Ultra-hypofractionated prostate cancer radiotherapy: Dosimetric impact of real-time intrafraction prostate motion and daily anatomical changes.

PURPOSE: To retrospectively assess the differences between planned and delivered dose during ultra-hypofractionated (UHF) prostate cancer treatments, by evaluating the dosimetric impact of daily anatomical variations alone, and in combination with prostate intrafraction motion. METHODS: Prostate intrafraction motion was recorded with a transperineal ultrasound probe in 15 patients treated by UHF radiotherapy (36.25 Gy/5 fractions). The dosimetric objective was to cover 99 % of the clinical target volume with the 100 % prescription isodose line. After treatment, planning CT (pCT) images were deformably registered onto daily Cone Beam CT to generate pseudo-CT for dose accumulation (accumulated CT, aCT). The interplay effect was accounted by synchronizing prostatic shifts and beam geometry. Finally, the shifted dose maps were accumulated (moved-accumulated CT, maCT). RESULTS: No significant change in daily CTV volumes was observed. Conversely, CTV V100% was 98.2 ± 0.8 % and 94.7 ± 2.6 % on aCT and maCT, respectively, compared with 99.5 ± 0.2 % on pCT (p < 0.0001). Bladder volume was smaller than planned in 76 % of fractions and D5cc was 33.8 ± 3.2 Gy and 34.4 ± 3.4 Gy on aCT (p = 0.02) and maCT (p = 0.01) compared with the pCT (36.0 ± 1.1 Gy). The rectum was smaller than planned in 50.3 % of fractions, but the dosimetric differences were not statistically significant, except for D1cc, found smaller on the maCT (33.2 ± 3.2 Gy, p = 0.02) compared with the pCT (35.3 ± 0.7 Gy). CONCLUSIONS: Anatomical variations and prostate movements had more important dosimetric impact than anatomical variations alone, although, in some cases, the two phenomena compensated. Therefore, an efficient IGRT protocol is required for treatment implementation to reduce setup errors and control intrafraction motion.

Minimum non-isotropic and asymmetric margins for taking into account intrafraction prostate motion during moderately hypofractionated radiotherapy.

PURPOSE: To investigate the impact on dose distribution of intrafraction motion during moderate hypofractionated prostate cancer treatments and to estimate minimum non-isotropic and asymmetric (NI-AS) treatment margins taking motion into account. METHODS: Prostate intrafraction 3D displacements were recorded with a transperineal ultrasound probe and were evaluated in 46 prostate cancer patients (876 fractions) treated by moderate hypofractionated radiation therapy (60 Gy in 20 fractions). For 18 patients (346 fractions), treatment plans were recomputed increasing CTV-to-PTV margins from 0 to 6 mm with an auto-planning optimization algorithm. Dose distribution was estimated using the voxel shifting method by displacing CTV structure according to the retrieved movements. Time-dependent margins were finally calculated using both van Herk's formula and the voxel shifting method. RESULTS: Mean intrafraction prostate displacements observed were -0.02 ± 0.52 mm, 0.27 ± 0.78 mm and -0.43 ± 1.06 mm in left-right, supero-inferior and antero-posterior directions, respectively. The CTV dosimetric coverage increased with increased CTV-to-PTV margins but it decreased with time. Hence using van Herk's formula, after 7 min of treatment, a margin of 0.4 and 0.5 mm was needed in left and right, 1.5 and 0.7 mm in inferior and superior and 1.1 and 3.2 mm in anterior and posterior directions, respectively. Conversely, using the voxel shifting method, a margin of 0 mm was needed in left-right, 2 mm in superior, 3 mm in inferior and anterior and 5 mm in posterior directions, respectively. With this latter NI-AS margin strategy, the dosimetric target coverage was equivalent to the one obtained with a 5 mm homogeneous margin. CONCLUSIONS: NI-AS margins would be required to optimally take into account intrafraction motion.

Comparison of electromagnetic transmitter and ultrasound imaging for intrafraction monitoring of prostate radiotherapy.

