Article Figures & Data
Figures
- Fig 1.
Examples demonstrating that the response to bevacizumab is independent of pretreatment tumor volumes: Shown are axial contrast-enhanced T1-weighted MRIs and TRAMs calculated 5 days before bevacizumab treatment and 79 days post-initiation of treatment of a nonresponding patient (left) with a relatively small pretreatment tumor. Also shown are contrast-enhanced T1-weighted MRIs and TRAMs calculated 7 days before bevacizumab treatment and 387 days post-initiation of treatment of a responding patient (right) with a relatively large pretreatment tumor. One month after the initiation of treatment, the nonresponding patient's tumor volumes increased (blue up to 131% of initial volume, and T1, up to 103%). Despite the large initial tumor volume, the responding patient showed significant reduction in tumor volume (blue down to 21% of initial volume, and T1, down to 25%), which remained low for >15 months posttherapy. Both patients showed decreased FLAIR volumes.
- Fig 2.
Response patterns. The mean values of the changes in lesion volumes relative to baseline were plotted separately for the responders (blue) and nonresponders (red) as a function of time (days) after initiation of bevacizumab treatment for the following parameters: enhancing volumes on contrast-enhanced T1-weighted MR imaging, FLAIR hyperintensity volumes on precontrast FLAIR, blue volumes on the TRAMs, and hyperperfused volumes on perfusion-weighted MR imaging–based maps.
- Fig 3.
Kaplan-Maier curves demonstrating the application of 3 MR imaging–based predictors for separating responders to bevacizumab from nonresponders. Shown are Kaplan-Maier curves by using 1-month change (ratio) in T1GdV ≤ 0.32 (upper left), BlueV ≤ 0.29 (upper middle), and HPV ≤ 0.19 (upper right) as predictors for OS. Receiver operating characteristic curves of the 3 predictors applied for prediction of 6-month PFS (left) and 1-year OS (right) are presented below.
- Fig 4.
An example of a patient progressing under bevacizumab and responding to re-irradiation under bevacizumab: Shown are axial contrast-enhanced T1WI (upper row), TRAMs (middle row), and T2 FLAIR images (lower row), at baseline, 27 days, 82 days, and 139 days after initiation of bevacizumab treatment. Lesion volumes at baseline were the following: enhancing T1: 54.1 mL; blue: 21.2 mL; and FLAIR hyperintensity: 165.9 mL. At 1 month, a reduction was seen in all: T1 reached 59% of its baseline volume; blue, 79%; and FLAIR, 43%. At day 83, progression was determined, consistent with the patient's clinical deterioration. T1 reached 84% of its baseline volume (but an increase to 142% relative to the previous scan volume), and blue reached 140% of its baseline volume (an increase to 177% relative to the previous scan), reflecting the stronger sensitivity of TRAMs to progression. FLAIR hyperintensity continued to decrease (25%). At this point, it was decided that the patient should undergo re-irradiation and continue bevacizumab treatment. The next follow-up, at day 139, was acquired 1 month after the initiation of re-radiation. Compared with the previous examination, there was a dramatic increase in FLAIR (172%), as can be expected postirradiation; no change in T1 (99.7%); and a dramatic decrease in blue (61%). In addition, hyperperfused volume increased to 132%; and average apparent diffusion coefficient, to 108% (data not shown). The patient was clinically stable after re-irradiation and lived 5 more months.
Tables
Log-rank analysis of suggested predictorsa
Method Median PFS (95% CI) (mo) (Responders/Nonresponders) P Value (Log-Rank Analysis) Median OS (95% CI) (mo) (Responders/Nonresponders) P Value (Log-Rank Analysis) T1GdV 11.3 (5.6–19.6) .0112 14.8 (11.6–20.7) .0022 2.8 (1.8–4.5) 8.2 (5.4–9.2) BlueV 15.4 (9.1–31.4) <.0001 20.7 (14.6–34.4) <.0001 2.8 (1.3–3.5) 6.9 (5.2–9.2) HPV 5.6 (3.3–9.1) .0837 11.6 (9.0–14.8) .0232 2.8 (1.8–4.5) 6.6 (5.2–9.2) ↵a The patients were divided into responders and nonresponders using predictors from T1GdV, BlueV, and HPV. The median PFS and OS values of the responders and nonresponders as determined by these thresholds are presented and compared with log-rank analysis.
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