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Purpose: Stereotactic body radiotherapy (SBRT) is emerging as a valuable treatment modality for localized prostate cancer, with promising biochemical progression-free survival rates. Longitudinal assessment of prostate-specific antigen (PSA) is the mainstay of follow-up after treatment. PSA kinetics and dynamics are well-established in the context of brachytherapy and conventionally fractionated radiotherapy, yet little is known in the context of prostate SBRT., Methods: A review of available literature in MEDLINE, Scopus, and Embase was performed, focusing on studies reporting PSA slope, nadir, bounce, and biochemical failure after prostate SBRT., Results: Thirty-three records (45 % prospective) encompassing 9949 patients were included. SBRT dose ranged from 32-50 Gy in 4-5 fractions and overall median follow-up time (range) was 41 (15-74) months. Use of androgen deprivation therapy ranged from 0-38 %. SBRT was characterized by a steep initial decline of PSA, slowing down over time and ultimately yielding a lower nadir in comparison with conventional radiotherapy, with a median value (range) of 0.24 (0.1-0.6) ng/mL after a median time (range) of 33.1 (6-54) months. There was an inverse correlation between the highest SBRT dose in a trial and PSA nadir (r = - 0.59; p < 0.001). Benign PSA bounce occurred in 30 % of patients across all studies, after a median time (range) of 14.8 (9-36) months and with a median size (range) of 0.5 (0.3-1.1) ng/mL. There was no significant correlation between bounce and dose, nadir nor biochemical failure. There was, however, a significant inverse correlation between ADT use and PSA bounce frequency (r = -0.49; p = 0.046)., Conclusion: PSA kinetics and dynamics after SBRT for localized prostate cancer are different from those in other established radiotherapy modalities. Benign PSA bounce is very common. Clinicians should be aware of these factors and patients should be counseled accordingly, preventing unnecessary distress or salvage treatment., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Rib fracture is a known complication after stereotactic body radiotherapy (SBRT). Patient-related parameters are essential to provide patient-tailored risk estimation, however, their impact on rib fracture is less documented compared to dosimetric parameters. This study aimed to predict the risk of rib fractures in patients with localized non-small cell lung cancer (NSCLC) post-SBRT based on both patient-related and dosimetric parameters with death as a competing risk., Materials and Methods: In total, 602 patients with localized NSCLC treated with SBRT between 2010-2020 at Odense University Hospital, Denmark were included. All patients received SBRT with 45-66 Gray (Gy)/3 fractions. Rib fractures were identified in CT-scans using a word embedding model. The cumulative incidence function was based on cause-specific Cox hazard models with variable selection based on cross-validation model likelihood performed using 50 bootstraps., Results: In total, 19 % of patients experienced a rib fracture. The cumulative risk of rib fracture increased rapidly from 6-54 months post-SBRT. Female gender, bone density, near max dose to the rib, V30 and V40 to the rib, gross tumor volume, and mean lung dose were significantly associated with rib fracture risk in univariable analysis. The final multi-variable model consisted of V20 and V30 to the rib and mean lung dose., Conclusion: Female gender and low bone density in male patients are significant predictors of rib fracture risk. The final model predicting cumulative rib fracture risk of 19 % in patients with localized NSCLC treated with SBRT contained no patient-related parameters, suggesting that dosimetric parameters are the primary drivers., 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 © 2024. Published by Elsevier B.V.)

Background: A novel approach using single-fraction preoperative partial breast irradiation (PBI) for low-risk breast cancer is under study. We sought to investigate the rate of pathologic response (pR), toxicities and cosmetic results related to this new treatment strategy., Methods: Women of 65 years or older with stage I unifocal luminal A breast cancer were eligible for inclusion in this phase I prospective trial. Patients received a single 20 Gy dose of PBI followed by breast-conserving surgery (BCS) 3 months later. The primary endpoint was the pR rate, and the secondary endpoints were radiation therapy-related toxicity and cosmetic results., Results: Thirteen patients were treated, with a median age of 71. Eleven patients (84.6 %) had pR with a median residual cellularity of 1 % (range: 0-10 %). At median follow-up of 48.5 months, no recurrences or cancer-related deaths were recorded. Acute radiation therapy-related toxicity were limited to grade 1 dermatitis and breast pain. At the 1-year follow-up, there were one grade 2 fat necrosis and two grade 3 toxicities (wound infection and hematoma). Only grade 1 toxicities remained at 2 years, but one grade 2 toxicity (fibrosis/induration) developed by the 3-year follow-up. Three-year patient-reported cosmetic outcomes were good or excellent in 60 % of patients., Conclusions: Single-fraction preoperative PBI preceding BCS for low-risk breast cancer is feasible, relatively well tolerated and leads to a high level of pR. The 3-month interval after PBI seems to place surgery in a post-radiation inflammatory phase. Further delay between PBI and surgery could improve pR and cosmetic outcome. NCT03917498., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate acute toxicity at 6 months after stereotactic body radiotherapy (SBRT) in patients with oligometastatic cancer within the OligoCare cohort., Material and Methods: OligoCare is a prospective, registry-based, single-arm, observational study that aims to report prospective real-world data of patients with oligometastases from solid cancer treated with SBRT (NCT03818503). Primary tumor included non-small cell lung cancer (NSCLC), breast cancer (BC), colorectal cancer (CRC), and prostate cancer (PC). This analysis addresses a secondary endpoint of the trial, acute toxicity within 6 months after SBRT., Results: Out of 1,597registered patients, 1'468 patients were evaluated for acute toxicity. Globally, 290 (20 %) had NSCLC primary disease, 227 (16 %) had BC, 293 (20 %) had CRC, and 658 (45 %) had PC. Concomitant systemic treatment was administered in 527 (35.9 %) patients. According to the EORTC/ESTRO oligometastatic disease (OMD) classification, 828 (56 %) patients had de novo OMD, 464 (32 %) repeat OMD, and 176 (12 %) induced OMD. Acute grade ≥ 3 SBRT related adverse events were reported in 8 (0.5 %) patients, including 2 (0.1 %) fatal AEs. In particular, 6 (0.4 %) grade 3 events were: 1 empyema, 1 pneumonia, 1 radiation pneumonitis, 1 radiation skin injury, 1 decreased appetite, and 1 bone pain. Among those 2 occurred in NSCLC patients, 2 in BC patients, and 1 in CRC and PC patients each. The two (0.1 %) grade 5 toxicity were represented by: pneumonitis and cerebral hemorrhage., Conclusion: OligoCare is the largest prospective registry cohort on oligometastatic disease. Acute toxicity within 6 months was low, confirming the safety of SBRT in the treatment of oligometastases., 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 © 2024 Elsevier B.V. All rights reserved.)

Purpose: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities., Materials and Methods: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis., Results: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively)., Conclusions: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice., 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 © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: To report mature results for local control and survival in oligometastatic (OM) breast cancer patients treated with stereotactic body radiotherapy (SBRT) on lung and/or liver lesions in a phase II trial., Methods: This is a prospective non-randomized phase II trial (NCT02581670) which enrolled patients from 2015 to 2021. Eligibility criteria included: age > 18 years, ECOG 0-2, diagnosis of breast cancer, maximum of 4 lung/liver lesions (with a maximum diameter < 5 cm), metastatic disease confined to the lungs and liver or extrapulmonary or extrahepatic disease stable or responding to systemic therapy. The primary end-points were local control (LC) and treatment-related toxicities. The secondary end-points included overall survival (OS), distant metastasis-free survival (DMFS), time to next systemic therapy (TTNS), poly-progression free survival (PPFS)., Results: The study included 64 patients with a total of 90 lesions treated with SBRT. LC at 1 and 2 years was 94.9 %, 91 % at 3 years. Median local control was not reached. Median OS was 16.5 months, OS at 1, 2 and 3 years was 87.5 %, 60.9 % and 51.9 %, respectively. Median DMFS was 8.3 months, DMFS at 1, 2 and 3 years was 38.1 %, 20.6 % and 16 % respectively. At univariate analysis, local response to SBRT was found to be statistically linked with better OS, DMFS and STFS., Conclusion: SBRT is a safe and valid option in oligometastatic breast cancer patients, with very high rates of local control. An optimal selection of patients is likely needed to improve survival outcomes and reduce the rate of distant progression., 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 © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: The SOFT trial is a prospective, multicenter, phase 2 trial investigating magnetic resonance (MR)-guided stereotactic ablative radiotherapy (SABR) for abdominal, soft tissue metastases in patients with oligometastatic disease (OMD) (clinicaltrials.gov ID NCT04407897). We present the primary endpoint analysis of 1-year treatment-related toxicity (TRAE)., Materials and Methods: Patients with up to five oligometastases from non-hematological cancers were eligible for inclusion. A risk-adapted strategy prioritized fixed organs at risk (OAR) constraints over target coverage. Fractionation schemes were 45-67.5 Gy in 3-8 fractions. The primary endpoint was grade ≥ 4 TRAE within 12 months post-SABR. The association between the risk of gastrointestinal (GI) toxicity and clinical and dosimetric parameters was tested using a normal tissue complication probability model., Results: We included 121 patients with 147 oligometastatic targets, mainly located in the liver (41 %), lymph nodes (35 %), or adrenal glands (14 %). Nearly half of all targets (48 %, n = 71) were within 10 mm of a radiosensitive OAR. No grade 4 or 5 TRAEs, 3.5 % grade 3 TRAEs, and 43.7 % grade 2 TRAEs were reported within the first year of follow-up. We found a significant association between grade ≥ 2 GI toxicity and the parameters GI OAR D 0.1cc, D 1cc, and D 20cc ., Conclusion: In this phase II study of MR-guided SABR of oligometastases in the infra-diaphragmatic region, we found a low incidence of toxicity despite half of the lesions being within 10 mm of a radiosensitive OAR. GI OAR D 0.1cc, D 1cc, and D 20cc were associated with grade ≥ 2 GI toxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MF has received research grant from Varian Medical Systems and support from The Danish National Research Centre for Radiotherapy and the Danish Cancer Society. CPB reports institutional research contracts with Brainlab, Varian Medical Systems, Siemens, and ViewRay and teaching contracts with Varian Medical Systems. Research funding from Danish Comprehensive Cancer Center National Thematic Center on radiotherapy (DCCC-RT). UB reports institutional research contracts with Elekta. IVR reports institutional research contracts with Brainlab, Varian Medical Systems, and ViewRay and teaching contracts with Varian Medical Systems. GP has received research grants from Varian Medical Systems, The Danish National Research Centre for Radiotherapy, and the Danish Cancer Society, Herlev & Gentofte Hospitals Internal Research Council, Villadsens Family Foundation. Conference participance from MSD, Daiichi Sankyo, and Pfizer, Pierre Fabre and honoraria for consultancies and lectures from Astra Zeneca. PP has received research grant from Viewray; not relevant to this article; Stock ownership of Nuvaira (COPD device company). MJ have received research support from The Danish National Research Centre for Radiotherapy and the Danish Cancer Society. MP have received honoraria for lectures from Astra Zeneca, BMS, MSD, Pfizer, Roche, Amgen. TS have received honoraria for lectures and travel expenses from Elekta and declares travel assistance from ELEKTA and is member of the MR-L consortium. SB have received research support from The Danish National Research Centre for Radiotherapy. PG reports institutional research contracts with Viewray. PK, ESH, and KJ has nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy., Materials and Methods: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression., Results: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-D max ) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-D max ) was 11.2 Gy (median) lower than BP-D max . Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BED max LQL and BP-BED 0.3cc LQL , α/β = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively., Conclusion: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED 0.3cc LQL and BP-BED max LQL as potential predictors of RIBP2., 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 Elsevier B.V. All rights reserved.)

