Predicting control of primary tumor and survival by DCE MRI during early therapy in cervical cancer

Abstract

Purpose: To assess the early predictive power of MRI perfusion and volume parameters, during early treatment of cervical cancer, for primary tumor control and disease-free-survival.

Materials and methods: Three MRI examinations were obtained in 101 patients before and during therapy (at 2-2.5 and 4-5 weeks) for serial dynamic contrast enhanced (DCE) perfusion MRI and 3-dimensional tumor volume measurement. Plateau Signal Intensity (SI) of the DCE curves for each tumor pixel of all 3 MRI examinations was generated, and pixel-SI distribution histograms were established to characterize the heterogeneous tumor. The degree and quantity of the poorly-perfused tumor subregions, which were represented by low-DCE pixels, was analyzed by using various lower percentiles of SI (SI%) from the pixel histogram. SI% ranged from SI2.5% to SI20% with increments of 2.5%. SI%, mean SI, and 3-dimensional volume of the tumor were correlated with primary tumor control and disease-free-survival, using Student t test, Kaplan-Meier analysis, and log-rank test. The mean post-therapy follow-up time for outcome assessment was 6.8 years (range: 0.2-9.4 years).

Results: Tumor volume, mean SI, and SI% showed significant prediction of the long-term clinical outcome, and this prediction was provided as early as 2 to 2.5 weeks into treatment. An SI5% of <2.05 and residual tumor volume of > or =30 cm(3) in the MRI obtained at 2 to 2.5 weeks of therapy provided the best prediction of unfavorable 8-year primary tumor control (73% vs. 100%, P = 0.006) and disease-free-survival rate (47% vs. 79%, P = 0.001), respectively.

Conclusions: Our results show that MRI parameters quantifying perfusion status and residual tumor volume provide very early prediction of primary tumor control and disease-free-survival. This functional imaging based outcome predictor can be obtained in the very early phase of cytotoxic therapy within 2 to 2.5 weeks of therapy start. The predictive capacity of these MRI parameters, indirectly reflecting the heterogeneous delivery pattern of cytotoxic agents, tumor oxygenation, and the bulk of residual presumably therapy-resistant tumor, requires future study.

Fig. 1. Favorable clinical outcome with high perfusion status early during treatment in a large tumor

Pre-contrast sagittal T₂-weighted image (A) shows a large cervical cancer (arrows) indicating poor prognosis as judged by FIGO criteria. Corresponding DCE MRI at the plateau phase of the DCE imaging (B) shows the large tumor (arrows) with intense and heterogeneous dynamic contrast enhancement, indicating high tumor perfusion during the early part (2 weeks) of the 8-week treatment course. Tumor SI-pixel histogram (C) of the tumor is generated with the SI of the entire tumor pixels by plotting the SI of each tumor pixel along the x-axis and the number of pixels with same SI (frequency) along the y-axis. From this tumor SI-histogram, tumor size (area under the DCE curve) can be calculated. The quantity and degree of low DCE sub-population was quantified by computing SI percentiles. In this case, the 5^th percentile (SI5%) (arrow, C) was 2.41, indicating that 5% of the pixels within the heterogeneous tumor fall below an SI of 2.41. This patient had excellent treatment outcome and survived for the past 8 years. Signal intensity-time DCE curves (D) again show abrupt and intense contrast enhancement of the tumor, indicating high tumor perfusion in both MRI 1 (gray-colored curve) and MRI 2 (blue-colored curve), and predicting excellent response and long-term outcome to treatment.

Fig. 2. Poor clinical outcome with low perfusion status early during treatment for a small tumor

Pre-contrast sagittal T₂-weighted image (A) showed a much smaller cervical cancer (arrows), as compared to Fig. 1, indicating a more favorable prognosis as judged by FIGO criteria. Corresponding DCE MRI at the plateau phase of the DCE imaging (B) showed the small tumor (arrows) with poor contrast enhancement indicating low tumor perfusion during early part (2 weeks) of the treatment course (8 weeks). From the tumor SI-pixel histogram (C), the low-DCE sub-population was characterized by 5^th percentile of SI (SI5%). SI5% was much lower (1.34) than that of Fig. 1 (2.41). This patient had a primary tumor recurrence at 2 months after completion of therapy, and died 6 months after completion of therapy. Signal intensity-time DCE curves (D) again show sluggish and low contrast enhancement of the tumor mass indicating low tumor perfusion and poor response to treatment. In contrast to Figure 1, tumor perfusion remains low even 2–3 weeks after initiation of therapy (blue-colored curve) and is similar to that of the pretreatment (gray-colored curve).

Fig. 3. Primary tumor control and disease-free survival based on SI5% at MRI 2

Kaplan Meier Life Table analysis shows a significantly better 8-year primary tumor control rate for patients with SI5% ≥2.05, compared to those patients with lower SI5% indicative of low DCE (100% vs. 73%, p= 0.006, Log rank test).

Fig. 4. Primary tumor control and disease-free survival based on tumor volume V2 at MRI 2

Kaplan Meier Life table analysis shows a significantly better 8-year disease-free survival for patients with a V2 <30 cm³, compared to those patients with higher V2 (79 vs. 47%, p= 0.001, Log rank test).