BACKGROUND AND PURPOSE: To compare two in-beam monitoring devices for prostate radiotherapy: intra-prostatic electromagnetic transmitters (EM-T) (RayPilot®, Micropos Medical) and ultrasound imaging using transperineal probe (TP-US) (Clarity®, Elekta) used concomitantly on phantom and on patients. MATERIALS AND METHODS: The phantom study evaluated accuracy in presence of known translations and rotations. Then intra-fraction motions were analyzed for 10 prostate cancer patients implanted with the EM-T 8 days before the simulation CT (171 sessions). The percent time in which the differences between the systems were 1-5 mm were scored for each direction. RESULTS: Experiments on phantom confirmed no interference between the systems and showed deviations of less than 0.5 mm when translations were applied progressively. In presence of rotations (5-15°), both systems displayed systematic shifts up to 6.9 and 3.8 mm for the TP-US and the EM-T, respectively. Absolute mean differences between displacements observed on patients with EM-T and TP-US were ≤0.55 mm in all directions except for one patient (≤1.77 mm). With an exception for this patient, a strong correlation was found in left-right direction: differences >2 mm were monitored less than 0.22% of the time (mean acquisition time:164 minutes) and never exceeded 5 s. Maximum differences were observed in supero-inferior direction with differences >2 mm monitored more than 6.5% of the time for 3 patients. Large prostate rotations, the presence of gas and EM-T location in the prostate may explain important differences. CONCLUSION: Apart from the systematic shifts induced by the rotations, the two systems were correlated and represent feasible solutions for monitoring prostate cancer treatment.

Evaluation of a new transperineal ultrasound probe for inter-fraction image-guidance for definitive and post-operative prostate cancer radiotherapy.

PURPOSE: The aim of this study was to evaluate a new system based on transperineal ultrasound (TP-US) acquisitions for prostate and post-prostatectomy pre-treatment positioning by comparing this device to cone-beam computed tomography (CBCT). METHODS: The differences between CBCT/CT and TP-US/TP-US registrations were analyzed on 427 and 453 sessions for 13 prostate and 14 post-prostatectomy patients, respectively. The inter-operator variability (IOV) of the registration process, and the impact and variability of the probe pressure were also evaluated. RESULTS: CBCT and TP-US shift agreements at ± 5 mm were 76.6%, 95.1%, 96.3% and 90.3%, 85.0%, 97.6% in anterior-posterior, superior-inferior and left-right directions, for prostate and post-prostatectomy patients, respectively. IOV values were similar between the 2 modalities. Displacements above 5 mm due to strong pressures were observed on both localizations, but such pressures were rarely reproduced during treatment courses. CONCLUSIONS: High concordance between CBCT/CT and TP-US/TP-US localization of prostates or prostatic beds was found in this study. TP-US based prepositioning is a feasible method to ensure accurate treatment delivery, and represents an attractive alternative to invasive and/or irradiating imaging modalities.

Ultrasound versus Cone-beam CT image-guided radiotherapy for prostate and post-prostatectomy pretreatment localization.

PURPOSE: To evaluate the accuracy of an intra-modality trans-abdominal ultrasound (TA-US) device against soft-tissue based Cone-Beam Computed tomography (CBCT) registration for prostate and post-prostatectomy pre-treatment positioning. METHODS: The differences between CBCT and US shifts were calculated on 25 prostate cancer patients (cohort A) and 11 post-prostatectomy patients (cohort B), resulting in 284 and 106 paired shifts for cohorts A and B, respectively. As a second step, a corrective method was applied to the US registration results to decrease the systematic shifts observed between TA-US and CBCT results. This method consisted of subtracting the mean difference obtained between US and CBCT registration results during the first 3 sessions from the US registration results of the subsequent sessions. Inter-operator registration variability (IOV) was also investigated for both modalities. RESULTS: After initial review, about 20% of the US images were excluded because of insufficient quality. The average differences between US and CBCT were: 2.8 ± 4.1 mm, -0.9 ± 4.2 mm, 0.4 ± 3.4 mm for cohort A and 1.3 ± 5.0 mm, -2.3 ± 4.6 mm, 0.5 ± 2.9 mm for cohort B, in the anterior-posterior (AP), superior-inferior (SI) and lateral (LR) directions, respectively. After applying the corrective method, only the differences in the AP direction remained significant (p < 0.05). The IOV values were between 0.6-2.0 mm and 2.1-3.5 mm for the CBCT and TA-US modalities, respectively. CONCLUSIONS: Based on the obtained results and on the image quality, the TA-US imaging modality is not safely interchangeable with CBCT for pre-treatment repositioning. Treatment margins adaptation based on the correction of the systematic shifts should be considered.

Semiautomatic registration of 3D transabdominal ultrasound images for patient repositioning during postprostatectomy radiotherapy.

