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David N Louis - One of the best experts on this subject based on the ideXlab platform.
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survey of treatment recommendations for anaplastic Oligodendroglioma
Neuro-oncology, 2007Co-Authors: Lauren E Abrey, Lisa M Deangelis, David R Macdonald, David N Louis, Andrew B. Lassman, Nina Paleologos, Jeffrey Raizer, Warren P Mason, Jonathan L Finlay, Gregory J CairncrossAbstract:Anaplastic Oligodendroglioma was first recognized as a chemosensitive glial tumor in 1988.1 In the 1990s, molecular genetic studies demonstrated that allelic loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) were important prognostic markers of chemosensitivity and longer survival.2–7 Identification of the chemosensitivity and the prognostic role of molecular markers in anaplastic Oligodendroglioma represents one of the most exciting and important discoveries in neuro-oncology in the last decade. However, at present, there is no defined standard of care for the management of anaplastic Oligodendrogliomas or specific guidelines for integrating the results of molecular studies into a therapeutic plan. Anaplastic Oligodendroglioma is a relatively rare tumor, so large prospective studies take many years to accrue and patterns of clinical practice have evolved independently of prospective data. The current recommended management of anaplastic Oligodendrogliomas by the National Comprehensive Cancer Network (NCCN) is maximal resection followed by focal radiotherapy (RT) with or without adjuvant chemotherapy. This recommendation is supported by the results of a Radiation Therapy Oncology Group (RTOG) 94-02 study which showed that neoadjuvant chemotherapy using procarbazine, lomustine (CCNU), and vincristine (PCV) administered prior to RT did not prolong patient survival significantly compared with postoperative RT alone. This lack of a difference in overall survival was attributed in part to the successful use of PCV at recurrence in those who received RT alone initially.8 However, the addition of PCV prolonged disease-free survival for patients with 1p/19q deletion only, and this group of patients had a much longer overall survival regardless of treatment. Similarly, the recent results of European Organization for Research and Treatment of Cancer (EORTC) 26951 demonstrated that adjuvant PCV did not improve overall survival for patients with newly diagnosed anaplastic Oligodendroglioma.9 These data suggest that the NCCN guidelines still represent the standard of care, but it is not clear how often neuro-oncologists follow these guidelines or recommend other therapies. Because there are a number of possible ways in which clinicians might integrate new or emerging data about oligodendroglial tumors into clinical practice, we developed a survey to assess current patterns of practice. We sent this survey to all members of the Society of Neuro-Oncology (SNO) to learn more about the ways in which experts in neuro-oncology were advising and managing their patients. SNO is a multidisciplinary organization of physicians and scientists with expertise in primary brain tumors with approximately 500 clinical members. This survey specifically addressed the availability and use of molecular studies for 1p and 19q, and treatment recommendations for patients with or without information regarding 1p and 19q status.
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Losses of chromosomes 1p and 19q are rare in pediatric Oligodendrogliomas
Acta Neuropathologica, 2005Co-Authors: Portia A. Kreiger, David N Louis, Yoshifumi Okada, Scott L. Simon, Lucy B. Rorke, Jeffrey A. GoldenAbstract:Pediatric Oligodendrogliomas are rare neoplasms and have not been characterized extensively either pathologically or genetically. Given the recent interest in the significance of chromosomal losses in predicting the clinical course and in establishing uniform diagnoses of adult Oligodendrogliomas, we reviewed the pathological and clinical features of a series of pediatric Oligodendrogliomas and determined their 1p and 19q status using fluorescence in situ hybridization. Of 19 tumors originally diagnosed as Oligodendroglioma, 7 were Oligodendroglioma, 3 were anaplastic Oligodendroglioma, 3 were oligoastrocytoma, and 6 were reclassified. Only one tumor, an anaplastic Oligodendroglioma, had 1p loss; none had 19q loss. The single patient whose tumor had 1p loss did not have a particularly favorable clinical course. These results suggest that pediatric Oligodendrogliomas arise by molecular alterations distinct from adult Oligodendrogliomas, and such molecular alterations do not hold immediate promise as an adjunct to the diagnosis of pediatric Oligodendrogliomas.
