Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer.

PURPOSE: Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. METHODS: From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (DMean). Combined treatment was delivered as 46 Gy (DMean) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D90%). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). RESULTS: The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5­year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5­year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5­year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively. CONCLUSION: Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity.

Moderately hypofractionated radiotherapy for localized prostate cancer: updated long-term outcome and toxicity analysis.

PURPOSE: Evaluation of long-term outcome and toxicity of moderately hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost treatment planning and cone beam CT-based image guidance for localized prostate cancer. METHODS: Between 2005 and 2015, 346 consecutive patients with localized prostate cancer received primary radiotherapy using cone beam CT-based image-guided intensity-modulated radiotherapy (IG-IMRT) and volumetric modulated arc therapy (IG-VMAT) with a simultaneous integrated boost (SIB). Total doses of 73.9 Gy (n = 44) and 76.2 Gy (n = 302) to the high-dose PTV were delivered in 32 and 33 fractions, respectively. The low-dose PTV received a dose (D95) of 60.06 Gy in single doses of 1.82 Gy. The pelvic lymph nodes were treated in 91 high-risk patients to 45.5 Gy (D95). RESULTS: Median follow-up was 61.8 months. The 5­year biochemical relapse-free survival (bRFS) was 85.4% for all patients and 93.3, 87.4, and 79.4% for low-, intermediate-, and high-risk disease, respectively. The 5­year prostate cancer-specific survival (PSS) was 94.8% for all patients and 98.7, 98.9, 89.3% for low-, intermediate-, and high-risk disease, respectively. The 5­year and 10-year overall survival rates were 83.8 and 66.3% and the 5­year and 10-year freedom from distant metastasis rates were 92.2 and 88.0%, respectively. Cumulative 5­year late GU toxicity and late GI toxicity grade ≥2 was observed in 26.3 and 12.1% of the patients, respectively. Cumulative 5­year late grade 3 GU/GI toxicity occurred in 4.0/1.2%. CONCLUSION: Moderately hypofractionated radiotherapy using SIB treatment planning and cone beam CT image guidance resulted in high biochemical control and survival with low rates of late toxicity.

Evaluation of intrafraction prostate motion tracking using the Clarity Autoscan system for safety margin validation.

BACKGROUND: The purpose of the study was to monitor intrafraction prostate motion in real-time using transperineal 4D ultrasound (TPUS) and analyze trajectories to validate clinical safety margins. METHODS: 401 trajectories of US monitoring sessions were retrospectively evaluated for 14 patients treated for prostate cancer. The Elekta Clarity Autoscan system was used for intrafraction monitoring along the 3 directions: superior-inferior (SI), left-right (LR) and anterior-posterior (AP). RESULTS: The intrafraction monitoring resulted in a mean prostate displacement of (-0.06 ± 0.49) mm, (-0.09 ± 0.61) mm and (-0.01 ± 0.78) mm in the SI, LR and AP directions, respectively. Even though large deviations up to 8 mm were detected, the frequency of occurrence was less than 0.1%. The prostate moved within ±2 mm in 99%, 98.1%, and 96.6% of the treatment time in the SI, LR and AP directions, respectively. During 100 s of monitoring, the median displacement increased from 0.2 mm to 0.8 mm and the maximum displacements increased from 5.2 mm to 7.8 mm. The majority of displacement values (99%) were within the clinical safety margins which ensures a good target coverage. CONCLUSIONS: The largest variation of intrafraction prostate displacement was observed along the AP direction. Throughout most of the treatment time, the prostate moved within a few millimeters. The extent of prostate displacement increased for longer monitoring times. During most of the tracking time, the prostate position was within the clinically safety margins.

Initial results for patient setup verification using transperineal ultrasound and cone beam CT in external beam radiation therapy of prostate cancer.

BACKGROUND: Evaluation of set up error detection by a transperineal ultrasound in comparison with a cone beam CT (CBCT) based system in external beam radiation therapy (EBRT) of prostate cancer. METHODS: Setup verification was performed with transperineal ultrasound (TPUS) and CBCT for 10 patients treated with EBRT for prostate cancer. In total, 150 ultrasound and CBCT scans were acquired in rapid succession and analyzed for setup errors. The deviation between setup errors of the two modalities was evaluated separately for each dimension. RESULTS: A moderate correlation in lateral, vertical and longitudinal direction was observed comparing the setup errors. Mean differences between TPUS and CBCT were (-2.7 ± 2.3) mm, (3.0 ± 2.4) mm and (3.2 ± 2.7) mm in lateral, vertical and longitudinal direction, respectively. The mean Euclidean difference between TPUS and CBCT was (6.0 ± 3.1) mm. Differences up to 19.2 mm were observed between the two imaging modalities. Discrepancies between TPUS and CBCT of at least 5 mm occurred in 58 % of monitored treatment sessions. CONCLUSION: Setup differences between TPUS and CBCT are 6 mm on average. Although the correlation of the setup errors determined by the two different image modalities is rather week, the combination of setup verification by CBCT and intrafraction motion monitoring by TPUS imaging can use the benefits of both imaging modalities.

Changes in penile bulb dose when using the Clarity transperineal ultrasound probe: A planning study.

PURPOSE: The Clarity system allows monitoring of intrafraction target organ movements in external beam radiation therapy of prostate cancer by using transperineal ultrasound. The probe positioning at the perineum could lead to a compression and shift of the penile bulb (PB) toward the high-dose region. Dose to the PB has been reported to be associated with the risk of posttreatment erectile dysfunction. This planning study reports on PB translations and changes in volume and dose when applying the transperineal ultrasound probe. METHODS AND MATERIALS: For 10 patients treated with external beam radiation therapy for prostate cancer between 2013 and 2014, a planning computed tomography scan with and without the ultrasound probe in place was acquired. The planning target volume and organs at risk including the PB were contoured in the computed tomography scan with and without the probe. Radiation therapy plans for both scenarios were calculated. In a second step, for planning with the probe in position, an additional objective for improved sparing of the PB was introduced. RESULTS: The median PB volume was 5.5 mL (range, 3.8-7.1 mL) without the probe and 3.5 mL (range, 2.0-5.8 mL) with the probe. The median shift of the PB was 1 mm in the posterior (range, 3 mm posterior-2 mm anterior) and 6 mm in the superior direction (range, 0-14 mm superior), with no relevant shift of the prostate. The median mean dose in 95% of the PB was 34.1 Gy (range, 6.0-50.4 Gy), 48.3 Gy (range, 7.2-56.8 Gy), and 39.4 Gy (range, 5.6-51.3 Gy) for plans without probe, with probe, and with probe and additional planning objective, respectively. CONCLUSIONS: Dose to the PB increased when using the transperineal probe. After introducing an additional plan-optimization objective for PB sparing, dose-volume parameters were below Quantitative Analyses of Normal Tissue Effects in the Clinic thresholds for all but one patient.