Recurrent rectal cancer occurs in 5-15% of patients after combined modality therapy. Local recurrences (LR) may be isolated, or occur with metastatic disease¹. Patients with LR following radiotherapy have severe morbidity and a poor quality of life associated with pain, bleeding and obstructive symptoms². Because of its potential to sensitize tumors to radiation and chemotherapy, hyperthermia may improve outcomes for patients with LR. For this purpose, target tissue must be heated in the range of 40 to 43°C over several minutes. In past studies the lack of adequate image guidance resulted in poor control of the energy deposition required to achieve thermal enhancement³. MR-HIFU uses MR temperature measurements acquired every 1-5 seconds in a feedback control loop to achieve a desired therapeutic outcome. Adapting MR-HIFU for mild heating over an extended period increases the requirements for precision and stability of temperature monitoring and control. In this study, we present the preliminary clinical experience on the use of MR-HIFU to deliver mild hyperthermia treatment in the context of recurrent rectal cancer.Figure 1 presents the clinical trial design for this Phase I study, which was approved by the Research Ethics Board of Sunnybrook Health Sciences Centre. In summary, the MR-HIFU mild hyperthermia is added to the standard care of LR performed at our cancer centre. Patients with LR receive fractionated radiation treatment over 17 days (1.8 Gy/day) for a total of 30.6 Gy with concurrent fluropyrimyidine-based chemotherapy. The patient receives three sessions of MR-HIFU mild hyperthermia on days 1, 8 and 15. Each hyperthermia session consists of heating the LR with MR-HIFU with a target temperature and treatment time of 42°C for 30 minutes. MR-HIFU mild hyperthermia was delivered using the Sonalleve MR-HIFU system and an Achieva 3T MRI (Philips Healthcare). Investigational Testing Authorization was granted by Health Canada to use a modified version of the treatment software adapted for hyperthermia. An electronically steered treatment cell with a diameter of 18 mm was used to focus the ultrasound beam and cover the target tissue.Patient was positioned in decubitus position on the treatment table and the three sessions of the MR-HIFU hyperthermia procedure were well tolerated. Figure 1 shows examples of treatment T1- and T2-weighted planning images for the treatment on day 15. Rectal filling with ultrasound gel was applied to reduce bowel motion. The LR was accessible for targeting with MR-HIFU through the sciatic foramen. The target zone was located 8 cm from the skin surface. As precaution, for the very first treatment session the sonication time and target temperature were set conservatively. Figures 2, 3, and 4, shows the observed mean temperature over time in the target zone for the sessions 1, 2 and 3, respectively. The achieved treatment time on session 1 (day 1) was 16 min with an average temperature of 39.8 ± 0.8°C. On session 2 (day 8), a complete 30 min delivery was completed with an average temperature of 39.8 ± 0.8°C. On session 3 (day 15), the treatment was split in 3 smaller hyperthermia deliveries, achieving a total treatment time of 41 min and an average temperature of 40.4 ± 1.3°C, 41.2 ± 0.8°C and 39.9 ± 0.8°C on each of three deliveries. No presence of a thermal lesion was observed in post-treatment T2-weighted imaging done in each session.As the team gained experience, subsequent sessions achieved better delivery of mild hyperthermia. A critical aspect to the success of the procedure was the constant communication with the patient to inquire about any abnormal or painful sensation as the was in close proximity to the sciatic nerve. Three months after the procedure, patient reports no sign of any complication associated to the treatment. A current limitation is the relative lack of maximal depth of LR attainable with the current setup, which is 8 cm.In this study we show the first Phase I clinical trial results of a successful mild hyperthermia delivery using MR-HIFU in the context of treating a local recurrence of rectal cancer. To our knowledge, this is the first reported use of MR–guided focused ultrasound to deliver mild hyperthermia in a patient setting.