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Aims In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario. Materials and methods Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03. Results After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09–5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17–6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52–14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity. Conclusion Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach.

To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual’s planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Radiosurgery (RS) is a well-established treatment in selected patients with brain metastasis. The aim of this study is to compare the differences between CyberKnife (CK) and TomoTherapy (HT) treatment plans of RS of single brain metastasis (BM) to define when HT should be used in cases beyond Cyberknife—when both systems are readily available for the radiation oncologist. Nineteen patients with single brain metastasis treated with CK were re-planned for radiosurgery using TomoTherapy Hi-ART system. Two planning approaches have been used for TomoTherapy plans: the classical one (HT) and the improved conformity (icHT) that produces dose distributions more similar to those of RS plans. PTV coverage, Conformity Index (CI), Paddick Conformity Index (nCI), Homogeneity Index (HI), Gradient Index (GI), and beam on time of CK, HT, and icHT plans were evaluated and compared. A good coverage was found for CK, HT, and icHT plans. A difference between mean HI of CK and icHT plans was observed (p = 0.007). Better dose gradients compared to both icHT and HT modalities were observed in CK plans. icHT modality showed improved mean CI respect to HT modality, similar to that obtained in CK plans. CK plans show higher conformity and lower GI than icHT and HT plans. TomoTherapy demonstrates the advantage of being a device capable to reach different clinical objectives depending on the different planning modality employed. CyberKnife and TomoTherapy are both optimal RS devices, the choice to use one over another has to be clinically guided.

Purpose To assess the performance of a new optimization system, VOLO, for CyberKnife MLC-based SBRT plans in comparison with the existing Sequential optimizer. Methods MLC-plans were created for 25 SBRT cases (liver, prostate, pancreas and spine) using both VOLO and Sequential. Monitor units (MU), delivery time (DT), PTV coverage, conformity (nCI), dose gradient (R50%) and OAR doses were used for comparison and combined to obtain a mathematical score (MS) of plan quality for each solution. MS strength was validated by changing parameter weights and by a blinded clinical plan evaluation. The optimization times (OT) and the average segment areas (SA) were also compared. Results VOLO solutions offered significantly lower mean DT (−19%) and MU (−13%). OT were below 15 min for VOLO, whereas for Sequential, values spanned from 8 to 160 min. SAs were significantly larger for VOLO: on average 10 cm2 versus 7 cm2. VOLO optimized plans achieved a higher MS than Sequential for all tested parameter combinations. PTV coverage and OAR sparing were comparable for both groups of solutions. Although slight differences in R50% and nCI were found, the parameters most affecting MS were MU and DT. VOLO solutions were selected in 80% of cases by both physicians with 88% inter-observer agreement. Conclusions The good performance of the VOLO optimization system, together with the large reduction in OT, make it a useful tool to improve the efficiency of CK SBRT planning and delivery. The proposed methodology for comparing different planning solutions can be applied in other contexts.

The dosimetric variability in spine stereotactic body radiation therapy (SBRT) planning was investigated in a large number of centres to identify crowd knowledge-based solutions.Two spinal cases were planned by 48 planners (38 centres). The required prescription dose (PD) was 3 × 10 Gy and the planning target volume (PTV) coverage request was: VIn all, 12.5% of plans did not meet the protocol requirements. After re-optimization, 98% of plans fulfilled the constraints, showing the positive impact of knowledge sharing. Statistical analysis showed a significant correlation (p 0.05) between the homogeneity index (HI) and PTV coverage for both cases, while the correlation between HI and spinal cord sparing was significant only for the single dorsal PTV case. Moreover, the multileaf collimator leaf thickness correlated with the spinal cord sparing. Planners using comparable delivery/planning system techniques produced different QI, highlighting the impact of the planner's skills in the optimization process.Both the technology and the planner's skills are fundamentally important in spine SBRT planning optimization. Knowledge sharing helped to follow the plan objectives.

