68Ga-PSMA-PET/CT imaging of localized primary prostate cancer patients for intensity modulated radiation therapy treatment planning with integrated boost.

PURPOSE: The purpose of our study was to show the feasibility and potential benefits of using 68Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model. METHODS: Twenty-one prostate cancer patients (70 years average) without previous local therapy received 68Ga-PSMA-PET/CT imaging. Organs-at-risk and standard prostate target volumes were manually defined on the obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the maximum activity uptake in the lesion as threshold followed by manual adaption. Five different treatment plan variations were calculated for each patient. Analysis of derived treatment plans was done according to QUANTEC with in-house developed software. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was calculated for all plan variations. RESULTS: Comparing the conventional plans to the plans with integrated boost and plans just treating the PET-positive tumor volume, we found that TCP increased to (95.2 ± 0.5%) for an integrated boost with 75.6 Gy, (98.1 ± 0.3%) for an integrated boost with 80 Gy, (94.7 ± 0.8%) for treatment of PET-positive volume with 75 Gy, and to (99.4 ± 0.1%) for treating PET-positive volume with 95 Gy (all p < 0.0001). For the integrated boost with 80 Gy, a significant increase of the median NTCP of the rectum was found, for all other plans no statistical significant increase in the NTCP neither of the rectum nor the bladder was found. CONCLUSIONS: Our study demonstrates that the use of 68Ga-PSMA-PET/CT image information allows for more individualized prostate treatment planning. TCP values of identified active tumor volumes were increased, while rectum and bladder NTCP values either remained the same or were even lower. However, further studies need to clarify the clinical benefit for the patients applying these techniques.

Practical implications for the quality assurance of modulated radiation therapy techniques using point detector arrays.

PURPOSE: Linac parameters potentially influencing the delivery quality of IMRT and VMAT plans are investigated with respect to threshold ranges, consequently to be considered in a linac based quality assurance procedure. Three commercially available 2D arrays are used to further investigate the influence of the measurement device. METHODS: Using three commercially available 2D arrays (Mx: MatriXXevolution , Oc: Octavius1500 , Mc: MapCHECK2), simple static measurements, measurements for MLC characterization and dynamic interplay of gantry movement, MLC movement and variable dose rate were performed. The results were evaluated with respect to each single array as well as among each other. RESULTS: Simple static measurements showed different array responses to dose, dose rate and profile homogeneity and revealed instabilities in dose delivery and profile shape during linac ramp up. Using the sweeping gap test, all arrays were able to detect small leaf misalignments down to ±0.1 mm, but this test also demonstrated up to 15% dose deviation due to profile instabilities and fast accelerating leaves during linac ramp up. Tests including gantry rotation showed different stability of gantry mounts for each array. Including gantry movement and dose rate variability, differences compared to static delivery were smaller compared to dose differences when simultaneously controling interplay of gantry movement, leaf movement and dose rate variability. CONCLUSION: Linac based QA is feasible with the tested commercially available 2D arrays. Limitations of each array and the linac ramp up characteristics should be carefully considered during individual plan generation and regularly checked in linac QA. Especially the dose and dose profile during linac ramp up should be checked regularly, as well as MLC positioning accuracy using a sweeping gap test. Additionally, dynamic interplay tests including various gantry rotation speeds and angles, various leaf speeds and various dose rates should be included.

Stereoscopic X-ray imaging, cone beam CT, and couch positioning in stereotactic radiotherapy of intracranial tumors: preliminary results from a cross-modality pilot installation.