Background and Purpose: Stereotactic radiotherapy potentially treats unresectable recurrences of previously irradiated head and neck (H&N) cancer. This study aimed to assess its efficacy and safety and evaluate prognostic factors., Materials and Methods: We conducted a large retrospective series that included 110 patients who had undergone 36-Gy, six-fraction stereotactic reirradiation (CyberKnife®) for recurrent/secondary H&N cancer between 2007 and 2020 at the Oscar Lambret Center. Patient characteristics and toxicities were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method., Results: Median follow-up time was 106.3 months. The 2-year OS rate was 43.8 % (95 % confidence interval, 95 % CI, 34.3-52.9) and the median survival was 20.8 months (95 % CI, 16.5-26.3). The cumulative 2-year local-recurrence, regional-recurrence, and distant-metastasis rates were 52.2 % (95 % CI, 42.4-61.1 %), 12.8 % (95 % CI, 7.4-19.8 %), and 11 % (95 % CI, 6.0-17.6 %), respectively. 73 patients received concomitant cetuximab, and it was not significantly beneficial (HR = 1.34; 95 % CI, 0.80-2.26; p = 0.26). The cumulative incidences of grade ≥ 2 late toxicity was 42 % (CI95%: 33-51) at 24 months. Two grade 4 bleedings and no treatment-related deaths were reported., Conclusion: In a large retrospective series of SBRT reirradiation for recurrent or second primary H&N cancers, we observed a median OS of 20.8 months, with a cumulative incidence of grade ≥ 2 late toxicity of 42 % at 24 months. Such a treatment is feasible. However, local recurrence rates remain non-negligible, warranting further research. Radiosensitizer use is currently under study. Therefore, establishing a balance between therapeutic modifications and toxicity is essential., 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 Elsevier B.V. All rights reserved.)

Background/purpose: Central/ultra-central thoracic tumors are challenging to treat with stereotactic radiotherapy due potential high-grade toxicity. Stereotactic MR-guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath-hold gating and real-time MR-imaging as well as the option for daily online adaptive replanning to account for changes in target and/or organ-at-risk (OAR) location., Materials/methods: 26 central (19 ultra-central) thoracic oligoprogressive/oligometastatic tumors treated with isotoxic (OAR constraints-driven) 5-fraction SMART (median 50 Gy, range 35-60) between 10/2019-10/2022 were reviewed. Central tumor was defined as tumor within or touching 2 cm around proximal tracheobronchial tree (PBT) or adjacent to mediastinal/pericardial pleura. Ultra-central was defined as tumor abutting the PBT, esophagus, or great vessel. Hard OAR constraints observed were ≤ 0.03 cc for PBT V40, great vessel V52.5, and esophagus V35. Local failure was defined as tumor progression/recurrence within the planning target volume., Results: Tumor abutted the PBT in 31 %, esophagus in 31 %, great vessel in 65 %, and heart in 42 % of cases. 96 % of fractions were treated with reoptimized plan, necessary to meet OAR constraints (80 %) and/or target coverage (20 %). Median follow-up was 19 months (27 months among surviving patients). Local control (LC) was 96 % at 1-year and 90 % at 2-years (total 2/26 local failure). 23 % had G2 acute toxicities (esophagitis, dysphagia, anorexia, nausea) and one (4 %) had G3 acute radiation dermatitis. There were no G4-5 acute toxicities. There was no symptomatic pneumonitis and no G2 + late toxicities., Conclusion: Isotoxic 5-fraction SMART resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk oligoprogressive/oligometastatic thoracic tumors., 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 Elsevier B.V. All rights reserved.)

Background and Purpose: Despite its increasing popularity, there are limited prospective data on stereotactic arrhythmia radioablation (STAR). In this trial, we assessed the safety and efficacy of STAR in patients with ventricular tachycardia (VT), focusing on early treatment-related grade ≥ 3 adverse events (AE)., Materials and Methods: This prospective trial was designed for adults with VT recurrence following catheter ablation (CA) despite adequate pharmacotherapy, or contraindications to CA. A single dose of 25 Gy was delivered to the arrhythmia substrate defined on electro-anatomic mapping and cardiac-gated CT. The primary endpoint was safety, defined as two or fewer treatment-related grade ≥ 3 AEs during the first three months in 11 patients. Additional endpoints included treatment efficacy, clinical and biological markers of cardiac injury, and quality of life., Results: Eleven patients with a median age of 67 years, structural heart disease, and a clinically significant recurrence of VT despite adequate pharmacotherapy and 1-4 previous CAs were enrolled between 2020/09 and 2022/10. Following the treatment, one patient developed a possibly treatment-related grade ≥ 3 AE, a grade 4 heart failure exacerbation at 87 days, which resolved after conservative treatment. There was a total 84.3% reduction in VT burden in 10 evaluable patients; however, VT recurrence was eventually observed in eight, and three patients required additional CAs. Three deaths due to unrelated causes were recorded., Conclusions: STAR appears to be safe and efficient. It is a promising treatment for selected patients; however, long-term outcomes remain to be evaluated, and controlled trials comparing STAR with standards of care are missing., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days., Material and Methods: Patients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule. The primary endpoint was radiation-induced acute toxicity (CTCAE v5.0). Changes in quality of life (QoL) were examined in terms of proportions achieving a minimal clinically important change (MCIC). Finally, acute toxicity and QoL scores of the BIW schedule were compared with the results of the prior QW hypo-FLAME schedule (n = 100)., Results: Between August 2020 and February 2022, 124 patients were enrolled and treated BIW. No grade ≥3 GU or GI toxicity was observed. The 90-days cumulative incidence of grade 2 GU and GI toxicity rates were 47.5% and 7.4%, respectively. Patients treated QW scored significant less grade 2 GU toxicity (34.0%, p = 0.01). No significant differences in acute GI toxicity were observed. Furthermore, patients treated QW had a superior acute bowel and urinary QoL., Conclusion: Semi-weekly prostate SBRT with iso-toxic focal boosting is associated with acceptable acute GU and GI toxicity. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule. Registration number ClinicalTrials.gov: NCT04045717., 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 Elsevier B.V. All rights reserved.)

Purpose: To present the multi-institutional data on patterns of recurrence, treatment approaches, and clinical outcomes for regional lymph node (LN) recurrence after stereotactic body radiation therapy (SBRT) for primary lung cancer., Materials and Methods: The medical records of 114 patients who experienced regional LN recurrence as the first recurrence after lung SBRT were retrospectively reviewed. Patterns of recurrence were classified as local recurrence, regional recurrence, and distant metastasis. Clinical outcomes including progression-free survival (PFS) and overall survival (OS) were analyzed., Results: Half of the patients had regional LN recurrence only. The most common simultaneous recurrence was distant metastasis (38.6 %). Common sites of regional recurrence were ipsilateral hilar (47.2 %), ipsilateral upper mediastinal (40.6 %), and subcarinal (42.5 %) LN stations. 24 (21.1 %) patients underwent salvage radiation therapy (RT), and 44 (38.6 %) patients underwent palliative treatment. Better OS was observed in the salvage RT group (p = 0.025). The 1-year PFS and OS rates were 27.7 % and 55.2 %, respectively, with salvage RT, 14.0 % and 39.9 %, respectively, with palliative treatment, and 22.8 % and 26.8 %, respectively, with no additional treatment. Multivariate analysis showed that salvage RT (PFS, HR 0.463, p = 0.050; OS, HR 0.312, p = 0.002), palliative treatment (PFS, HR 0.436, p = 0.013; OS, HR 0.553, p = 0.050), and simultaneous distant metastasis (PFS, HR 2.335, p = 0.005; OS, HR 1.726, p = 0.054) affected clinical outcomes., Conclusion: Many cases of regional LN recurrence are confined to the locoregional area of patients, and appropriate treatment can improve the prognosis of these patients., 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 Elsevier B.V. All rights reserved.)

