Abstract
We aimed to analyze the value of seizure reduction and radiological response as prognostic markers of survival in patients with low-grade glioma (LGG) treated with temozolomide (TMZ) chemotherapy. We retrospectively reviewed adult patients with a progressive LGG and uncontrolled epilepsy in two hospitals (VUmc Amsterdam; MCH The Hague), who received chemotherapy with TMZ between 2002 and 2014. End points were a ≥50 % seizure reduction and MRI response 6, 12 and 18 months (mo) after the start of TMZ, and their relation with progression-free survival (PFS) and overall survival (OS). We identified 53 patients who met the inclusion criteria. Seizure reduction was an independent prognostic factor for both PFS (HR 0.38; 95 % CI 0.19–0.73; p = 0.004) and OS (HR 0.39; 95 % CI 0.18–0.85; p = 0.018) after 6mo, adjusting for age and histopathological diagnosis, as well as after 12 and 18mo. Patients with an objective radiological response showed a better OS (median 87.5mo; 95 % CI 62.0–112.9) than patients without a response (median 34.4mo; 95 % CI 26.1–42.6; p = 0.046) after 12mo. However, after 6 and 18mo OS was similar in patients with and without a response on MRI. Seizure reduction is an early and consistent prognostic marker for survival after treatment with TMZ, that seems to precede the radiological response. Therefore, seizure reduction may serve as a surrogate marker for tumor response.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-015-1975-y) contains supplementary material, which is available to authorized users.
Highlights
Diffuse low-grade gliomas (LGGs) are slowly growing, diffuse infiltrative brain tumors, including astrocytomas, mixed oligoastrocytomas and oligodendrogliomas, that mainly affect young adults [1, 2]
We previously showed that a seizure reduction 6 months after the start of TMZ is associated with a longer survival in LGG patients [20]
Response to TMZ treatment based on radiological assessment is difficult in LGG, as on MRI a minor response is often the best achievable response category and measuring tumor size can be challenging [7]
Summary
Diffuse low-grade gliomas (LGGs) are slowly growing, diffuse infiltrative brain tumors, including astrocytomas, mixed oligoastrocytomas and oligodendrogliomas, that mainly affect young adults [1, 2]. Median survival generally ranges between 2 and 20 years, depending on histopathological subtype, age, tumor size and performance status [3,4,5]. Assessing response to antitumor treatment is a major challenge in LGG patients. Diffuse LGGs are predominantly non-contrast enhancing diffusely infiltrative tumors, hampering radiographic assessment. The use of objective radiological response as an outcome measure has serious drawbacks, and there is a strong need for complementary measures to determine outcome and to define the benefit of antitumor treatment [8]
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