Tag: Isocitrate dehydrogenase

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Long-term survivors in 976 supratentorial glioblastoma, IDH-wildtype patients

J Neurosurg 142:174–186, 2025

Glioblastoma, isocitrate dehydrogenase (IDH)–wildtype is the most aggressive glioma with poor outcomes. The authors explored survival rates and factors associated with long-term survival in patients harboring a glioblastoma, IDH-wildtype.

METHODS In an observational, retrospective, single-center study, the authors examined the medical records of 976 adults newly diagnosed with supratentorial glioblastomas, IDH-wildtype between January 2000 and January 2021. They analyzed clinical-, imaging-, and treatment-related factors associated with 2-year and 5-year survival.

RESULTS The median overall survival was 11.2 months (12.2 months for patients included after 2005 and the introduction of standard combined chemoradiotherapy). The median progression-free survival was 9.4 months (10.0 months for patients included after 2005). Overall, 17.6% of patients reached a 2-year overall survival, while 2.2% of patients reached a 5-year overall survival. Furthermore, 6.6% of patients survived 2 years without progression, while 1.1% of patients survived 5 years without progression. Two factors that were consistently associated with 2-year and 5-year survival were first-line oncological treatment with standard combined chemoradiotherapy and methylated O 6 -methylguanineDNA methyltransferase promoter. Other factors that were significantly associated with 2-year or 5-year survival were age at diagnosis ≤ 60 years, headaches or signs of raised intracranial pressure at diagnosis, cortical contact of contrast enhancement, no contrast enhancement crossing the midline on initial imaging, total or subtotal tumor resection, and a second line of oncological treatment at recurrence. Within 21 cases of 5-year survival, 18 were confirmed to be glioblastomas, IDH-wildtype, and 7 of the 5-year survivors (38.9%) had additional genetic alterations: 3 cases had an FGFR mutation or fusion, 3 cases had a PIK3CA mutation, 1 case had a PTPN11 mutation, and 1 case had a PMS2 mutation in the context of constitutional mismatch repair deficiency syndrome.

CONCLUSIONS Five-year overall survival in patients with glioblastoma, IDH-wildtype is extremely low. Predictors of a longer survival are mostly treatment factors, emphasizing the importance of a complete oncological treatment plan, when achievable. Glioblastoma, IDH-wildtype 5-year survivors could be screened for actionable targets in case of recurrence.

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To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment

J Neurosurg 133:273–280, 2020

The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called “high-risk” patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery.

METHODS Based on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma.

RESULTS One hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8–6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance.

CONCLUSIONS In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.

 

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Primary Leptomeningeal Gliomatosis in Children and Adults

Primary Leptomeningeal Gliomatosis in Children and Adults

Neurosurgery 78:343–352, 2016

Primary leptomeningeal gliomatosis (PLG) is a poorly recognized tumor of the central nervous system.

OBJECTIVE: To describe the histopathological, immunohistochemical, and molecular features of PLG.

METHODS: Results of our multicentric retrospective study of 6 PLG cases (3 pediatric and 3 adult) were compared with literature data.

RESULTS: The mean age was 54.7 years for adults and 8.7 years for children, with 3 males and 3 females. Clinical symptoms were nonspecific. Cerebrospinal fluid analyses showed a high protein level often associated with pleocytosis but without neoplastic cells. On neuroimaging, diffuse leptomeningeal enhancement and hydrocephalus were observed, except in 1 case. PLG was mostly misinterpreted as infectious or tumoral meningitis. The first biopsy was negative in 50% of cases. Histopathologically, PLG cases corresponded to 1 oligodendroglioma without 1p19q codeletion and 5 astrocytomas without expression of p53. No immunostaining for IDH1R132H and no mutations of IDH1/2 and H3F3A genes were found. Overall survival was highly variable (2-82 months) but seems to be increased in children treated with chemotherapy.

CONCLUSION: This study shows the difficulties of PLG diagnosis. The challenge is to achieve an early biopsy to establish a diagnosis and to begin a treatment, but the prognosis remains poor. PLG seems to have a different molecular and immunohistochemical pattern compared with intraparenchymal malignant gliomas.

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