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Purpose We present the preliminary results of the STRA-MI-VT Study (NCT04066517), a spontaneous, phase Ib/II study, designed to prospectively test the safety and efficacy of stereotactic body radiotherapy (SBRT) in patientswith advanced cardiac disease and intractable ventricular tachycardia (VT). Methods Cardiac computed tomography (CT) integrated by electroanatomical mapping was used for substrate identification and merged with dedicated CT scans for treatment plan preparation. A single 25-Gy radioablation dose was delivered by a LINAC-based volumetric modulated arc therapy technique in a non-invasive matter. The primary safety endpoint was treatment-related adverse effects during acute and long-term follow-up (FU), obtained by regular in-hospital controls and implantable cardioverter defibrillator (ICD) remote monitoring. The primary efficacy endpoint was the reduction at 3 and 6 months of VT episodes and ICD shocks. Results Seven out of eight patients (men; age, 70 ± 7 years; ejection fraction, 27 ± 11%; 3 ischemic, 4 non-ischemic cardiomyopathies) underwent SBRT. At a median 8-month FU, no treatment-related serious adverse event occurred. Three patients died from non-SBRT-related causes. Four patients completed the 6-month FU: the number of VT decreased from 29 ± 33 to 11 ± 9 (p = .05) and 2 ± 2 (p = .08), at 3 and 6 months, respectively; shocks decreased from 11 to 0 and 2, respectively. At 6 months, all patients. showed a significant reduction of VT episodes and no electrical storm recurrence, with the complete regression of iterative VTs in 2/2 patients. Conclusion The STRA-MI-VT Study suggests that SBRT can be considered an alternative option for the treatment of VT in patients with structural heart disease and highlights the need for further clinical investigation addressing safety and efficacy.

Background Ventricular tachycardia (VT) is a life-threatening condition, which usually implies the need of an implantable cardioverter defibrillator in combination with antiarrhythmic drugs and catheter ablation. Stereotactic body radiotherapy (SBRT) represents a common form of therapy in oncology, which has emerged as a well-tolerated and promising alternative option for the treatment of refractory VT in patients with structural heart disease. Objective In the STRA-MI-VT trial, we will investigate as primary endpoints safety and efficacy of SBRT for the treatment of recurrent VT in patients not eligible for catheter ablation. Secondary aim will be to evaluate SBRT effects on global mortality, changes in heart function, and in the quality of life during follow-up. Methods This is a spontaneous, prospective, experimental (phase Ib/II), open-label study (NCT04066517); 15 patients with structural heart disease and intractable VT will be enrolled within a 2-year period. Advanced multimodal cardiac imaging preceding chest CT-simulation will serve to elaborate the treatment plan on different linear accelerators with target and organs-at-risk definition. SBRT will consist in a single radioablation session of 25 Gy. Follow-up will last up to 12 months. Conclusions We test the hypothesis that SBRT reduces the VT burden in a safe and effective way, leading to an improvement in quality of life and survival. If the results will be favorable, radioablation will turn into a potential alternative option for selected patients with an indication to VT ablation, based on the opportunity to treat ventricular arrhythmogenic substrates in a convenient and less-invasive manner.

CyberKnife® Lung Optimized Treatment (LOT) allows the treatment of lung cancer without invasive fiducial implantation. The aim of this retrospective analysis was to evaluate the feasibility, toxicity and clinical outcome. One hundred fifteen patients (124 lesions) were treated with CyberKnife® using LOT. The median age was 72.6 years (range 31.8-90.3). From 124 treated lesions, 52 were with histopathological confirmation (41 primitive pulmonary cancers, 8 pulmonary metastases) and 72 as untyped tumors. For 5 patients (6 lesions) treatment was an in-field re-irradiation. Concomitant therapy was administered in 7 patients. Zero-View tracking was applied in 69 patients, 1-View in 33 patients, 2-View in 22 patients. The median total dose was 45 Gy (range 18-54), median dose/fraction was 15 Gy (range 4-18) with a median prescription isodose of 80% (range 68-85). The median planning target volume (PTV) was 25 cm3 (range 3-195). The median follow-up was 20 months (range 7-47). Thirty-seven patients (32%) were alive with no evidence of disease, 39 patients (34%) were alive with clinically evident disease, and 38 patients (33%) died of the disease. The 1- and 2-year overall survival (OS) rate was 83% and 61%. The median time to progression was 19 months (95% confidence interval: 11-19 months), 1- and 2-year progression-free survival (PFS) rates were 62% and 41%, respectively. Smaller PTV was significantly associated with better OS, PFS and in-field PFS in univariate and multivariate analyses. Acute toxicity was observed in 36 patients (41%). Late toxicity was registered in 25 patients (29%). G3 late toxicity was observed in one patient (1.1%). Our data suggest that fiducial less-stereotactic body radiation therapy (SBRT) is a feasible, well-tolerated and potentially effective treatment with high compliance in the setting of inoperable patients due to concomitant disease or previous treatments.

