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To assess the incidence of both acute and late gastrointestinal (GI) and genitourinary (GU) side effects in patients with organ-confined unfavorable prostate cancer (PCa) treated with single-dose ablative radiotherapy (SDART). Thirty patients enrolled in a single-arm prospective trial (NCT04831983) received 24 Gy SDART to the whole prostate with urethra-sparing and organ motion control. The treatment was delivered on a Linac platform using a 10MV FFF single partial arc. ADT was prescribed as per standard of care. Treatment-related GU and GI toxicities (CTCAE_v5 scale) and QoL outcomes (EORTC QLQ-PR25/C30, IPSS, IIEF 5) were assessed at different time points. Minimal Important Difference (MID) was established as a change of >0.5 pooled SD from baseline. The significance of the differences between QoL outcomes at baseline, 3-month, and last follow-up was tested through the analysis of variances. A logistic regression univariate and multivariate (MVA) analysis was performed to evaluate potential associations between specific patient-related, tumor-related, or treatment-related factors and clinical outcomes. All patients completed the treatment according to the protocol's schedule. The median follow-up was 18 months (range = 6-31), with no ≥G3 side effects observed. Within 3 months post-treatment, there was only one instance of G1 acute GI toxicity, while 2 patients had G2 acute urinary toxicity. G2 late GI and G2 late GU toxicities occurred in 1 and 2 patients, respectively. Late GI toxicity of any grade correlated with maximum rectal dose (P = 0.021), while lower baseline QoL score (P = 0.025), higher baseline IPSS score (P = 0.049), acute GU toxicity (P = 0.029), and acute urinary domain MID (P = 0.045) predicted late GU toxicity of any grade. In MVA, only baseline QoL score (OR 0.95, P = 0.031) and acute GU toxicity (OR 8.4, P = 0.041) remained significant. Significant QoL change was observed only in the urinary domain (P = 0.005), with a median increase from 8 to 17 in the questionnaire score. Late urinary MID correlated with acute urinary MID (P = 0.003), acute QoL MID (P = 0.029), acute GU toxicity (p = 0.030), and lower baseline urinary score (P = 0.033). In MVA, only acute urinary MID predicted late urinary MID (OR 9.7, P = 0.035). All patients were found biochemically controlled at the time of analysis, with median PSA level decreased from 8.05 ng/ml (range = 3.41 – 18.27) at baseline to 0.10 ng/ml (range = 0.01 – 1.46) at the last follow-up. Our findings provide promising data on the feasibility and safety of 24 Gy SDART of the whole prostate with urethra-sparing and organ motion control associated with ADT in organ-confined unfavorable PCa. Long-term follow-up is needed to confirm these results. [ABSTRACT FROM AUTHOR]

In stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) of brain metastases (BM) using single-isocenter VMAT, intra-fraction positioning errors may affect target coverage. This study aims to investigate geometric and dosimetric accuracy in single and multiple BM treatments. Seventy patients with single (n = 38) and multiple (n = 32) BM treated with 15-21 Gy in 1 (n = 59) or 27 Gy in 3 (n = 11) fractions using coplanar FFF-VMAT technique were analyzed. PTV was defined by a 2 mm isotropic GTV expansion. Pre-treatment setup errors were evaluated with CBCT and corrected with a robotic six degrees-of-freedom couch. For each fraction, intra-fractional errors were measured by post-treatment CBCT and applied to the planning CT. Plans involving translations and rotations (Fx-plan) were recalculated with Monte Carlo TPS. Original and Fx-plans were compared in terms of target and brain dose parameters, performing the Wilcoxon-Mann-Whitney test (alpha = 0.05). The relationships of the BM volume, maximum dimension, distance-to-isocenter (for multiple BM cases only) and barycenter shift with the difference in target coverage between the two plans were investigated. The median post-treatment 3D error and maximum rotational error over all 129 BM were 0.5 mm [0.1–2.7] and 0.3° [0.0–1.3], respectively. The resulting median BM barycenter shift was 0.5 mm [0.1–2.7]. The percentage of fractions in which at least one BM barycenter shifted by more than 2 mm from the planned position was 4% and 1% for single and multiple BM cases, respectively. The median single GTV volume was 0.27 cc [0.01–10.48], while the PTV had a median volume of 1.05 cc [0.12–17.05]. The median BM maximum dimension was 10.7 mm [2.9–34.1] and for multiple BM the median distance-to-isocenter was 5.15 cm [0.89–7.52]. For single BM patients, the GTV D95% was never reduced by > 5%, while PTV D95% reductions > 1% occurred in only 11 (29%) PTV. For multiple BM patients, the target statistics were slightly worse, with dose deficits larger than 5% and 1% occurring respectively