angeles School of Medicine, Los Angeles, California, USA.
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Blondin NA, Becker KP. Anaplastic gliomas: radiation, chemotherapy, or both? Hematol Oncol Clin North Am 2012; 26:811-23. [PMID: 22794285 DOI: 10.1016/j.hoc.2012.04.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The optimal treatment of anaplastic gliomas is controversial. Options for treatment include radiation, chemotherapy or a combination of modalities. This article describes how treatment algorithms for anaplastic gliomas have evolved and interprets the results of recent studies. The available evidence indicates that patients can be treated with either chemotherapy or radiation as initial therapy, with use of the other treatment modality at relapse. Whether subpopulations exist for whom one treatment modality is superior to the other at initial diagnosis must be studied prospectively.
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Affiliation(s)
- Nicholas A Blondin
- Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA.
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Scoccianti S, Magrini SM, Ricardi U, Detti B, Krengli M, Parisi S, Bertoni F, Sotti G, Cipressi S, Tombolini V, Dall'oglio S, Lioce M, Saieva C, Buglione M, Mantovani C, Rubino G, Muto P, Fusco V, Fariselli L, de Renzis C, Masini L, Santoni R, Pirtoli L, Biti G. Radiotherapy and temozolomide in anaplastic astrocytoma: a retrospective multicenter study by the Central Nervous System Study Group of AIRO (Italian Association of Radiation Oncology). Neuro Oncol 2012; 14:798-807. [PMID: 22539339 DOI: 10.1093/neuonc/nos081] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Although the evidence for the benefit of adding temozolomide (TMZ) to radiotherapy (RT) is limited to glioblastoma patients, there is currently a trend toward treating anaplastic astrocytomas (AAs) with combined RT + TMZ. The aim of the present study was to describe the patterns of care of patients affected by AA and, particularly, to compare the outcome of patients treated exclusively with RT with those treated with RT + TMZ. Data of 295 newly diagnosed AAs treated with postoperative RT ± TMZ in the period from 2002 to 2007 were reviewed. More than 75% of patients underwent a surgical removal. All the patients had postoperative RT; 86.1% of them were treated with 3D-conformal RT (3D-CRT). Sixty-seven percent of the entire group received postoperative chemotherapy with TMZ (n = 198). One-hundred sixty-six patients received both concomitant and sequential TMZ. Prescription of postoperative TMZ increased in the most recent period (2005-2007). One- and 4-year survival rates were 70.2% and 28.6%, respectively. No statistically significant improvement in survival was observed with the addition of TMZ to RT (P = .59). Multivariate analysis showed the statistical significance of age, presence of seizures, Recursive Partitioning Analysis classes I-III, extent of surgical removal, and 3D-CRT. Changes in the care of AA over the past years are documented. Currently there is not evidence to justify the addition of TMZ to postoperative RT for patients with newly diagnosed AA outside a clinical trial. Results of prospective and randomized trials are needed.
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Affiliation(s)
- Silvia Scoccianti
- Radiotherapy Unit, Azienda Ospedaliera Universitaria Careggi, Viale Morgagni 85, 50134 Florence, Italy.
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Prognostic factors and survival in a prospective cohort of patients with high-grade glioma treated with carmustine wafers or temozolomide on an intention-to-treat basis. Acta Neurochir (Wien) 2012; 154:211-22; discussion 222. [PMID: 22002506 DOI: 10.1007/s00701-011-1199-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Accepted: 09/29/2011] [Indexed: 10/17/2022]
Abstract
BACKGROUND Patients with high-grade glioma can be treated with carmustine wafers or following the Stupp protocol. As far as we are aware, no scientific evidence has been published comparing the two treatments. The primary objective of this study was to analyse the survival of groups of patients with each of these treatment modalities. The secondary objective was to assess the influence of the usual prognostic factors on the patients in our hospital. METHODS A prospective cohort of 110 patients with single, supratentorial high-grade glioma treated by craniotomy and tumour resection was retrospectively studied. Half of the patients had carmustine wafers placed during this operation while the others (55) did not, the latter group receiving first-line systemic chemotherapy on an intention-to-treat basis. FINDINGS Patients treated with carmustine wafers had a median survival of 13.414 months compared with 11.047 in the group without implants (p = 0.856). For the overall cohort of patients, the following factors were found to influence survival: age (p < 0.0001), postoperative KPS score (p = 0.001), histological grade (p = 0.004), RPA class (p = 0.001), extent of resection (p = 0.002) and salvage surgery (p = 0.028). CONCLUSIONS In this prospective cohort of patients, analysed on the basis of intention-to-treat at the time of the first surgery, no statistically significant differences in survival were found between the two treatment modalities (carmustine wafers vs. first-line systemic chemotherapy). On the other hand, age, preoperative KPS, histological grade, and RPA class were confirmed to be prognostic factors in this cohort. Finally, the extent of resection was also found to influence survival.
