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Purpose: STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia. However, clinical data are scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization., Methods and Materials: Planning target volumes (PTVs) overlapping extracardiac organs-at-risk and/or cardiac substructures were generated for 3 STAR cases. Participating centers were asked to create single-fraction treatment plans with 25 Gy dose prescriptions based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for International Commission on Radiation Units and Measurements report 91 relevant parameters and crowd dose-volume histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process., Results: Twenty centers submitted 67 treatment plans for this study. In most plans (75%) intensity modulated arc therapy with 6 MV flattening filter free beams was used. Dose prescription was mainly based on PTV D 95% (49%) or D 96%-100% (19%). Many participants preferred to spare close extracardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D 0.035cm3 ranged from 25.5 to 34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged from 2 to 80 minutes. For the consensus statements, a strong agreement was reached for beam technique planning, dose calculation, prescription methods, and trade-offs between target and extracardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target., Conclusions: This STOPSTORM multicenter treatment planning benchmark study not only showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established; however, clinical data are urgently needed for actionable guidelines for treatment planning., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Part of the current stereotactic arrythmia radioablation (STAR) workflow is transfer of findings from the electroanatomic mapping (EAM) to computed tomography (CT). Here, we analyzed inter- and intraobserver variation in a modified EAM-CT registration using automatic registration algorithms designed to yield higher robustness., Materials and Methods: This work is based on data of 10 patients who had previously undergone STAR. Two observers participated in this study: (1) an electrophysiologist technician (cardiology) with substatial experience in EAM-CT merge, and (2) a clinical engineer (radiotherapy) with minimum experience with EAM-CT merge. EAM-CT merge consists of 3 main steps: segmentation of left ventricle from CT (CT LV), registration of the CT LV and EAM, clinical target volume (CTV) delineation from EAM specific points. Mean Hausdorff distance (MHD), Dice Similarity Coefficient (DSC) and absolute difference in Center of Gravity (CoG) were used to assess intra/interobserver variability., Results: Intraobserver variability: The mean DSC and MHD for 3 CT LVs altogether was 0.92 ± 0.01 and 1.49 ± 0.23 mm. The mean DSC and MHD for 3 CTVs altogether was 0,82 ± 0,06 and 0,71 ± 0,22 mm. Interobserver variability: Segmented CT LVs showed great similarity (mean DSC of 0,91 ± 0,01, MHD of 1,86 ± 0,47 mm). The mean DSC comparing CTVs from both observers was 0,81 ± 0,11 and MHD was 0,87 ± 0,45 mm., Conclusions: The high interobserver similarity of segmented LVs and delineated CTVs confirmed the robustness of the proposed method. Even an inexperienced user can perform a precise EAM-CT merge following workflow instructions., Competing Interests: Conflict of interest: Authors declare no conflict of interests., (© 2024 Greater Poland Cancer Centre.)

Background: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality., Methods: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy 10 in all patients, and 60 Gy was applied in 3-5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30-33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI)., Results: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01-2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58)., Conclusion: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care., (© 2024. The Author(s).)

Introduction: In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment., Methods: To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023. We focused on the expression of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) relative to overall survival (OS) and specific survival rates. Associations between biomarkers and survival rates were assessed by crude and adjusted hazard ratios (cHR, aHR, respectively) obtained from Cox proportional hazards regression., Results: Among a total of 55 patients within a median follow-up of 19.7 months, there were 21 (38.2%) all-cause deaths and 15 (27.3%) cancer-related deaths. An overall survival (OS) rate of 61.8% and a disease-specific survival (DSS) rate of 72.7% were recorded. A significant association between survival rates and a ≥10% difference in PD-L1 expression on immune versus tumor cells (high PD-L1 IC expression) was documented regardless of the type of analysis (univariate or multivariate). In addition, a stronger association was confirmed for OS and the composite biomarker high PD-L1 IC expression along with either median-higher CD8+ TIL count or increased TIL density ≥30%, as indicated by an aHR of 0.08 (95% CI, 0.01 to 0.52) and 0.07 (95% CI, 0.01 to 0.46), respectively. Similar results were demonstrated for other specific survival rates., Discussion: The early outcomes of the present study suggest the utility of a strong prognostic factor involving a composite biomarker high PD-L1 IC expression along with increased TIL density in HNSCC patients undergoing definitive radiotherapy and radiochemotherapy., Trial Registration: The study is registered with Clinicaltrials.gov. - NCT05941676., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Blažek, Petráš, Hurník, Matoušek, Knybel, Čermáková, Štembírek, Cvek and Soumarová.)