in 2 BM and 34 (37%) PTV. Anyway, the majority of single and multiple BM had a loss of coverage for both GTV and PTV below 1% in Fx-plans. Larger than 5% brain V12 Gy (SRS) and V20 Gy (fSRS) increases were observed for only one single BM patient. None of the two dosimetric comparisons resulted statistically significant (p>0.05). The differences in target coverage showed a moderate-to-strong correlation only with the BM barycenter shift in both cases (R2 = 0.70-0.73 for single and R2 = 0.44-0.50 for multiple BM). Due to the optimal patient setup, as well as the full six degrees-of-freedom corrections, the safety PTV margin, and the fast beam delivery, the dosimetric effects of residual setup and patient motion errors for both single and multiple BM cases were negligible. These findings warrant a potential reduction in the PTV margin with this treatment technique. [ABSTRACT FROM AUTHOR]

This study validated a not yet commercially available fully-automated lexicographic optimization planning system (LOps) for single and multiple lesions intracranial stereotactic radiosurgery (SRS). Forty-four consecutive SRS treatment plans (21 Gy/1 fx) delivered between November 2019 and August 2022 were retrospectively selected and automatically re-planned by LOps: 25 of them has 1 lesion, 13 had 2 lesions, 4 had 3 lesions, and 2 had 4 lesions. An a-priori assigned priority list, Wish List (WL), was used to define the sequential LO: 4 patient sets (tuning set) were necessary to tune each WL, for single lesion-plans (SLp) and multiple lesion-plans (MLp). While in manual plans (MP), the arc setup is freely chosen, the WL was tuned to use 2 coplanar arcs of 140° and 360° for SLp and MLp, respectively. A 0° and 90° collimator rotation were set for counter-clockwise and clockwise arcs, respectively. The fluence optimization is followed by a Monte Carlo calculation (MCc) with 1 mm-dose grid and 0.5%-statistical uncertainty. A target coverage as high as possible was requested, with at least 80% of the prescription dose covering 99% of the PTV. The main criteria for SLp approval were a brain V 12Gy <10 cm3. In MLp this criterion can be overcome to get the minimum target coverage. The remaining 36 SRS plans (21 SL and 15 MLp) were automatically re-planned (testing set). Testing plans were compared in terms of dose-volume constraints, conformality, and monitor units (MUs). Statistical significance was assessed by performing the Wilcoxon test and plan delivery accuracy was verified by pre-treatment QA. WLs-tuning took 3 days. Overall manual and automatic MCc time can be estimated at 8 hours and 3 hours, respectively. Statistically significant increases in SLp and MLp target coverage (GTV_D 98% : +3.0% SL, +5.7% ML, PTV_D 98% : +4.4% SL, +13.4% ML) and conformity index were registered. Automatic plans showed acceptably higher median brain V 12Gy (SL: MP 7.2 cm3, SLp 7.6 cm3; ML: MP 8.7 cm3, MLp 10.3 cm3). The SLp registered a lower median MU number (-4.2%) while MLp were obtained with a higher median number of MU (+9.8%). This not statistically significant difference did not affect gamma passing rates. The novel LOps produced high-quality clinically acceptable SRS SL and ML plans with coplanar arcs according to institutional-specific planning protocols, significantly reducing the overall planning time from about one working day for one MP to about 3 hours for one automatic plan. Together with comparable OAR sparing, the target coverage was significantly increased and the plan deliverability preserved. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the impact of intrafraction prostate motion and interfraction anatomical changes on dose metrics and the effect of beam gating and motion correction in dose-escalated Linac-based SBRT. Thirteen patients (56 fractions) with organ-confined prostate cancer underwent dose-escalated FFF-VMAT SBRT. Accurate patient setup was ensured by CBCT, and real-time 3D prostate motion data were obtained using a novel electromagnetic tracking device. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and couch position was corrected unless the offset was transient. Prostate trajectories with and without beam gating and motion correction events were reconstructed and analyzed. Rectum and bladder volumes on each daily CBCT were recorded and compared with volumes at simulation. The prostate motion observed for each fraction was incorporated into the patient original treatment plan with an isocenter shift method. Actually, delivered treatments were then obtained by recalculating the reconstructed motion-encoded plan on deformed CTs reflecting the patient CBCT-anatomy of the day. Non-gated treatments were also simulated using the prostate motion data assuming that no treatment interruptions have occurred. Treatment interruptions because of target motion trespassing the predefined threshold