Dosimetric and volumetric changes in the rectum and bladder in patients receiving CBCT-guided prostate IMRT: analysis based on daily CBCT dose calculation.

Delivered dose can be calculated by transferring the planned treatment beams onto the daily CBCT. Bladder and rectum volumetric doses were calculated and cor-related to the daily bladder and rectum fullness. Patients for this study underwent hypofractionated prostate IMRT to 70 Gy in 28 fractions. Daily CBCT was utilized for image guidance. A clinically acceptable plan was created using a CTV-to-PTV uniform margin of 5 mm. Image fusion was performed to transfer the bladder and rectum contours onto each CBCT. Contours were then edited to match the anatomy of each CBCT. Using the daily treatment isocenter, the planned beams were transferred onto the CBCT and daily and cumulative DVHs calculated. For the results a total of 168 daily CBCTs were evaluated. The bladder was found to be smaller for 74.7% of the 168 daily CBCTs accessed in this study. This reduction in volume correlated to an increase in the cumulative bladder V70 Gy from 9.47% on the planning CT to 10.99% during treatment. V70Gy for the rectum was 7.27% on the planning CT, when all six patients were averaged, and increased to 11.56% on the average of all daily treatment CBCTs. Increases in volumetric rectum dose correlated with increases in rectal volume. For one patient, the rectum and blad-der absolute V70 Gy, averaged over the course of treatment, increased by 295% and 61%, respectively. Larger variations in the daily bladder and rectal volume were observed and these correlated to large deviations from the volumetric dose received by these structures. In summary, bladder and rectum volume changes during treatment have an effect on the cumulative dose received by these organs. It was observed that the volumetric dose received by the bladder decreases as the volume of the bladder increases. The inverse was true for the rectum.

Determination of optimal PTV margin for patients receiving CBCT-guided prostate IMRT: comparative analysis based on CBCT dose calculation with four different margins.

Variations in daily setup and rectum/bladder filling lead to uncertainties in the delivery of prostate IMRT. The purpose of this study is to determine the optimal PTV margin for CBCT-guided prostate IMRT based on daily CBCT dose calculations using four different margins. Five patients diagnosed with low-risk prostate cancer were treated with prostate IMRT to 70 Gy in 28 fractions using daily CBCT for image guidance. The prostate CTV and OARs were contoured on all CBCTs. IMRT plans were created using 1 mm, 3 mm, 5 mm, and 7 mm CTV to PTV expansions. For each delivered fraction, dose calculations were generated utilizing the pretreatment CBCT translational shifts performed and dosimetric analysis was performed. One hundred and forty total treatment fractions (CBCT sessions) were evaluated. The planned prostate CTV V100% was 100% for all PTV margins. Based on CBCT analysis, the actual cumulative CTVs V100% were 96.55% ± 2.94%, 99.49% ± 1.36%, 99.98% ± 0.26%, and 99.99% ± 0.05% for 1, 3, 5, and 7 mm uniform PTV margins, respectively. Delivered rectum and bladder doses were different as compared to expected planned doses, with the magnitude of differences increasing with PTV margin. Daily setup variation during prostate IMRT yields differences in the actual vs. expected doses received by the prostate CTV, rectum, and bladder. The magnitude of these differences is significantly affected by the PTV margin utilized. It was found that when daily CBCT was used for soft-tissue alignment of the prostate, a 3 mm PTV margin allowed for CTV to be covered for 99% of cases.

Development of a high-resolution melting genotyping assay for the angiotensin I converting enzyme insertion/deletion polymorphism and establishment of genotype-specific reference intervals in a Danish population.

BACKGROUND: The serum-angiotensin I converting enzyme (s-ACE) activity is influenced by a genetic insertion/deletion (I/D) polymorphism in the ACE gene, and the resulting large interindividual variation in s-ACE limits the use of normal reference intervals in the evaluation of sarcoidosis. In this study, we developed a new method for genotyping the I/D polymorphism in ACE and established genotype-specific reference intervals in order to improve the diagnostic accuracy and the value for treatment of sarcoidosis. METHODS: The new genotyping assay is based on high-resolution melting (HRM) using LCGreen + and was used to genotype 400 healthy Danish individuals. The assay was compared to a real-time polymerase chain reaction (RT-PCR) assay in a validation set of 86 samples. Enzyme activity in serum was measured using the Infinity™ ACE Liquid Stable Reagent from Thermo adapted for the ABX Pentra analyzer. RESULTS: There was full concordance between genotyping assays. The three genotypes II, ID and DD were present with a frequency of 0.23, 0.51 and 0.26. The distribution of s-ACE values in the total population was non-Gaussian (non-parametric 95% reference interval 12.0-60.0 U/L). The median activities of the genotypes differed significantly (P<0.0001). Ninety-five per cent non-parametric reference intervals for the subpopulations were determined to 6.3-38.5, 14.0-56.0 and 23.3-71.2 U/L for II, ID and DD, respectively. CONCLUSION: We have developed a simple and robust method for ACE genotyping and determined genotype-specific reference intervals for s-ACE concentrations in the Danish population. The new reference intervals may increase the value of s-ACE measurements.