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histopathological molecular genetic correlations in referral pathologist diagnosed low grade Oligodendroglioma
Journal of Neuropathology and Experimental Neurology, 2002Co-Authors: Hikaru Sasaki, Magdalena C Zlatescu, Rebecca A Betensky, Loki Johnk, Andrea N Cutone, Gregory J Cairncross, David N LouisAbstract:: Allelic loss of chromosome 1p predicts increased chemosensitivity and better survival in oligodendroglial tumors. Clinical testing for 1p loss in oligodendroglial tumors at our hospital has allowed us to postulate that certain histological appearances are associated with 1p allelic status. Forty-four cases received for genetic testing were diagnosed by referring pathologists as pure low-grade Oligodendroglioma. Central neuropathological review divided the series equally into 22 cases with classical Oligodendroglioma histology and 22 with more astrocytic features. Molecular genetic analyses demonstrated 1p loss in 19 of 22 classic Oligodendrogliomas (86%) and maintenance of both 1p alleles in 16 of 22 gliomas with astrocytic features (73%). No glial fibrillary acidic protein-positive cell type (gliofibrillary oligodendrocyte, minigemistocyte, cellular processes) was associated with 1p allelic status. Fourteen of the 44 cases were treated with chemotherapy at tumor progression: 3 "astrocytic" gliomas with 1p loss responded to PCV chemotherapy and 2 classic Oligodendrogliomas that maintained both 1p alleles included a responder and a non-responder. These results suggest that histological appearance correctly predicts genotype in approximately 80% of low-grade gliomas, but that tumor genotype more closely predicts chemosensitivity. As a result, such objective molecular genetic analyses should be incorporated into patient management and into clinical trials of low-grade diffuse gliomas.
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molecular subtypes of anaplastic Oligodendroglioma implications for patient management at diagnosis
Clinical Cancer Research, 2001Co-Authors: Rebecca A Betensky, Magdalena C Zlatescu, David R Macdonald, Hikaru Sasaki, Gregory J Cairncross, Anat Stemmerrachamimov, David A Ramsay, David N LouisAbstract:Purpose: In a prior study of anaplastic Oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival. Experimental Design: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic Oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic Oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. Results: We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. Conclusions: These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic Oligodendroglioma.
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allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with Oligodendrogliomas
International Journal of Radiation Oncology Biology Physics, 2000Co-Authors: Glenn Bauman, Magdalena C Zlatescu, Barbara Fisher, David R Macdonald, Larry Stitt, David N Louis, Keisuke Ueki, J. Gregory CairncrossAbstract:Abstract Introduction: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic Oligodendrogliomas. Using a database of patients with Oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. Materials and Methods: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III Oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic Oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. Results: Fifty-five patients (29 male, 26 female; ages 18–75 years; median, 44 years; KPS 50–90, median 80) were irradiated for either a WHO Grade II ( n = 19) or Grade III ( n = 36) Oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p ( p p = 0.004). Conclusion: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy ± chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of Oligodendroglioma.
Robert B Jenkins - One of the best experts on this subject based on the ideXlab platform.
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genetically defined Oligodendroglioma is characterized by indistinct tumor borders at mri
American Journal of Neuroradiology, 2017Co-Authors: Derek R. Johnson, Robert B Jenkins, Felix E Diehn, Caterina Giannini, Sarah M Jenkins, Ian F Parney, Timothy J KaufmannAbstract:BACKGROUND AND PURPOSE: In 2016, the World Health Organization revised the brain tumor classification, making IDH mutation and 1p/19q codeletion the defining features of Oligodendroglioma. To determine whether imaging characteristics previously associated with oligodendroglial tumors are still applicable, we evaluated the MR imaging features of genetically defined Oligodendrogliomas. MATERIALS AND METHODS: One hundred forty-eight adult patients with untreated World Health Organization grade II and III infiltrating gliomas with histologic oligodendroglial morphology, known 1p/19q status, and at least 1 preoperative MR imaging were retrospectively identified. The association of 1p/19q codeletion with tumor imaging characteristics and ADC values was evaluated. RESULTS: Ninety of 148 (61%) patients had 1p/19q codeleted tumors, corresponding to genetically defined Oligodendroglioma, and 58/148 (39%) did not show 1p/19q codeletion, corresponding to astrocytic tumors. Eighty-three of 90 (92%) genetically defined Oligodendrogliomas had noncircumscribed borders, compared with 26/58 (45%) non-1p/19q codeleted tumors with at least partial histologic oligodendroglial morphology (P CONCLUSIONS: Imaging characteristics of World Health Organization 2016 genetically defined Oligodendrogliomas differ from the previously considered characteristics of morphologically defined Oligodendrogliomas. We found that genetically defined Oligodendrogliomas were commonly poorly circumscribed and were almost always heterogeneous in signal intensity.
