Dynamic contrast enhanced magnetic resonance imaging for hypoxia mapping and potential for brachytherapy targeting

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) may be used to visualize tumor hypoxia, and was in this work explored in treatment planning of hypoxia-guided brachytherapy of patients with locally advanced cervical cancer (LACC). Pharmacokinetic ABrix maps were derived from DCE-MR images taken prior to chemoradiotherapy of 78 patients with LACC. A logistic regression procedure was used to segment the tumor volume fraction from the ABrix maps that showed the strongest association with patient survival, denoted biological target volume (BTV) fraction. A hypoxia gene score was calculated from a biopsy-based gene signature and correlated against the BTV fraction. Brachytherapy planning based on the ABrix maps was performed, for 23 patients. A general planning aim was a minimum D90 dose of 7.5Gy to the tumor per brachytherapy fraction. Two planning approaches were explored: (1) a conventional uniform and (2) a non-uniform approach targeting the BTV to the highest dose possible. The segmented BTV fraction was significantly associated local and locoregional control (P=0.025) and the hypoxia gene score (P=0.002). Comparing brachytherapy approaches 1 and 2, it was possible to dose escalate the BTV with 0.4Gy per fraction in median (D90; cohort range [0, 3.8]). Some tumors could not be dose escalated without violating the dose constraints to the organs at risk. Tumor regions associated with hypoxia may be targeted with brachytherapy. The presented methodology may become useful in future strategies to improve cure probability of resistant tumors.