BACKGROUND: To assess the accuracy and precision of a fully integrated pilot installation of stereoscopic X-ray imaging and kV-CBCT for automatic couch positioning in stereotactic radiotherapy of intracranial tumors. Positioning errors as detected by stereoscopic X-ray imaging are compared to those by kV-CBCT (i.e. the accuracy of the new method is verified by the established method), and repeated X-ray images are compared (i.e. the precision of new method is determined intra-modally). METHODS: Preliminary results are reported from a study with 32 patients with intracranial tumors. Patients were treated with stereotactic radiotherapy guided by stereoscopic X-ray imaging and kV-CBCT. Patient positioning was automatically corrected by a robotic couch. Cross-modal discrepancies in position detection were measured (N = 42). Intra-modal improvements after correction and re-verification by stereoscopic X-ray imaging were measured (N = 70). The accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were confirmed in phantom measurements (N = 12 shifts of a ball bearing phantom, N = 24 shifts of a head phantom). RESULTS: After correction based on stereoscopic X-ray imaging 95% of residual mean errors were below 0.4, 0.4, 0.5, and 0.7 mm (lateral, longitudinal, vertical, radial, respectively). Stereoscopic X-ray imaging and CBCT were in close agreement with an average discrepancy of 0.1, 0.5, 0.3 and 0.8 mm, respectively. 95% of discrepancies were below 0.8, 1.2, 1.0, and 1.4 mm, respectively. After correction and re-verification by stereoscopic X-ray imaging, the remaining intra-modal residual error was consistent with zero (p = 0.31, p = 0.48, p = 0.81 in lateral, longitudinal, and vertical direction; p-values from two-tailed t-test). The inherent technical accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were found to be of the order of 0.1 mm in controlled phantom settings. CONCLUSIONS: In a routine clinical setting, both stereoscopic X-ray imaging and CBCT were able to reduce positioning errors by an order of magnitude. The end-to-end precision of the system, measured from the discrepancy (mean) between ExacTrac and CBCT, in a clinical setting seems to be about 0.8 mm radially, including couch positioning. The precision (measured from repeatability of ExacTrac, intra-modal) was found to be about 0.7 mm radially in a clinical setting.

Hippocampal sparing radiotherapy for glioblastoma patients: a planning study using volumetric modulated arc therapy.

BACKGROUND: The purpose of this study is to investigate the potential to reduce exposure of the contralateral hippocampus in radiotherapy for glioblastoma using volumetric modulated arc therapy (VMAT). METHODS: Datasets of 27 patients who had received 3D conformal radiotherapy (3D-CRT) for glioblastoma with a prescribed dose of 60Gy in fractions of 2Gy were included in this planning study. VMAT plans were optimized with the aim to reduce the dose to the contralateral hippocampus as much as possible without compromising other parameters. Hippocampal dose and treatment parameters were compared to the 3D-CRT plans using the Wilcoxon signed-rank test. The influence of tumour location and PTV size on the hippocampal dose was investigated with the Mann-Whitney-U-test and Spearman's rank correlation coefficient. RESULTS: The median reduction of the contralateral hippocampus generalized equivalent uniform dose (gEUD) with VMAT was 36 % compared to the original 3D-CRT plans (p < 0.05). Other dose parameters were maintained or improved. The median V30Gy brain could be reduced by 17.9 % (p < 0.05). For VMAT, a parietal and a non-temporal tumour localisation as well as a larger PTV size were predictors for a higher hippocampal dose (p < 0.05). CONCLUSIONS: Using VMAT, a substantial reduction of the radiotherapy dose to the contralateral hippocampus for patients with glioblastoma is feasible without compromising other treatment parameters. For larger PTV sizes, less sparing can be achieved. Whether this approach is able to preserve the neurocognitive status without compromising the oncological outcome needs to be investigated in the setting of prospective clinical trials.

Impact of MLC properties and IMRT technique in meningioma and head-and-neck treatments.

PURPOSE: The impact of multileaf collimator (MLC) design and IMRT technique on plan quality and delivery improvements for head-and-neck and meningioma patients is compared in a planning study. MATERIAL AND METHODS: Ten previously treated patients (5 head-and-neck, 5 meningioma) were re-planned for step-and-shoot IMRT (ssIMRT), sliding window IMRT (dMLC) and VMAT using the MLCi2 without (-) and with (+) interdigitation and the Agility-MLC attached to an Elekta 6MV linac. This results in nine plans per patient. Consistent patient individual optimization parameters are used. Plans are generated using the research tool Hyperion V2.4 (equivalent to Elekta Monaco 3.2) with hard constraints for critical structures and objectives for target structures. For VMAT plans, the improved segment shape optimization is used. Critical structures are evaluated based on QUANTEC criteria. PTV coverage is compared by EUD, Dmean, homogeneity and conformity. Additionally, MU/plan, treatment times and number of segments are evaluated. RESULTS: As constrained optimization is used, all plans fulfill the hard constraints. Doses to critical structures do not differ more than 1 Gy between the nine generated plans for each patient. Only larynx, parotids and eyes differ up to 1.5 Gy (Dmean or Dmax) or 7% (volume-constraint) due to (1) increased scatter, (2) not avoiding structures when using the full range of gantry rotation and (3) improved leaf sequencing with advanced segment shape optimization for VMAT plans. EUD, Dmean, homogeneity and conformity are improved using the Agility-MLC. However, PTV coverage is more affected by technique. MU increase with the use of dMLC and VMAT, while the MU are reduced by using the Agility-MLC. Fastest treatments are always achieved using Agility-MLC, especially in combination with VMAT. CONCLUSION: Fastest treatments with the best PTV coverage are found for VMAT plans with Agility-MLC, achieving the same sparing of healthy tissue compared to the other combinations of ssIMRT, dMLC and VMAT with either MLCi2(-/+) or Agility.