Aims and Background Radiobiological and technical considerations have traditionally limited the role of radiation therapy in the context of primary and secondary cardiac malignancies. Stereotactic body radiotherapy (SBRT) is a promising modality for the delivery of focused high-dose radiation with ablative potential to complex targets such as small, deep-seated, moving lesions, allowing also for re-irradiation. Methods Between January 2013 and October 2013, 3 patients underwent SBRT for cardiac lesions: 2 patients had recurrent, previously irradiated cardiac angiosarcomas (PCA) and 1 patient had a cardiac metastasis from melanoma. They were treated with fiducial-guided robotic radiotherapy with CyberKnife. As for dose prescription, 24 Gy in 3 fractions (80% isodose) and 30 Gy in 5 fractions (80% isodose) were administered to the recurrent PCAs and cardiac metastasis, respectively. Results At 2 months after SBRT, cardiac MRI showed a partial response in the patients treated for recurrent PCA while the cardiac metastasis remained stable. In all cases, absence of local progression was subsequently confirmed by contrast-enhanced cardiac MRI after 6 months, without any evidence of treatment-related side effects. Conclusions Fiducial-guided SBRT proved to be feasible and effective in preventing local disease progression in selected patients with cardiac malignancies.

To report a clinical experience in stereotactic body radiation therapy (SBRT) for isolated nodal metastases from prostate cancer. Between November 2011 and December 2013, 30 patients (39 lesions) were treated with SBRT, delivered using Cyberknife, for recurrent prostate cancer with isolated nodal metastases. Prescribed doses and schedules of fractionation varied, ranging from 24 Gy in 1 fraction to 36 Gy in 3 fractions. Most commonly used schedules were 30 Gy in 3 fractions and 36 in Gy in 3 fractions on alternating days. Biochemical response, acute and late toxicity were analyzed. At a median follow-up of 12 months (range 2–24.9), a significant reduction of PSA was observed in 24 cases, while PSA was stable in 1 case and raised in 9 cases. At the time of analysis, among the 30 patients treated, two were dead for systemic disease; 12 patients experienced a relapse of disease in other sites. Sixteen patients were still free of disease. In 24 cases, imaging evaluation 3 months after treatment was available. No in-field recurrence was detected. SBRT was well tolerated: One patient experienced G2 acute genitourinary toxicity. Late toxicity was evaluated in patients with more than 6 months of follow-up, and only one complained G1 proctitis. We did not observe any acute or late severe toxicity (≥G3). Our experience shows that SBRT for isolated nodal relapse from prostate cancer is a safe treatment, with promising results in terms of efficacy.

Purpose Accurate and reliable patient-specific QA is required for CyberKnife (CK) MLC treatment plans. Films are the current method of choice, but filmless solutions are starting to be introduced in the routine [1] . Aim of this study is to test the sensitivity of a filmless QA technique to simulated delivery errors for CK MLC plans, and to discuss which γ -index criteria are adequate; DVH implications were also analyzed. Methods Preliminarily, routine garden fence tests were employed to assess MLC leaf positioning accuracy. Test plans were then delivered to Octavius 1000SRS array (PTW) and EBT3 (Ashland), editing leaf positions of five clinical plans (prostate/pancreas) with three error types: MLC banks opened, both of 0.3 mm (03 mm OUT)/0.5 mm (05 mm OUT), one of 1 mm (1 mm X2)), closed (both of 0.5 mm (05 mm IN)) and shifted (both of 1 mm (1 mm X1X2)). Γ-index analysis was performed comparing the measured plans to the unedited dose distributions using three criteria: 2%2 mm, 3%1 mm, 2%1 mm. For patient plans, DVH implications were also considered. Results The garden fence leaf positioning distribution mean over 11578 values is 0.07 ± 0.16 mm. The 95% percentile is 0.34 mm, with 141 values (1.2%) outside the 0.5 mm tolerance. In Fig. 1 1000SRS passing rates for the edited and the unedited plans are reported for two cases. For all plans, the highest influence on pass-rate is found for increased segments size. With both banks opened of 0.3 mm a mean passing rate decrease from 94.0% to 80.2% was observed (3%1 mm). EBT3 show analogous results. In Table 1 the simulated errors effect on DVH parameters is reported for Plan2. A 0.3 mm opening produced a total of 7 OAR constraint violations over all plans. Conclusions High sensitivity in the detection of small delivery errors, slightly affecting DVHs, is achievable for CK MLC plans delivery QA even employing filmless solutions. A 2%2 mm criteria is not always tight enough.