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primary leptomeningeal Oligodendroglioma with documented progression to anaplasia and t 1 19 q10 p10 in a child
Acta Neuropathologica, 2009Co-Authors: Sabrina Rossi, Robert B Jenkins, Fausto J Rodriguez, Renan A Mota, Francesco Di Paola, Matteo Bendini, Silvana Agostini, Pierluigi Longatti, Caterina GianniniAbstract:Oligodendrogliomas are infiltrating gliomas typically arising in the cerebral cortex and white matter. Rare examples present with diffuse leptomeningeal involvement in the absence of a clinically/radiologically detectable intraparenchymal tumor [1–5, 7, 8, 10, 14, 15]. Although Oligodendrogliomas are rare in children, most primary leptomeningeal Oligodendrogliomas have occurred in the first decade of life (Table 1). We report the case of a 3-year-old girl, who presented with progressive regression of her ability to walk and an increase of cranial circumference. MRI showed marked hydrocephalus and diffuse leptomeningeal enhancement without supratentorial intraparenchymal lesions (Fig. 1a–c). A C3–C4 mildly enhancing 5 mm nodule was present, which could not be defined with certainty as meningeal or intraparenchymal (Fig. 1c). Cerebrospinal fluid (CSF) was xanthochromic, with high protein (177 mg/dl), normal glucose (63 mg/dl) and increased white blood cells (47 cells/mm, 50% mononuclear). Bacterial cultures were negative, but polymerase chain reaction showed CSF positivity for M. tuberculosis. A diagnosis of basal meningitis was made and the child was unsuccessfully treated with anti-tuberculosis therapy. When a meningeal biopsy demonstrated a low-grade neuroectodermal tumor consistent with low-grade Oligodendroglioma, the patient was started on chemotherapy, according to the SIOP protocol for low-grade gliomas, based on vincristine and carboplatin, changed later to vincristine and cisplatin alternating with cyclophosphamide every 6 weeks due to an allergic reaction to carboplatin. Chemotherapy was suspended at 18 months, after remarkable improvement of her clinical condition. She also received radiotherapy at the level of C2–C4, because of the gradual increase of the cervical nodule (54 Gy in 30 fractions). The child remained stable for the following 3 years, when her tumor progressed to anaplastic Oligodendroglioma, as confirmed by a new biopsy of a left frontal paraventricular nodule. At this time, MRIs demonstrated multiple enhancing nodules filling the ventricles, suggesting involvement of the sub-ependymal parenchyma (Fig. 1d–f). The patient received temozolomide, but her clinical condition continued to deteriorate and she expired, 7 years from the original diagnosis. The first biopsy consisted of a very small fragment of leptomeninges showing dominant reactive changes with hyperplastic meningothelial cells and inflammation. A small focus of monomorphous cells with round nuclei diffusely expressing S100 protein and focally GFAP was seen (Fig. 2a). The second biopsy revealed a highly cellular neoplasm with small cells with hyperchromatic round nuclei and perinuclear halos similar to the original ones (Fig. 2b). Numerous mitoses were identified (up to 8/10 HPF). S100 protein expression was extensive, GFAP was focal. Neu-N, synaptophysin, EMA and CKAE1/AE3 stains were negative. p53 was expressed in rare nuclei. MIB-1 labeling index was high (up to 50%). Electron microscopy demonstrated round cells with scant organelles lacking ependymal features. 1p/19q co-deletion and S. Rossi A. P. Dei Tos F. D. Paola M. Bendini S. Agostini P. Longatti Departments of Pathology, Neuroradiology, Pediatrics and Neurosurgery, Regional Hospital, Treviso, Italy
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a t 1 19 q10 p10 mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with Oligodendroglioma
Cancer Research, 2006Co-Authors: Robert B Jenkins, Karla V Ballman, Caterina Giannini, Hilary E Blair, Robert M Arusell, Heather C Flynn, Sandra M Passe, Sara J Felten, Paul D Brown, Edward G ShawAbstract:Combined deletion of chromosomes 1p and 19q is associated with improved prognosis and responsiveness to therapy in patients with anaplastic Oligodendroglioma. The deletions usually involve whole chromosome arms, suggesting a t(1;19)(q10;p10). Using stem cell medium, we cultured a few tumors. Paraffin-embedded tissue was obtained from 21 Mayo Clinic patients and 98 patients enrolled in 2 North Central Cancer Treatment Group (NCCTG) low-grade glioma trials. Interphase fusion of CEP1 and 19p12 probes detected the t(1;19). 