Author: Himanshu Bhat, Bruce Lewis Daniel, Junghoon Lee, Michael B. Roumeliotis, Ehud J. Schmidt, Ravi Seethamraju, Khadija Sheikh, Pan Su, Akila N. Viswanathan 👨🔬
Affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Siemens Medical Solutions USA Inc., Stanford Medical School, Department of Cardiology, Johns Hopkins University 🌍
Purpose: To perform frequent MRI during EBRT and brachytherapy (BT) to evaluate RT-induced fibrosis and remnant tumor changes, identified using ultrashort echo-time (UTE) and multiparametric (mpMRI), in gynecologic cancer patients.
Methods: Patients underwent whole-pelvis EBRT followed by interstitial HDR-BT, receiving 71-79.8Gy total dose. MR images were acquired on a 1.5T scanner pre-RT, during EBRT weeks 1,2,3,6, and 1-week post-BT. Diffuse-fibrosis (FDiffuse) and Dense-fibrosis (FDense) UTE-imaging (research application) was performed, as previously detailed (Sheikh, Radiation Oncology (2024)). MR images at all RT time-points (i=1,2..5) were co-registered to the Pre-RT (i=0) scan. The remnant tumor-volume at all time-points (GTVi) was contoured using mpMRI by a radiologist. The mean FDiffuse and FDense signal-intensities within the pre-treatment tumor volume (GTV0), the remnant tumor, and the responsive region (=GTV0-GTVi) at each time-point were calculated. The rate of tumor-volume change as a function of dose was correlated with the rate of change in FDense as a function of dose using Spearman correlation.
Results: Across three gynecologic cancer patients with squamous-cell-carcinoma (tumor-volume: 58±16 cm³), mean FDense within the pre-RT GTV (GTV0) increased with dose, but at variable rates, resulting in a 200% increase. FDiffuse peaked in a specific dose-range (14.4-21.6Gy), coinciding with a strong increase in FDense accumulation. Focusing on different tissue regions; in the responsive region, FDiffuse decreased after 14.4-21.6Gy, while FDense first strongly increased and then plateaued. In the remnant tumor, FDense rose by 20% following brachytherapy. Tumor-volume rates-of-change significantly correlated with FDense rates of change (r=-0.58, p=.03).
Conclusion: The similarity between the patients, and the distinct patterns of FDense and FDiffuse evolution during RT indicate that fibrosis accumulation is not uniform. The FDense rate change and the peak of FDiffuse at 14.4-21.6Gy suggest that fibrosis type and progression serve as indicators of transition between dose-response phases, which may permit its use to adapt therapy.