MRI-guided focal boost to dominant intraprostatic lesion using volumetric modulated arc therapy in prostate cancer. Results of a phase II trial.

OBJECTIVE: To determine morphological and biological control as well as toxicity and quality of life (QoL) of men with localized prostate cancer (PCa) treated with MRI-guided focal boost radiotherapy. MATERIAL AND METHODS: 30 patients with PCa and a visible dominant intraprostatic lesion (DIL) identified on mpMRI were included in a prospective Phase II trial. Matching point registration of planning CT and T2W, diffusion-weighted and a gradient-recalled echo (GRE) MRI images made in treatment position was used for prostate and tumour delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the DIL of 2.43 Gy using volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with intraprostatic fiducial markers. Biochemical failure was analysed using PSA nadir +2 ng/mL criteria and local control using mpMRI evaluation at 6-9 months following RT. Acute and late toxicity were defined according to CTCAE v.4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires. RESULTS: The median radiation dose to the prostate was 77.6 Gy (IQR 77.3-78.1), and to the DIL was 85.5 Gy (IQR 85.0-86.0). With a median follow up of 30.0 months (IQR 25.5-40.27), all patients remain free of biochemical relapse. An mpMRI complete response was observed in 25 patients during the first post-treatment evaluation at 6 months. The remaining five patients achieved a complete disappearance of the DIL both on T2 and DWI on the second mpMRI performed at 9 months following treatment. Six out of 30 (20%) patients presented acute Grade 2 urinary toxicity with no Grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both Grade 1). Only late Grade 1 urinary and rectal complications were observed in 3/30 patients, respectively, with no Grade 2 or more late toxicity. The urinary, bowel and sexual bother EPIC scores were slightly and insignificantly increased in the first 3 months post-treatment, returning to normal afterwards. CONCLUSIONS: mpMRI-guided focal boost using VMAT hypofractionated technique is associated with an excellent morphological and functional response control and a safe toxicity profile. ADVANCES IN KNOWLEDGE: In the present trial, we examined the potential role of mpMRI for radiological assessment (functional and morphological) of treatment response in high-risk prostate cancer patients treated with MRI-guided focal radiotherapy dose intensification to dominant Intraprostatic lesion.

A collapsed-cone based transit EPID dosimetry method.

PURPOSE: To develop a transit-dose portal dosimetry method based on a commercial collapsed-cone algorithm. METHODS: A Varian Clinac21EX (Varian Medical Systems, USA), equipped with an amorphous-silicon EPID aS1000, was used. Dose calculations were performed with the collapsed-cone algorithm of Pinnacle3 v8.0 m (Philips Medical Systems, USA). A model for the energy of 6 MV was made in Pinnacle3 and afterwards validated for clinical use. A virtual phantom with different densities was contoured and superimposed on the patient images, simulating the presence of the EPID during the treatment. Corrections for photon spectral variations were introduced using Matlab (Mathworks, USA). Transit dosimetry was verified with an anthropomorphic phantom, on which different treatment fields were simulated in locations of skull, thorax and pelvis. In addition, a prostate treatment with IMRT was administered thereon. Dose distributions were compared with gamma index. RESULTS: The dose differences at the central point did not exceed 2%, except for the 20 x 20 cm2 field size centered in the skull. The model presented in this work, assumes that the dimensions of the solid water phantom, are infinite, except for the thickness. The mean values for the gamma index pass rates were 85.62% for (3%, 3 mm), 91.73% (4%, 3 mm) and 95.68% (5%, 3 mm). CONCLUSIONS: The value of 95% for γ (5%, 3 mm) can be established as the value below which the origin of the discrepancies should be investigated. It should be considered that the proposed method is complementary and not a substitute for pre-treatment dosimetry.

A retrospective tomotherapy image-guidance study: analysis of more than 9,000 MVCT scans for ten different tumor sites.