Purpose The CyberKnife (CK) M6 series is equipped with a MLC intended to achieve higher delivery efficiency than the circular IRIS variable collimator and to expand the feasibility of CK treatments to larger tumors. This study aimed to evaluate the CK-MLC performance for SBRT plans focusing on (i) comparison with IRIS (ii) large volume tumor treatments (iii) dosimetric delivery accuracy. Methods (i) IRIS and MLC plans in 3–5 fractions were created for 30 liver, 15 pancreas and 10 prostate cases and compared in terms of coverage, conformity (nCI), dose gradient (R50), homogeneity (HI), OAR doses, PTV gEUD, MU normalized to prescription dose (MU/PD), treatment time both estimated by TPS (tTPS) and measured (tmeas). Prostate plans MU/PD and tTPS were compared with similar published data [1] , [2] . (ii) SBRT MLC plans (30 Gy/5 fractions) were optimized for large PTVs (240 cm3 ÷ 1140 cm3, diameters 8 cm ÷ 14 cm) in one pancreas and three liver cases. Plan quality, treatment time and feasibility to meet OAR constraints were evaluated. (iii) Delivery QA was performed for 50 MLC plans using different techniques. Results (i) Compared to IRIS ( Table 1 ), MLC achieved equivalent coverage, conformity, homogeneity and EUD without compromising OAR sparing and improving (p Conclusions MLC improves dose fall-off and delivery efficiency compared to IRIS. Time reduction is partially lost when measured and is highly variable among different studies. MLC permits to extend CK SBRT treatments to larger PTVs maintaining high dosimetric accuracy.

Purpose New promising detectors are available for measuring small field size output factors (OFs). This study focused on a multicenter evaluation of two new generation detectors for OF measurements on CyberKnife systems. Methods PTW-60019 microDiamond and W1 plastic scintillation detector (PSD) were used to measure OFs on eight CyberKnife units of various generations for 5–60 mm fixed cones. MicroDiamond and PSD OF were compared to routinely used silicon diodes data corrected applying published Monte Carlo (MC) factors. PSD data were corrected for Cerenkov Light Ratio (CLR). The uncertainties related to CLR determination were estimated. Results Considering OF values averaged over all centers, the differences between MC corrected diode and the other two detectors were within 1.5%. MicroDiamond exhibited an over-response of 1.3% at 7.5 mm and a trend inversion at 5 mm with a difference of 0.2%. This behavior was consistent among the different units. OFs measured by PSD slightly under-responded compared to MC corrected diode for the smaller cones and the differences were within 1%. The observed CLR variability was 2.5% and the related variation in OF values was 1.9%. Conclusion This study indicates that CyberKnife microDiamond OF require corrections below 2%. The results are enhanced by the consistency observed among different units. Scintillator shows a good agreement to MC corrected diode but CLR determination remains critical requiring further investigations. The results emphasized the value of a multi-center validation over a single center approach.

Cyberknife is an emerging treatment for early stage prostate cancer. Between October 2012 and January 2014, 32 patients were treated in our institution. Prescribed dose was 35-36.25 Gy in five fractions. Biochemical response was observed in 22 patients. Four patients experienced G2 acute genitourinary toxicity and in two cases we recorded G3 acute GU toxicity. 5 patients experienced G2 acute proctitis. At last follow up visit, all patients were still alive. 29 remained free of disease at last follow up appointment, while three developed a biochemical recurrence. Our experience confirms the efficacy and safety of Cyberknife for localized prostate cancer.

To report a clinical experience of stereotactic body radiation therapy (SBRT) for isolated recurrence in the prostatic bed from prostate cancer. Between November 2011 and November 2013, 16 patients were treated with SBRT for a macroscopic isolated recurrence of prostate cancer in the prostatic bed. All patients were initially treated with radical prostatectomy, and half of them also received radiotherapy. Two schedules of SBRT were used: 30 Gy in 5 fractions in previously irradiated patients, 35 Gy in five fractions in radiotherapy-naive patients. At a median follow-up of 10 months (range 2–21 months), a significant biochemical response was found in all but one patient. At imaging evaluation, no local progression was noted: 10 patients showed partial response while four stable disease. At the moment of analysis, all 16 patients were alive. Seven of them experienced distant relapse, while nine maintained biochemical control, with no further therapy. Median time to relapse was 9.3 months (range 3–15.2 months). The treatment was well tolerated: One patient experienced G2 acute genitourinary and gastrointestinal toxicity. Our experience shows that SBRT with CyberKnife for isolated nodal relapse is a safe and well-tolerated treatment.

