Transformation of low grade glioma and correlation with outcome: an NCCTG database analysis

Abstract

Introduction Glioblastomas (GBM) may originate de novo (primary), or following transformation from a lower grade glioma (secondary), and it has been postulated that these tumors may have different biological behaviors. Methods We performed a correlative analysis involving 204 patients with glioma treated prospectively on NCCTG clinical trials. Central pathology review of tumor tissues taken at the time of initial diagnosis and at recurrence were performed in all patients. Results Tumors progressed from low (WHO grade 2) to high (grade 3–4) at recurrence in 45% low grade oligodendroglioma patients, in 70% with low grade oligoastrocytoma, and 74% with low grade astrocytoma (p=0.031). Median overall survival (OS) from initial diagnosis varied by histology: oligodendroglioma, 8.8 years; (95% CI 5.7–10.2); oligoastrocytoma, 4.4 years (95% CI 3.5–5.6); astrocytoma grade 2 3.1 years (astrocytoma grade 2–4, 2.1 years) (95% CI 1.7–2.5, p<0.001). Mean time to recurrence (TTR) also varied between patients with de novo GBM, those secondary GBM, and those that remained non-GBM at recurrence (1.1 ± 1.1 years vs. 2.9 ± 1.8 vs. 4.0 ± 2.9, respectively, p < 0.001). Median OS from time of recurrence also varied between these three categories (0.7 years, 95% CI: 0.5–1.1 vs.0.6 years, CI: 0.5–1.0 vs. 1.4 years, 95% CI: 1.1–2.0, respectively) (p <0.001). Conclusions At time of relapse, transformation to higher grade is frequent in low grade pure and mixed astrocytomas, but is observed in less than half of those with low grade oligodendroglioma. From time of recurrence, OS was not significantly different for those with primary versus secondary GBM, and it may thus be reasonable include patients with secondary GBM in clinical therapeutic trials for recurrent disease.

Diffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers

“…The favourable clinical prognostic factors of astrocytomas include younger age, preoperative high KPS and gross total removal of the tumour. The clinical course of astrocytoma patients largely depends on the timing of malignant progression [26,55].…”

Multiparametric evaluation of low grade gliomas at follow-up: comparison between diffusion and perfusion MR with 18F-FDOPA PET

“…1 The natural history of these lesions is constant disease progression towards malignant transformation, with different times and percentages according to histology. 2 The main imaging challenges at diagnosis and follow-up consist of correct tumour grading, delineation of disease volume and prognosis definition. This is especially important because so far, there is no clear consensus on the correct therapeutic management and a holistic knowledge of the tumour on an individual-based approach has been suggested.…”

Genomic Profiles of Glioma

“…Primary and secondary GBM are histologically indistinguishable, but at the molecular level each type demonstrates distinct patterns of genetic alterations and these have long been thought to represent different routes of molecular pathogenesis to a common histopathologic end point [4]. Diffuse astrocytomas (or low-grade astrocytoma, WHO II) and anaplastic astrocytoma (WHO III) appear to share a common lineage with secondary GBM such that there is an accumulation of mutations that, over time, lead to transformation to higher histologic grade [5,6].…”