The purpose of this study was to quantify the systematic and random errors for various disease sites when daily MVCT scans are acquired, and to analyze alterna- tive off-line verification protocols (OVP) with respect to the patient setup accuracy achieved. Alignment data from 389 patients (9,418 fractions) treated at ten differ- ent anatomic sites with daily image-guidance (IG) on a helical tomotherapy unit were analyzed. Moreover, six OVP were retrospectively evaluated. For each OVP, the frequency of the residual setup errors and additional margins required were calculated for the treatment sessions without image guidance. The magnitude of the three-dimensional vector displacement and its frequency were evaluated for all OVP. From daily IG, the main global systematic error was in the vertical direction (4.4-9.4 mm), and all rotations were negligible (less than 0.5°) for all anatomic sites. The lowest systematic and random errors were found for H&N and brain patients. All OVP were effective in reducing the mean systematic error to less than 1 mm and 0.2° in all directions and roll corrections for almost all treatment sites. The treatment margins needed to adapt the residual errors should be increased by 2-5 mm for brain and H&N, around 8 mm in the vertical direction for the other anatomic sites, and up to 19 mm in the longitudinal direction for abdomen patients. Almost 70% of the sessions presented a setup error of 3 mm for OVPs with an imaging frequency above 50%. Only for brain patients it would be feasible to apply an OVP because the residual setup error could be compensated for with a slight margin increase. However, daily imaging should be used for anatomic sites of difficult immobilization and/or large interfraction movement. 

The influence of respiratory motion on CT image volume definition.

PURPOSE: Radiotherapy treatments are based on geometric and density information acquired from patient CT scans. It is well established that breathing motion during scan acquisition induces motion artifacts in CT images, which can alter the size, shape, and density of a patient's anatomy. The aim of this work is to examine and evaluate the impact of breathing motion on multislice CT imaging with respiratory synchronization (4DCT) and without it (3DCT). METHODS: A specific phantom with a movable insert was used. Static and dynamic phantom acquisitions were obtained with a multislice CT. Four sinusoidal breath patterns were simulated to move known geometric structures longitudinally. Respiratory synchronized acquisitions (4DCT) were performed to generate images during inhale, intermediate, and exhale phases using prospective and retrospective techniques. Static phantom data were acquired in helical and sequential mode to define a baseline for each type of respiratory 4DCT technique. Taking into account the fact that respiratory 4DCT is not always available, 3DCT helical image studies were also acquired for several CT rotation periods. To study breath and acquisition coupling when respiratory 4DCT was not performed, the beginning of the CT image acquisition was matched with inhale, intermediate, or exhale respiratory phases, for each breath pattern. Other coupling scenarios were evaluated by simulating different phantom and CT acquisition parameters. Motion induced variations in shape and density were quantified by automatic threshold volume generation and Dice similarity coefficient calculation. The structure mass center positions were also determined to make a comparison with their theoretical expected position. RESULTS: 4DCT acquisitions provided volume and position accuracies within ± 3% and ± 2 mm for structure dimensions >2 cm, breath amplitude ≤ 15 mm, and breath period ≥ 3 s. The smallest object (1 cm diameter) exceeded 5% volume variation for the breath patterns of higher frequency and amplitude motion. Larger volume differences (>10%) and inconsistencies between the relative positions of objects were detected in image studies acquired without respiratory control. Increasing the 3DCT rotation period caused a higher distortion in structures without obtaining their envelope. Simulated data showed that the slice acquisition time should be at least twice the breath period to average object movement. CONCLUSIONS: Respiratory 4DCT images provide accurate volume and position of organs affected by breath motion detecting higher volume discrepancies as amplitude length or breath frequency are increased. For 3DCT acquisitions, a CT should be considered slow enough to include lesion envelope as long as the slice acquisition time exceeds twice the breathing period. If this requirement cannot be satisfied, a fast CT (along with breath-hold inhale and exhale CTs to estimate roughly the ITV) is recommended in order to minimize structure distortion. Even with an awareness of a patient's respiratory cycle, its coupling with 3DCT acquisition cannot be predicted since patient anatomy is not accurately known.