Single-fraction Stereotactic Body Radiotherapy Research Articles

ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial

PurposeTo assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. Material and methodsPatients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. ResultsAmong the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. ConclusionsIn this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

Differences between Survival Rates and Patterns of Failure of Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma Who Received Single-Fraction Stereotactic Body Radiotherapy.

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC (p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus?

Stereotactic body radiotherapy (SBRT) is an emerging treatment option for localized prostate cancer. There is increasing interest to reduce the number of fractions for prostate SBRT. We provide a narrative review and summary of prospective trials of different fractionation schedules for prostate SBRT, focusing on efficacy, toxicities, and quality of life outcomes. There are two randomized phase 3 trials comparing standard external beam radiotherapy with ultra-hypofractionated radiotherapy. HYPO-RT-PC compared 78Gy in 39 fractions vs 42.7Gy in 7 fractions (3D-CRT or IMRT) showing non-inferiority in 5-year biochemical recurrence-free survival and equivalent tolerability. PACE-B trial compared 78Gy in 39-fraction or 62Gy in 20-fraction vs 36.25Gy in 5-fraction prostate SBRT, with no significant differences in toxicity outcomes at 2years. Five-year efficacy data for PACE-B are expected in 2024. Five-fraction prostate SBRT is currently the most common and well-established fractionation schedule with multiple prospective phase 2 trials published to date. There is more limited data on 1-4 fraction prostate SBRT. All fractionation schedules had acceptable toxicity outcomes. Experience from a high-dose-rate brachytherapy randomized trial showed inferior efficacy with single-fraction compared to two-fraction brachytherapy. Hence, caution should be applied in adopting single-fraction prostate SBRT. Two-fraction SBRT is likely the shortest fractionation schedule that maintains the therapeutic ratio. Several randomized trials currently recruiting will likely provide us with more definite answers about whether two-fraction prostate SBRT should become a standard-of-care option. Enrollment of eligible patients into these trials should be encouraged.

Cardiac and Great Vessel Toxicity with Single Fraction Stereotactic Body Radiotherapy in Early-Stage Lung Cancer

The relationship between thoracic radiotherapy and cardiovascular (CV) morbidity is an area of interest. When considering stereotactic body radiotherapy (SBRT) in the management of early-stage lung cancer, reports suggest CV dose may correlate with survival. To study this association for single fraction SBRT (SF-SBRT), we performed a retrospective review of patients treated at our institution assessing for associations between this dose schedule and CV toxicity. For the interval 2010-2022, we surveyed our IRB-approved prospective registry for SF-SBRT patients with tumors within 1 cm of the heart or any of the great vessels (GVs). Distance of the tumor to these structures was stratified as: directly contacting, within 0.5 cm, from 0.5-1 cm, or > 1 cm. Medical records were reviewed post-SBRT for CV events including: myocardial infarction (MI), heart failure (HF), structural heart damage (valvular or wall abnormalities), vascular damage (aneurysm, dilation, other abnormalities), hemoptysis, and arrhythmia which were correlated with lesion location and history. Four hundred four patients treated with SF-SBRT to 34 Gy in 1 fraction were identified. 35 patients (8.7%) had 36 lesions within 1 cm of the heart or GVs. 68.6% of patients were female and 74.3% were Caucasian. The median age was 72.5 years (range: 60-91), median Charlson comorbidity score was 6, median KPS was 80, and median ASCVD score was 21.0%. 33 patients had a smoking history with a median of 50 pack years. 12 patients (34.3%) had an arrhythmia prior to SBRT, 5 (14.2%) had prior HF, and 9 (25.7%) had prior MI or CV disease. All cases were non-small cell lung cancer or radiographic malignancy with 1 case of small cell lung cancer. Median tumor size was 1.6 cm. 91.4% of patients had stage I disease. Median follow-up was 2.26 years (0.37-4.0). Seven lesions (19.4%) were abutting the heart or GVs, 14 (38.9%) were within 0.5 cm, and 15 (41.7%) were from 0.5-1 cm. 54 events were observed with a median of 1 event per patient (0-5). The most common events were arrhythmia (15), vascular damage (9), structural damage (12), heart failure (9), and MI (6). The most commonly associated vascular structure was the aortic arch, while the most commonly involved substructures of the heart were the right atrium and left ventricle. 12 events occurred in the direct contact group, 17 in the < 0.5 cm group, and 25 in the 0.5-1 cm group. Patients with heart associated lesions accounted for 8 events, while those with vessel associated tumors accounted for 46. While cardiac events are relatively common in the medically inoperable SBRT population, they did not appear to be more common with tumors directly contacting major cardiovascular structures than for those with some separation. Most events could be attributed to medical causes other than SBRT. Further study is needed to clarify the potential role of radiation in events without direct explanation.

Bone Only Oligometastatic Renal Cell Carcinoma Patients Treated with Stereotactic Body Radiotherapy: A MULTI-Institutional Study