occurred in 25 fractions (45%). Rectum and bladder volume changes were relevant in most patients. The mean relative dose differences between actually delivered and planned treatments were -3.0% [-18.5 – 2.8] for CTV D99% and -2.6% [-17.8 – 1.0] for PTV D95% over all 56 fractions. However, the median cumulative CTV coverage with 93% of the prescribed dose turned out to be satisfactory. Urethra sparing was slightly degraded and a mean reduction of rectum and bladder dose was seen in all but two dose metrics: the maximum dose to rectum mucosa and the bladder D40%. Nevertheless, only 2 major deviations in rectum mucosa D0.035cc were observed at the end of the treatment. The greatest contribution to target missing and OARs doses came from the interfraction anatomical variations, while intrafraction prostate motion marginally contributed in gated treatments. In non-gated treatments, further deteriorations by 2.4 – 2.8% in minimum target coverage metrics and by 3.1 – 11.6% in bladder dose parameters would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with current PTV margins, robustness of original treatment plans, and fast FFF beam delivery, ensured no significant degradations of dose metrics due to both intrafraction motion and interfraction anatomical changes. Non-gated treatments would have more widely deteriorated the dosimetry of some individual fractions. Thus, continuous monitoring, beam gating and motion correction are recommended to safely deliver dose-escalated prostate SBRT. [ABSTRACT FROM AUTHOR]

This study aimed to validate a not yet commercially available fully-automated lexicographic optimization planning for intracranial stereotactic radiosurgery (SRS) with coplanar arcs. Twenty-one single-lesion SRS treatment plans (21 Gy/1 fx) delivered between November 2019 and December 2021 were retrospectively selected and automatically re-planned. An a-priori assigned priority list, a so-called Wish List (WL), was used to define the sequential multi-criterial optimization: four patient sets were necessary to achieve a robust WL. All plans were optimized with 2 coplanar 140°-arcs and calculated with the Monte Carlo algorithm (1 mm-dose grid, 0.5%-statistical uncertainty). The main criteria for planning approval was a brain volume receiving more than 12 Gy less than 10 cm3 (V 12Gy <10 cm3). A target coverage as high as possible was requested, with at least the 80% of the prescription dose covering the 99% of the planning target volume (PTV). Manual plans (MP) and automatic plans (AP) were compared in terms of dose-volume constraints and monitor units (MUs). Statistical significance was assessed performing the Wilcoxon-Mann-Whitney test with Bonferroni correction for multiple tests (alpha=0.05). Plan deliverability was verified by pre-treatment QA and gamma index analysis. The 21 AP re-planning took only 5 working days. The median D 98% of the gross tumor volume (GTV) and the PTV for MP and AP was 20.4 Gy [18.5-21.6] and 18.1 Gy [16.8-19.9], and 21.1 Gy [19.2-21.7] and 19.1 Gy [17.6-19.4], respectively. These increases were statistically significant (p<0.03). A significant improvement in PTV Paddick's conformity index has been registered: 0.3[0.0-0.6] for MP and 0.5[0.3-0.9] for AP with a p<0.001. The brain V 12Gy was 7.3 cm3 [4.4-12.7] and 7.6 cm3[4.2-13.3] for MP and AP, respectively (p>0.05). Other organs at risk were never significantly interested by clinically relevant doses. These AP results were obtained with a lower median number of MU (-11.6%) even if this difference was not statistically significant and plans registered a comparable gamma analysis (local 2%/2mm). The novel autoplanning produced high-quality clinically acceptable radiosurgery plans with coplanar arcs, significantly reducing the overall planning time from about one working day for one MP to about 2 hours for one AP. While the OAR sparing was comparable between MP and AP, the target coverage was significantly increased, reducing the MU number and preserving the plan deliverability. The validation proved the capability to generate high-quality deliverable plans according to institutional-specific planning protocols. [ABSTRACT FROM AUTHOR]