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Affiliation(s)
- Christine Marosi
- Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
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Blakeley J, Grossman SA. Chemotherapy with cytotoxic and cytostatic agents in brain cancer. HANDBOOK OF CLINICAL NEUROLOGY 2012; 104:229-54. [PMID: 22230447 DOI: 10.1016/b978-0-444-52138-5.00017-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Elliott RE, Parker EC, Rush SC, Kalhorn SP, Moshel YA, Narayana A, Donahue B, Golfinos JG. Efficacy of gamma knife radiosurgery for small-volume recurrent malignant gliomas after initial radical resection. World Neurosurg 2011; 76:128-40; discussion 61-2. [PMID: 21839964 DOI: 10.1016/j.wneu.2010.12.053] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2010] [Revised: 12/20/2010] [Accepted: 12/20/2010] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To review the authors' experience with Gamma Knife radiosurgery (GKR) for small recurrent high-grade gliomas (HGGs) following prior radical resection, external-beam radiation therapy (EBRT), and chemotherapy with temozolomide (TMZ). METHODS The authors retrospectively analyzed 26 consecutive adults (9 women and 17 men; median age 60.4 years; Karnofsky Performance Status [KPS]≥70) who underwent GKR for recurrent HGGs from 2004-2009. Median lesion volume was 1.22 cc, and median treatment dose was 15 Gy. Pathology included glioblastoma multiforme (GBM; n=16), anaplastic astrocytoma (AA; n=5), and anaplastic mixed oligoastrocytoma (AMOA; n=5). Two patients lost to follow-up were excluded from radiographic outcome analyses. RESULTS Median overall survival (OS) for the entire cohort from the time of GKR was 13.5 months. Values for 12-month actuarial survival from time of GKR for GBM, AMOA, and AA were 37%, 20% and 80%. Local failure occurred in 9 patients (37.5%) at a median time of 5.8 months, and 18 patients (75%) experienced distant progression at a median of 4.8 months. Complications included radiation necrosis in two patients and transient worsening of hemiparesis in one patient. Multivariate hazard ratio (HR) analysis showed KPS 90 or greater, smaller tumor volumes, and increased time to recurrence after resection to be associated with longer OS following GKR. CONCLUSIONS GKR provided good local tumor control in this group of clinically stable and predominantly high-functioning patients with small recurrent HGGs after radical resection. Meaningful survival times after GKR were seen. GKR can be considered for selected patients with recurrent HGGs.
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Affiliation(s)
- Robert E Elliott
- Department of Neurosurgery, New York University Langone Medical Center, New York, New York, USA
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Lee DS, Yu M, Jang HS, Kim YS, Choi BO, Kang YN, Lee YS, Kim DC, Hong YK, Jeun SS, Yoon SC. Radiation-induced brain injury: retrospective analysis of twelve pathologically proven cases. Radiat Oncol J 2011; 29:147-55. [PMID: 22984665 PMCID: PMC3429897 DOI: 10.3857/roj.2011.29.3.147] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2011] [Revised: 06/08/2011] [Accepted: 06/15/2011] [Indexed: 12/25/2022] Open
Abstract
Purpose This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). Materials and Methods The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were finally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. Results Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p = 0.061) and biologically equivalent dose (BED)3 (p = 0.084) were the only marginally influencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed <6 months after radiotherapy was associated with inferior overall survival rates compared to cases of RIBI that occurred ≥6 months (p = 0.085). Conclusion Our study demonstrated that RIBI could occur in early periods after conventional fractionated brain radiotherapy within normal tolerable dose ranges. Studies with a larger number of patients are required to identify the strong influencing factors for RIBI development.