Background and Purpose: We examined the interfractional variations of clinical target volumes (CTVs), planning target volumes (PTVs), and organs-at-risk (OARs) in patients receiving MRI-guided stereotactic body radiotherapy (SBRT) to the prostate bed and evaluated the potential role of adaptive planning., Materials and Methods: 31 patients received 30-34 Gy in five fractions to the prostate bed on a phase II clinical trial. OARs, CTVs, and PTVs were retrospectively contoured on daily pretreatment MRIs (n = 155). Geometric comparisons were made between initial planning contours and daily pretreatment contours. Predicted treatment plans for each fraction were evaluated using the following constraints: CTV V95%>93%, PTV V95%>90%, bladder Dmax < 36.7 Gy, bladder V32.5 Gy < 35%, rectum Dmax < 36.7 Gy, rectum V27.5 Gy < 45%, rectum 32.5 Gy < 30%, and rectal wall V24Gy < 50%. Adaptive planning was simulated for all fractions that failed to meet these criteria. Plans were then re-evaluated., Results: Median change in volume was 0.48% for CTV, -24.5% for bladder, and 6.95% for rectum. Median DSC was 0.89 for CTV, 0.79 for bladder, and 0.76 for rectum. 145/155 fractions (93.5%) met CTV V95%>93%. 75/155 fractions (48.4%) failed at least one OAR dose constraint. Overall, 83/155 fractions (53.5%) met criteria for adapting planning. This affected 24/31 patients (77.4%). Following adaptive planning, all fractions met CTV V95%>93% and PTV V95%>90% and 120/155 fractions (77.4%) met all OAR constraints., Conclusion: Due to significant interfractional variations in anatomy, a majority of fractions failed to meet both target volume and OAR constraints. However, adaptive planning was effective in overcoming these anatomic changes. Adaptive planning should be routinely considered in prostate bed SBRT., 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. Funding support for the SCIMITAR trial was provided by ViewRay, Inc., but ViewRay, Inc. had no role in the conduct of this analysis., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Local control (LC) is an important outcome of local cancer therapy, besides overall survival (OS). We conducted a comprehensive literature search to investigate whether a high LC rate contributes to good OS in radiotherapy for early-stage non-small cell lung cancer (ES-NSCLC)., Materials and Methods: Studies in patients receiving radiotherapy for peripheral ES-NSCLC, mainly staged as T1-2N0M0 were included for a systematic review. Relevant information was collected including, dose fractionation, T stage, median age, 3-year LC, cancer-specific survival (CSS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and OS. Correlations between outcomes and clinical variables were evaluated., Results: After screening, 101 data points from 87 studies including 13,435 patients were selected for the quantitative synthesis. Univariate meta-regression analysis revealed that the coefficients between the 3-year LC and 3-year DFS, DMFS, CSS, and OS were 0.753 (95% confidence interval (CI): 0.307-1.199; p < 0.001), 0.360 (95% CI: 0.128-0.593; p = 0.002), 0.766 (95% CI: 0.489-1.044; p < 0.001), and 0.574 (95% CI: 0.275-0.822; p < 0.001), respectively. Multivariate analysis revealed that the 3-year LC (coefficient, 0.561; 95% CI: 0.254-0.830; p < 0.001) and T1 proportion (coefficient, 0.207; 95% CI: 0.030-0.385; p = 0.012) were significantly associated with the 3-year OS and CSS (coefficient for 3-year LC, 0.720; 95% CI: 0.468-0.972; p < 0.001 and T1 proportion, 0.002; 95% CI: 0.000-0.003; p = 0.012). Toxicities ≥ grade 3 were low (3.4%)., Conclusions: Three-year LC was correlated with three-year OS in patients receiving radiotherapy for ES-NSCLC. A 5% increase in 3-year LC is expected to improve the 3-year CSS and OS rates by 3.8% and 2.8%, respectively., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: In this phase I/II trial, non-progressive locally advanced pancreatic cancer (LAPC) patients after (modified)FOLFIRINOX therapy were treated with stereotactic body radiotherapy (SBRT) combined with heat-killed mycobacterium (IMM-101) vaccinations. We aimed to assess safety, feasibility, and efficacy of this treatment approach., Materials and Methods: On five consecutive days, patients received a total of 40 Gray (Gy) of SBRT with a dose of 8 Gy per fraction. Starting two weeks prior to SBRT, they in addition received six bi-weekly intradermal vaccinations with one milligram of IMM-101. The primary outcomes were the number of grade 4 or higher adverse events and the one-year progression free-survival (PFS) rate., Results: Thirty-eight patients were included and started study treatment. Median follow-up was 28.4 months (95 %CI 24.3 - 32.6). We observed one grade 5, no grade 4 and thirteen grade 3 adverse events, none related to IMM-101. The one-year PFS rate was 47 %, the median PFS was 11.7 months (95 %CI 11.0 - 12.5) and the median overall survival was 19.0 months (95 %CI 16.2 - 21.9). Eight (21 %) tumors were resected, of which 6 (75 %) were R0 resections. Outcomes were comparable with the outcomes of the patients from the previous LAPC-1 trial, in which LAPC patients were treated with SBRT, without IMM-101., Conclusion: Combination treatment with IMM-101 and SBRT was safe and feasible for non-progressive locally advanced pancreatic cancer patients after (modified)FOLFIRINOX. No improvement in the progression-free survival could be demonstrated by adding IMM-101 to SBRT., 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. Published by Elsevier B.V.)

Introduction: Radiation-induced brachial plexopathy (RIBP), resulting in symptomatic motor or sensory deficits of the upper extremity, is a risk after exposure of the brachial plexus to therapeutic doses of radiation. We sought to model dosimetric factors associated with risks of RIBP after stereotactic body radiotherapy (SBRT)., Methods: From a prior systematic review, 4 studies were identified that included individual patient data amenable to normal tissue complication probability (NTCP) modelling after SBRT for apical lung tumors. Two probit NTCP models were derived: one from 4 studies (including 221 patients with 229 targets and 18 events); and another from 3 studies (including 185 patients with 192 targets and 11 events) that similarly contoured the brachial plexus., Results: NTCP models suggest ≈10% risks associated with brachial plexus maximum dose (D max ) of ∼32-34 Gy in 3 fractions and ∼40-43 Gy in 5 fractions. RIBP risks increase with increasing brachial plexus D max . Compared to previously published data from conventionally-fractionated or moderately-hypofractionated radiotherapy for breast, lung and head and neck cancers (which tend to utilize radiation fields that circumferentially irradiate the brachial plexus), SBRT (characterized by steep dose gradients outside of the target volume) exhibits a much less steep dose-response with brachial plexus D max  > 90-100 Gy in 2-Gy equivalents., Conclusions: A dose-response for risk of RIBP after SBRT is observed relative to brachial plexus D max . Comparisons to data from less conformal radiotherapy suggests potential dose-volume dependences of RIBP risks, though published data were not amenable to NTCP modelling of dose-volume measures associated with RIBP after SBRT., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce. We report clinical results of this therapeutic option., Methods: We retrospectively included STS patients treated between 2009 and 2020, with dRT for unresectable or with a measurable residual disease after R2 surgery. Response rate, local failure (LF), progression-free survival (PFS) and overall survival (OS) were evaluated., Results: 116 patients with localized/locally advanced STS were treated from 2009 to 2020, with a median age of 71 years (range 18-92). Most tumors were deep-seated (96.6%), grade 2-3 (85.1%), located in the trunk or extremities (74.2%). Helical tomotherapy, volumetric modulated arc therapy, or stereotactic radiotherapy was performed in 39.7%, 19% and 8.6% of patients, respectively. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR 52-65). At first follow-up, 66 (58.9%) and 25 (22%) patients had stable disease and partial response. After a median follow-up of 54.8 months (IQR 40.3-95.4), 3-year LF, PFS and OS were 43.2%, 16.6% and 34%, respectively. Median OS was 21.4 months (95%CI 14-26). The multivariate analysis identified grade 3 and AJCC T3-T4 stage to be associated with both shorter PFS and OS (all p < 0.001). Macroscopically incomplete resection and EQD2 ≥ 64 Gy were associated with better OS (p = 0.016 and p = 0.007). Acute and late severe adverse events occurred in 24 (19.7%) and 5 (4.3%) patients., Conclusion: In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients., 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 © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: This study aimed to evaluate the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) for lung tumors., Materials and Methods: Patients with cStage I primary lung cancer or metastatic lung cancer with an expected range of respiratory motion of ≥10 mm were eligible for the study. The prescribed dose was 50 Gy in four fractions. A gimbal-mounted linac was used for DTT-SBRT delivery. The primary endpoint was local control at 2 years., Results: Forty-eight patients from four institutions were enrolled in this study. Forty-two patients had primary non-small-cell lung cancer, and six had metastatic lung tumors. DTT-SBRT was delivered for 47 lesions in 47 patients with a median treatment time of 28 min per fraction. The median respiratory motion during the treatment was 13.7 mm (range: 4.5-28.1 mm). The motion-encompassing method was applied for the one remaining patient due to the poor correlation between the abdominal wall and tumor movement. The median follow-up period was 32.3 months, and the local control at 2 years was 95.2% (lower limit of the one-sided 85% confidence interval [CI]: 90.3%). The overall survival and progression-free survival at 2 years were 79.2% (95% CI: 64.7%-88.2%) and 75.0% (95% CI: 60.2%-85.0%), respectively. Grade 3 toxicity was observed in one patient (2.1%) with radiation pneumonitis. Grade 4 or 5 toxicity was not observed., Conclusion: DTT-SBRT achieved excellent local control with low incidences of severe toxicities in lung tumors with respiratory motion., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: We aim to compare health-related quality of life (HRQoL) deterioration at 12 months in low-and intermediate-risk prostate cancer (PCa) patients treated with stereotactic ablative radiotherapy (SABR), high dose-rate brachytherapy (HDR) monotherapy and HDR boost., Material and Methods: Patients treated as part of 7 prospective clinical trials were included. All patients had low-or intermediate-risk PCa. Three strategies were considered: SABR, HDR monotherapy and HDR boost. HRQoL was prospectively measured at baseline and 12 months in all trials, using the Expanded Prostate Index Composite (EPIC). A minimally important difference (MID) was defined as a deterioration of HRQoL scores at 12 months compared to baseline ≥0.5 standard deviation of baseline score. Univariate and multivariable logistic regression using generalized estimating equations were used to compare the proportion of patients having MID between groups. A set of sensitivity analyses was conducted., Results: 648 patients were included: 288, 173 and 187 respectively in the SABR, HDR monotherapy and HDR boost group. On univariate and multivariable analyses, SABR and HDR monotherapy compared to HDR boost, were associated with less deterioration in the urinary (38%, 40% vs. 55%; OR:0.543, 95%CI:0.320-0.922, p = 0.024; OR:0.468, 95%CI:0.432-0.507, p < 0.001) and sexual domains (38%, 42% vs. 47%; OR:0.762, 95%CI:0.645-0.900, p = 0.001; OR: 0.786, 95%CI:0.650-0.949, p = 0.012). These findings wererobust to a variety ofsensitivity analyses., Conclusion: Recent monotherapeutic approaches for low- and intermediate-risk PCa are associated with the preservation of patients HRQoL. Ultimately, the questions of efficacy, toxicity, and HRQoL will be best answered by a randomized clinical trial., 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 © 2022 Elsevier B.V. All rights reserved.)