Purpose: The optimal motion management strategy for patients receiving stereotactic arrhythmia radioablation (STAR) for the treatment of ventricular tachycardia (VT) is not fully known. We developed a framework using a digital phantom to simulate cardiorespiratory motion in combination with different motion management strategies to gain insight into the effect of cardiorespiratory motion on STAR., Methods and Materials: The 4-dimensional (4D) extended cardiac-torso (XCAT) phantom was expanded with the 17-segment left ventricular (LV) model, which allowed placement of STAR targets in standardized ventricular regions. Cardiac- and respiratory-binned 4D computed tomography (CT) scans were simulated for free-breathing, reduced free-breathing, respiratory-gating, and breath-hold scenarios. Respiratory motion of the heart was set to population-averaged values of patients with VT: 6, 2, and 1 mm in the superior-inferior, posterior-anterior, and left-right direction, respectively. Cardiac contraction was adjusted by reducing LV ejection fraction to 35%. Target displacement was evaluated for all segments using envelopes encompassing the cardiorespiratory motion. Envelopes incorporating only the diastole plus respiratory motion were created to simulate the scenario where cardiac motion is not fully captured on 4D respiratory CT scans used for radiation therapy planning., Results: The average volume of the 17 segments was 6 cm 3 (1-9 cm 3 ). Cardiac contraction-relaxation resulted in maximum segment (centroid) motion of 4, 6, and 3.5 mm in the superior-inferior, posterior-anterior, and left-right direction, respectively. Cardiac contraction-relaxation resulted in a motion envelope increase of 49% (24%-79%) compared with individual segment volumes, whereas envelopes increased by 126% (79%-167%) if respiratory motion also was considered. Envelopes incorporating only the diastole and respiration motion covered on average 68% to 75% of the motion envelope., Conclusions: The developed LV-segmental XCAT framework showed that free-wall regions display the most cardiorespiratory displacement. Our framework supports the optimization of STAR by evaluating the effect of (cardio)respiratory motion and motion management strategies for patients with VT., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To identify the optimal STereotactic Arrhythmia Radioablation (STAR) strategy for individual patients, cardiorespiratory motion of the target volume in combination with different treatment methodologies needs to be evaluated. However, an authoritative overview of the amount of cardiorespiratory motion in ventricular tachycardia (VT) patients is missing., Methods: In this STOPSTORM consortium study, we performed a literature review to gain insight into cardiorespiratory motion of target volumes for STAR. Motion data and target volumes were extracted and summarized., Results: Out of the 232 studies screened, 56 provided data on cardiorespiratory motion, of which 8 provided motion amplitudes in VT patients (n = 94) and 10 described (cardiac/cardiorespiratory) internal target volumes (ITVs) obtained in VT patients (n = 59). Average cardiac motion of target volumes was < 5 mm in all directions, with maximum values of 8.0, 5.2 and 6.5 mm in Superior-Inferior (SI), Left-Right (LR), Anterior-Posterior (AP) direction, respectively. Cardiorespiratory motion of cardiac (sub)structures showed average motion between 5-8 mm in the SI direction, whereas, LR and AP motions were comparable to the cardiac motion of the target volumes. Cardiorespiratory ITVs were on average 120-284% of the gross target volume. Healthy subjects showed average cardiorespiratory motion of 10-17 mm in SI and 2.4-7 mm in the AP direction., Conclusion: This review suggests that despite growing numbers of patients being treated, detailed data on cardiorespiratory motion for STAR is still limited. Moreover, data comparison between studies is difficult due to inconsistency in parameters reported. Cardiorespiratory motion is highly patient-specific even under motion-compensation techniques. Therefore, individual motion management strategies during imaging, planning, and treatment for STAR are highly recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JC reports personal fees from Accuray, and Roche for lectures. JK reports personal fees from Abbott-St Jude Medical, Bayer, Biosense Webster, Biotronik, Boston Scientific, Cath Vision, Medtronic, Boehringer Ingelheim, Pfizer, and ProMedCS for lectures, advisory boards, and consultancy. JC, JK, and LK report grants from Ministry of Health, Czech Republic and European Commission H2020.

