Marieke van Son

88 CHAPTER 5 biopsies at their referring center. All patients had at least two years recurrence-free interval after primary radiation treatment. We analyzed the first consecutive 50 patients, treated between July 2013 and April 2017. This group consists of 23 patients from the feasibility study and 27 patients treat- ed off-protocol. All patients were followed in the same prospective manner. Informed consent was obtained from all study patients. For patients treated off- protocol, the IRB waived the requirement for informed consent. Ultrafocal salvage HDR-BT The treatment procedure has been described in a previous paper. 11 In summary, the radiation plan is based on delineations of the gross tumor volume (GTV), the clinical target volume (CTV, GTV+5mm margin) and the organs at risk (OAR’s), namely bladder, rectum and urethra. Under spinal anesthesia, MR-compatible brachytherapy catheters are perineally inserted into the CTV, guided by fused TRUS/MR images. Another 1.5T MRI is made for catheter reconstruction, contour adaptation and a simulation of dose distribution by the Oncentra Prostate treatment planning system (Elekta, The Nether- lands). The dosimetric goal is to deliver ≥19 Gy to 95% of the CTV (CTV D95%), with a lower threshold of >17 Gy to 90% of the CTV (CTV D90%). Dose constraints for bladder and rectum D1cc (minimal dose to the most exposed 1 cc) is <12 Gy and for the urethra D10% (minimal dose to 10% of the urethra) <17.7 Gy. An additional 1.5T MRI-scan is made just before dose administration to check for any catheter displacements to ensure safe delivery of the planned radiation dose. Outcome assessment Follow-up is scheduled four weeks after treatment and every three months in the first year, every six months in the second year and annually thereafter for up to 10 years. At each time point, outcome assessment is performed by (1) grading GU, GI and erectile toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and by obtaining IPSS and International Index of Erectile Function (IIEF-5) scores, (2) assessing patient-reported QoL using the RAND-36, EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires and (3) routine PSA-testing. In case of biochemical recur- rence after treatment (defined as PSA nadir+2 ng/ml, i.e. Phoenix definition), patients undergo 68Ga-PSMA PET-CT for disease status evaluation, followed by 3T mp-MRI in case of intraprostatic disease. Statistical analysis Descriptives were used for patient and tumor characteristics. Follow-up time after treatment was calculated as time from treatment to death or last PSA-measurement. QoL scores were linearly transformed to a 0-100 scale. Wilcoxon signed rank tests were used for testing differences between median scores at baseline and each follow-up time point (with p<0.001 considered statistically significant to correct for multiple testing). Apart from statistical definitions, QoL score differences of ≥10 points were considered