This study reports the first clinical experience worldwide using a novel electromagnetic (EM) tracking device for intrafraction prostate motion management during dose-escalated Linac-based stereotactic body radiation therapy (SBRT). Thirteen patients with organ-confined prostate cancer underwent dose-escalated SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The prescribed dose was 40 Gy in 5 fractions or 38 Gy in 4 fractions. The EM tracking device consisted of an integrated Foley catheter with a transmitter. Patients were simulated and treated with a filled bladder and an empty rectum. Setup accuracy was achieved by ConeBeam-CT (CBCT) matching and the prostate motion was tracked during all the procedure. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating CBCT. Moreover, the displacements that would have occurred without any intrafraction organ motion management (i.e., no interruptions and repositionings) were simulated and analyzed. In 31 out of 56 monitored fractions (55%), no intervention was required to correct the target position as a result of an excessive displacement. In 25 (45%) a correction was mandated, but only in 10 (18%), the beam delivery was interrupted. Total treatment time lasted on average 10.2 minutes, 6.7 minutes for setup, and 3.5 minutes for beam delivery. The prostate was found inside the 2 mm threshold from its initial position in 96% of the treatment time, i.e., in 94% of the time during the setup, and in 98% during the delivery (beam on + interruptions). Without any intrafraction motion management, the overall mean treatment time and the mean delivery time would have been 6.9 minutes and 3.2 minutes, respectively. The prostate would have been found outside the tolerance in 8% of the total session time, in 4% of the time during the setup, and in 14% during the beam-on phase. The probability of motion > 2 mm in the lateral, longitudinal, and vertical direction after 5 minutes was 3.6% (2/56), 8.9% (5/56), and 14.3% (8/56), respectively. The predominant motion pattern was posterior with a mean motion ≤ 2 mm occurring within 10 minutes. Moreover, the analysis of the rotation angles from all patients showed a systematic rotation in the pitch axis which is absent in the yaw axis. Concurrently, the range and standard deviation of rotation angles were larger in the pitch axis. EM real-time tracking was successfully implemented for intrafraction motion management during dose-escalated prostate SBRT. Results showed that most of the observed displacements were < 2 mm in any direction; however, there were a non-insignificant number of fractions with motion exceeding the predefined threshold, which would have otherwise gone undetected without intrafraction motion management. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the impact of observed intrafraction prostate motion on dose metrics and the effect of beam gating and motion correction using a novel electromagnetic (EM) tracking device in dose-escalated Linac-based SBRT. Thirteen patients (56 fractions) with organ-confined prostate cancer received 40 Gy in 5 fractions or 38 Gy in 4 fractions using VMAT technique with flattening filter-free (FFF) arcs. The EM tracking device consisted of an integrated Foley catheter with a transmitter and provided real-time 3D prostate motion data. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating a ConeBeam-CT (CBCT). Prostate trajectories with and without beam gating and motion correction events were reconstructed and analyzed. Both actually delivered treatments (case A) and non-gated treatments (case B) were simulated by incorporating the observed prostate motion for each fraction into the patient original treatment plan with an isocenter shift method. Target and organs at risk (OARs) dosimetric parameters of the two motion-inclusive plans were compared to planned values and protocol dose constraints. Treatment interruptions were needed in 25 fractions (45%) because of target motion beyond the predefined threshold. The prostate was found within 2 mm from its initial position in 96% of the treatment time, i.e., in 94% of the time during the setup, and in 98% during the delivery. In non-gated treatments, the prostate would have been found outside the tolerance in 8% of the total session time, in 4% of the time during the setup, and in 14% during beam-on. The predominant motion pattern was posterior and its probability increased with time, with a mean motion ≤ 2 mm occurring within 10 minutes. Mean relative dose differences respect to original plans were -0.1% [-1.8 – 1.0] for CTV D99% and -0.2% [-1.6 – 0.7] for PTV D95% in case A. The same values were -1.2% [-8.8 – 0.8] and -1.2% [-5.9 – 0.7] in case B. In both cases, urethra planning organ at risk volume was slightly degraded after taking motion into account, and the rectum and bladder dose metrics showed a favorable underexposition of rectum and an undesirable overdose to bladder. Nevertheless, no protocol dose constraints violations were observed. Our findings showed that the majority of the observed prostate motion was modest; however, there were a non-insignificant number of fractions with motion exceeding the predetermined threshold. The current CTV to PTV margins, the robustness of original treatment plans, and the fast FFF beams delivery led to minimal degradations of dose metrics for the target and OARs in both cases. Anyway, real-time monitoring with beam gating and motion correction ensured superior results and are recommended in dose-escalated prostate SBRT. [ABSTRACT FROM AUTHOR]