A Phase I Prospective Clinical Trial Using Volumetric Magnetic Resonance-Guided High Intensity Focused Ultrasound (MR-HIFU) Hyperthermia (HT) Combined with Radiotherapy and Chemotherapy for Recurrent Rectal Cancer

Abstract

Non-operable locally recurrent rectal cancer following chemotherapy (CT), radiation therapy (RT) and surgery (Sx) presents an extremely challenging clinical scenario as it portends both poor outcomes and challenging palliation. The addition of HT may improve the local control and quality of life by providing additional sensitization. Herein, we report on the results of our first in human phase I prospective clinical trial of MR-HIFU hyperthermia combined with RT and CT for non-operable recurrent rectal cancer. This ethics-approved study enrolled 6 patients with recurrent inoperable rectal cancer following CT, RT and Sx who were candidates for re-irradiation and chemotherapy; and with an MRI-visible and HIFU-accessible lesion. Patients were prescribed 30.6 Gy delivered in 1.8Gy fractions delivered daily with concurrent oral capecitabine. MR-HIFU HT was delivered immediately before RT on days 1, 8, and 15 under procedural sedation. Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Colorectal cancer (FACT-C) were collected prospectively at baseline and 1, 2, 3, 4 and 12 weeks after treatment. Statistical analysis was performed using paired-samples t-test and repeated measures ANOVA. A p value of ≤ 0.05 was considered significant. Median age of patients was 59.5 (range: 39-76). All had received previous CT, RT and Sx for a prior adenocarcinoma of rectum. 1 patient withdrew from the study due to pre-existing pain issues and received only 1/3 planned HT treatments. There were no intraoperative complications, no adverse events or unintended tissue damage attributable to HT, RT, or CT. Table 1 shows the best single continuous HT and mean temperatures (T90, T10), cumulative time in range (TIR), cumulative number of equivalent minutes at 43oC (CEM43) and day 90 imaging response. There were no attributable grade 2-5 toxicities associated with the intervention. 2 patients had transient grade 1 GI toxicity following intervention. At 90 day follow up, 2 patients had partial response, 2 patients had stable disease and 1 patient had progressive disease. There was no statistically significant difference found using repeated measures ANOVA in FACT-C scores (p = 0.63) and BPI (p = 0.45). Table 1 – HT quality and T2 weighted MRI response. The addition of MR-HIFU HT to re-irradiation with chemotherapy is a novel, feasible and safe treatment modality with no negative impact on patients’ quality of life. Further investigation with a phase II clinical trial in primary rectal cancer may be warranted.Abstract 3424; TableBest Session TemperatureCumulative TIR 40-45°CCumulative CEM43,T50Radiologic ResponsePtMean [oC]T90 [oC]T10 [oC][min][min]0140.6 ± 1.040.1 ± 1.642.1 ± 1.022.72.5PR0242.5 ± 0.241.6 ± 0.243.3 ± 0.251.841.3SD0341.9 ± 0.540.9 ± 2.043.1 ± 0.449.017.7PD0441.5 ± 0.539.9 ± 0.542.8 ± 0.516.36.8Withdrew0539.4 ± 0.638.9 ± 0.940.2 ± 0.54.20.4SD0642.3 ± 0.740.5 ± 0.743.7 ± 0.732.313.5PR Open table in a new tab