Introduction: SBRT of central lung tumours implies significant risk of toxicity. We are initiating two phase II trials prescribing 56 Gy/eight fractions to PTV, allowing for dose escalation of GTV. We prioritize organs at risk (OAR) constraints over target coverage, making the treatment plans very sensitive to OAR delineation variations. The aim of this study is to quantify the dosimetric impact of contouring variations and to provide a thorough description of pre-trial quality assurance to be used in upcoming trials to provide consistent clinical care., Materials and Methods: Delineation: Seven physicians delineated OAR in three rounds, with evaluations in-between. For each patient case, seven treatment plans, repeatedly using each of the OAR structure sets from the seven physicians, were made and compared to evaluate the dosimetric effect of delineation variability. Treatment planning: Treatment plans for seven cases were made at six departments in two rounds, with discussion in-between., Results: OAR delineation variation between centres resulted in high variabilities in OAR dose for simulated plans and led to potential overdosage of the lobar bronchus (constraint: D 0.03cc  < 45 Gy), with maximum doses ranging between 58 Gy (first round), and 50 Gy (third round). For mediastinal tissue, the constraint (D 0.03cc  < 45 Gy) was violated for the majority of the delineations in all three rounds, with maximum doses of 84 Gy (first round), and 72 Gy (third round).For the treatment planning study, the range of the standard deviation for GTV mean dose was 12.8-18.5 Gy (first round) and 2.8-3.5 Gy (second round)., Conclusions: Even small variations in OAR delineation led to high OAR overdosage. The study demonstrates the importance of having extensive QA procedures in place before initiating clinical trials on dose escalation in SBRT., Competing Interests: Conflict of interest statement The authors have no conflicts of interests to report., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Contemporary radiotherapy for localized prostate cancer (PCa) is deliverable via stereotactic ablative radiotherapy (SABR) and high dose rate (HDR) brachytherapy. Here we report on a parallel cohort analysis of two prospective, phase II clinical trials of two-fraction prostate SABR versus two-fraction HDR monotherapy., Materials and Methods: Enrolled patients had histologically-confirmed PCa (clinical stage T1c-T2b; grade group 1, 2, or 3; and PSA < 20 ng/mL). SABR and HDR doses were 26 Gy and 27 Gy in 2 weekly fractions, respectively. Patient-level data from each cohort was analysed to assess prostate specific antigen (PSA) response kinetics, biochemical failure, toxicity, and quality of life (QOL)., Results: Thirty patients receiving SABR and 83 receiving HDR were included. Fifty percent and 30% of patients had unfavourable-intermediate risk disease, respectively. SABR patients had higher mean baseline PSA (8.7 versus 6.8 ng/mL, p = 0.016). Median follow-up was 72.7 and 65.3 months, respectively. Mean dose delivered (D mean ) was 26.6-26.8 Gy for SABR versus 35.5-45.5 Gy for HDR. Both cohorts achieved a median nadir PSA of 0.16 ng/mL at a median of 57 months post-treatment. Cumulative biochemical failure probability (±SE) at 72 months was 3.5% (±3.5%) for SABR versus 12.8% (±4.8%) for HDR (p = 0.19). Low rates of CTCAE grade ≥2 toxicity were observed in both cohorts. No differences in EPIC scores over time were observed between cohorts., Conclusions: Two-fraction SABR yields similar rates of biochemical failure, acute and late toxicities, and QOL as two-faction HDR brachytherapy. These data support the design of a randomized controlled trial comparing these treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: Interfraction volumetric changes/rotations in the prostate and proximal seminal vesicles (SVs) might compromise target coverage when tight margins are used for prostate stereotactic body radiotherapy (SBRT). We investigated on-board MRI images from MRI-guided SBRT to better understand this., Materials and Methods: Twenty consecutive patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) enrolled on the MRI arm of a phase III randomized trial were included. A 2 mm isotropic margin was used for prostate and proximal SVPTV. Target volume, prostate dimensions, angles of the proximal SV on axial (angle α) and sagittal view (angle θ) were measured on a 0.35 T simulation MRI and five on-board pre-treatment MRIs. Dice coefficient of the targets and target dosimetry were calculated., Results: All patients experienced an isotropic increase in prostate volume during SBRT (p = 0.0016): 0.1%, 9.0%, 12.1%, 15.1%, and 14.2% (median) at fractions 1-5, respectively, regardless of baseline volume, which was significantly reduced with neoadjuvant ADT (p = 0.0042). There was minimal interfraction rotation of prostate, however, considerable variations in proximal SV angle α (median 21.5°) and angle θ (median 17.6°) were seen. Median V100% was 97.5% and 87.1% for prostate and proximal SV CTV, respectively. V95%≥95% was achieved in 94% of fractions for the prostate and in 59% for proximal SV., Conclusion: Prostate volume consistently increased during SBRT. Interfraction prostatic rotation was minimal while rotation of the proximal SV was considerable. Prostate dosimetry was favorable, but online adaptive therapy may be indicated occasionally to account for prostatic swelling and in particular proximal SV rotations., Competing Interests: Conflict of interest statement A.U.K. reports honoraria, consulting fees, research support from ViewRay, Inc., honoraria and consulting fees from Varian Medical Systems, Inc., consulting fees from Intelligent Automation, Inc., and stock ownership in ViewRay, Inc., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: A potential challenge in single-isocenter multi-lesion lung stereotactic body radiotherapy (SBRT) is that patient positioning is not based on each lesion individually, but on the average position of all lesions. This may lead to larger margins compared to treating with one isocenter per lesion, but increases workflow efficiency. The aim of this study was to investigate whether a single-isocenter technique leads to increased normal lung dose compared to a conventional multiple-isocenters technique., Materials and Methods: A cohort of 15 NSCLC patients with two or three lesions previously treated with SBRT was subjected to treatment planning with a multiple-isocenter technique and a single-isocenter technique. For the latter, two margin approaches were evaluated: (1) identical margins for each internal target volume (ITV), assuming an average registration for all lesions in cone-beam CT (CBCT) positioning verification and (2) a smaller margin for the largest lesion, assuming an optimal registration for that lesion. For all 45 treatment plans, mean lung dose (MLD) and lungs-V 20Gy were evaluated. The study was performed following RATING guidelines., Results: The MLD was 4.9 ± 1.9 Gy (mean ± SD) for multiple-isocenters and 5.4 ± 2.1 Gy and 5.3 ± 2.2 Gy for single-isocenter approach 1 and 2, respectively. V 20Gy was 5.5 ± 3.7%, 5.5 ± 3.2% and 5.4 ± 3.3%. A median [range] increase in MLD of 11.6% [-14.9 - 26.8] was observed when comparing single-isocenter treatment plans to those with multiple isocenters. V 20Gy increased by 0.2 [-3.4 - 1.3] percentage points., Conclusion: A single-isocenter SBRT technique for lung patients with multiple targets results in clinically acceptable increases in normal lung dose., Competing Interests: Conflict of interest statement Dr. Hoogeman reports grants from Elekta, grants from Accuray, grants from Varian, other from Accuray, outside the submitted work. Dr. Tanadini-Lang reports that her husband works at Varian Medical Systems. Dr. van Timmeren, dr. Ehrbar, miss Chamberlain, dr. Mayinger, dr. Andratschke and dr. Guckenberger report no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The outcome of radiotherapy is a direct consequence of the dose delivered to the patient. Yet image-guidance and motion management to date focus on geometrical considerations as a practical surrogate for dose. Here, we propose real-time dose-guidance realized through continuous motion-including dose reconstructions and demonstrate this new concept in simulated liver stereotactic body radiotherapy (SBRT) delivery., Materials and Methods: During simulated liver SBRT delivery, in-house developed software performed real-time motion-including reconstruction of the tumor dose delivered so far and continuously predicted