Dynamic contrast-enhanced magnetic resonance imaging as a prognostic factor in predicting event-free and overall survival in pediatric patients with osteosarcoma

Abstract

Background: The objective of this study was to prospectively evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event-free survival (EFS) and overall survival in pediatric patients with newly diagnosed, nonmetastatic osteosarcoma who were treated on a single, multi-institutional phase 2 trial.

Methods: Three serial DCE-MRI examinations at week 0 (before treatment), week 9, and week 12 (tumor resection) were performed in 69 patients with nonmetastatic osteosarcoma to monitor the response to preoperative chemotherapy. Four DCE-MRI kinetic parameters (the influx volume transfer constant [K(trans) ], the efflux rate constant [k(ep) ], the relative extravascular extracellular space [v(e) ], and the relative vascular plasma space [v(p) ]) and the corresponding differences (ΔK(trans) , Δk(ep) , Δv(e) , and Δv(p) ) of averaged kinetic parameters between the outer and inner halves of tumors were calculated to assess their associations with tumor histologic response, EFS, and overall survival.

Results: The parameters K(trans) , v(e) , v(p) , and k(ep) decreased significantly from week 0 to week 9 and week 12. The parameters K(trans) , v(p) , and Δk(ep) at week 9 were significantly different between responders and nonresponders (P = .046, P = .021, and P = .008, respectively). These 3 parameters were indicative of histologic response. The parameter Δv(e) at week 0 was a significant prognostic factor for both EFS (P = .02) and overall survival (P = .03).

Conclusions: DCE-MRI was identified as a prognostic factor for EFS and overall survival before treatment on this trial and was indicative of a histologic response to neoadjuvant therapy. Further studies are needed to verify these findings with other treatment regimens and establish the potential role of DCE-MRI in the development of risk-adapted therapy for osteosarcoma.

Figure 1

Schedule diagram of serial DCE-MRI examinations (white background) and tumor treatment (gray background).

Figure 2

The contrast-enhanced image, K^trans map, and v_e map in baseline examination are displayed from left to right. The red line is the boundary of tumor ROI drawn by a radiologist, and the black line was automatically generated to divide each tumor ROI into inner and outer halves. Images in the upper row are for a patient who was a responder and was alive without event at the time of analysis; images in the lower row are for a nonresponder who died after disease relapse. All the grayscale images are in the same gray scale. All the color maps are in the same color scale, and the color bar is displayed on the right.

Figure 3

Bar plots of average values of DCE-MRI parameters of interest for all patients. (a) K^trans, v_e, and v_p are measured on the left axis and k_ep on the right axis; (b) ΔK^trans (outer-inner), Δv_e, and Δv_p on the left axis and Δk_ep on the right axis. Std represents standard deviation.

Figure 4

Bar plots of DCE-MRI parameters K^trans (a) and v_p (b) for responders and nonresponders at three time points. P-values less than 0.1 are displayed at the corresponding time points. Dark bars represent nonresponders; lighter gray bars represent responders.

Figure 5

Bar plots of DCE-MRI parameters ΔK^trans (a) and Δk_ep (b) for responders and nonresponders at three time points. P-values less than 0.1 are displayed at the corresponding time points. Dark bars represent nonresponders; lighter gray bars represent responders. Std represents standard deviation.

Figure 6

Bar plots of DCE-MRI parameters ΔK^trans (a) and Δv_e (b) at three time points for patients with and without events. P-values less than 0.1 are displayed at the corresponding time points. Lighter gray bars represent patients without events; Dark bars represent patients with events. Std represents standard deviation.

Figure 7

Event-free survival curves for subgroups stratified by the median value of ΔK^trans (a) and Δv_e (b) at week 0. P-values were obtained from exact log-rank tests.

Figure 8

ROC curve of Δv_e at baseline examination in discriminating between EFS and non-EFS patients. Area under curve is equal to 0.70 with a sensitivity (True Positive Rate) of 0.68 and a specificity (1- False Postive Rate) of 0.7 at the optimal cutpoint of Δv_e=0.032. Similarly, the median value of Δv_e=0.026 in Figure 7b corresponds to a sensitivity of 0.68 and a specificity of 0.65.

Figure 9

Bar plots of DCE-MRI parameters ΔK^trans (a) and Δv_e (b) at three time points for patient survival status. P-values less than 0.1 are displayed at the corresponding time points. Lighter gray bars represent patients alive at the time of analysis; Dark bars represent dead patients. Std represents standard deviation.