The presence of a neobladder constitutes a limitation for the radiation oncologist, as there is no clear evidence about its tolerance to radiotherapy (RT). The limited literature only concerns the conventional postoperative treatment in patients with bladder cancer after cystectomy. Here we report a case of a patient with neobladder who underwent a stereotactic RT for a pelvic recurrence of disease, with response to treatment and no toxicity to the neobladder. This case represents a promising example of the chance to perform RT with ablative intent, using advanced techniques, even on lesions close to the neobladder.

This paper presents a retrospective report on radiotherapy (RT) in the oligometastastic recurrence of bladder cancer. Thirteen patients treated for low-volume metastatic transitional cell urinary bladder carcinoma (TCC) were reviewed, with the primary endpoint to evaluate the safety and efficacy of RT, proposed as an alternative to systemic treatment and/or to defer commencement of systemic therapy. The inclusion criteria were: patients who received RT without other local/systemic therapy for oligometastatic TCC with lymph node, bone and lung lesions or local recurrence. Previous systemic therapy and surgery on the primary tumor were allowed in this tumor response, and toxicity evaluation and progression free-survival was also assessed. Thirteen patients with 21 lesions were treated with stereotactic body radiotherapy (SBRT) or conformal 3D radiotherapy (3D-CRT) between 2012 and 2017. All participants were discussed by a multidisciplinary urological board. The median age at RT was 68 years (range 50-80), the median Karnofsky performance status (KPS) was 90 (range 80-90) and the median interval between TCC diagnosis and commencement of RT on oligometastasis was 23 months (range 8-105). The median treatment dose was 25 Gy (range 20-36 Gy) given over a median of 5 fractions (range 3-10 fractions) with a median follow-up of 25 months (range 3-43 months). Imaging assessment was available for 20 lesions. The radiological progression of disease was registered in 9 patients at the median of 4.2 months from radiotherapy (range 1.9-18.8 months). This identified in-field and out-field progression in 6 patients and only out-field progression in the remaining 3. At last contact, 3 patients were alive with no evidence of disease, 3 had evidence of disease, 6 died of cancer-related disease and one died from another cause. No severe acute and late toxicity was observed. The literature contains no consistent data on TCC oligometastatic setting, but radiotherapy on lymph node, bone and/or lung oligo-recurrence from TCC offers durable disease control in a small number of patients with a very low toxicity profile. Further studies are required to establish the radiotherapy role in oligometastatic recurrent bladder cancer.

The aim is to present the technical feasibility and efficacy of multiple re-irradiation (re-EBRT) for local recurrence of prostate cancer (PCa) using retrospective analysis of an updated series of patients who received ablative re-EBRT with stereotactic image-guided technique for isolated local recurrence of PCa. Eight patients received three RT courses (2 re-RTs); of those 2 received 4 RT courses (3 re-RTs). Local relapse in the prostate was assessed by multiparametric magnetic resonance and/ or choline positron emission tomography. Before treatment planning, all patients had been evaluated for late toxicity from previous RT according to RTOG/EORTC. Biochemical control was assessed according to Phoenix definition. Mean age at the third RT course was 68 (standard deviation, SD: 7.2); all patients had a good performance status. At diagnosis, four cases were classified as high risk PCa, three as intermediate and one as low per NCCN 2017. Biochemical progression free interval after first and second RT-course were 74 (IQR: 59.3-133.6) months and 33 (IQR: 20.8-53.1) months, respectively. Biochemical and radiological response was registered in all patients. At present, seven out of eight patients are disease free. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Multiple RT courses with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent, low-burden PCa recurrence in adequately selected patients. Deeper understanding of radiobiological effects of hypofractionation and larger series of patients are warranted to fully evaluate the applicability of multiple RT courses in the setting of locally recurrent PCa.