1p/19q deletions were evaluated by fluorescence in situ hybridization. Upon culture, one Oligodendroglioma contained an unbalanced 45,XX,t(1;19)(q10;p10). CEP1/19p12 fusion was observed in all metaphases and 74% of interphase nuclei. Among Mayo Clinic Oligodendrogliomas, the prevalence of fusion was 81%. Among NCCTG patients, CEP1/19p12 fusion prevalence was 55%, 47%, and 0% among the Oligodendrogliomas, mixed oligoastrocytomas, and astrocytomas, respectively. Ninety-one percent of NCCTG gliomas with 1p/19q deletion and 12% without 1p/19q deletion had CEP1/19p12 fusion ( P 2 test). The median overall survival (OS) for all patients was 8.1 years without fusion and 11.9 years with fusion ( P = 0.003). The median OS for patients with low-grade Oligodendroglioma was 9.1 years without fusion and 13.0 years with fusion ( P = 0.01). Similar significant median OS differences were observed for patients with combined 1p/19q deletions. The absence of alterations was associated with a significantly shorter OS for patients who received higher doses of radiotherapy. Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined 1p/19q deletion in human gliomas. Like combined 1p/19q deletion, the 1;19 translocation is associated with superior OS and progression-free survival in low-grade glioma patients. (Cancer Res 2006; 66(20): 9852-61)
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current strategies in treatment of Oligodendroglioma evolution of molecular signatures of response
Journal of Clinical Oncology, 2006Co-Authors: Kurt A Jaeckle, Karla V Ballman, Robert B Jenkins, Jan C. BucknerAbstract:Oligodendroglioma frequently (≥ 70%) responds to radiation and chemotherapy, and is the first CNS neoplasm in which a genetic signature (1p and 19q deletion) has been associated with outcome within the context of large clinical trials. Current translational investigations focus on deletions or mutations of potential tumor suppressor genes, epigenetic alterations, amplification or mutation of growth factor and regulatory genes, and characterization of signaling events and regulatory protein expression. The most compelling data has involved 1p and 19q loss, which is observed in over 50% of anaplastic Oligodendrogliomas. In two randomized phase III trials (Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951), the addition of neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV; respectively) to radiotherapy did not produce superior survival as compared with radiotherapy alone. A modest increase in progression-free survival was observed w...
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polymorphisms in gltscr1 and ercc2 are associated with the development of Oligodendrogliomas
Cancer, 2005Co-Authors: Ping Yang, M Thomas B A M Kollmeyer, Kristin Buckner, M William S Bamlet, Karla V Ballman, Robert B JenkinsAbstract:BACKGROUND Deletions of 19q have been associated with gliomas, especially Oligodendrogliomas. In addition, cases with Oligodendrogliomas with the 19q deletion have been observed to have a better survival compared with cases without the 19q deletion. The authors have previously described a 150-kilobase minimal deletion region in gliomas that maps to 19q13.33 and contains 3 novel candidate genes (GLTSCR1, EHD2, and GLTSCR2). METHODS The authors performed an association study using 141 cases with gliomas (61 cases with astrocytomas, 40 cases with Oligodendrogliomas, 40 cases with mixed oligoastrocytomas) and 108 general controls. They evaluated 7 single nucleotide polymorphisms (SNPs) in 6 genes within and nearby the minimal 19q deletion region (ERCC2, RAI, ASE-1, ERCC1, GLTSCR1, and LIG1). RESULTS The prevalence of a germline GLTSCR1-exon-1 T allele (SNP rs1035938) was 40% in cases with Oligodendrogliomas compared with 27% in controls (P = 0.029), and the prevalence of an ERCC2-exon-22 T allele (SNP rs1052555) was 35% in cases with Oligodendrogliomas compared with 18% in controls (P = 0.043). One high-risk and 1 low-risk haplotype were associated with Oligodendroglioma development (P = 0.003 and 0.026, respectively). Cases with Oligodendrogliomas with the 19q deletion had a significantly higher frequency of the GLTSCR1-exon-1 T allele compared with cases without the 19q deletion (P = 0.01). It was noteworthy that cases with gliomas who were homozygous for the GLTSCR1-exon-1 T allele had a significantly better survival: 77% and 68% survival at 2 and 5 years compared with 56% and 34% for other genotypes (P = 0.02, log-rank test). Multivariable analysis identified grade, age, and the GLTSCR1-exon-1 and ERCC2-exon-22 genotypes as independent predictors for survival. CONCLUSIONS These results suggested that alterations in GLTSCR1 (or a closely linked gene) were associated with the development and progression of Oligodendroglioma. Cancer 2005. © 2005 American Cancer Society.