Importance: The failure or success of radical treatment in patients with head and neck squamous cell carcinoma (HNSCC) is associated with many known and unknown factors; hence, there is a search for further prognostic markers to help optimize therapeutic strategy and improve treatment outcomes., Objective: To assess the association of programmed cell death ligand 1 (PD-L1) expression on immune or tumor cells, including its composite expression on both cell types, with overall survival (OS) or specific survival., Data Sources: MEDLINE, Embase, PQSciTech, and HCAPlus databases were systematically searched for cohort studies focused on the prognostic role of PD-L1 expression in patients with HNSCC in curative stages of the disease. Search results generated publications from January 1, 2010, to January 6, 2023., Study Selection: Of 3825 publications identified, a total of 17 cohort studies in the English language met inclusion criteria of this systematic review and meta-analysis. Eligible studies reported adjusted hazard ratios (aHRs) with 95% CIs for the association of PD-L1 expression levels with OS and arbitrary specific survival., Data Extraction and Synthesis: Data from studies were extracted independently by 2 researchers strictly adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines and recommendations. The risk of bias was assessed using the Quality in Prognosis Studies tool and Newcastle-Ottawa Scale. Pooled effect estimates were obtained using a random-effect or fixed-effect model based on homogeneity of studies., Main Outcomes and Measures: The primary outcome was to investigate whether there was an association between PD-L1 expression on immune or tumor cells and OS., Results: In 17 cohort studies of the association of PD-L1 expression with survival in 3190 patients with HNSCC, high PD-L1 expression on immune cells was associated with a favorable OS (pooled aHR, 0.39; 95% CI, 0.25-0.59). There was no association between composite PD-L1 expression on immune and tumor cells and OS (pooled aHR, 0.79; 95% CI, 0.55-1.14) or between PD-L1 expressed only on tumor cells and OS (pooled aHR, 1.22; 95% CI, 0.87-1.70). A high level of PD-L1 expression on immune cells was associated with favorable specific survival (pooled aHR, 0.52; 95% CI, 0.38-0.72). There were no interactions between tumor location or type of primary treatment (ie, surgery vs radiotherapy or radiochemotherapy) and the association between PD-L1 expression and OS., Conclusions and Relevance: This study's findings suggest that PD-L1 expression on immune cells may serve as a new prognostic biomarker in patients with HNSCC. However, future studies may be warranted to verify this potential role given the limited number of studies on this topic conducted and published to date.

Introduction: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway., Objective: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival., Method: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined., Results: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year ( p = 0.083), 5-year ( p = 0.159), and overall survival ( p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year ( p = 0.083) and 5-year ( p = 0.159) survival., Conclusion: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

We performed a histological and immunohistochemical analysis of myocardia from 3 patients who underwent radiosurgery and died for various reasons 3 months to 9 months after radiotherapy. In Case 1 (death 3 months after radiotherapy) we observed a sharp transition between relatively intact and irradiated regions. In the myolytic foci, only scattered cardiomyocytes were left and the area was infiltrated by immune cells. Using immunohistochemistry we detected numerous inflammatory cells including CD68+/CD11c+ macrophages, CD4+ and CD8+ T-lymphocytes and some scattered CD20+ B-lymphocytes. Mast cells were diminished in contrast to viable myocardium. In Case 2 and Case 3 (death 6 and 9 months after radiotherapy, respectively) we found mostly fibrosis, infiltration by adipose tissue and foci of calcification. Inflammatory infiltrates were less pronounced. Our observations are in accordance with animal experimental studies and confirm a progress from myolysis to fibrosis. In addition, we demonstrate a role of pro-inflammatory macrophages in the earlier stages of myocardial remodeling after stereotactic radioablation for ventricular tachycardia., (Copyright © 2022. Published by Elsevier Inc.)

