Increased toxicities associated with dose escalation of stereotactic body radiation therapy in prostate cancer: results from a phase I/II study.

BACKGROUND: This dose-escalation study evaluated the toxicity and efficacy of different stereotactic body radiation therapy (SBRT) doses for selecting an optimal dose for prostatic adenocarcinoma (PCa). MATERIALS AND METHODS: This clinical trial was registered at UMIN (UMIN000014328). Patients with low- or intermediate-risk PCa were equally assigned to 3 SBRT dose levels: 35, 37.5, and 40 Gy per 5 fractions. The primary endpoint was the occurrence rate of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) adverse events at 2 years, while the secondary endpoint was the 2-year biochemical relapse-free (bRF) rate. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Seventy-five patients (median age, 70 years) were enrolled from March 2014 to January 2018, of whom 10 (15%) and 65 (85%) had low- and intermediate-risk PCa, respectively. The median follow-up time was 48 months. Twelve (16%) patients received neoadjuvant androgen deprivation therapy. The 2-year occurrence rates of grade 2 late GU and GI toxicities were 34 and 7% in all cohorts, respectively (35 Gy: 21 and 4%; 37.5 Gy: 40 and 14%; 40 Gy: 42 and 5%). The occurrence risk of GU toxicities significantly increased with dose escalation (p = 0.0256). Grades 2 and 3 acute GU toxicities were observed in 19 (25%) and 1 (1%), respectively. Grade 2 acute GI toxicity was observed in 8 (11%) patients. No grade ≥3 GI or ≥4 GU acute toxicity or grade ≥3 late toxicity was observed. Clinical recurrence was detected in 2 patients. CONCLUSIONS: An SBRT dose of 35 Gy per 5 fractions is less likely to cause adverse events in patients with PCa than 375- and 40-Gy SBRT doses. Higher doses of SBRT should be applied with caution.

Dosimetric Evaluation of CyberKnife Synchrony System for Liver Tumors With Respiratory Phase Shifts.

BACKGROUND/AIM: This study evaluated the effects of the respiratory phase shifts between liver tumor and chest wall motions on the dose distribution for the CyberKnife Synchrony respiratory tracking system (SRTS). PATIENTS AND METHODS: Eight patients who received stereotactic body radiotherapy for hepatocellular carcinoma or liver metastases were analyzed. Three-dimensional (3D) motion of the implanted fiducial markers and vertical motion of the sternal bone were derived from the four-dimensional computed tomography (4D-CT) images acquired with a 320-row area detector CT. For each patient, Gaussian random numbers were generated for the standard deviation of the tracking error calculated from the phase shift and a literature. For each voxel of the target, the dose delivered from each beam was calculated 100 times with the random 3D offsets representing the tracking error. RESULTS: The median respiratory phase shifts were 6.0% and 4.6% for the anterior-posterior (AP) and superior-inferior (SI) directions, respectively. The median motion tracking errors influenced by respiratory phase shifts were 1.21 mm and 0.96 mm for the AP and SI directions, respectively. The change in the dose covering 90% of the target (D90%) was within 1.1% when median phase shifts were considered. When evaluating the 90th percentile of the phase shifts, the D90% decreased up to 6.6%. CONCLUSION: We have developed a technique to estimate the impact of the respiratory phase shifts on the dose distribution of a liver tumor treated with the SRTS. The calculation of the respiratory phase shifts from the area-detector 4D-CT will be valuable to improve the tracking accuracy of the SRTS.

Stereotactic Body Radiotherapy Using CyberKnife® for Localized Low- and Intermediate-risk Prostate Cancer: Initial Report on a Phase I/II Trial.

BACKGROUND: The present study aimed to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer. PATIENTS AND METHODS: We investigated 25 patients treated with SBRT of 35 Gy per five fractions from May 2014 to March 2015. RESULTS: The median age of patients was 70 years, four (16%) patients were low risk and 21 (84%) were intermediate risk. Seven (28%) patients received neoadjuvant androgen-deprivation therapy. The median follow-up time was 53 months. Grade 2 acute and late genitourinary toxicities were observed in five (20%) and two (8%) patients and there were no Grade 2 gastrointestinal toxicities. There were no Grade 3 or higher acute or late toxicities at 2 years follow-up. The biochemical relapse-free survival rate at 2 years was 100%. CONCLUSION: SBRT of 35 Gy per five fractions is a promising treatment method in the short term for prostate cancer.

[Potential uncertainty about image registration in thoracic image-guided radiotherapy].

PURPOSE: Although image-guided radiotherapy (IGRT) is widely used to determine and correct daily setup errors, the additional interpretation for image registration would provide another error. We evaluated the uncertainty in image registration in IGRT. METHOD: The subjects consisted of 12 consecutive patients treated with IGRT for thoracic esophageal cancer. Two radiation therapists had consensually achieved daily 3D registration between planning computed tomography (CT) and cone beam CT (CBCT). The original data sets of image registration in all fractions except for boost irradiations with a change in the isocenter positions were selected for evaluation. There were 20 to 32 data sets for each patient: a total of 318 data sets. To evaluate daily setup errors, the mean 3D displacement vector was calculated for each patient. To assess the reproducibility of image registration, two other radiation therapists reviewed the data sets and recorded geometric differences as uncertainty in the image registration. RESULTS: The mean 3D displacement vector for each patient ranged from 4.9 to 15.5 mm for setup errors and 0.7 to 2.2 mm for uncertainty in image registration. There was a positive correlation between the 3D vectors for setup error and uncertainty in image registration (r = 0.487, p = 0.016). CONCLUSION: Although IGRT can correct the setup errors, potential uncertainty exists in image registration. The setup error would disturb the image registration in IGRT.

Interimager variability in ADC measurement of the human brain.

PURPOSE: Routine clinical practice involves the application of diverse scanning parameters that can affect apparent diffusion coefficient (ADC) values. We evaluated interimager variability in ADC values with respect to their potential effect in clinical applications. METHODS: In 7 healthy volunteers, we obtained diffusion-weighted (DW) images using routine clinical parameters and 1.5- (n = 9) and 3-tesla (n = 3) magnetic resonance (MR) imagers from 5 different vendors, performing 84 MR imaging studies. To evaluate the differences in ADC values among the imagers, vendors, and magnetic field strengths, we measured the mean pixel values of the frontal white matter and thalamus (gray matter) in both cerebral hemispheres of the 7 volunteers and used repeated-measures analysis of variance for multiple comparisons. RESULTS: The laterality of ADC values in the bilateral structures ranged from one to 3% for the 12 imagers. Although the relative difference in ADC values of white matter was 7% for scanners yielding the highest and lowest mean ADC values (P < 0.01), it was within 2 to 4% for instruments from the same vendors. For gray matter, the interimager difference was 4 to 12%, even among the same vendors (P < 0.05). Among the 3T imagers, the difference for white and gray matter was approximately 3%. CONCLUSIONS: There were significant interimager differences in ADC values, especially with respect to gray matter. Taking into consideration the existing laterality, however, the differences among our 3T imagers may be acceptable despite the use of diverse scanning parameters. In routine clinical practice, the existing variability must be considered imager by imager.