David R Macdonald - One of the best experts on this subject based on the ideXlab platform.
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survey of treatment recommendations for anaplastic Oligodendroglioma
Neuro-oncology, 2007Co-Authors: Lauren E Abrey, Lisa M Deangelis, David R Macdonald, David N Louis, Andrew B. Lassman, Nina Paleologos, Jeffrey Raizer, Warren P Mason, Jonathan L Finlay, Gregory J CairncrossAbstract:Anaplastic Oligodendroglioma was first recognized as a chemosensitive glial tumor in 1988.1 In the 1990s, molecular genetic studies demonstrated that allelic loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) were important prognostic markers of chemosensitivity and longer survival.2–7 Identification of the chemosensitivity and the prognostic role of molecular markers in anaplastic Oligodendroglioma represents one of the most exciting and important discoveries in neuro-oncology in the last decade. However, at present, there is no defined standard of care for the management of anaplastic Oligodendrogliomas or specific guidelines for integrating the results of molecular studies into a therapeutic plan. Anaplastic Oligodendroglioma is a relatively rare tumor, so large prospective studies take many years to accrue and patterns of clinical practice have evolved independently of prospective data. The current recommended management of anaplastic Oligodendrogliomas by the National Comprehensive Cancer Network (NCCN) is maximal resection followed by focal radiotherapy (RT) with or without adjuvant chemotherapy. This recommendation is supported by the results of a Radiation Therapy Oncology Group (RTOG) 94-02 study which showed that neoadjuvant chemotherapy using procarbazine, lomustine (CCNU), and vincristine (PCV) administered prior to RT did not prolong patient survival significantly compared with postoperative RT alone. This lack of a difference in overall survival was attributed in part to the successful use of PCV at recurrence in those who received RT alone initially.8 However, the addition of PCV prolonged disease-free survival for patients with 1p/19q deletion only, and this group of patients had a much longer overall survival regardless of treatment. Similarly, the recent results of European Organization for Research and Treatment of Cancer (EORTC) 26951 demonstrated that adjuvant PCV did not improve overall survival for patients with newly diagnosed anaplastic Oligodendroglioma.9 These data suggest that the NCCN guidelines still represent the standard of care, but it is not clear how often neuro-oncologists follow these guidelines or recommend other therapies. Because there are a number of possible ways in which clinicians might integrate new or emerging data about oligodendroglial tumors into clinical practice, we developed a survey to assess current patterns of practice. We sent this survey to all members of the Society of Neuro-Oncology (SNO) to learn more about the ways in which experts in neuro-oncology were advising and managing their patients. SNO is a multidisciplinary organization of physicians and scientists with expertise in primary brain tumors with approximately 500 clinical members. This survey specifically addressed the availability and use of molecular studies for 1p and 19q, and treatment recommendations for patients with or without information regarding 1p and 19q status.
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molecular subtypes of anaplastic Oligodendroglioma implications for patient management at diagnosis
Clinical Cancer Research, 2001Co-Authors: Rebecca A Betensky, Magdalena C Zlatescu, David R Macdonald, Hikaru Sasaki, Gregory J Cairncross, Anat Stemmerrachamimov, David A Ramsay, David N LouisAbstract:Purpose: In a prior study of anaplastic Oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival. Experimental Design: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic Oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic Oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. Results: We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. Conclusions: These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic Oligodendroglioma.