the remaining fraction tumor dose. The total fraction dose was estimated as the sum of the delivered and predicted doses, both with and without the emulated couch correction that maximized the predicted final CTV D95% (minimum dose to 95% of the clinical target volume). Dose-guided treatments were simulated for 15 liver SBRT patients previously treated with tumor motion monitoring, using both sinusoidal tumor motion and the actual patient-measured motion. A dose-guided couch correction was triggered if it improved the predicted final CTV D95% with 3, 4 or 5 %-points. The final CTV D95% of the dose-guidance strategy was compared with simulated treatments using geometry guided couch corrections (Wilcoxon signed-rank test)., Results: Compared to geometry guidance, dose-guided couch corrections improved the median CTV D95% with 0.5-1.5 %-points (p < 0.01) for sinusoidal motions and with 0.9 %-points (p < 0.01, 3 %-points trigger threshold), 0.5 %-points (p = 0.03, 4 %-points threshold) and 1.2 %-points (p = 0.09, 5 %-points threshold) for patient-measured tumor motion., Conclusion: Real-time dose-guidance was proposed and demonstrated to be superior to geometrical adaptation in liver SBRT simulations., Competing Interests: Declaration of Competing Interest Mr. Muurholm has a pending patent application on ‘System and method for dose guidance and repeated estimation of final delivered radiation dose for a radiotherapy system’. Dr. Ravkilde has a pending patent application on ‘System and method for dose guidance and repeated estimation of final delivered radiation dose for a radiotherapy system’. Dr. Skouboe has a pending patent application on ‘System and method for dose guidance and repeated estimation of final delivered radiation dose for a radiotherapy system’. Dr. Worm has nothing to disclose. Mr. Hansen has nothing to disclose. Dr. Høyer has nothing to disclose. Dr. Keall reports grants from Various publicly disclosed as part of my conflict management plan with the University of Sydney, outside the submitted work; In addition, Dr. Keall has a pending patent application on ‘System and method for dose guidance and repeated estimation of final delivered radiation dose for a radiotherapy system‘. Dr. Poulsen has a pending patent application on ‘System and method for dose guidance and repeated estimation of final delivered radiation dose for a radiotherapy system‘., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints., Materials and Methods: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants' practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2., Results: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints., Conclusions: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of practice where consensus was not achieved., Competing Interests: Declarations/conflicts of interest statement FS is a Clinical Research Fellow supported by a Cancer Research UK Centres Network Accelerator Award to the ART-NET consortium (grant number A21993). FA reports speaker honoraria and consultancy for Varian and Elekta. BAJF reports institutional research funding grants from Italian Association for Cancer Research (AIRC), FIEO-CCM & FUV and Accuray, outside of the submitted work. BAJF reports travel expenses/speaker fees from Janssen, Ferring, Bayer, Roche, Astellas, Elekta, Carl Zeiss, Ipsen, Accuray and IBA, outside of the submitted work. MAH is supported by funding from the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. AMH is supported by grants from Cancer Research UK (award number 108036), National Institute for Health Research (NIHR) (award number 111218), Medical Research Council (MRC) (award number 107154) and Sir John Fisher Foundation (charity, no award number). LJM is an associate professor supported by a Yorkshire Cancer Research funded by Yorkshire Cancer Research (award number L389LM)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT)., Materials and Methods: Between 2013-2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition)., Results: One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p < 0.0001), bowel (p = 0.0018) and sexual (p < 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%., Conclusion: ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In patients with bone metastases (BM), radiotherapy (RT) is used to alleviate symptoms, reduce the risk of fracture, and improve quality of life (QoL). However, with the emergence of concepts like oligometastases, minimal invasive surgery, ablative therapies such as stereotactic ablative RT (SABR), radiosurgery (SRS), thermal ablation, and new systemic anticancer therapies, there have been a paradigm shift in the multidisciplinary approach to BM with the aim of preserving mobility and function survival. Despite guidelines on using single-dose RT in uncomplicated BM, its use remains relatively low. In uncomplicated BM, single-fraction RT produces similar overall and complete response rates to RT with multiple fractions, although it is associated with a higher retreatment rate of 20% versus 8%. Complicated BM can be characterised as the presence of impending or existing pathologic fracture, a major soft tissue component, existing spinal cord or cauda equina compression and neuropathic pain. The rate of complicated BM is around 35%. Unfortunately, there is a lack of prospective trials on RT in complicated BM and the best dose/fractionation regimen is not yet established. There are contradictory outcomes in studies reporting BM pain control rates and time to pain reduction when comparing SABR with Conventional RT. While some studies showed that SABR produces a faster reduction in pain and higher pain control rates than conventional RT, other studies did not show differences. Moreover, the local control rate for BM treated with SABR is higher than 80% in most studies, and the rate of grade 3 or 4 toxicity is very low. The use of SABR may be preferred in three circumstances: reirradiation, oligometastatic disease, and radioresistant tumours. Local ablative therapies like SABR can delay change or use of systemic therapy, preserve patients' Qol, and improve disease-free survival, progression-free survival and overall survival. Moreover, despite the potential benefit of SABR in oligometastatic disease, there is a need to establish the optial indication, RT dose fractionation, prognostic factors and optimal timing in combination with systemic therapies for SABR. This review evaluates the role of RT in BM considering these recent treatment advances. We consider the definition of complicated BM, use of single and multiple fractions RT for both complicated and uncomplicated BM, reirradiation, new treatment paradigms including local ablative treatments, oligometastatic disease, systemic therapy, physical activity and rehabilitation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Several studies have suggested stereotactic arrhythmia radioablation (STAR) as a treatment option for patients suffering from therapy-refractory ventricular tachycardia or fibrillation (VT/VF)., Material and Methods: We performed a systematic review of human reports of STAR for structural VT/VF to assess its effectivity and safety. All identified publications were assessed for inclusion. This study adheres to the PRISMA guidelines and was registered on PROSPERO (CRD42020183044)., Results: Thirteen studies were included resulting in a population of 57 patients. Median age was 64 (range 34-83), 31 patients (54%) had ischemic cardiomyopathy and 50 patients (88%) had prior catheter ablation (CA) for VT/VF. A mean planned target volume of 64.4 cc (range 3.5-238) with a mean safety margin of 3.3 mm (0-5) was treated with 25 Gy. Immediately following STAR, four patients (7%) experienced an electrical storm. During a mean follow-up duration of 410 days, all patients suffering from sustained VT/VF prior to STAR (n = 55) had a reduction of their sustained VT/VF-burden after STAR, but recurrence occurred in 41 patients (75%) during follow-up. Forty-six patients (81%) had an adverse effect from therapy, but no treatment-related death occurred. Evidence of scar-formation after STAR either by imaging, invasive mapping or histopathology was found in six of nine examined patients (67%)., Conclusion: From the still very limited experience, STAR appears effective and safe in patients with structural heart disease and therapy-refractory sustained VT/VF. It is associated with a significant short-term reduction of sustained VT/VF-burden, but recurrences are common., (Copyright © 2021. Published by Elsevier B.V.)