Background: Common primary brain tumors are meningiomas with year incidence 3-8 cases per 100 000 people. Even though we mainly speak about benign disease, with its character and localization, it worsens the life quality to its bearer. The main therapeutic methods are neurosurgery extirpation and stereotactic radiosurgery. Despite reaching very good therapeutic results with both methods, some of the patients suffer with recurrence of the disease requiring other interventions with the risk of creating or worsening a neurological deficit. Small meningiomas without growing tendency and with the absence of symptomatology are observed. On the other hand, we cannot be satisfied with long-term results of the therapy of meningiomas with more aggressive bio-logical behavior. A higher grade is a known risk of meningioma recurrence; however, it is often difficult to identify subgroups that show advantage of a combination of neurosurgery and radiosurgery, respectfully at which it is appropriate to look for ways to treatment escalation, and that is with the risk of side effects. The analysis of hormonal, cytogenetics and epigenetics tumor equipment seems to be the most promising for the development of personalized treatment., Purpose: The aim of this work is to sum up the facts about epidemiology, treatment algorithms and the prognosis of brain meningiomas and to suggest perspective prognostic and predictive factors for maximally individualized therapy.

Background and Purpose: Stereotactic arrhythmia radioablation (STAR) has been suggested as a promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardias in patients with structural heart disease. Cyberknife ® robotic radiosurgery system utilizing target tracking technology is one of the available STAR treatment platforms. Tracking using implantable cardioverter-defibrillator lead tip as target surrogate marker is affected by the deformation of marker-target geometry. A simple method to account for the deformation in the target definition process is proposed., Methods: Radiotherapy planning CT series include scans at expiration and inspiration breath hold, and three free-breathing scans. All secondary series are triple registered to the primary CT: 6D/spine + 3D translation/marker + 3D translation/target surrogate-a heterogeneous structure around the left main coronary artery. The 3D translation difference between the last two registrations reflects the deformation between the marker and the target (surrogate) for the respective respiratory phase. Maximum translation differences in each direction form an anisotropic geometry deformation margin (GDM) to expand the initial single-phase clinical target volume (CTV) to create an internal target volume (ITV) in the dynamic coordinates of the marker. Alternative GDM-based target volumes were created for seven recent STAR patients and compared to the original treated planning target volumes (PTVs) as well as to analogical volumes created using deformable image registration (DIR) by MIM ® and Velocity ® software. Intra- and inter-observer variabilities of the triple registration process were tested as components of the final ITV to PTV margin., Results: A margin of 2 mm has been found to cover the image registration observer variability. GDM-based target volumes are larger and shifted toward the inspiration phase relative to the original clinical volumes based on a 3-mm isotropic margin without deformation consideration. GDM-based targets are similar (mean DICE similarity coefficient range 0.80-0.87) to their equivalents based on the DIR of the primary target volume delineated by dedicated software., Conclusion: The proposed GDM method is a simple way to account for marker-target deformation-related uncertainty for tracking with Cyberknife ® and better control of the risk of target underdose. The principle applies to general radiotherapy as well., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dvorak, Knybel, Dudas, Benyskova and Cvek.)

Background: This retrospective analysis evaluated the long-term outcome of spinal stereotactic body radiotherapy (SBRT) treatment for hemangioblastomas., Materials and Methods: Between 2010 and 2018, 5 patients with 18 Von-Hippel Lindau-related pial-based spinal hemangioblastomas were treated with fractionated SBRT. After precisely registering images of all relevant datasets, we delineated the gross tumor volume, spinal cord (including intramedullary cysts and/or syrinxes), and past radiotherapy regions. A sequential optimization algorithm was used for dose determinations, and patients received 25-26 Gy in five fractions or 24 Gy in three fractions. On-line image guidance, based on spinal bone structures, and two orthogonal radiographs were provided. The actuarial nidus control, surgery-free survival, cyst/syrinx changes, and progression-free survival were calculated with the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0., Results: The median follow-up was 5 years after SBRT. Patients displayed one nidus progression, one need of neurosurgery, and two cyst/syrinx progressions directly connected to symptom worsening. No SBRT-related complications or acute adverse radiation-related events occurred. However, one asymptomatic radiological sign of myelopathy occurred two years after SBRT. All tumors regressed; the one-year equivalent tumor volume reduction was 0.2 mL and the median volume significantly decreased by 28% (p = 0.012). Tumor volume reductions were not correlated with the mean (p = 0.19) or maximum (p = 0.16) dose., Conclusions: SBRT for pial-based spinal hemangioblastomas was an effective, safe, viable alternative to neurosurgery in asymptomatic patients. Escalating doses above the conventional dose-volume limits of spinal cord tolerance showed no additional benefit., Competing Interests: Conflict of interest Dr. Knybel and Dr. Cvek reports grants from Ministry of Health, Czech Republic, during the conduct of the study., (© 2022 Greater Poland Cancer Centre.)