Introduction: In case of pelvic recurrence of colorectal cancer, reirradiation of previously irradiated patients may increase the rate of salvage radical resection. Due to the high cumulative dose, one of the main concerns is radiation-induced lumbosacral plexopathy. This report describes multiple irradiations of a lesion adjacent to the lumbosacral plexus, using a highly selective technique, which allows optimal sparing of such a critical structure. Case description A 53-year-old woman treated in 2008 for a locally advanced rectal adenocarcinoma with preoperative pelvic irradiation and concomitant chemotherapy followed by surgery had disease recurrence in 2011 and underwent a second course of pelvic radiotherapy. In December 2015, magnetic resonance imaging showed a single local recurrence infiltrating the muscle next to the right lumbosacral plexus and close to the cauda equina. Repeat reirradiation was planned. The total dose deriving from the previous treatment plans was assessed by nonrigid image registration using the dedicated tool implemented in MIM 6.1.7 (MIMvista Corp., Cleveland, OH). The treatment was performed with Cyberknife (Accuray, Sunnyvale, CA) with a schedule of 20 Gy in 5 fractions (4 Gy per fraction). The dose was prescribed to 70% isodose and target coverage was 97%. Two months after the treatment, magnetic resonance imaging showed a decreased signal and stable disease with no change in tumor size. Conclusions This case report suggests that pelvic re-reirradiation might be a possibility in very carefully selected cases of rectal cancer, using high-precision radiation modalities.

Atlas-based automatic segmentation (ABAS) addresses the challenges of accuracy and reliability in manual segmentation. We aim to evaluate the contribution of specific-purpose in ABAS of breast cancer (BC) patients with respect to generic-purpose libraries.One generic-purpose and 9 specific-purpose libraries, stratified according to type of surgery and size of thorax circumference, were obtained from the computed tomography of 200 BC patients. Keywords about contralateral breast volume and presence of breast expander/prostheses were recorded. ABAS was validated on 47 independent patients, considering manual segmentation from scratch as reference. Five ABAS datasets were obtained, testing single-ABAS and multi-ABAS with simultaneous truth and performance level estimation (STAPLE). Center of mass distance (CMD), average Hausdorff distance (AHD) and Dice similarity coefficient (DSC) between corresponding ABAS and manual structures were evaluated and statistically significant differences between different surgeries, structures and ABAS strategies were investigated.Statistically significant differences between patients who underwent different surgery were found, with superior results for conservative-surgery group, and between different structures were observed: ABAS of heart, lungs, kidneys and liver was satisfactory (median values: CMD2 mm, DSC≥0.80, AHD1.5 mm), whereas chest wall, breast and spinal cord obtained moderate performance (median values: 2 mm ≤ CMD5 mm, 0.60 ≤ DSC0.80, 1.5 mm ≤ AHD4 mm) and esophagus, stomach, brachial plexus and supraclavicular nodes obtained poor performance (median CMD≥5 mm, DSC0.60, AHD≥4 mm). The application of STAPLE algorithm generally yields higher performance and the use of keywords improves results for breast ABAS.The homogeneity in the selection of atlases based on multiple anatomical and clinical features and the use of specific-purpose libraries can improve ABAS performance with respect to generic-purpose libraries.

Intensity-modulated radiotherapy (IMRT) is considered the preferred option in squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but the technique is more demanding as deep understanding of target structures is required. To evaluate genital marginal failure in a cohort of patients with non-metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy, 117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT and 3DCRT techniques, respectively. All patients underwent clinical and radiological examination during their follow-up. Tumor response was evaluated with response evaluation criteria in solid tumors v1.1 guideline on regular basis. All patients’ data were analyzed, and patients with marginal failure were identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow-up was 25 months (range 6–78). Progressive disease was registered in 15.6% of patients; infield recurrence, distant recurrence and both infield recurrence and distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal septum and left perineal region. In the 3DCRT group, the median follow-up was 71.3 months (range 6–194 months). Two out of 53 patients (3.8%) had marginal failures, localized at recto-vaginal septum and perigenital structures. The rate of marginal failures was comparable in IMRT and 3DCRT groups (χ2 test p = 0.85). In this series, the use of IMRT for the treatment of SCAC did not increase the rate of marginal failures offering improved dose conformity to the target. Dose constraints should be applied with caution—particularly in females with involvement of the vagina or the vaginal septum.