Background and Purpose: A single-isocenter stereotactic body radiotherapy (SBRT) approach for multiple lung metastases has the potential to lower cumulative patient dose and reduce overall treatment time. However, the magnitude of inter-lesion position variation is currently unknown and not incorporated in margin calculations. The aim of this study was to quantify inter-lesion position variation and calculate safety margins for single-isocenter lung SBRT., Materials and Methods: A total of 83 pairs of pulmonary metastases from 42 NSCLC patients were used to calculate relative inter-lesion position variation by lesion-based registration of planning CT and verification CBCT. Furthermore, β-value assessment of van Herk's margin formula was performed by evaluating the distance between planned and blurred dose profiles of simulated spherical lesions, to evaluate its validity for heterogeneously planned dose distributions. Population-based ITV to PTV margins were calculated using the entire dataset and using subgroups with significant differences in relative inter-lesion position variation., Results: The mean ± SD inter-lesion position variation was 1.2 ± 1.1 mm as 3D-vector. Inter-lesion position variation was significantly increased if ≥1 lesion was not attached to the pleura or lesions were distant. The simulation showed that the combined SD of the random errors contributed to the margin only in the SI direction with 0.25∙σ tot for a 65% dose prescription. When incorporating inter-lesion position variation, the safety margins increased from 5.6, 5.8, 5.2 mm (AP, SI, LR) to 6.0, 6.6, 5.5 mm for the entire cohort., Conclusion: Relative inter-lesion position variation is influenced by inter-target distance and location and can be compensated with additional safety margins of <1 mm using single-isocenter SBRT., Competing Interests: Conflict of interest statement Dr. Hoogeman reports grants from Elekta, grants from Accuracy, grants from Varian, other from Accuracy, outside the submitted work. Dr. Tanadini-Lang reports that her husband works at Varian Medical Systems. Dr. van Timmeren, dr. Ehrbar, dr. Mayinger, dr. Andratschke and dr. Guckenberger report no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To summarize the clinical outcomes of stereotactic body radiotherapy (SBRT) for metastatic breast cancer (mBC) from a large institution., Materials and Methods: Patients with mBC who received extra-cranial SBRT to metastatic lesions from 2011 to 2017 were identified. Treatment indications were: oligometastases, oligoprogression, and local control of dominant tumor (CDT). Endpoints included overall survival (OS), progression-free survival (PFS), local control (LC) and cumulative incidence of starting/changing chemo or hormonal therapy (SCT). Univariate and multivariate analyses were used to identify predictive factors., Results: We analyzed 120 patients (193 treated metastatic lesions) with a median follow up of 15.25 months. 1-and 2-year LC rates were 89% and 86.6%, respectively. 1-and 2-year OS rates were 83.5% and 70%, respectively, with treatment indication and molecular subtype being the predictive factors on MVA. 1-year OS was 91.0%, 78.5% and 63.9% for oligometastases, oligoprogression and CDT, respectively (p = 0.003). The worst OS was seen in basal subtype with 1-and 2-year OS rates of 59.2% and 39.5% (p = 0.01). Treatment indication was found to be predictive for PFS and lower rates of SCT on MVA. 1-and 2-year PFS rates were 45% and 32%, respectively. The 1-year PFS for oligometastases, oligoprogression, and CDT was 66%, 19.6%, and 14.3%, respectively (p < 0.001). The cumulative incidence of SCT at 1-year was 12% for oligometastases, 39.7% for oligoprogression and 53.3% for CDT (p < 0.001)., Conclusion: Patients treated for oligometastases have better OS and PFS than those treated for oligoprogression or CDT. SBRT may delay SCT in mBC patients, particularly those with oligometastases. SBRT provided an excellent LC in mBC patients., Competing Interests: Conflict of Interest statement Alexander V. Louie has received honoraria from AstraZeneca, RefleXion and Varian Medical Systems. Sten Myrehaug has received research funding from AAA/Novartis. Ian Poon has received honoraria from AstraZeneca and Sanofi. Arjun Sahgal reported being an advisor/consultant with AbbVie, Merck, Roche, Varian (Medical Advisory Group), Elekta (Gamma Knife Icon), BrainLAB, and VieCure (Medical Advisory Board); Board member for International Stereotactic Radiosurgery Society (ISRS); Co-Chair for AO Spine Knowledge Forum Tumor. Arjun Sahgal also reported conducting educational educational seminars with Elekta AB, Accuray Inc., Varian (CNS Teaching Faculty), BrainLAB, Medtronic Kyphon; receiving research grant from Elekta AB; travel accommodations/expenses from Elekta, Varian, BrainLAB; and being part of the Elekta MR Linac Research Consortium, Elekta Spine, Oligometastases and Linac Based SRS Consortia. Hany Soliman has received honoraria from Elekta AB. The remaining authors have no COI to declare., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Mean dose (EQD2) to 3-cm shell of lung surrounding the PTV was evaluated for association with distant metastasis and PFS after SBRT for stage I NSCLC. Dose was uniformly above previously determined threshold and metastasis was uncommon. An association between outcomes and mean EQD2 could not be confirmed or refuted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer., Materials and Methods: 257 patients treated with prostate SBRT to dose levels of 32.5 Gy to >40 Gy in 5-6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n = 187) and the remaining 17% (n = 43) and 10% (n = 27) had low-risk and high-risk disease, respectively., Results: The incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n = 9/24), 21.4% (n = 6/28), 19.4% (n = 6/31), and 10.9% (n = 19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and >40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of <40 Gy and those with unfavorable-intermediate-risk or high-risk disease had higher likelihood of a positive post-treatment biopsy. A positive post-SBRT biopsy was associated with a significantly higher likelihood of subsequent PSA relapse at five years (Positive biopsy: 57%, 95% CI: 29-77% compared to negative biopsy: 7%, 95% CI: 3-14%; p < 0.001)., Conclusion: Based on two-year post-SBRT biopsies, excellent tumor control was achieved when dose levels of 40 Gy or higher were used. Standard SBRT dose levels of 35-37.5 Gy were associated with a higher likelihood of a positive post-treatment biopsy. Two-year positive post-treatment biopsies pre-dated the development of PSA failure in the majority of patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Both gating and tracking can mitigate the deteriorating dosimetric impact of intrafraction translation during prostate stereotactic body radiotherapy (SBRT). However, their ability to manage intrafraction rotation has not yet been thoroughly investigated. The dosimetric accuracy of gating, MLC tracking and couch tracking to manage intrafraction prostate rotation was investigated., Materials and Methods: Treatment plans for end-to-end tests of prostate SBRT with focal boosting were generated for a dynamic anthropomorphic pelvis phantom. The phantom applied internal lateral rotation (up to 25°) and coupled vertical and longitudinal translation of a radiochromic film stack that was used for dose measurements. Dose was delivered for each plan while the phantom applied motion according to three typical prostate motion traces without compensation (i), with gating (ii), with MLC tracking (iii) or with couch tracking (iv). Measured doses for the four motion compensation strategies were compared with the planned dose in terms of γ-index analysis, target coverage and organs at risk (OAR) sparing., Results: Intrafraction rotation reduced the 3%(global)/2mm γ-index passing rate (γPR) for the prostate target volume by median (range) -33.2% (-68.6%, -4.1%) when no motion compensation was applied. The use of motion compensation improved the γPR by 13.2% (-0.4%, 32.9%) for gating, by 6.0% (-0.8%, 27.7%) for MLC tracking and by 11.1% (1.2%, 22.9%) for couch tracking. The three compensation techniques improved the target coverage in most cases. Gating showed better OAR sparing than MLC tracking or couch tracking., Conclusions: Compensation of intrafraction prostate rotation with gating, MLC tracking and couch tracking was investigated experimentally for the first time. All three techniques improved the dosimetric accuracy, but residual motion-related dose errors remained due to the lack of rotation correction., 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 © 2020. Published by Elsevier B.V.)