The aim of our study was to retrospectively evaluate the feasibility and clinical benefit of cyberknife stereotactic radiosurgery (CSRS) in patients treated at Florence University for recurrent, pre-irradiated brain lesions. Thirteen patients were retreated with cyberknife. Mean age was 47.1 years (range 33–77 years). Karnofsky performance status ranged from 60 to 100 (median 80). Eleven (84.6 %) out of 13 patients had metastatic lesions: four (36.4 %) had primary lung, three (27.2 %) had primary breast cancer and four (36.4 %) other types of solid malignancies. Two (15.4 %) out of 13 patients had recurrent of glioblastoma. In terms of compliance with CSRS, the majority of patients did not develop any acute side effects. However, two (15.4 %) out of 13 patients developed acute grade 2 toxicity requiring an increase of steroid medication. At the time of the last follow-up, response rates were as follows: complete response in one case (16.6 %), partial response in three (50 %) and stable disease in two (33.4 %). Re-irradiation with CSRS is a feasible and effective option for pre-irradiated, recurrent brain lesions to obtain clinical benefit without excessive acute toxicity.

This study sought to evaluate acute toxicity and local control in patients who underwent extracranial stereotactic body radiation therapy (SBRT) for paracardiac and cardiac metastatic lesions, defined as such when located at a maximum distance of 1 cm from the heart or inside its parenchyma.Between January 2009 and May 2011, 16 patients with paracardiac and cardiac lesions were treated with SBRT. For dose specification, in 15 of 16 patients, the prescription dosage was 36 Gy in three fractions (70% isodose). In one patient, the target lesion was inside the heart, and the prescription dosage was 30 Gy in three fractions (70% isodose).Regarding response to stereotactic radiotherapy, we recorded one (6%) complete response (CR), six (37%) partial responses (PR), five (32%) stable disease (SD) and four (25%) local failures. Median interval to local failure was 5.2 (range, 3-12) months. The cause of death was distant progression of disease in all four patients. Compliance to treatment was excellent; no patient developed cardiological symptoms or electrocardiographic abnormalities, even months after SBRT.Results of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.

To compare and evaluate different dosimetric techniques and devices for the QA of VMAT plans created by two treatment planning systems (TPSs).A total of 50 VMAT plans were optimized for treatment of anatomical sites of various complexities by two TPSs which use rather different approaches to VMAT optimization. Dosimetric plan verifications were performed both as part of commissioning and as patient specific QA of clinical treatments. Absolute point doses were measured for all plans by a micro ion chamber inserted in a dedicated water-filled cylindrical phantom. Delivered dose distributions were verified by four techniques based on different detectors: radiographic and gafchromic films, two systems based on 2D diode arrays and an ion chamber array. Gamma index analysis with various tolerance levels (3%, 3 mm and 3%, 2 mm) was used to analyze differences between calculated and delivered doses. Sensitivity to possible delivery errors was also evaluated for three of the considered devices introducing +/-3 mm shifts along the three directions and a 3 degrees gantry offset.Ion chamber measured point doses were within 3% of calculated ones for 48 out of 50 values. For delivered dose distribution, the average fraction of passed gamma values using 3% and 3 mm criteria was above 95% for both TPSs and all detectors except gafchromic film which yielded on average of 91.4%. For 49 out of 50 plans, a pass-rate above 94% was obtained by at least one of the four techniques. Shrinking the tolerance to 3% and 2 mm, the average pass-rate by all detectors (except film) was still above 95% for one of the two TPSs, but lower for the other one. The detector sensitivity to 3 mm shifts and to gantry angle offset was strongly plan and partially detector dependent: the obtained pass-rate reduction ranged from 2% to 30%.The presented results for VMAT plans QA assess the reliability of the delivered doses for both TPSs. The slightly lower pass-rate obtained for one of the considered TPS can be attributed to a higher level of complexity of the optimized plans. The results by different dosimetric techniques are coherent, apart from a few measurements by gafchromic films. The detector sensitivity to delivery errors, being strongly plan dependent, is not easy to evaluate.