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Affiliation(s)
- Dong-Soo Lee
- Department of Radiation Oncology, The Cancer Center of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
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Galanis E, Wu W, Sarkaria J, Chang SM, Colman H, Sargent D, Reardon DA. Incorporation of biomarker assessment in novel clinical trial designs: personalizing brain tumor treatments. Curr Oncol Rep 2011; 13:42-9. [PMID: 21125354 DOI: 10.1007/s11912-010-0144-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Advances in molecular genetics have aided the identification of potential biomarkers with significant clinical promise in neurooncology. These advances and the evolution of targeted therapeutics necessitate the development and incorporation of innovative clinical trial designs that can effectively validate and assess the clinical utility of biomarkers. In this article, we review the use and potential of several such designs in neurooncology trials in order to support the development of personalized treatment approaches for brain tumor patients.
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Morita N, Wang S, Chawla S, Poptani H, Melhem ER. Dynamic susceptibility contrast perfusion weighted imaging in grading of nonenhancing astrocytomas. J Magn Reson Imaging 2011; 32:803-8. [PMID: 20882610 DOI: 10.1002/jmri.22324] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To evaluate if the relative tumor blood volume (rTBV) using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) can aid in distinguishing low- from high-grade nonenhancing astrocytomas. MATERIALS AND METHODS Seventeen patients with histologically proven astrocytomas underwent MRI including DSC-MRI. Maximum TBV regions of interest were recorded from each neoplasm and normalized to contralateral normal white matter. Demographic features, diagnostic MRI findings including tumor volumes, and the normalized rTBV ratios were compared between low-grade (I and II, LGA, n = 6) and high-grade (III) astrocytomas (HGA, n = 11) using Mann-Whitney's U-test and receiver operating characteristic (ROC) analysis. RESULTS Maximum rTBV ratios were statistically higher for HGA (1.11 ± 0.13) than LGA (0.66 ± 0.17, P < 0.005) with the best cutoff threshold at 0.94 (sensitivity of 90.9%, specificity of 100%). Differences in mean age and tumor volume on fluid-attenuated inversion recovery (FLAIR) imaging between the two groups did not reach statistical difference (P = 0.22, 0.36). CONCLUSION The addition of DSC-MRI can aid in accurate grading of nonenhancing astrocytomas with high sensitivity and specificity.
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Affiliation(s)
- Naomi Morita
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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von Deimling A, Korshunov A, Hartmann C. The next generation of glioma biomarkers: MGMT methylation, BRAF fusions and IDH1 mutations. Brain Pathol 2011; 21:74-87. [PMID: 21129061 PMCID: PMC8094257 DOI: 10.1111/j.1750-3639.2010.00454.x] [Citation(s) in RCA: 125] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2010] [Accepted: 10/11/2010] [Indexed: 01/12/2023] Open
Abstract
For some, glioma biomarkers have been expected to solve common diagnostic problems in routine neuropathology service caused by insufficient material, technical shortcomings or lack of experience. Further, biomarkers should predict patient outcome and direct optimal therapy for the individual patient. Unfortunately, current biomarkers still fall somewhat short of these grand expectations. While there has been some progress, it has generally been slow and in small steps. In this review, the newest set of glioma biomarkers: O(6) -methylguanine-DNA methyltransferase (MGMT) methylation, BRAF fusion and IDH1 mutation are discussed. MGMT methylation is well established as a prognostic/predictive marker for glioblastoma; however, technical questions regarding testing remain, it is not currently utilized widely in guiding patient management, and it has proven to be of no assistance in diagnostics. In contrast, BRAF fusion and IDH1 mutation analyses promise to be very helpful for classifying and grading gliomas, while their potential predictive value has yet to be established.
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Affiliation(s)
- Andreas von Deimling
- Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, and Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany.
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