Background and Purpose: Current nomograms predicting survival prognosis after stereotactic body radiation therapy (SBRT) in non-small cell lung cancer (NSCLC) are based on peripherally located tumors. However, patients with a central lung tumor tend to be older, the tumor is often larger and fraction-schedules are risk-adapted. Therefore, we developed and externally validated a nomogram to predict overall survival (OS) in patients having centrally located early-stage NSCLC treated with SBRT., Materials and Methods: Patients who underwent SBRT for centrally located NSCLC were identified and baseline characteristics were obtained. A nomogram was built to predict 6-month, 1-, 2- and 3-year OS using Cox proportional hazards model. The model building procedure was validated using bootstrap sampling. To determine generalizability, external validation was performed on a cohort of patients with central NSCLC treated with SBRT from another center. Discriminatory ability was measured with the concordance index (C-index) and calibration plots were used to compare Kaplan-Meier-estimated and nomogram-predicted OS., Results: The nomogram was built on data of 220 patients and consisted of the following variables: PTV, age, WHO performance status, tumor lobe location and ultracentral location. The C-index of the nomogram (corrected for optimism) was moderate at 0.64 (95% confidence interval (CI) 0.59-0.69). Calibration plots showed favorable predictive accuracy. The external validation showed acceptable validity with a C-index of 0.62 (95% CI 0.61-0.64)., Discussion: We developed and externally validated the first nomogram to estimate the OS-probability in patients with centrally located NSCLC treated with SBRT. This nomogram is based on 5 patient and tumor characteristics and gives an individualized survival prediction., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To reconstruct the dose delivered during single-fraction urethra-sparing prostate stereotactic body radiotherapy (SBRT) accounting for intrafraction motion monitored by intraprostatic electromagnetic transponders (EMT)., Methods: We analyzed data of 15 patients included in the phase I/II "ONE SHOT" trial and treated with a single fraction of 19 Gy to the planning target volume (PTV) and 17 Gy to the urethra planning risk volume. During delivery, prostate motion was tracked with implanted EMT. SBRT was interrupted when a 3-mm threshold was trespassed and corrected unless the offset was transient. Motion-encoded reconstructed (MER) plans were obtained by splitting the original plans into multiple sub-beams with isocenter shifts based on recorded EMT positions, mimicking prostate motion during treatment. We analyzed intrafraction motion and compared MER to planned doses., Results: The median EMT motion range (±SD) during delivery was 0.26 ± 0.09, 0.22 ± 0.14 and 0.18 ± 0.10 cm in the antero-posterior, supero-inferior, and left-right axes, respectively. Treatment interruptions were needed for 8 patients because of target motion beyond limits in the antero-posterior (n = 6) and/or supero-inferior directions (n = 4). Comparing MER vs. original plan there was a median relative dose difference of -1.9% (range, -7.9 to -1.0%) and of +0.5% (-0.3-1.7%) for PTV D 98% and D 2% , respectively. The clinical target volume remained sufficiently covered with a median D 98% difference of -0.3% (-1.6-0.5%). Bladder and rectum dosimetric parameters showed significant differences between original and MER plans, but mostly remained within acceptable limits., Conclusions: The dosimetric impact of intrafraction prostate motion was minimal for target coverage for single-fraction prostate SBRT with real-time electromagnetic tracking combined with beam gating., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Vacuum cushion immobilization is commonly used during stereotactic body radiotherapy (SBRT) to reduce intrafraction motion. We investigated target and bony anatomy intrafraction motion (translations and rotations) during online adaptive SBRT on an MR-linac for pelvic/para-aortic lymph node metastases with and without vacuum cushion., Materials and Methods: Thirty-nine patients underwent 5x7 Gy SBRT on a 1.5T MR-linac, 19 patients were treated with vacuum cushion, 19 without and 1 patient sequentially with and without. Intrafraction motion was calculated for target lymph nodes (GTVs) and nearby bony anatomy, for three time intervals (pre-position verification (PV), pre-post, PV-post, relating to the online MRI scans) per treatment fraction., Results: Vacuum cushion immobilization significantly reduced anterior-posterior translations for the pre-PV and pre-post intervals, for bony anatomy and pre-post interval for GTV (p < 0.05). Mean GTV intrafraction motion reduction in posterior direction was 0.7 mm (95% confidence interval 0.3-1.1 mm) for pre-post interval (mean time = 32 min). Shifts in other directions were not significantly reduced. More motion occurred in pre-PV interval than in PV-post interval (mean time = 16 min for both); vacuum cushion immobilization did not reduce intrafraction motion during the beam-on period., Conclusion: A vacuum cushion reduces GTV and bony anatomy intrafraction motion in posterior direction during pelvic/para-aortic lymph node SBRT. This motion reduction was found for the first 16 min per session. For single targets this motion can be corrected for directly with an MR-linac. Intrafraction motion was not reduced during the second half of the session, the period of radiotherapy delivery on an MR-linac. Vacuum cushion immobilization may not be necessary for patients with single lymph node oligometastases undergoing SBRT on an MR-linac., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The overarching University Medical Center Utrecht MR-linac scientific project, including employment of multiple authors, has been partly funded by Elekta AB (Stockholm, Sweden). Elekta did not have any part in the design, execution or analysis of this study. The authors declared that there is no other conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Spine stereotactic radiosurgery (SSRS) offers high rates of local control in a critical anatomic area by delivering precise, ablative doses of radiation for treatment of spine metastases. However, the dose tolerance of the spinal cord (SC) after SSRS with relation to radiation myelopathy (RM) is not well-described., Materials and Methods: We reviewed patients who underwent single fraction, de novo SSRS from 2012-2017 and received >12 Gy Dmax to the SC, defined using MRI-CT fusion without PRV expansion. The standard SC constraint was D0.01cc ≤ 12 Gy. Local control was estimated with the Kaplan-Meier method. Bayesian analysis was used to compute posterior probabilities for RM., Results: A total of 146 SSRS treatments among 132 patients were included. The median SC Dmax was 12.6 Gy (range, 12.1-17.1 Gy). The SC Dmax was >12 and <13 Gy for 109 (75%) treatments, ≥13 and <14 Gy for 28 (19%) treatments, and ≥14 Gy for 9 (6%) treatments. The 1-year local control rate was 94%. With a median follow-up time of 42 months, there were zero (0) RM events observed. Assuming a prior 4.3% risk of RM, the true rate of RM for SC Dmax of ≤14 Gy was computed as <1% with 98% probability., Conclusion: In one of the largest series of patients treated with single fraction, de novo SSRS, there were no cases of RM observed with a median follow-up of 42 months. These data support safe relaxation of MRI-defined SC dose up to D0.01cc ≤ 12 Gy, which corresponds to <1% risk of RM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Stereotactic body radiotherapy (SBRT) for spine metastases is associated with post-treatment vertebral compression fracture (VCF). The purpose of this study is to identify clinical and radiation planning characteristics that predict post-SBRT VCF through a novel normal tissue complication probability (NTCP) analysis., Methods: Patients with de novo spine metastases treated with SBRT between 2009 and 2018 at a single institution were included. Those who had surgical stabilization or radiation to the same site prior to SBRT were excluded. VCF was defined as new development or progression of existing vertebral body height loss not attributable to tumor growth. Probit NTCP models were constructed and fitted using a maximum likelihood approach. A multivariate proportional hazard model was used to estimate time to VCF using the Fine and Gray method., Results: Three hundred and two vertebral segments from 193 patients were treated with a median dose of 24 Gy in 3 fractions (range 15-30 Gy in 1-5 fractions). With a median follow up of 13.9 months, local control was 89.3% at 1 year. A total of 26 SBRT-induced VCFs were observed, with 1 and 2-year cumulative incidences of 4.6% and 6.7%. NTCP modeling demonstrated a steep response of VCF risk to the dose to 80% and 50% volume of the planning target volume (PTV D80% and D50%), but not maximum dose or dose to 1 cc or 10% of PTV. D80% of 25 Gy and D50% of 28 Gy in 3 fractions corresponded to 10% VCF risk. On multivariate analysis, lower body mass index (HR 0.90 per unit increase, p = 0.04), total spinal instability neoplastic score (SINS, HR 2.44 unstable vs stable, p = 0.04), and PTV D80% (HR 1.11 for every Gy increase, p = 0.003) were associated with increased VCF risk., Conclusions: SBRT provides excellent tumor control for spinal metastases and is associated with low rate of VCF in our cohort. NTCP modeling suggests that the larger volume of spine receiving lower doses are more closely associated with post-SBRT VCF than high dose regions. Under current target delineation methods, common SBRT regimens such as 24 Gy in 2 fractions or 27 Gy in 3 fractions may be inherently associated with VCF risk of 10% or greater. Consensus contouring guidelines should be reevaluated to minimize the volume of irradiated spine in light of these new data., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity., Methods: Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy., Findings: 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases., Interpretation: Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Stereotactic body radiotherapy (SBRT) in the post-prostatectomy setting is investigational. A major concern is the deformable prostate bed clinical target volume (CTV) and the closely juxtaposed organs-at-risk (OARs). We report a volumetric and dosimetric analysis of kilovoltage cone-beam CT (CBCT) data from the first 18 patients enrolled on a phase II trial of post-prostatectomy SBRT. With instructions on bladder filling and rectal preparation, we hypothesized acceptable CTV coverage while minimal overdosing to OARs could be achieved., Methods: All patients received 5 fractions of 6-6.8 Gy to the prostate bed. CBCT were taken prior to and halfway through each fraction. CTV and OARs were contoured for each CBCT. Changes in inter- and intra-fraction volume and dose were calculated. Relative changes in CTV V95%, bladder V32.5 Gy, and rectal V32.5 Gy and V27.5 Gy were evaluated., Results: Interfraction CTV volume remained stable, with median change +5.69% (IQR -1.73% to +9.84%). CTV V95% exhibited median change -0.74% (IQR -9.15% to -0.07%). Volumetric and dosimetric changes were minor from interfraction rotation and intrafraction motion. CTV V95% was ≥93% in 13 of 18 (72%) patients; in the remaining five, median change was -14.09% (IQR -16.64% to -13.56%). Interfraction CTV volume change was significantly larger among patients with CTV V95% <93% (+25.04% vs. +2.85%, p = 0.002)., Conclusions: With specific bladder and rectum filling protocols, CTV underdosing and overdosing to bladder and rectum are avoided in majority of patients. Changes in CTV shape may account for the underdosing that may be observed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy., Materials and Methods: Patients with intermediate or high risk PCa were enrolled in a prospective phase II trial, called hypo-FLAME. