Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Based Clinical Target Volume Delineation Guideline for Postprostatectomy Salvage Radiation Therapy: The PERYTON Guideline.

PURPOSE: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs). METHODS AND MATERIALS: Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC). RESULTS: After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83). CONCLUSIONS: This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%.

Pretrial Quality Assurance for Hypofractionated Salvage Radiation Therapy After Prostatectomy in the Multi-Institutional PERYTON-trial.

Purpose: The PERYTON trial is a multicenter randomized controlled trial that will investigate whether the treatment outcome of salvage external beam radiation therapy (sEBRT) will be improved with hypofractionated radiation therapy. A pretrial quality assurance (QA) program was undertaken to ensure protocol compliance within the PERYTON trial and to assess variation in sEBRT treatment protocols between the participating centers. Methods and Materials: Completion of the QA program was mandatory for each participating center (N = 8) to start patient inclusion. The pretrial QA program included (1) a questionnaire on the center-specific sEBRT protocol, (2) a delineation exercise of the clinical target volume (CTV) and organs at risk, and (3) a treatment planning exercise. All contours were analyzed using the pairwise dice similarity coefficient (DSC) and the 50th and 95th percentile Hausdorff distance (HD50 and HD95, respectively). The submitted treatment plans were reviewed for protocol compliance. Results: The results of the questionnaire showed that high-quality, state-of-the-art radiation therapy techniques were used in the participating centers and identified variations of the sEBRT protocols used concerning the position verification and preparation techniques. The submitted CTVs showed significant variation, with a range in volume of 29 cm3 to 167 cm3, a mean pairwise DSC of 0.52, and a mean HD50 and HD95 of 2.3 mm and 24.4 mm, respectively. Only in 1 center the treatment plan required adaptation before meeting all constraints of the PERYTON protocol. Conclusions: The pretrial QA of the PERYTON trial demonstrated that high-quality, but variable, radiation techniques were used in the 8 participating centers. The treatment planning exercise confirmed that the dose constraints of the PERYTON protocol were feasible for all participating centers. The observed variation in CTV delineation led to agreement on a new (image-based) delineation guideline to be used by all participating centers within the PERYTON trial.

Determinants of induction and duration of remission of Paget's disease of bone after bisphosphonate (olpadronate) therapy.

Bisphosphonates are the treatment of choice of Paget's disease of bone. For optimal patient care determinants of the induction and duration of remission of the disease after bisphosphonate therapy must be defined. We addressed these issues in a longitudinal study of 157 patients with biochemically active disease (serum alkaline phosphatase activity >120 U/L) treated with the bisphosphonate olpadronate and followed for a median period of 37 months (range 3-162, mean 46 +/- 30). Two different total doses of olpadronate were used: an effective dose (40 mg intravenously given over 5 or 10 consecutive days) and a high dose consisting of the effective dose followed by oral olpadronate 200 mg/day for 15 days. Treatment induced biochemical remission, defined as normalization of serum alkaline phosphatase activity, in 89.2% of the patients. There were no differences between the two treatment regimens. The only independent determinants of induction of remission were baseline serum alkaline phosphatase activity and number of affected bones. In contrast, duration of remission depended on the dose of olpadronate given (high versus effective dose, RR of relapse 0.49, 95% CI 0.27-0.89). Additional independent determinants of relapse were nadir value of serum alkaline phosphatase activity after treatment, number of previous therapies, and number of affected bones. Pain scores decreased with therapy in 88% of patients with pain complaints. Pain scores were significantly related to the probability of relapse (RR1.54, 95% CI 1.04-2.27). In this long-term study of a large cohort of patients with Paget's disease we confirmed the efficacy of olpadronate therapy. In addition, we identified and quantified determinants of the response to bisphosphonate that can help in improving the management of patients with Paget's disease with bisphosphonates.