Background: To report prostate deformation during treatment, based on an analysis of fiducial marker positional differences in a large sample., Material and Methods: This study included 144 patients treated with prostate stereotactic body radiation therapy after implantation in each of 4 gold fiducial markers (FMs), which were located and numbered consistently. The center of mass of the FMs was recorded for every pair of X-ray images taken during treatment. The distance between each pair of fiducials in the live X-ray images is calculated and compared with the respective distances as determined in the CT volume. The RBE is the difference between these distances. Mean RBE and intrafraction and interfraction RBE were evaluated. The intrafraction and intefraction RBE variability were defined as the standard deviation, respectively, of all RBE during 1 treatment fraction and of the mean daily RBE over the whole treatment course., Results: We analyzed 720 treatment fractions comprising 24,453 orthogonal X-ray image acquisitions. We observed a trend to higher RBE related to FM4 (apex) during treatment. The fiducial marker in the prostate apex could not be used in 16% of observations, in which RBE was > 2.5 mm. The mean RBEavg was 0.93 ± 0.39 mm (range 0.32-1.79 mm) over the 5 fractions. The RBEavg was significantly lower for the first and second fraction compared with the others (P < .001). The interfraction variability of RBEavg was 0.26 ± 0.16 mm (range 0.04-0.74 mm). The mean intrafraction variability of all FMs was 0.45 ± 0.25 mm. The highest Pearson correlation coefficient was observed between FM2 and FM3 (middle left and right prostate) (R = 0.78; P < .001). Every combination with FM4 yielded lower coefficients (range 0.66-0.71; P < .001), indicating different deformation of the prostate apex., Conclusions: Ideally, prostate deformation is generally small, but it is very sensitive to rectal and bladder filling. We observed RBE up to 11.3 mm. The overall correlation between FMs was affected by shifts of individual fiducials, indicating that the prostate is not a "rigid" organ. Systematic change of RBE average between subsequent fractions indicates a systematic change in prostate shape., (© 2021. The Author(s).)

Purpose: We evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer., Methods: Thirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70-72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables-tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4., Results: After a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%)., Conclusion: The combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.

Background: Here we aimed to evaluate the respiratory and cardiac-induced motion of a ICD lead used as surrogate in the heart during stereotactic body radiotherapy (SBRT) of ventricular tachycardia (VT). Data provides insight regarding motion and motion variations during treatment., Materials and Methods: We analyzed the log files of surrogate motion during SBRT of ventricular tachycardia performed in 20 patients. Evaluated parameters included the ICD lead motion amplitudes; intrafraction amplitude variability; correlation error between the ICD lead and external markers; and margin expansion in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions to cover 90% or 95% of all amplitudes., Results: In the SI, LL, and AP directions, respectively, the mean motion amplitudes were 5.0 ± 2.6, 3.4. ± 1.9, and 3.1 ± 1.6 mm. The mean intrafraction amplitude variability was 2.6 ± 0.9, 1.9 ± 1.3, and 1.6 ± 0.8 mm in the SI, LL, and AP directions, respectively. The margins required to cover 95% of ICD lead motion amplitudes were 9.5, 6.7, and 5.5 mm in the SI, LL, and AP directions, respectively. The mean correlation error was 2.2 ± 0.9 mm., Conclusions: Data from online tracking indicated motion irregularities and correlation errors, necessitating an increased CTV-PTV margin of 3 mm. In 35% of cases, the motion variability exceeded 3 mm in one or more directions. We recommend verifying the correlation between CTV and surrogate individually for every patient, especially for targets with posterobasal localization where we observed the highest difference between the lead and CTV motion., Competing Interests: Conflict of interest The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript. Authors have no financial interests related to the material in the manuscript. L.K., J.C., R.N., O.J., J.H., M.P., M.S. have nothing to disclose. J.K. reports personal fees and other from Biosense Webster, personal fees and other from Bostron Scientific, personal fees and other from Epix , personal fees from LIva Nova (MicroPort), personal fees and other from Medtronic, from null, personal fees and other from Abbott (SJM), personal fees and other from Daiichi Sankyo, personal fees from Boehringer Ingelheim, personal fees from Bayer, personal fees from Pfizer, personal fees from MSD, personal fees and other from Affera, outside the submitted work., (© 2021 Greater Poland Cancer Centre.)

