Method and timing of tumor volume measurement for outcome prediction in cervical cancer using magnetic resonance imaging

Recently, imaging-based tumor volume before, during, and after radiation therapy (RT) has been shown to predict tumor response in cervical cancer. However, the effectiveness of different methods and timing of imaging-based tumor size assessment have not been investigated. The purpose of this study was to compare the predictive value for treatment outcome derived from simple diameter-based ellipsoid tumor volume measurement using orthogonal diameters (with ellipsoid computation) with that derived from more complex contour tracing/region-of-interest (ROI) analysis 3D tumor volumetry.Serial magnetic resonance imaging (MRI) examinations were prospectively performed in 60 patients with advanced cervical cancer (Stages IB2-IVB/recurrent) at the start of RT, during early RT (20-25 Gy), mid-RT (45-50 Gy), and at follow-up (1-2 months after RT completion). ROI-based volumetry was derived by tracing the entire tumor region in each MR slice on the computer work station. For the diameter-based surrogate "ellipsoid volume," the three orthogonal diameters (d1, d2, d3) were measured on film hard copies to calculate volume as an ellipsoid (d1 x d2 x d3 x pi/6). Serial tumor volumes and regression rates determined by each method were correlated with local control, disease-free and overall survival, and the results were compared between the two measuring methods. Median post-therapy follow-up was 4.9 years (range, 2.0-8.2 years).The best method and time point of tumor size measurement for the prediction of outcome was the tumor regression rate in the mid-therapy MRI examination (at 45-50 Gy) using 3D ROI volumetry. For the pre-RT measurement both the diameter-based method and ROI volumetry provided similar predictive accuracy, particularly for patients with small (<40 cm3) and large (> or =100 cm3) pre-RT tumor size. However, the pre-RT tumor size measured by either method had much less predictive value for the intermediate-size (40-99 cm3) tumors, which accounted for the majority of patients (55%). Tumor regression rate (fast vs. slow) obtained during mid-RT (45-50 Gy), which could only be appreciated by 3D ROI volumetry, had the best outcome prediction rate for local control (84% vs. 22%, p < 0.0001) and disease-free survival (63% vs. 20%, p = 0.0005). Within the difficult to classify intermediate pre-RT size group, slow ROI-based regression rate predicted all treatment failures (local control rate: 0% vs. 91%, p < 0.0001; disease-free survival: 0% vs. 73%, p < 0.0001). Mid-RT regression rate based on simple diameter measurement did not predict outcome. The early-RT and post-RT measurements were least useful with either measuring method.Our preliminary data suggest that for the prediction of treatment outcome in cervical cancer, initial tumor volume can be estimated by simple diameter-based measurement obtained from film hard copies. When initial tumor volume is in the intermediate size range, ROI volumetry and an additional MRI during RT are needed to quantitatively analyze tumor regression rate for the prediction of treatment outcome.