Ultra‐early predictive assay for treatment failure using functional magnetic resonance imaging and clinical prognostic parameters in cervical cancer

Abstract

BACKGROUND We prospectively evaluated MRI-parameters quantifying heterogeneous perfusion pattern and residual tumor volume early during treatment in cervical cancer, and compared their predictive power for primary tumor recurrence and cancer death with the standard clinical prognostic factors (CPFs). A novel approach of augmenting the predictive power of CPFs with MRI-parameters was assessed. MATERIALS AND METHODS Sixty-two cervical cancer patients underwent dynamic contrast-enhanced (DCE) MRI before and during early radiation/chemotherapy (2-2.5 weeks into treatment). Heterogeneous tumor perfusion was analyzed by signal intensity (SI) of each tumor voxel. Poorly-perfused tumor regions were quantitated as lower 10th percentile of SI (SI(10%)). DCE-MRI and three-dimensional (3D) tumor volumetry MRI-parameters were assessed as predictors of recurrence and cancer death (median follow-up, 4.1 years). Their discriminating capacity was compared with CPFs (stage, lymphnode status, histology) using sensitivity/specificity and Cox regression analysis. RESULTS SI(10%) and 3D-volume 2-2.5 weeks into therapy independently predicted recurrence (HR=2.6 [1.0-6.5], P=.04; HR=1.9 [1.1-3.5], P=.03, respectively) and death (HR=1.9 [1.0--3.5], P=.03; HR=1.9 [1.2-2.9], P=.01), and were superior to CPFs. The addition of MRI-parameters to CPFs increased sensitivity and specificity of CPFs from 71% and 51% to 100% and 71% for predicting recurrence; and from 79% and 54% to 93% and 60% for predicting death. CONCLUSIONS MRI-parameters reflecting heterogeneous tumor perfusion and subtle tumor volume change early during radiation/chemotherapy are independent and better predictors of tumor recurrence and death than CPFs. Combination of CPFs and MRI-parameters further improves early prediction of treatment failure and may enable a window of opportunity to alter treatment strategy.

Evaluation of Gynecologic Cancer with MR Imaging, 18F-FDG PET/CT, and PET/MR Imaging

“…Quantitative DCE MR imaging parameters have been reported to predict the outcome of cervical cancer radiotherapy (39) and to aid in discriminating benign from malignant adnexal masses (40). These results, if verified by independent investigators, would represent useful tools for development of adaptive therapy and noninvasive diagnosis, respectively.…”

Imaging Tumor Hypoxia to Advance Radiation Oncology

“…DCE-MRI parameters reflecting heterogenous tumor perfusion and subtle tumor volume change early during treatment were independent and better predictors of tumor recurrence and death than clinically accepted prognostic factors (e.g., stage, lymph node status, and histology). The combination of clinical prognostic factors and DCE-MRI parameters improved early prediction of treatment even further (148).…”

Functional magnetic resonance imaging in cervical cancer: Current evidence and future directions

“…A summary of DCE studies evaluating tumor response is provided in Table 2. [44,45,[47][48][49][50][51][52] However, differences in opinion exist regarding baseline tumor enhancement, signal intensity, and clinical outcome. Unlike other studies, Hawighorst and colleagues reported that high contrast tissue exchange rate constant, i.e., >5.4 /min on presurgical DCE-MRI was associated with decreased survival probability.…”

“…[44][45][46] Tumor enhancement or an increase in signal intensity within the first two weeks of treatment are associated with better tumor regression, [47][48][49] local control, disease-free survival, and overall survival. A summary of DCE studies evaluating tumor response is provided in Table 2.…”