Background and Aims: Modern stereotactic body radiotherapy (SBRT) techniques and systems that use online image guidance offer frameless radiotherapy of spinal tumors and the ability to control intrafraction motion during treatment. These systems allow precise alignment of the patient during the entire treatment session and react immediately to random changes in this alignment. Online tracking data provide information about intrafractional changes, and this information can be useful for designing treatment strategies even if online tracking is not being used. The present study evaluated spine motion during SBRT treatment to assess the risk of verifying patient alignment only prior to starting treatment., Methods: This study included 123 patients treated with spine SBRT. We analyzed different locations within the spine using system log files generated during treatment, which contain information about differences in the pretreatment reference spine positions by CT versus positions during SBRT treatment. The mean spine motion and intra/interfraction motion was evaluated. We defined and assessed the spine stability and spine significant shifts (SSHs) during treatment., Results: We analyzed 462 fractions. For the cervical (C) spine, the greatest shifts were in the anterior-posterior (AP) direction (2.48 mm) and in pitch rotation (1.75 deg). The thoracic (Th) spine showed the biggest shift in the AP direction (3.68 mm) and in roll rotation (1.66 deg). For the lumbar-sacral (LS) spine, the biggest shift was found for left-right (LR) translation (3.81 mm) and roll rotation (3.67 deg). No C spine case exceeded 1 mm/1 deg for interfraction variability, but 7 of 54 Th spine cases exceeded 1 mm interfraction variability for translations (maximum value, 2.5 mm in the AP direction). The interfraction variability for translations exceeded 1 mm in 2 of 24 LS spine cases (maximum value, 1.7 mm in the LR direction). Only 13% of cases had no SSHs. The mean times to SSH were 6.5±3.9 min, 8.1±5.9 min, and 8.8±7.1 min for the C, Th, and LS spine, respectively, and the mean recorded SSH values were 1.6±0.66, 1.43±0.33, and 1.46±0.47 mm/deg, respectively., Conclusion: Positional tracking during spine SBRT treatments revealed low mean translational and rotational shifts. Patient immobilization did not improve spine shifts compared with our results for the Th and LS spine without immobilization. For the most precise spine SBRT, we recommend checking the patient's position during treatment.

