Response Assessment Challenges in Clinical Trials of Gliomas

Abstract

Accurate, reproducible criteria for determining tumor response and progression after therapy are critical for optimal patient care and effective evaluation of novel therapeutic agents. Currently, the most widely used criteria for determining treatment response in gliomas is based on two-dimensional tumor measurements using neuroimaging studies (Macdonald criteria). In recent years, the limitation of these criteria, which only address the contrast-enhancing component of the tumor, have become increasingly apparent. This review discusses challenges that have emerged in assessing response in patients with gliomas and approaches being introduced to address them.

L’épilepsie associée aux tumeurs cérébrales

“…La fréquence de survenue des crises d'épilepsie au cours de la maladie croît à 50 % lorsque l'on se limite aux lésions supratentorielles limitées à un hémisphère. La fréquence des crises épilepti-ques est plus faible chez les sujets âgés que chez les sujets jeunes [1,9,[11][12][13][14][15][16]. Alors que l'épilepsie est un symptôme inaugural plus fréquent dans les gliomes infiltrants de bas grade de malignité que dans ceux de haut grade, la fréquence cumulée de l'épilepsie au cours de l'histoire naturelle de la maladie est similaire dans les gliomes infiltrants de haut grade et de bas grade de malignité [1].…”

Response Assessment in Neuro-Oncology

“…This is a particular limitation for tumors that are primarily nonenhancing, including some anaplastic gliomas. In addition, contrast enhancement is nonspecific and primarily reflects passage of contrast material across a disrupted blood-brain barrier [13]. The amount and extent of enhancement may be influenced by factors that are not related to the tumor, such as differences in radiologic techniques, the amount of contrast enhancement administered, the timing of the contrast enhancement in relationship to image acquisition, postsurgical changes [15], infarction [16], treatment-related inflammation, seizure activity [17], subacute radiation effects, radiation necrosis [18], and changes in corticosteroid doses [19,20].…”

“…While this phenomenon has been described with radiation alone, it is enhanced by the addition of temozolomide to radiotherapy, particularly in GBM patients with methylated O6-methylguanine-DNA methyltransferase (MGMT) [13,21,22]. In studies of GBM patients treated with radiation and concurrent temozolomide, the first post-radiation MRI showed increased enhancement in approximately 40% to 50% [21,23,24].…”

Neuroradiological Response Criteria for High-grade Gliomas

“…Progression-free survival (PFS), radiographic response rate (RR) and overall survival (OS) are the most commonly used endpoints in clinical studies. In contrast to OS, both PFS and RR rely on accurate and reproducible methods to determine tumor progression [5,6]. with more effective therapies expected to come the definition of progression also influences the decision whether and when to switch from one form of treatment to another and could therefore guide relevant daily clinical decisions.…”

“…in most cases the effecti- [6] veness of an experimental therapy is overestimated, as the change of therapy was based on pseudoprogression. this limits the validity of the PFS of a tumor-specific therapy and has significant implications for selecting patients for clinical relapse studies.…”