Stereotactic Body Radiation Therapy for Intermediate-risk Prostate Cancer With VMAT and Real-time Electromagnetic Tracking: A Phase II Study.

OBJECTIVES: Stereotactic body radiation treatment represents an intriguing therapeutic option for patients with early-stage prostate cancer. In this phase II study, stereotactic body radiation treatment was delivered by volumetric modulated arc therapy with flattening filter free beams and was gated using real-time electromagnetic transponder system to maximize precision of radiotherapy and, potentially, to reduce toxicities. MATERIALS AND METHODS: Patients affected by histologically proven prostate adenocarcinoma and National Comprehensive Cancer Network (NCCN) intermediate class of risk were enrolled in this phase II study. Beacon transponders were positioned transrectally within the prostate parenchyma 7 to 10 days before simulation computed tomography scan. The radiotherapy schedule was 38 Gy in 4 fractions delivered every other day. Toxicity assessment was performed according to Common Terminology Criteria for Adverse Events (CTCAE), v4.0. RESULTS: Thirty-six patients were enrolled in this study. Median initial prostate-specific antigen was 7.0 ng/mL (range: 2.3 to 14.0 ng/mL). Median nadir-prostate-specific antigen after treatment was 0.2 ng/mL (range: 0.006 to 4.8 ng/mL). A genitourinary acute toxicity was observed in 21 patients (dysuria grade [G] 1: 41.7%, G2: 16.7%). Gastrointestinal acute toxicity was found in 9 patients (proctitis G1: 19.4%, G2: 5.6%). Late toxicity was mild (genitourinary toxicity G1: 30.6%; G2: 8.3%; gastrointestinal toxicity G1: 13.9%; G2: 19.4%). At a median follow-up time of 41 months, 3 biochemical recurrences were observed (2 local recurrences, 1 distant metastasis). Three-year biochemical recurrence-free survival was 89.8% (International Society of Urologic Pathology Grade Group 2: 100%, Grade Group 3: 77.1%, P=0.042). CONCLUSION: Ultrahypofractionated radiotherapy, delivered with flattening filter free-volumetric modulated arc therapy and gated by electromagnetic transponders, is a valid option for intermediate-risk prostate cancer.

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is considered an effective and safe treatment in patients with low- and intermediate-risk prostate cancer (PC). However, due to a lack of long-term follow-up and late toxicity data, this treatment is not universally accepted. The present study aimed to evaluate outcome and early and late toxicity in a cohort of patients with low- and intermediate-risk PC treated prospectively with linear accelerator (linac)-based SBRT. PATIENTS AND METHODS: Patients with low- or intermediate-risk (NCCN criteria) PC were included. All patients received linac-based SBRT to 35 Gy in 5 fractions delivered on alternate days. Endpoints were toxicity, biochemical relapse-free survival (BRFS), metastatic progression-free survival (mPFS), and overall survival (OS). RESULTS: From 2012 to 2018, 178 patients were treated. Median baseline prostate-specific antigen (iPSA) was 6.37 ng/ml (range 1.78-20). Previous transurethral resection of the prostate (TURP) was present in 23 (12.9%) patients. Median follow-up was 58.9 months (range 9.7-89.9). BRFS rates at 1, 3, and 5 years were 98.3 (95% confidence interval, CI, 94.7-99.4%), 94.4 (95%CI 89.4-97), and 91.6% (95%CI 85.4-95.2), respectively. In univariate analysis, performance status (PS), iPSA, and nadir PSA (nPSA) were correlated with BRFS. In multivariable analysis iPSA and nPSA remained significant. BRFS rates at 5 years were 94.9% (95%CI 86.8-98) for International Society of Urological Pathology (ISUP) grade group 1, 93.2% (95%CI 80.5-97.7) for ISUP group 2, and 74.8% (95%CI 47.1-89.5) for ISUP group 3. At 1, 3, and 5 years, mPFS rates were 98.8 (95%CI 95.5-99.7), 96.2 (95%CI 91.9-98.3), and 92.9% (95%CI 87.2-96.2), respectively; OS rates were 100, 97.2 (95%CI 92.9-98.9), and 95.1% (95%CI 90-97.6), respectively. One (0.56%) case of grade 3 acute genitourinary (GU), one case of acute gastrointestinal (GI), and one case of grade 3 late GU toxicity were observed. GI toxicity positively correlated with prostate volume. CONCLUSION: At long-term follow-up, linac-based SBRT continues to be a valid option for the management localized PC. Biochemical control remains high at 5 years, albeit with some concerns regarding the optimal schedule for unfavorable intermediate-risk PC. Considering the excellent prognosis, patient selection is crucial for prevention of severe late toxicity.