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allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with Oligodendrogliomas
International Journal of Radiation Oncology Biology Physics, 2000Co-Authors: Glenn Bauman, Magdalena C Zlatescu, Barbara Fisher, David R Macdonald, Larry Stitt, David N Louis, Keisuke Ueki, J. Gregory CairncrossAbstract:Abstract Introduction: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic Oligodendrogliomas. Using a database of patients with Oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. Materials and Methods: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III Oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic Oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. Results: Fifty-five patients (29 male, 26 female; ages 18–75 years; median, 44 years; KPS 50–90, median 80) were irradiated for either a WHO Grade II ( n = 19) or Grade III ( n = 36) Oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p ( p p = 0.004). Conclusion: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy ± chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of Oligodendroglioma.
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Specific Genetic Predictors of Chemotherapeutic Response and Survival in Patients With Anaplastic Oligodendrogliomas
Journal of the National Cancer Institute, 1998Co-Authors: J. Gregory Cairncross, Magdalena C Zlatescu, Keisuke Ueki, David K. Lisle, Dianne M. Finkelstein, Robert R. Hammond, Jonathan S. Silver, Paul Stark, David R MacdonaldAbstract:Background/Methods: Gliomas are common malignant neoplasms of the central nervous system. Among the major subtypes of gliomas, Oligodendrogliomas are distinguished by their remarkable sensitivity to chemotherapy, with approximately two thirds of anaplastic (malignant) Oligodendrogliomas responding dramatically to combination treatment with procarbazine, lomustine, and vincristine (termed PCV). Unfortunately, no clinical or pathologic feature of these tumors allows accurate prediction of their response to chemotherapy. Anaplastic Oligodendrogliomas also are distinguished by a unique constellation of molecular genetic alterations, including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We have hypothesized that these or other specific genetic changes might predict the response to chemotherapy and prognosis in patients with anaplastic Oligodendrogliomas. Therefore, we have analyzed molecular genetic alterations involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39 patients with anaplastic Oligodendrogliomas for whom chemotherapeutic response and survival could be assessed. Results/Conclusions: Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic Oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic Oligodendrogliomas.
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Salvage chemotherapy for Oligodendroglioma.
Journal of Neurosurgery, 1996Co-Authors: Peterson K, David R Macdonald, Nina Paleologos, Peter Forsyth, Cairncross JgAbstract:✓ The authors present their experience with salvage chemotherapy for Oligodendroglioma, an uncommon brain tumor that responds predictably to PCV (procarbazine, lomustine (CCNU), and vincristine) when given as initial therapy. The authors reviewed the records of patients with Oligodendrogliomas who received a second, third, or fourth cytotoxic regimen prescribed to combat tumor recurrence documented by computerized tomography or magnetic resonance imaging following an initial chemotherapy program. Initial regimens were prescribed at various time points: as neoadjuvant therapy prior to radiotherapy, as adjuvant therapy in conjunction with radiotherapy, or at recurrence following radiotherapy. Response criteria were based on measurable changes in tumor size following published guidelines. Twenty-three patients (14 men and nine women) aged 25 to 58 years (median 36 years) received 33 salvage regimens. When non-PCV chemotherapy had been the prior regimen, seven (88%) of eight patients responded to salvage chem...
Jan C. Buckner - One of the best experts on this subject based on the ideXlab platform.
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The use of PCV chemotherapy in Oligodendrogliomas
Oligodendroglioma, 2020Co-Authors: Michael W. Ruff, Jan C. BucknerAbstract:Abstract Oligodendrogliomas are now defined by the presence of whole-arm co-deletion in chromosomal arms 1p and 19q. The treatment paradigm for Oligodendroglioma has shifted, owing to new diagnostic criteria and phase III clinical trial evidence. The treatment with radiation therapy plus chemotherapy with procarbazine, lomustine, and vincristine (PCV) results in prolongation of both progression-free and OS compared to treatment with radiation alone. Clinical trials, including RTOG 9402, EORTC 26951, and RTOG 9802, in contrast to NOA-04 and EORTC 22033, have conclusively demonstrated that chemoradiation is superior to either radiation therapy alone or chemotherapy alone for patients with Oligodendroglioma. Regardless of grade, PCV chemotherapy, in addition to radiation, has a clear benefit in patients with Oligodendroglioma and IDH mutated astrocytoma. Temozolomide may be less effective in the treatment of Oligodendroglioma, but clearly has a benefit in astrocytoma.