Purpose To evaluate a retrospective single-institution outcome after hypofractionated stereotactic body radiotherapy (SBRT) for adrenal metastases. Methods and Materials Between February 2002 and December 2009, we treated 48 patients with SBRT for adrenal metastases. The median age of the patient population was 62.7 years (range, 43–77 years). In the majority of patients, the prescription dose was 36 Gy in 3 fractions (70% isodose, 17.14 Gy per fraction at the isocenter). Eight patients were treated with single-fraction stereotactic radiosurgery and forty patients with multi-fraction stereotactic radiotherapy. Results Overall, the series of patients was followed up for a median of 16.2 months (range, 3–63 months). At the time of analysis, 20 patients were alive and 28 patients were dead. The 1- and 2-year actuarial overall survival rates were 39.7% and 14.5%, respectively. We recorded 48 distant failures and 2 local failures, with a median interval to local failure of 4.9 months. The actuarial 1-year disease control rate was 9%; the actuarial 1- and 2-year local control rate was 90%. Conclusion Our retrospective study indicated that SBRT for the treatment of adrenal metastases represents a safe and effective option with a control rate of 90% at 2 years.

Free-breathing stereotactic radiotherapy for lung malignancies requires reliable prediction of respiratory motion and accurate target localization. A protocol was adopted for reproducibility and reduction of respiratory motion and for target localization by CBCT image guidance. Tumor respiratory displacements and tumor positioning errors relative to bony anatomy alignment are analyzed.Image guided SRT was performed for 99 lung malignancies. Two groups of patients were considered: group A did not perform any breathing control; group B controlled visually their respiratory cycle and volumes on an Active Breathing Coordinator (ABC) monitor during the acquisition of simulation CT and CBCT, and treatment delivery. GTV on end inhale and exhale CT data sets were fused in an ITV and the extent of tumor motion evaluated between these 2 phases. A pre-treatment CBCT was acquired and aligned to the reference CT using bony anatomy; for tumor positioning the ITV contour on the reference CT was matched to the visible tumor on CBCT. Interobserver variability of tumor positioning was evaluated. ITV and CBCT tumor dimensions were compared.3D tumor breathing displacement (mean+/-SD) was significantly higher for group A (14.7+/-9.9 mm) than for group B (4.7+/-3.1 mm). The detected differences between tumor and bony structure alignment below 3 mm were 68% for group B and 45% for group A, reaching statistical significance. Interobserver variability was 1.7+/-1.1 mm (mean+/-SD). Dimensions of tumor image on CBCT were consistent with ITV dimensions for group B (max difference 14%).The adopted protocol seems effective in reducing respiratory internal movements and margin. Tumor positioning errors relative to bony anatomy are also reduced. However bony anatomy as a surrogate of the target may still lead to some relevant positioning errors. Target visualization on CBCT is essential for an accurate localization in lung SRT.

Sedentary behavior-related diseases can be prevented by lifestyle changes. Part of the cardiovascular benefits of physical activity (PA) may be due to low-grade inflammation. This study describes the PA of a population of Japanese and analyses its association with metabolic syndrome (MS) adjusted a number of variables. This was based on a database previously created following a population-based study of Japanese-Brazilians. 1,330 subjects agedor = 30 years, of both sexes, living in Bauru, were included and they were submitted to interviews, being obtained sociodemographic, health, physical activity and dietary data, as well as clinical and laboratory data. Physical activity assessment focused on activities during work and leisure times. Diagnosis of MS was based on an adaptation of NCEP criteria for Asians. Non-conditional logistic regression had MS as the dependent variable. Men (46.1%) and women showed similar mean ages (57.0 +/- 12.8 and 56.9 +/- 12.2 years, respectively). A slight preponderance of females was observed. Men had a higher level of education and more frequently were smokers (p0.001); their mean values of BMI, waist and blood pressure (p0.001) were higher than the womens. For both sexes, the majority referred light and moderate activities (81.2% of men and 86.6% of women). As far as work time is concerned, 87.8% of men classified their effort as light or moderate versus 96.1% of women. Distribution by PA levels showed that women were always less active than men (p= 0.01). Stratifying by the presence of MS, men and women with MS were significantly older and showed greater anthropometric values. Considering the walking duration for work, there was a tendency of shorter periods among those with MS (p0.078). As expected, subjects with MS showed significantly higher levels of blood pressure, plasma glucose, lipids and HOMA-IR when compared to those without MS. HDL levels were lower in the MS group, being significant for the female sex. The mean values of CRP were higher in subjects with MS. In logistic regression, age, BMI, HOMA-IR and CRP were shown to be independently associated with MS, but not parameters used to measure physical activity. Our findings do not allow to state that physical inactivity is associated with MS in a Japanese-Brazilian population. High frequencies of physical inactivity should have contributed to the negative findings concerning protective effects of physical activity. The association of MS and serum CRP favors the hypothesis that a low-grade inflammatory state may participate in this syndrome.