PURPOSE: The aim of the present work is to propose and evaluate registration algorithms of three-dimensional (3D) transabdominal (TA) ultrasound (US) images to setup postprostatectomy patients during radiation therapy. METHODS: Three registration methods have been developed and evaluated to register a reference 3D-TA-US image acquired during the planning CT session and a 3D-TA-US image acquired before each treatment session. The first method (method A) uses only gray value information, whereas the second one (method B) uses only gradient information. The third one (method C) combines both sets of information. All methods restrict the comparison to a region of interest computed from the dilated reference positioning volume drawn on the reference image and use mutual information as a similarity measure. The considered geometric transformations are translations and have been optimized by using the adaptive stochastic gradient descent algorithm. Validation has been carried out using manual registration by three operators of the same set of image pairs as the algorithms. Sixty-two treatment US images of seven patients irradiated after a prostatectomy have been registered to their corresponding reference US image. The reference registration has been defined as the average of the manual registration values. Registration error has been calculated by subtracting the reference registration from the algorithm result. For each session, the method has been considered a failure if the registration error was above both the interoperator variability of the session and a global threshold of 3.0 mm. RESULTS: All proposed registration algorithms have no systematic bias. Method B leads to the best results with mean errors of -0.6, 0.7, and -0.2 mm in left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively. With this method, the standard deviations of the mean error are of 1.7, 2.4, and 2.6 mm in LR, SI, and AP directions, respectively. The latter are inferior to the interoperator registration variabilities which are of 2.5, 2.5, and 3.5 mm in LR, SI, and AP directions, respectively. Failures occur in 5%, 18%, and 10% of cases in LR, SI, and AP directions, respectively. 69% of the sessions have no failure. CONCLUSIONS: Results of the best proposed registration algorithm of 3D-TA-US images for postprostatectomy treatment have no bias and are in the same variability range as manual registration. As the algorithm requires a short computation time, it could be used in clinical practice provided that a visual review is performed.

Impact of probe pressure variability on prostate localization for ultrasound-based image-guided radiotherapy.

PURPOSE: To evaluate the impact of transabdominal probe pressure on prostate positioning with an intramodality ultrasound (US) image-guided-radiotherapy system and to quantify pressure variability over the treatment course. MATERIAL AND METHODS: 8 prostate cancer patients (group A) and 17 healthy volunteers underwent 3 consecutive US images with increasing probe pressure levels, and 1 CT acquisition for the group A only. Prostate positions were compared after manual registration of the first US image contour projected on 2 others. Group A's pressure levels were quantified by measuring skin-to-skin distances between corresponding CT-US images. The same methodology was used on paired CT/CBCT-US images acquired during treatments of 18 prostate cancer patients to determine whether the different pressure levels applied to the group A were close to the clinical practices and to quantify pressure variability along the treatment course. RESULTS: 84% of 3D prostate displacements were above 2mm for at least one pressure level. Probe pressures deliberately applied were similar to the ones observed clinically. The latter drastically varied between sessions. CONCLUSION: Even with an intramodality system, probe pressure can impact prostate localization because of the pressure variability along the treatment course. Therefore, margins should be expanded from 0.5 to 1.2mm to ensure treatment accuracy.

Toxoplasmose em coelhos: comparação do perfil bioquímico hepático com os achados patológicos em infecção pelo toxoplasma gondii / Toxoplasmosis in rabbits: profile hepatic biochemistry and its relationship with pathological found due to toxoplasma gondii

To determine the hepatic profiles due to Toxoplasma gondii infection in rabbits, 15 animals were divided in three groups of five animals each. The first and second groups were inoculated subcutaneously with 106 and 103 tachyzoites of T. gondii respectively, while the third was left as control. Blood samples were taken on days 0, 4, 8, e 11 after inoculation (DAI). Livers of each rabbit was analyzed in other to observed lesions. Hepathomegaly was observed in all of the infected groups, independently of the dose used, where was observed a significant increase of AST e ALT at 8th DAI. Tachyzoites were observed in all infected animals, and were reisolated in 90 percent of livers bioassed in mice. Histopathology was consisted by diffuse infiltration inflammatory, consisted mainly by lymphocytes at sinusoids e portal space. The increase of AST and ALT during acute toxoplasmosis in rabbits was justified by presence of tachyzoites in tissue smears associated with gross and histopathologic lesions