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current strategies in treatment of Oligodendroglioma evolution of molecular signatures of response
Journal of Clinical Oncology, 2006Co-Authors: Kurt A Jaeckle, Karla V Ballman, Robert B Jenkins, Jan C. BucknerAbstract:Oligodendroglioma frequently (≥ 70%) responds to radiation and chemotherapy, and is the first CNS neoplasm in which a genetic signature (1p and 19q deletion) has been associated with outcome within the context of large clinical trials. Current translational investigations focus on deletions or mutations of potential tumor suppressor genes, epigenetic alterations, amplification or mutation of growth factor and regulatory genes, and characterization of signaling events and regulatory protein expression. The most compelling data has involved 1p and 19q loss, which is observed in over 50% of anaplastic Oligodendrogliomas. In two randomized phase III trials (Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951), the addition of neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV; respectively) to radiotherapy did not produce superior survival as compared with radiotherapy alone. A modest increase in progression-free survival was observed w...
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chemotherapy for anaplastic Oligodendroglioma national cancer institute of canada clinical trials group
Journal of Clinical Oncology, 1994Co-Authors: Gregory Cairncross, David R Macdonald, Jan C. Buckner, Samuel K Ludwin, T Cascino, Dorcas Fulton, E Dropcho, David J Stewart, C ScholdAbstract:PURPOSETo examine the rate and duration of response of anaplastic Oligodendrogliomas to a dose-escalated combination chemotherapy regimen consisting of procarbazine, lomustine (CCNU), and vincristine (PCV) and to evaluate the side effects of this treatment.METHODSIn this single-arm multicentered phase II study, patients with measurable, newly diagnosed or recurrent, contrast-enhancing anaplastic Oligodendrogliomas were treated with up to six cycles of PCV. Central pathology and radiology review were mandatory, and rigorous response criteria based on imaging were used.RESULTSThirty-three patients entered the trial; nine were excluded subsequently, seven due to ineligible pathology. Eighteen of 24 eligible patients (75%) responded, nine completely (38%), four had stable disease (SD), and two progressed during the first cycle of PCV. Responses were observed in nine of 10 patients (90%) with a preexisting low-grade Oligodendroglioma and 10 of 15 (67%) with necrotic tumors, called glioblastoma multiforme by so...
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spinal cord glioneuronal tumor with neuropil like islands with 1p 19q deletion in an adult with low grade cerebral Oligodendroglioma
Journal of Neuro-oncology, 2012Co-Authors: Tyler J Fraum, Stephanie Barak, Svetlana Pack, Russell R Lonser, Howard A Fine, Martha Quezado, Fabio M IwamotoAbstract:Glioneuronal tumor with neuropil-like islands (GTNI) is considered a rare variant of astrocytoma, characterized by discrete aggregates of cells expressing neuronal markers that punctuate a GFAP-positive glial background. Of the 24 published GTNI cases, only two occurred in adult spinal cords; none occurred concurrent with another CNS tumor; and none of those tested exhibited the 1p/19q deletion typical of Oligodendroglioma. A 48-year-old man without significant past medical history was diagnosed with a WHO grade II Oligodendroglioma by stereotactic biopsy of a lesion discovered after the patient suffered a generalized tonic-clonic seizure. By FISH analysis, this tumor exhibited the 1p/19q deletion present in up to 80% of Oligodendrogliomas. The patient received 14 monthly cycles of temozolomide, and his cerebral tumor had a minor response. When the patient subsequently reported progressive paresthesias of his lower extremities, an MRI revealed an enhancing, cystic tumor of the thoracic spinal cord that was diagnosed as GTNI by histological analysis. By FISH analysis, this lesion exhibited the same 1p/19q deletion present in the concurrent cerebral Oligodendroglioma. This case of a spinal cord GTNI with 1p/19q deletions constitutes the third report of a spinal cord GTNI in an adult patient; the first report of a GTNI in an individual with a separate CNS neoplasm; and the first report of a GTNI with 1p/19q deletions. This case establishes a potential genetic kinship between GTNI and Oligodendroglioma that warrants further investigation.