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric (mp) MRI-defined tumour(s). Treatment-related toxicity was measured using the CTCAE v4.0. The primary endpoint of the trial was treatment-related acute toxicity., Results: Between April 2016 and December 2018, 100 men were treated in 4 academic centres. All patients were followed up for a minimum of 6 months. The median mean dose delivered to the visible tumour nodule(s) on mpMRI was 44.7 Gy in this trial. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. Furthermore, 90 days after start of treatment, the cumulative acute grade 2 GU and GI toxicity rates were 34.0% and 5.0%, respectively., Conclusion: Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Radiofrequency ablation (RFA) is a standard ablative modality for small liver malignancies. Stereotactic body radiotherapy (SBRT) has emerged although yet suffers a lack of high-level evidence. We performed meta-analyses and a systematic review to integrate the literature and help in clinical decision-making., Methods: Systemic searches were performed of the PubMed, Medline, and EMBASE databases to identify controlled studies comparing RFA and SBRT., Results: Eleven studies involving 2238 patients were included. Among them, eight studies were for treating early hepatocellular carcinomas (HCCs) and three for liver metastases. Including HCCs and liver metastases studies, the pooled two-year local control (LC) rate was higher in the SBRT arm (83.8%, 95% confidence interval [CI]: 77.6-88.4) than that in the RFA arm (71.8%, 95% CI: 61.5-80.2) (p = 0.024). Among studies on liver metastases, the pooled two-year LC rate was higher in the SBRT arm (83.6% vs. 60.0%, p < 0.001). No significant difference was found between arms in HCC studies (SBRT vs. RFA: 84.5 vs. 79.5% p = 0.431). Pooled analysis of overall survival (OS) in HCC studies showed an odds ratio of 1.43 (95% CI: 1.05-1.95, p = 0.023), favoring RFA. Among the two liver metastases studies with comparative survival data, no significant difference was observed., Conclusion: LC was equivalent between RFA and SBRT for HCC and better for SBRT for the treatment of liver metastases. RFA was associated with better OS for HCC, but discrepancy between LC and OS requires further investigation, as they are local modalities having comparable efficacy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background & Purpose: Stereotactic ablative radiation therapy (SABR) is an emerging treatment option for patients with pulmonary metastases; identifying patients who would benefit from SABR can improve outcomes., Materials & Methods: We retrospectively analyzed local failure (LF), distant failure (DF), overall survival (OS), and toxicity in 317 patients with 406 pulmonary metastases treated with SABR in January 2006-September 2017 at a tertiary cancer center., Results: Median follow-up time was 23 months. Primary adrenal, colorectal, sarcoma, or pancreatic ("less responsive") tumors led to high rates of LF. LF rates for patients with less responsive vs. responsive tumors were 4.6% vs. 1.6% at 12 months and 12.8% vs. 3.9% at 24 months (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.11-0.73; Log-Rank P = 0.0087). A nomogram for 24-month local control was created using Cox multivariate factors (surgical history, planning target volume, primary disease site, lung lobe location). Treating patients with ≤3 pulmonary metastases vs. >3 pulmonary metastases was associated with improved 24-month (74.2% vs. 59.3%) and 48-month (47.7% vs. 35.1%) OS (HR 0.66, 95% CI 0.47-0.95; Log-Rank P = 0.043), and reduced 12-month (22.5% vs. 50.8%) and 24-month (31.8% vs. 61.4%) intrathoracic DF (HR 0.53, 95% CI 0.38-0.74; Log-Rank P < 0.0001). The most common toxicity was asymptomatic pneumonitis (14.8%). Six patients had grade 3 events (5 pneumonitis, 1 brachial plexus)., Conclusions: SABR for pulmonary metastases was effective and well tolerated. Irradiating limited intrathoracic sites of disease led to improved OS and intrathoracic DM. Higher SABR doses or surgery could be considered for less radio-responsive primary tumors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: The optimal neoadjuvant approach in patients with resectable pancreas cancer is unclear. We investigated outcomes after preoperative chemotherapy alone, chemotherapy with conventionally-fractionated radiation (CFRT), or chemotherapy with stereotactic body radiotherapy (SBRT)., Materials and Methods: The NCDB was queried for patients with resectable pancreatic adenocarcinoma (pretreatment stage T1-3, N0-1, M0) who received preoperative, multiagent chemotherapy and definitive surgery from 2010 to 2015. CFRT was 40-60 Gy in 20-35 fractions. SBRT was 20-25 Gy in 1 fraction or 30-50 Gy using at least 5 Gy per fraction. Multivariable regression and propensity score matching were used to adjust for potential confounders, including age, comorbidity score, and pretreatment extent of disease. The primary outcome was overall survival measured from surgery., Results: In total, 1355 patients received preoperative chemotherapy alone, 552 patients received preoperative chemotherapy with CFRT, and 175 patients received preoperative chemotherapy with SBRT. Receipt of SBRT was associated with significantly improved overall survival compared to chemotherapy alone (median 30 vs 21 months, p = 0.02; adjusted hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.47-0.90, p = 0.01). Similarly, SBRT was associated with significantly improved overall survival compared to CFRT (median 29 vs 16 months, p = 0.002; adjusted HR 0.53, 95% CI 0.37-0.76, p = 0.001). Additionally, SBRT was associated with significantly increased rates of pathological complete response and margin-negative resection. Rates of postoperative readmissions and mortality were comparable., Conclusions: Neoadjuvant chemotherapy with SBRT is associated with favorable survival and pathological outcomes, warranting consideration for prospective validation., 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 © 2020 Elsevier B.V. All rights reserved.)

Purpose: Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR., Methods: Patients had low or intermediate risk PCa. The doses prescribed were 26 Gy/2 and 40 Gy/5. Expanded prostate cancer index composite was collected. Urinary, bowel and sexual domains were analyzed. Minimal clinically important change (MCIC) was defined as >0.5 standard deviation., Results: 30 and 152 patients were treated with 2-fraction and 5-fraction SABR. Median follow-up was 55 and 62 months. Five-year biochemical failure rate was 3.3% and 4.6%. The 2-fraction cohort had a significantly better mean QOL over time in the bowel domain (p = 0.0004), without a significant difference in the urinary or sexual domains. The 2-fraction cohort had a significantly lower rate of bowel MCIC (17.8% vs 42.3%, p = 0.01), but there was no difference in urinary (24.1% vs 35.7%) or sexual (15.3% vs 29.2%) MCIC. For MCIC x2 (moderate QOL change), the 2-fraction trial had significantly lower MCIC rates in both the bowel (7.1% vs 24%, p = 0.04) and sexual (0 vs 17.6%, p = 0.01) domains., Conclusions: 2-Fraction SABR is feasible to deliver and well tolerated, with significant signals of improved bowel and sexual QOL. A randomized trial of two vs. five fractions for prostate SABR is needed to confirm the promising findings of this study., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Stereotactic body radiotherapy (SBRT) for prostate cancer (PCa) is gaining interest by the recent publication of the first phase III trials on prostate SBRT and the promising results of many other phase II trials. Before long term results became available, the major concern for implementing SBRT in PCa in daily clinical practice was the potential risk of late genitourinary (GU) and gastrointestinal (GI) toxicity. A number of recently published trials, including late outcome and toxicity data, contributed to the growing evidence for implementation of SBRT for PCa in daily clinical practice. However, there exists substantial variability in delivering SBRT for PCa. The aim of this topical review is to present a number of prospective trials and retrospective analyses of SBRT in the treatment of PCa. We focus on the treatment strategies and techniques used in these trials. In addition, recent literature on a simultaneous integrated boost to the tumor lesion, which could create an additional value in the SBRT treatment of PCa, was described. Furthermore, we discuss the multicenter consensus of the FLAME consortium on SBRT for PCa with a focal boost to the macroscopic intraprostatic tumor nodule(s)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Ultrahypofractionation is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index. Here we report the outcomes of a phase II prostate SABR trial using two fractions., Methods: Patients had low or intermediate risk prostate cancer. Three gold fiducials were implanted for image guidance. The clinical target volume (CTV) included the prostate only, and the planning target volume (PTV) was a 3 mm expansion enabled through the use of a rectal immobilization device. The dose prescribed was 26 Gy in 2 weekly fractions (EQD2 110 Gy 1.4 ). The primary endpoint was quality of life using EPIC, and minimal clinically important change (MCIC) was defined as an EPIC QOL decrease >0.5 SD., Results: 30 patients were accrued with a median follow-up of 49.3 months. 10% had low-risk, 33% had favourable intermediate-risk and 57% had unfavourable intermediate-risk PCa. Five patients received a short course of ADT. Median nPSA was 0.2 ng/ml. One patient had BF and is being observed. 56.6% of patients had a 4yPSARR. Six (20.7%) patients had a MCIC in the urinary domain, 6 (21.4%) had a MCIC in the bowel domain, and 3 (20%) had a MCIC in the sexual domain., Conclusions: Two-fraction SABR in prostate cancer is safe and feasible, with a minimal change in QOL and a low rate of late grade 3-4 toxicity. The PSA kinetics and biochemical control rates are encouraging given that the majority had unfavourable intermediate-risk disease, although longer follow-up is required., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Although adjuvant systemic therapy (ST) is often recommended for the treatment of patients with high-risk, early-stage non-small cell lung carcinoma (NSCLC) after surgery, there is little evidence supporting the use of ST with stereotactic body radiotherapy (SBRT)., Methods: We conducted a retrospective cohort study using a multi-institutional database to identify consecutive patients with T1-3N0M0 NSCLC treated with definitive SBRT from 2006-2015. Treatment groups were defined as those who received SBRT + ST or SBRT alone. Regional-distant failure (RDF) was analyzed with Fine and Gray competing risks regression. Progression-free (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox regression. Additional comparisons were made after 2:1 nearest-neighbor propensity-score matching on clinical risk factors., Results: We identified 54 patients who received SBRT + ST. The most common ST regimen was a platinum doublet (n = 38; 70.4%). Compared with patients receiving SBRT (n = 1269), SBRT + ST patients were younger (median age: 70 v 77 years, p < 0.001), had larger tumors (>3 cm: 38.9% v 21.6%, p = 0.02) and higher T-stage (T2-3: 42.6% v 22.5%, p = 0.002). Compared with SBRT patients, SBRT + ST patients had lower 2-year RDF (3.1% v 16.9%, p = 0.02). On multivariable analysis, SBRT + ST was associated with reduced RDF (HR: 0.15, 95%CI: 0.04-0.62), with a trend toward improved PFS (HR: 0.70, 95%CI: 0.48-1.03), but not OS (HR: 0.74, 95%CI: 0.49-1.11). After propensity-score matching, the SBRT + ST cohort demonstrated improved RDF (HR: 0.17, 95%CI: 0.04-0.76) and PFS (HR: 0.59, 95%CI: 0.38-0.93)., Conclusion: In this multi-institutional analysis, adjuvant ST was independently associated with reduced RDF in early-stage NSCLC patients treated with SBRT., (Copyright © 2018 Elsevier B.V. All rights reserved.)