Are patients with oligodendroglioma at higher risk for radiation neurotoxicity?
Haroon AhmadSohil H. PatelJoseph DonahueM. Beatriz S. LopesBenjamin PurowDavid SchiffCamilo E. Fadul
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2061 Background: Symptomatic radiation neurotoxicity (RN), manifesting on MRI as focal necrosis and/or T2 signal abnormality, is a dreaded complication of radiation therapy (RT). While RT is standard of care for anaplastic gliomas, the long-term benefit vs risk profile in low-grade gliomas is not well defined. Patients with oligodendroglioma carry a better overall survival than those with astrocytoma. Anecdotally, they are more prone to experience RN than astrocytomas, as suggested by Acharya et al in 2017. We hypothesized that, independent of grade, oligodendrogliomas have a higher incidence of RN as compared to astrocytomas. Methods: We reviewed the records of 628 patients with WHO grade II and III gliomas from our institution. Study population comprised 326 patients with: standard fractionated RT, pathology confirmation by a neuropathologist, and follow up of at least 2 years after diagnosis. RN was defined as either histologically confirmed by pathology or requiring intervention for clinically presumed RN (bevacizumab or high-dose steroids.) A separate category included patients with dramatic cognitive decline with increased T2 signal abnormality, in the absence or tumor progression. Results: There were 131 patients with oligodendroglioma, based upon 1p/19q co-deletion (105 cases) or histology in the absence of molecular testing (26 cases). The remaining 195 patients had astrocytoma with intact 1p/19q, isocitrate dehydrogenase (IDH) wild-type, or diagnosed histologically absent molecular testing. The incidence of RN were 18.3% and 8.2% for oligodendroglioma and astrocytoma, respectively (p = 0.0063). An additional four patients with oligodendroglioma and two with astrocytoma had significant cognitive deterioration with increased T2 signal abnormality, without tumor progression. Conclusions: The greater than two-fold increase in RN incidence for oligodendrogliomas is significant and suggests patients with oligodendrogliomas may be more at risk to develop RN. Therefore, in patients with oligodendroglioma, the consideration of fractionated RT needs to be weighed against the increased potential for RN. Analysis of baseline imaging and patient characteristics variables that correlate with development of RN are ongoing and will be presented at the meeting.Objective To study the significance of molecular genetic alterations of chromosome 1p/19q in differential diagnosis of oligodendroglioma and astrocytoma.Methods Molecular genetic alterations of chromosome 1p/19q were detected with fluorescence in situ hybridization in 63 patients with oligodendroglioma or astrocytoma.Results Polyploid of 1p/19q was in 5 cases(3 cases of astrocytoma and 2 cases of oligodendroglioma).Loss 1p/19q heterozygosity was in 58 cases(41 cases oligodendroglioma and 17 cases of astrocytoma).The loss rates of chromosome 1p,19q and 1p/19q were 65.9%,68.5% and 58.5% respectively in 41 cases of oligodendroglioma,and were 17.6%,29.4% and 17.6% respectively in 17 cases of astrocytoma,which showed significant differences between two groups(P=0.001,P=0.006,P=0.004).Twenty-one cases(87.5%) and 9 cases(52.9%) had typical oligodendrocyte morphological characteristics in 24 oligodendroglioma cases of 1p/19q heterozygosity loss and 17 oligodendroglioma cases of no 1p/19q heterozygosity loss resprctively,which showed significant differences between two groups(P=0.014).Conclusion Loss rate of 1p/19q heterozygosity is higher in oligodendroglioma than that in astrocytoma,and more likely to occur in oligodendroglioma with typical histological features.Polyploidy of chromosome 1p/19q is more common in astrocytoma subtypes.