Aims: Stereotactic body radiotherapy (SBRT) for ventricular tachycardias (VTs) could be an option after failed catheter ablation. In this study, we analysed the long-term efficacy and toxicity of SBRT applied as a bail-out procedure., Methods and Results: Patients with structural heart disease and unsuccessful catheter ablations for VTs underwent SBRT. The planning target volume (PTV) was accurately delineated using exported 3D electroanatomical maps with the delineated critical part of re-entry circuits. This was defined by detailed electroanatomic mapping and by pacing manoeuvres during the procedure. Using the implantable cardioverter-defibrillator lead as a surrogate contrast marker for respiratory movement compensation, 25 Gy was delivered to the PTV using CyberKnife. We evaluated occurrences of sustained VT, electrical storm, antitachycardia pacing, and shock; time to death; and radiation-induced events. From 2014 until March 2017, 10 patients underwent radiosurgical ablation (mean PTV, 22.15 mL; treatment duration, 68 min). After radiosurgery, four patients experienced nausea and one patient presented gradual progression of mitral regurgitation. During the follow-up (median 28 months), VT burden was reduced by 87.5% compared with baseline (P = 0.012) and three patients suffered non-arrhythmic deaths. After the blanking period, VT recurred in eight of 10 patients. The mean time to first antitachycardia pacing and shock were 6.5 and 21 months, respectively., Conclusion: Stereotactic body radiotherapy appears to show long-term safety and effectiveness for VT ablation in structural heart disease inaccessible to catheter ablation. We report one possible radiation-related toxicity and promising overall survival, warranting evaluation in a prospective multicentre clinical trial., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aim: The aim of this study was to evaluate overall survival (OS) and prognostic factors in patients ineligible for chemotherapy who were treated with a hyperfractionated accelerated schedule with simultaneous integrated boost., Material and Methods: From May, 2008, to April, 2013, 122 patients with locally advanced nonmetastatic squamous laryngeal (14%), hypopharyngeal (30%), oropharyngeal (30%), and oral cavity (27%) cancer were treated at our institution. The median age, Karnofsky Performance Status (KPS), and gross tumor volume (GTV) of the patients were 63 years (range, 46-87 years), 80% (range, 50-100%), and 46 ml (range, 5-250 ml), resp. The median total dose of radiotherapy was 72.6 Gy (range, 62-77 Gy) at 1.4-1.5 Gy per fraction, and 55 Gy at 1.1 Gy per fraction was delivered for GTV (primary and lymphadenopathy) with a margin of 0.7 cm and regional lymphatic areas with a margin of 0.3 cm. The dose was delivered 2× a day, with a 6-8 hour interval between doses, via a 6 MeV linear accelerator. OS was estimated using the Kaplan-Meier method, and predictors of OS were analyzed using Cox proportional hazards regression., Results: The median duration of the radiotherapy series was 37 days (range, 32-45 days). The incidence of grade 3 acute toxicity was 62% for mucosa (oral cavity and/or pharynx) and 0% for skin. Confluent mucositis cleared in all cases within 21 days. No grade 4 or 5 toxicities were recorded. PEG was introduced before treatment in 55 patients (45%). The 1-and 2-year OS was 65% and 32%, resp. KPS less than 80% (RR 2.4, 95% CI 1.3-4.2; p = 0.004), cancers other than oropharyngeal or laryngeal cancer (RR 2.0, 95% CI 1.1-3.5; p = 0.016), and capacity of high GTV (RR 1.006, 95% CI 1.001-1.011; p = 0.017) were found to be negative prognostic factors for OS., Conclusion: More than 30% of patients with poor prognosis survived for longer than 2 years. KPS before treatment was the strongest prognostic factor for better OS.Key words: head and neck cancer - radiotherapy dose fractionation - survival analysis - acceleration - hyperfractionation This work was supported by RVO-FNOs/2016 (HPV status as predictive and prognostic factor for primary and secondary head and neck cancer). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 9. 3. 2017Accepted: 19. 4. 2017.

Background: Prostate cancer is the most prevalent cancer in males and its incidence is steadily increasing. Most cases of prostate cancer are diagnosed during the early asymptomatic period, in which case the prognosis is very good. Therapies differ widely in their efficacies and toxicities, and this is an important consideration when it comes to deciding which treatment is optimal for a particular patient. One treatment method for early stage prostate cancer is stereotactic body radiotherapy (SBRT). We present the first results obtained using this modality at our institution., Patients and Methods: A total of 261 patients with low or intermediate risk prostate cancer were treated with SBRT between August 2010 and July 2012. Patients received a total dose of 36.25 Gy in five fractions of 7.25 Gy every other day. The toxicity of the treatment was evaluated according to RTOG criteria. For assessment of quality of life, patients filled out a modified EPIC questionnaire (Expanded Prostate Composite index)., Results: Overall survival (OS) in this study was 93.1%. Biochemical relapse free survival (bRFS) was 97.7%. As expected, OS and bRFS were worse in the group of patients with an intermediate risk of recurrence. Acute and chronic urinary and gastrointestinal RTOG toxicity was very low. Quality of life after treatment, as determined using the EPIC questionnaire, was slightly reduced immediately after treatment but returned to baseline or even improved during long term follow-up., Conclusion: SBRT is an effective therapeutic modality for early prostate cancer and has acceptable rates of acute and low late toxicity.Key words: prostate cancer - stereotactic body radiotherapy - quality of life The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 1. 2017Accepted: 1. 2. 2017.

