gms | German Medical Science

Objective: The transition from WHO grade II to grade III/IV is detrimental for the prognosis of patients with low-grade gliomas. It remains unclear whether improvement of both imaging and surgical techniques has reduced the risk of malignant transformation (MT) over time. In this retrospective, two-institutional study, we estimated malignant transformation rates (MTRs) in 3 cohorts of adult patients with supratentorial WHO grade II gliomas covering a time span of 37 years (1979-2009). All patients received surgically based highly localized initial treatment.

Methods: Study populations referred to 3 distinct treatment epochs, i.e. epoch I (1979-1992; 239 patients undergoing initial brachytherapy), II (1991-1998; 159 patients undergoing tumor resection), and III (1998-2009; 71 patients treated with brachytherapy and/or resection). Median follow-up for the survivors in the respective treatment epochs was >120 months. Adjuvant treatment was always withheld until tumor progression occurred. Reference point was the date of initial treatment. Endpoint was the date of MT which was considered to have occurred in case of i) histologically verified WHO Grade III/IV disease and/or ii) multilocular tumor appearance and/or iii) contrast enhancement of an initially non-enhancing lesion in combination with rapid tumor growth. Secondary endpoint was survival after MT. For survival analyses the Kaplan-Meier method was used. Prognostic factors were assessed with proportional hazards models. Patients’ informed consent and approval by the local ethical review board was obtained.

Results: Patients of the respective treatment epochs did not differ in terms of age and Karnofsky score. Tumors were smaller (p<0.001) and more often left-sided (p=0.002) in epoch I; lobarly located tumors were most often seen in epoch II (p<0.001). 5- (10-) year MTRs ranged from as low as 30.3% (47.1%) to as high as 34% (61%) with no significant difference between the 3 treatment epochs (p=0.4). Kaplan-Meier curves did not level-off even ten years after treatment in either of the cohorts. A larger tumor volume (> 25ml; p=0.002) was a risk factor for MT in each of the cohorts and overall. Neither treatment mode nor extent of resection affected the risk of MT. 1- (2-) year survival after MT ranged from as low as 51.1% (25.5%) to as high as 75.6% (40.1%); it was shortest in epoch I (p=0.02).

Conclusion: Despite advances in imaging and surgical techniques, the risk of MT after localized initial treatment still seems to be predominantly determined by the natural course of the disease.