To check the interobserver agreement between radiation oncologists and therapists (RTT) using an on- and off-line cone-beam computer tomography (CBCT) protocol for setup verification in the radiotherapy of prostate cancer. The CBCT data from six prostate cancer patients treated with hypofractionated intensity-modulated radiotherapy (IMRT) were independently reviewed off-line by four observers (one radiation oncologist, one junior and two senior RTTs) and benchmarked with on-line CBCT positioning performed by a radiation oncologist immediately prior to treatment. CBCT positioning was based on manual soft-tissue registration. Agreement between observers was evaluated using weighted Cohen’s kappa statistics. In total, 152 CBCT-based prostate positioning procedures were reviewed by each observer. The mean (± standard deviation) of the differences between off- and on-line CBCT–simCT registration translations along the three directions (antero-posterior, latero-lateral and cranio-caudal) and rotation around the antero-posterior axis were − 0.7 (3.6) mm, 1.9 (2.7) mm, 0.9 (3.6) mm and − 1.8 (5.0) degrees, respectively. Satisfactory interobserver agreement was found, being substantial (weighted kappa > 0.6) in 10 of 16 comparisons and moderate (0.41–0.60) in the remaining six comparisons. CBCT interpretation performed by RTTs is comparable to that of radiation oncologists. Our study might be helpful in the quality assurance of radiotherapy and the optimization of competencies. Further investigation should include larger sample sizes, a greater number of observers and validated methodology in order to assess interobserver variability and its impact on high-precision prostate cancer IGRT. In the future, it should enable the wider implementation of complex and evolving radiotherapy technologies.

To compare our standard technique for postprostatectomy radiotherapy of prostate cancer, i.e. using two lateral conformal dynamic arcs with volumetric-modulated arc therapy (VMAT) performed with the RapidArc® (Varian Medical Systems, Palo Alto, CA, USA). The plans were referred to as DA and RA, respectively. The treatment plans of 44 patients receiving adjuvant/salvage radiotherapy in the first months of 2010 were compared. In all cases, the prescribed total dose was 66–68.2 Gy (2.2 Gy per fraction). Both DA and RA plans were optimized in terms of dose coverage and constraints. Small differences between the techniques were observed for planning target volume (PTV) dose distribution, whereas significant differences in sparing of organs at risk (OARs) were recorded (p

A planning study was performed to evaluate RapidArc (RA), a volumetric modulated arc technique, on malignant pleural mesothelioma. The benchmark was conventional fixed-field intensity-modulated radiotherapy (IMRT).The computed tomography data sets of 6 patients were included. The plans for IMRT with nine fixed beams were compared against double-modulated arcs with a single isocenter. All plans were optimized for 15-MV photon beams. The dose prescription was 54 Gy to the planning target volume. The planning objectives for the planning target volume were a minimal dose of95% and maximal dose of107%. For the organs at risk, the parameters were as follows: contralateral lung, percentage of volume receiving 5 Gy (V(5 Gy))60%, V(20 Gy)10%, mean10.0 Gy; liver, V(30 Gy)33%, mean31 Gy; heart, V(45 Gy)30%, V(50 Gy)20%, dose received by 1% of the volume (D(1%))60 Gy; contralateral kidney, V(15 Gy)20%; spine, D(1%)45 Gy; esophagus, V(55 Gy)30%; and spleen, V(40 Gy)50%. The monitor units (MUs) and delivery time were scored to measure the treatment efficiency. The pretreatment portal dosimetry scored delivery to the calculation agreement with the Gamma Agreement Index.RA and IMRT provided equivalent coverage and homogeneity. Both techniques fulfilled objectives on organs at risk with a tendency of RA to improve sparing. The conformity index was 1.9 +/- 0.1 for RA and IMRT. The number of MU/2 Gy was 734 +/- 82 for RA and 2,195 +/- 317 for IMRT. The planning vs. delivery agreement revealed a Gamma Agreement Index for IMRT of 96.0% +/- 2.6% and for RA of 95.7% +/- 1.5%. The treatment time was 3.7 +/- 0.3 min for RA and 13.4 +/- 0.1 min for IMRT.RA demonstrated compared with conventional IMRT, similar target coverage and better dose sparing to the organs at risks. The number of MUs and the time required to deliver a 2-Gy fraction were much lower for RA, allowing the possibility to incorporate this technique in the treatment options for mesothelioma patients.