Purpose/objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy., Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis., Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and -0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors., Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe tumors; higher interfraction amplitude variability indicated tumors in contact with mediastinal structures, although adhesion to parietal pleura did not necessarily reduce tumor motion amplitudes. The most variable lung tumors were metastatic lesions in women., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To evaluate liver tumor motion and how well reference measurement predicts motion during treatment., Material and Methods: This retrospective study included 20 patients with colorectal cancer that had metastasized to the liver who were treated with stereotactic ablative radiotherapy. An online respiratory tumor tracking system was used. Tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were collected to generate patient-specific margins. Reference margins were generated as the mean motion and 95th percentile of motion from measurements recorded for different lengths of time (1, 3, and 5 min). We analyzed the predictability of tumor motion in each axis, based on the reference measurement and intra-/interfraction motions., Results: About 96,000 amplitudes were analyzed. The mean tumor motions were 9.9 ± 4.2 mm, 2.6 ± 0.8 mm, and 4.5 ± 1.8 mm in the SI, LL, and AP directions, respectively. The intrafraction variations were 3.5 ± 1.8 mm, 0.63 ± 0.35 mm, and 1.4 ± 0.65 mm for the SI, LL, and AP directions, respectively. The interfraction motion variations were 1.32 ± 0.79 mm, 0.31 ± 0.23 mm, and 0.68 ± 0.62 mm for the SI, LL, and AP directions, respectively. The Pearson's correlation coefficients for margins based on the reference measurement (mean motion or 95th percentile) and margins covering 95% of the motion during the whole treatment were 0.8-0.91, 0.57-0.7, and 0.77-0.82 in the SI, LL, and AP directions, respectively., Conclusion: Liver tumor motion in the SI direction can be adequately represented by the mean tumor motion amplitude generated from a single 1 min reference measurement. Longer reference measurements did not improve results for patients who were well-educated about the importance of regular breathing. Although the study was based on tumor tracking data, the results are useful for ITV delineation when tumor tracking is not available.

Purpose: The goal of this work was to evaluate the efficacy and toxicity of hyperfractionated stereotactic reirradiation (re-RT) as a treatment for inoperable, recurrent, or second primary head and neck squamous cell cancer (HNSCC) that is not suitable for systemic treatment., Patients and Materials: Forty patients with recurrent or second primary HNSCC were included in this study. The patients had a median gross tumor volume of 76 ml (range 14-193 ml) and a previous radiotherapy dose greater than 60 Gy. Treatment was designed to cover 95 % of the planning target volume (PTV, defined as gross tumor volume [GTV] + 3 mm to account for microscopic spreading, with no additional set-up margin) with the prescribed dose (48 Gy in 16 fractions b.i.d.). Treatment was administered twice daily with a minimum 6 h gap. Uninvolved lymph nodes were not irradiated., Results: Treatment was completed as planned for all patients (with median duration of 11 days, range 9-14 days). Acute toxicity was evaluated using the RTOG/EORTC scale. A 37 % incidence of grade 3 mucositis was observed, with recovery time of ≤ 4 weeks for all of these patients. Acute skin toxicity was never observed to be higher than grade 2. Late toxicity was also evaluated according to the RTOG/EORTC scale. Mandible radionecrosis was seen in 4 cases (10 %); however, neither carotid blowout syndrome nor other grade 4 late toxicity occurred. One-year overall survival (OS) and local progression-free survival (L-PFS) were found to be 33 and 44 %, respectively. Performance status and GTV proved to be significant prognostic factors regarding local control and survival., Conclusion: Hyperfractionated stereotactic re-RT is a reasonable treatment option for patients with recurrent/second primary HNSCC who were previously exposed to high-dose irradiation and who are not candidates for systemic treatment or hypofractionation.