RESUMO
BACKGROUND AND OBJECTIVES: Isocitrate dehydrogenase (IDH)-mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the premolecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival (OS) in patients with IDH-mutant astrocytomas. METHODS: Patient data from 2 centers (Sahlgrenska University Hospital, Center A; LMU University Hospital, Center B) were collected retrospectively. Inclusion criteria were as follows: pre and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003 and 2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and OS. RESULTS: The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median OS was 134 months and did not differ between the cohorts (P = .29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 vs 4.6 cm3, P = .03). The median extent of resection in these patients was 65% vs 90% (P = .03). The ratio itself did not correlate with OS. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (hazard ratio 1.02, 95% CI 1.01-1.03, P < .01). CONCLUSION: The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.
RESUMO
The 2021 World Health Organization (WHO) grading system of isocitrate dehydrogenase (IDH)-mutant astrocytomas relies on histological features and the presence of homozygous deletion of the cyclin-dependent kinase inhibitor 2A and 2B (CDKN2A/B). DNA methylation profiling has become highly relevant in the diagnosis of central nervous system (CNS) tumors including gliomas, and it has been incorporated into routine clinical diagnostics in some countries. In this study, we, therefore, examined the value of DNA methylation-based classification for prognostication of patients with IDH-mutant astrocytomas. We analyzed histopathological diagnoses, genome-wide DNA methylation array data, and chromosomal copy number alteration profiles from a cohort of 385 adult-type IDH-mutant astrocytomas, including a local cohort of 127 cases and 258 cases from public repositories. Prognosis based on WHO 2021 CNS criteria (histological grade and CDKN2A/B homozygous deletion status), other relevant chromosomal/gene alterations in IDH-mutant astrocytomas and DNA methylation-based subclassification according to the molecular neuropathology classifier were assessed. We demonstrate that DNA methylation-based classification of IDH-mutant astrocytomas can be used to predict outcome of the patients equally well as WHO 2021 CNS criteria. In addition, methylation-based subclassification enabled the identification of IDH-mutant astrocytoma patients with poor survival among patients with grade 3 tumors and patients with grade 4 tumors with a more favorable outcome. In conclusion, DNA methylation-based subclassification adds prognostic information for IDH-mutant astrocytomas that can further refine the current WHO 2021 grading scheme for these patients.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Metilação de DNA , Isocitrato Desidrogenase , Mutação , Humanos , Astrocitoma/genética , Astrocitoma/patologia , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Adulto , Idoso , Gradação de Tumores/métodos , Estudos de Coortes , Inibidor p16 de Quinase Dependente de Ciclina/genéticaRESUMO
Background: The Mediterranean Region of the West Palearctic is one of the most species-rich biomes in the world, hosting a high level of endemism and relict species with important conservation value. The North Africa Atlas Mountains (spanning Morocco, Algeria and Tunisia) belong to a poorly-investigated region of the Mediterranean area, with overlooked aquatic biodiversity; hence, a number of species still remain to be discovered. New information: The subgenus Antocha (Antocha) Osten Sacken, 1860 is recorded for the first time from Africa, with a description of A. (A.) staryi Keresztes & Mabrouki sp. nov. from hilly regions of the Middle Atlas region, Morocco. The unique design of the male terminalia differentiates well the newly-discovered species from its closely-related and range-restricted A. (A.) phoenicia Thomas and Dia, 1982. This is in contrast with the high intraspecific and geographically poorly-defined variability of the widespread A. (A.) vitripennis (Meigen, 1830), for which morphological variability of male genital structures is discussed.Illustrations of male genital parts, distribution data and key to the species from the West Palearctic area are also provided.