Contrast‐enhancing tumor growth dynamics of preoperative, treatment‐naive human glioblastoma

Abstract

BACKGROUND:Little is known about the natural growth characteristics of untreated glioblastoma before surgical or therapeutic intervention, because patients are rapidly treated after preliminary radiographic diagnosis. Understanding the growth characteristics of uninhibited human glioblastoma may be useful for characterizing changes in response to therapy. Thus, the objective of the current study was to explore tumor growth dynamics in a cohort of patients with untreated glioblastoma before surgical or therapeutic intervention. METHODS: Ninety-five patients with glioblastoma who had measurable enhancing disease on >2 magnetic resonance imaging scans before surgery were identified. Tumor growth rates were quantified in 4 different ways (the percentage change per day, the absolute rate of change per day, the estimated volumetric doubling time, and the radial expansion rate) using 3 different approaches (bidirectional product, enhancing disease, and total lesion volume). RESULTS: The median volumetric doubling time was 21.1 days, the percentage change in tumor volume was 2.1% per day, and the rate of change in total lesion volume was 0.18 cc per day. The length of follow-up between magnetic resonance imaging examinations should be >28 days to detect progressive disease with high specificity. Small initial tumor sizes (<3 cm in greatest dimension) are biased toward a large percentage change at follow-up. CONCLUSIONS: Presurgical, treatment-naive glioblastoma growth dynamics can be estimated in a variety of ways with similar results. The percentage changes in tumor size and volume depend on baseline tumor size and the time interval between scans.

Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials

“…For example, the current RANO criteria requires use of bidirectional measurements of contrast enhancing tumor size, which have been shown to overestimate tumor volume [53] and result in higher reader discordance [8, 54–59], presumably due to differences in head tilt and accurate identification of longest and perpendicular diameter in relatively irregular tumors. Other studies have shown reasonable agreement between bidimensional and volumetric measurements [60, 61], suggesting quick bidimensional assessment of contrast enhancing tumor size may be a practical alternative to more sophisticated volumetric segmentation. Additionally, the thresholds used to define response and progression is relatively arbitrary and not optimized based on scientific data showing the best correlation with survival benefit or time to treatment failure.…”

“…(Note: The efficacy of these thresholds remains to be sufficiently challenged). Also, the use of thresholds based on “percentage change” with respect to baseline tumor size are significantly biased toward small tumors where relatively low absolute changes in tumor size are interpreted as a large percentage change [61]. This is particularly an issue in newly diagnosed GBM studies, where patients with tiny tumors often progress early due to triggering of progression (PD) when “non-measurable disease”, defined as having the two largest perpendicular diameters of a contrast enhancing target lesion less than 10mm, reaches the subtle threshold of “measurable disease”.…”

Angiogenesis and radiological tumor growth in patients with glioblastoma

“…Biological reasons for why some GBMs grow faster than others are sparsely studied in human patients, which is mainly due to difficulties in acquiring in vivo pretreatment growth estimates [10, 11]. In addition, most research on growth processes have been conducted on in vitro or animal models which fail to accurately imitate the unique micro-milieu of the human GBM [30].…”

“…GBMs are characterized by a highly heterogenous histopathology [3–5], a high secretion of pro-angiogenic factors [6, 7], extensive vascularity [8, 9], and rapid pretreatment growth [10, 11]. The pretreatment growth has been shown to vary considerably among patients [10] and slower growth to be an independent predictor of long term survival in patients with GBM [12].…”

Glioblastoma Segmentation: Comparison of Three Different Software Packages

“…This is a commonly used glioblastoma tumor volume definition, but it could be seen as a limitation to our study that we lack information about segmentation of tumor in T 2 /FLAIR images. The contrast enhancing compartment, with or without the central necrosis, is currently being used for measuring extent of tumor resection, preoperative tumor growth, and progression of tumors after treatment, as suggested in the RANO criteria [6, 31, 32]. For primary glioblastomas, the most relevant additional tumor compartment to segment would be the edema surrounding the tumor, as seen on T 2 or FLAIR images, which is known to encompass varying degrees of infiltrating tumor cells.…”