Role of 11C-choline PET/CT in radiation therapy planning of patients with prostate cancer.

BACKGROUND: In the era of image-guided radiotherapy, PET has become an important tool for tumor delineation in several types of cancer. The aim of this study was to evaluate the effect of this imaging modality in treatment planning of a cohort of patients with prostate cancer eligible for radiotherapy. METHODS: From September 2011 to January 2016, 135 consecutive patients (median age 69 years, range: 53-89) were referred to our department for radiation therapy with radical intent (n=28), for postoperative adjuvant (n=13) or salvage treatment (n=50), for re-irradiation (n=19), or for radiotherapy on oligometastases (n=25). Before planning the radiotherapy course, patients were submitted to carbon-11-choline PET (Cho-PET) to confirm the indication to radiotherapy and the irradiation volumes. RESULTS: Among the 135 patients subjected to Cho-PET, the indication to radiotherapy was modified in 66 (48.8%) cases based on the Cho-PET result. In particular, Cho-PET helped to better define the radiotherapy programme in 12 out of 28 (42.8%) patients who were candidates for primary radiation therapy, 33 (52.4%) of 63 patients undergoing adjuvant/salvage radiotherapy, and 21 out of 44 (47.7%) patients with relapsed/metastatic disease. Overall biochemical response is documented by mean and median prostate specific antigen values, which changed from 15.29 to 4.00 ng/ml, respectively, before to mean 4.74 ng/ml and median 0.81 ng/ml after therapy (P=0.05). CONCLUSION: In our series, Cho-PET had a significant effect on radiotherapy planning of patients affected by prostate cancer, determining a change in management in 48.8% of cases, considering all therapeutic indications.

Use of PTW-microDiamond for relative dosimetry of unflattened photon beams.

PURPOSE: The increasing interest in SBRT treatments encourages the use of flattening filter free (FFF) beams. Aim of this work was to evaluate the performance of the PTW60019 microDiamond detector under 6MV and 10MVFFF beams delivered with the EDGE accelerator (Varian Medical System, Palo Alto, USA). A flattened 6MV beam was also considered for comparison. METHODS: Short term stability, dose linearity and dose rate dependence were evaluated. Dose per pulse dependence was investigated in the range 0.2-2.2mGy/pulse. MicroDiamond profiles and output factors (OFs) were compared to those obtained with other detectors for field sizes ranging from 40×40cm2 to 0.6×0.6cm2. In small fields, volume averaging effects were evaluated and the relevant correction factors were applied for each detector. RESULTS: MicroDiamond short term stability, dose linearity and dependence on monitor unit rate were less than 0.8% for all energies. Response variations with dose per pulse were found within 1.8%. MicroDiamond output factors (OF) values differed from those measured with the reference ion-chamber for less than 1% up to 40×40cm2 fields where silicon diodes overestimate the dose of ≈3%. For small fields (<3×3cm2) microDiamond and the unshielded silicon diode were in good agreement. CONCLUSIONS: MicroDiamond showed optimal characteristics for relative dosimetry even under high dose rate beams. The effects due to dose per pulse dependence up to 2.2mGy/pulse are negligible. Compared to other detectors, microDiamond provides accurate OF measurements in the whole range of field sizes. For fields <1cm correction factors accounting for fluence perturbation and volume averaging could be required.

Treatment: Outcome and Toxicity of Volumetric Modulated Arc Therapy in Oropharyngeal Carcinoma.

BACKGROUND/AIM: Radiotherapy is a common approach for treating squamous cell carcinoma (SCC) of the oropharynx. We aimed to analyze toxicity and outcome of patients affected by oropharyngeal SCC treated with volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Fifty-four patients presenting advanced orophayngeal carcinoma who were treated with radical radiotherapy were analyzed. All patients were treated with VMAT-RapidArc, with simultaneous integrated boost in 33 fractions for a dose of 69.96 Gy to the high-risk, and of 54.45 Gy to the low-risk volume. RESULTS: Median follow-up was 23 months. In eight cases, locoregional relapse was observed (median time to relapse=10.7 months). Four among eight local recurrences appeared in the high-dose target volume. The 1- and 2-year actuarial disease-free survival rates were 88% and 80%, respectively. The 1- and 2-year actuarial overall survival rates were 94% and 87%, respectively. CONCLUSION: VMAT for oropharyngeal SCC treatment is effective and safe, with interesting rates of control of disease and survival.