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Astrocytoma and oligodendroglioma are histologically and genetically well-defined entities. The majority of astrocytomas harbor concurrent TP53 and ATRX mutations while most oligodendrogliomas carry the 1p/19q co-deletion. Both entities share high frequencies of IDH mutations. In contrast, oligoastrocytomas (OA) appear less clearly defined and, therefore, there is an ongoing debate whether these tumors indeed constitute an entity or whether they represent a mixed bag containing both, astrocytomas and oligodendrogliomas. We investigated 43 OA diagnosed in different institutions employing histology, immunohistochemistry and in-situ hybridization addressing the molecular genetic markers IDH1R132H, TP53, ATRX and 1p/19q loss. In all but one OA the combination of nuclear p53 accumulation and ATRX loss was mutually exclusive with 1p/19q co-deletion. In 31/43 OA only alterations typical for oligodendroglioma were observed while in 11/43 OA only indicators typical for astrocytomas were detected. A single case exhibited both, nuclear expression of p53, ATRX loss, IDH1 mutation and 1p/19q loss. However, this was the only patient undergoing radiotherapy prior to surgery, possibly resulting in acquisition of this uncommon combination. In fact, evaluation of the initial lesion demonstrated retained ATRX expression and no p53 upregulation. In OA with oligodendroglioma typical alterations, the portions corresponding to astrocytic part were determined as reactive (harbouring none of the alterations), while in OA with astrocytoma typical alterations the portions corresponding to oligodendroglial differentiation were neoplastic (harbouring identical alterations as the histologically astrocytic part). These data provide strong evidence against the existence of an independent OA entity. (under revision for Acta Neuopathologica)
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Abstract Oligodendroglioma was initially classified in 1926 by Bailey and Cushing1 and was considered to be a differentiated form of medulloblastoma. Three years later, Bailey and Bucy,2 applying a new histological technique developed by Rio-Hortega, proved the presence of oligodendroglia in oligodendrogliomas, and reclassified the tumor to glial lineage. Oligodendroglioma is composed of oligodendroglia (>80%); if greater than 20% of the cells are astrocytic, the tumor is an oligo-astrocytoma.
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One hundred and two cases of central nervous system glial neoplasms composed of varying mixtures of oligodendroglioma, astrocytoma, a n d ependymoma were reviewed.T h e tumors were divided into Grades I a n d 11, and into "compact" types where representative tumor types were located i n separate areas, and "diffuse" types where representative tumor cells were intermingled.
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Data were analysed from 4859 patients with different histological types of intracranial glioma registered by the Norwegian Cancer Registry between 1955 and 1984. Glioblastoma comprised 57.9% of all cases. The second most common primary brain tumour was astrocytoma (19.0%), then mixed glioma (9.2%), oligodendroglioma (7.9%), medulloblastoma (3.1%) and ependymoma (2.9%). A primary brain tumour in a child is approximately twice as likely to be an astrocytoma as a medulloblastoma. The age-specific incidence for glioblastoma increases with age, whereas the incidence of astrocytoma and oligodendroglioma peaks at middle age. Both glioblastoma and astrocytoma showed increased incidence rates over the study period and this was most pronounced in the age-group above 60 years. The prognosis for gliomas varied with age at time of diagnosis, generally being better the younger the patient. For oligodendroglioma patients, survival prospects were independent of age at time of diagnosis. The best prognosis was seen in patients up to 30 years with astrocytoma. Applied in epidemiology, the data indicate that astrocytoma, oligodendroglioma, mixed glioma and ependymoma may be treated as a group which should be separated from both glioblastoma and medulloblastoma.
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Data were analysed from 4859 patients with different histological types of intracranial glioma registered by the Norwegian Cancer Registry between 1955 and 1984. Glioblastoma comprised 57.9% of all cases. The second most common primary brain tumour was astrocytoma (19.0%), then mixed glioma (9.2%), oligodendroglioma (7.9%), medulloblastoma (3.1%) and ependymoma (2.9%). A primary brain tumour in a child is approximately twice as likely to be an astrocytoma as a medulloblastoma. The age‐specific incidence for glioblastoma increases with age, whereas the incidence of astrocytoma and oligodendroglioma peaks at middle age. Both glioblastoma and astrocytoma showed increased incidence rates over the study period and this was most pronounced in the age‐group above 60 years. The prognosis for gliomas varied with age at time of diagnosis, generally being better the younger the patient. For oligodendroglioma patients, survival prospects were independent of age at time of diagnosis. The best prognosis was seen in patients up to 30 years with astrocytoma. Applied in epidemiology, the data indicate that astrocytoma, oligodendroglioma, mixed glioma and ependymoma may be treated as a group which should be separated from both glioblastoma and medulloblastoma.
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