Stereotactic radiotherapy of intrapulmonary lesions: comparison of different dose calculation algorithms for Oncentra MasterPlan®.

BACKGROUND: The use of high accuracy dose calculation algorithms, such as Monte Carlo (MC) and Collapsed Cone (CC) determine dose in inhomogeneous tissue more accurately than pencil beam (PB) algorithms. However, prescription protocols based on clinical experience with PB are often used for treatment plans calculated with CC. This may lead to treatment plans with changes in field size (FS) and changes in dose to organs at risk (OAR), especially for small tumor volumes in lung tissue treated with SABR. METHODS: We re-evaluated 17 3D-conformal treatment plans for small intrapulmonary lesions with a prescription of 60 Gy in fractions of 7.5 Gy to the 80% isodose. All treatment plans were initially calculated in Oncentra MasterPlan® using a PB algorithm and recalculated with CC (CCre-calc). Furthermore, a CC-based plan with coverage similar to the PB plan (CCcov) and a CC plan with relaxed coverage criteria (CCclin), were created. The plans were analyzed in terms of Dmean, Dmin, Dmax and coverage for GTV, PTV and ITV. Changes in mean lung dose (MLD), V10Gy and V20Gy were evaluated for the lungs. The re-planned CC plans were compared to the original PB plans regarding changes in total monitor units (MU) and average FS. RESULTS: When PB plans were recalculated with CC, the average V60Gy of GTV, ITV and PTV decreased by 13.2%, 19.9% and 41.4%, respectively. Average Dmean decreased by 9% (GTV), 11.6% (ITV) and 14.2% (PTV). Dmin decreased by 18.5% (GTV), 21.3% (ITV) and 17.5% (PTV). Dmax declined by 7.5%. PTV coverage correlated with PTV volume (p < 0.001). MLD, V10Gy, and V20Gy were significantly reduced in the CC plans. Both, CCcov and CCclin had significantly increased MUs and FS compared to PB. CONCLUSIONS: Recalculation of PB plans for small lung lesions with CC showed a strong decline in dose and coverage in GTV, ITV and PTV, and declined dose in the lung. Thus, switching from a PB algorithm to CC, while aiming to obtain similar target coverage, can be associated with application of more MU and extension of radiotherapy fields, causing greater OAR exposition.

Arc therapy for total body irradiation--a robust novel treatment technique for standard treatment rooms.

BACKGROUND AND PURPOSE: We developed a simple and robust total body irradiation (TBI) method for standard treatment rooms that obviates the need for patient translation devices. METHODS AND MATERIALS: Two generic arcs with rectangular segments for a patient thickness of 16 and 20 cm (arc16/arc20) were generated. An analytical fit was performed to determine the weights of the arc segments depending on patient thickness and gantry angle. Stability and absolute dose for both arcs were measured using EBT3 films in a range of solid water slab phantom thicknesses. Additionally ionization chamber measurements were performed every 10 cm at a source surface distance (SSD) of ∼ 200 cm. RESULTS: The measured standard deviation for arc16 is ± 3% with a flatness ⩽ 9.0%. Arc20 had a standard deviation of ± 3% with a flatness ⩽ 7.3% for all measured thicknesses. The theoretical curves proved to be accurate for the prediction of the segment weightings for the two arcs. In vivo measurements for the first 22 clinical patients showed a dose deviation of less than 3%. CONCLUSIONS: Arc therapy is a convenient and stable method for TBI. This cost-effective approach has been introduced clinically, obviating the need for field patches and to physically move the patient.