J. Noteboom

Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer : Toxicity in the FLAME randomized controlled trial

PURPOSE To compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the macroscopically visible tumour. MATERIAL AND METHODS FLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures. RESULTS Ninety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19 95%CI 0.82-1.73p = 0.38), respectively. CONCLUSIONS In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.

Challenges in MR‐only seed localization for postimplant dosimetry in permanent prostate brachytherapy

Purpose: An MR‐only postimplant dosimetry workflow for low dose rate (LDR) brachytherapy could reduce patient burden, improve accuracy, and improve cost efficiency. However, localization of brachytherapy seeds on MRI scans remains a major challenge for this type of workflow. In this study, we propose and validate an MR‐only seed localization method and identify remaining challenges. Methods and materials: The localization method was based on template matching of simulations of complex‐valued imaging artifacts around metal brachytherapy seeds. The method was applied to MRI scans of 25 prostate cancer patients who underwent LDR brachytherapy and for whom postimplant dosimetry was performed after 4 weeks. The seed locations found with the MR‐only method were validated against the seed locations found on CT. The circumstances in which detection errors were made were classified to gain an insight in the nature of the errors. Results: A total of 1490 of 1557 (96%) seeds were correctly detected, while 67 false‐positive errors were made. The correctly detected seed locations had a high spatial accuracy with an average error of 0.8 mm compared with CT. A majority of the false positives occurred near other seeds. Most false negatives were found in either stranded configurations without spacers or near other seeds. Conclusions: The low detection error rate and high localization accuracy obtained by the complex‐valued template matching approach are promising for future clinical application of MR‐only dosimetry. The most important remaining challenge is robustness with regard to configurations of multiple seeds in close vicinity, such as in strands of seeds without spacers. This issue could potentially be resolved by simulating specific configurations of multiple seeds or by constraining the treatment planning to avoid these configurations, which could make the proposed method competitive with CT‐based seed localization.

Re-salvage MRI-guided Focal High-dose-rate Brachytherapy for Locally Recurrent Prostate Cancer

Prostate cancer recurrences are common, even with twenty-first-century primary prostate cancer treatment modalities. The most common salvage treatment is (delayed) hormonal therapy, which is often associated with serious side-effects. Due to the risk of significant toxicity, whole-gland targeted salvage treatments remain unpopular. Consequently, developments in focal therapies have arisen. Magnetic resonance imaging (MRI)-guided focal salvage high-dose-rate brachytherapy (HDR-BT) is a novel treatment aiming for minimal toxicity in recurrent prostate cancer patients. Repeating focal treatment could, therefore, be possible in case of post-salvage recurrence. We report the case of a 77-year-old man who underwent repeat focal HDR-BT.

Electronic Poster: RTT track: Motion management and adaptive strategiesEP-1844: Clinical introduction of simple adaptive radiotherapy for transitional cell bladder carcinoma

Purpose or Objective Radiotherapy of bladder carcinoma requires substantial CTV-PTV margins to account for day-to-day bladder volume variations. A method to reduce these margins, and hence organs at risk (OAR) dose, is the Plan of the Day method (PotD). In preparation of a PotD approach, we introduced an offline adaptive radiotherapy (ART) procedure based on ConeBeam CT (CBCT) analysis to select individualized adequate margins for the bladder. Tight PTV margins were defined on a retrospective CBCT analysis (N=9, 56 CBCTs) (table 1).

OC-0056: FLAME: Influence of dose escalation to 95Gy for prostate cancer on urethra-related toxicity and QOL

Purpose or Objective: Following EBRT for prostate cancer, patients can develop aggravation of urinary symptoms mostly due to urethral dose. With dose-escalated EBRT it is suggested that genitourinary toxicity increases with increasing dose. In the experimental arm of the FLAME-trial (284 patients) a dose of 77Gy to the entire prostate gland in 35 fractions was administered, with an integrated boost up to 95Gy to the macroscopic lesions. No dose constraints for the urethra were set during the trial. The objective of this study is to evaluate urethral dose parameters, urethra-related toxicity and prostate-specific QoL scores for patients treated with and without dose-escalated EBRT.

Perineal recurrence of prostate cancer six years after trans-perineal brachytherapy.

We report a case of perineal recurrence of prostate cancer 6 years after low-dose-rate (LDR) brachytherapy for localized prostate cancer. The most common approach to treat such perineal masses, including those occurring after prior biopsy or surgery, is local excision. We report the use of stereotactic radiotherapy with volumetric modulated arc therapy (VMAT) as a novel non-invasive, potentially curative, and patient-friendly alternative to local excision.