Marieke van Son

124 CHAPTER 7 Intervention Before treatment, patients underwent 3T multiparametric (mp)-MRI (T2-weighted, dif- fusion-weighted and dynamic contrast enhanced imaging) without an endorectal coil and 68Ga-PSMA or Choline PET-CT. Both imaging modalities were used to delineate the gross tumor volume (GTV), clinical target volume (CTV, defined as five-millimeter margin around GTV, excluding the urethra) and organs at risk (OARs: bladder, rectum, and urethra). Suspicious areas on MRI- or PET-imaging were included in the GTV, even if exclusively present on one of them. Patients treated before 2018 also underwent sys- tematic (21/150) or (systematic and) MRI-targeted biopsies (67/150). After that, patients were treated without biopsy confirmation. Treatment was performed by trans-perineal insertion of MR-compatible catheters in and around the CTV, with the patient under spinal anesthesia. Rigidly fused MRI/transrectal ultrasound images offered image guid- ance(10). After the implantation a subsequent 1.5T MRI scan was used for delineation adjustment and catheter reconstruction. The goal was to deliver 1x19 Gy to the CTV (D95%), with dosimetry constraints for the bladder and rectum (D1cc <12Gy) and for the urethra (D10% <17.7Gy). Since radiation is fully targeted at the CTV (and not a quarter or half of the gland), this treatment is generally described as ultrafocal. Outcome assessment Toxicity before and after treatment was graded by the treating physician using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0. Prostate cancer-specific domains were GU toxicity (6 subdomains), GI toxicity (10 subdomains) and ED. Each domain/subdomain was graded according to the severity of the symptoms, with a gen- eral range from grade 1 (asymptomatic or mild) to grade 2 (moderate), grade 3 (severe but not immediately life-threatening), grade 4 (life-threatening) and grade 5 (death). Toxicity grading was performed at baseline and during follow-up visits after 1, 3, 6, 9, 12, 18 and 24 months, and yearly thereafter. Statistical analysis To assess the effect of ultrafocal salvage HDR-BT on toxicity, post-treatment toxicity grades were compared to baseline grade. Any score above baseline was considered new-onset toxicity and therefore potentially treatment-related. The overall grade for the domains GU and GI toxicity was determined by the highest score of the respective subdomains. For the domains showing substantial (≥10%) new-onset grade ≥2 toxicity, an explor- ative risk factor assessment was performed to study the effect of (pre)-treatment char- acteristics. Potential risk factors included patient-reported baseline symptoms (IPSS and IIEF-5) and physician-graded baseline toxicity (CTCAE 4.0), dose to the respec- tive OAR, stage/location of the tumor, prostate size, CTV size, primary treatment type, history of previous salvage treatment, interval between primary and current salvage treatment, history of transurethral resection of the prostate (TURP) or ADT and number of brachytherapy catheters used. Using the lme4 package(11), mixed effects logistic