<h3>Purpose/Objective(s)</h3> Previous studies demonstrated the efficacy of stereotactic-body radiotherapy (SBRT) for oligometastatic renal cell carcinoma (RCC) patients. However, it has not been well-studied in patients with bone-only metastatic RCC. This study aimed to analyze the prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in patients with bone-only metastatic RCC who have five or fewer lesions treated with SBRT. <h3>Materials/Methods</h3> The clinical data of 54 patients with 70 bone metastases undergoing SBRT treated between 2013 and 2020 with a fraction dose of at least 6 Gy per fraction, and a biologically effective dose (BED) of at least 90 Gy was retrospectively evaluated. The prognostic factors associated with OS and PFS were assessed. <h3>Results</h3> The majority of lesions were located in the spine (57.4%), and had only one metastasis (64.8%). The median SBRT fraction and total doses were 10 Gy (range: 6–18 Gy) and 20 Gy (range: 12–40 Gy), and SBRT was administered with a median fraction of 3 (range, 1–5). The median BED of SBRT was 108.4 Gy (range: 90.0–202.2 Gy). After a median follow-up of 22.4 months, the 1- and 2-year OS rates were 84.6% and 67.3%, respectively, and median OS was 43.1 months. The 1- and 2-year PFS rate, and median PFS were 63.0%, 38.9%, and 15.3 months, respectively. After completion of metastasis-directed treatment (MDT), disease progression occurred in 26 patients (48.1%) at a median of 12.7 months (IQR 7.1–29.9 months). There were 22 (84.6%) with distant metastasis, one (3.8%) with in-field local recurrence, and three (11.6%) with both distant metastasis and local recurrence. In SBRT-treated lesions, only 4 patients (7.4%) experienced local recurrence, and the 1- and 2-year LC rates per lesion were 94.9% and 92.0% per lesion. Age, metastasis localization, and number of fractions for SBRT were significant prognostic factors for OS in univariate analysis. In multivariate analysis, patients with spine metastasis had a better OS [HR=3.1 (95% CI, 1.3–7.7; p = 0.001)] compared to their counterparts, and patients who received single fraction SBRT [HR=2.2 (95%, 1.2–4.2; p = 0.01)] had a better PFS than those who did not. No patient experienced acute or late toxicities of grade 3 or greater. <h3>Conclusion</h3> To the best of our knowledge, this is the first multicenter study of bone-only oligometastatic RCC patients treated with SBRT. Despite excellent LC at the oligometastatic site treated with SBRT, disease progression was observed in nearly half of patients 13 months after MDT, particularly as distant disease progression other than treated lesion, necessitating an effective systemic treatment to improve treatment outcomes. Prospective trials of SBRT for oligometastatic bone sites are warranted because they may shed light on disease control, survival, and quality of life after such therapy.

Single-fraction prostate-specific membrane antigen positron emission tomography- and multiparametric magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer local recurrences.

To analyse the efficacy and safety of focal prostate-specific membrane antigen positron emission tomography (PSMA-PET)- and multiparametric magnetic resonance imaging (mpMRI)-guided single-fraction stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer (PCa) local recurrences. Patients with PSMA-PET-positive PCa local recurrences treated with single-fraction SBRT between 2016 and 2020 were included. Identification for subsequent recurrences or metastatic spread based on increasing prostate-specific antigen (PSA) levels were evaluated using PSMA-PET imaging. A total of 64 patients were identified. Patients received various treatments before SBRT (31 patients with radical prostatectomy [RP], 18 external beam radiotherapy [EBRT] with RP, five EBRT, and the remaining 10 other combinations). The median follow-up was 21.6 months. The median PSA level before SBRT was 1.47 ng/mL. All patients received a single-fraction treatment with a median prescription dose and isodose line of 21 Gy and 65%, respectively. At the time of SBRT, six patients (9%) received an androgen deprivation therapy (ADT). PSA levels decreased after SBRT (P = 0.03) and three local recurrences were detected during the follow-up. The progression-free survival after 1-, 2-, and 3-years was 85.3%, 65.9%, and 51.2%, respectively. Six patients (9%) started ADT after SBRT due to disease progression. The rates of newly started ADT after 1-, 2-, and 3-years were 1.8%, 7.3%, and 22.7%, respectively. Grade 1 or 2 toxicities occurred in six patients (9%); no high-grade toxicity was observed. While the available data for SBRT in the PCa local recurrence setting describe outcomes for fractionated irradiations, the findings of this first analysis of single-fraction, PSMA-PET- and mpMRI-guided focal SBRT are encouraging. Such treatment appears to be a safe, efficient, and time-saving therapy even in intensively pretreated patients. Recurrence-directed treatments can delay the use of ADT and could avoid prostate bed irradiation in selected patients.

Radiation-induced electrophysiological remodelling in neonatal rat ventricular cardiomyocytes

Abstract Background Ventricular tachycardia (VT) carries a relatively high risk of recurrence and significantly impacts patients' quality of life, despite state of the art treatment including antiarrhythmic drug therapy and catheter ablation. Cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising non-invasive treatment option for refractory VT. A marked reduction in VT episodes is observed within days of treating high-risk patients with a single fraction SBRT. The cellular mechanisms underlying the clinically demonstrated antiarrhythmic effect are still poorly understood. Radiation-induced fibrosis is observed several months after irradiation, suggesting other mechanisms that explain the immediate benefit of radiotherapy on the VT substrate. Purpose We hypothesized that early antiarrhythmic effects of single-fraction radiation are produced by direct molecular and functional electrophysiological changes, independent of fibrosis. Our aim was to investigate the effects of 20 Gy ionizing photon radiation on the electrophysiology of ventricular neonatal rat cardiomyocytes at time periods from 24 hours to 96 hours after irradiation. Methods Ventricular neonatal rat cardiomyocytes were isolated, cultivated for 24 to 96 hours and then exposed to photon beam with a single dose of 20 Gy. Expression changes of ion channels, calcium handling proteins and structural proteins affecting cellular electrophysiology were assessed via RT-qPCR and Western blotting. Beat frequency was evaluated by video analysis and action potentials (APD) were recorded using the whole-cell voltage clamp technique in current-clamp mode. Intracellular calcium transients in Fura-2 AM loaded cardiomyocytes were recorded with an IonOptix recording system. Results Irradiation lead to significant changes in the mRNA and protein level of ion channels, with most distinct changes being observed 96h after radiation. Increased mRNA and protein expression of (Cav1.2) and of the potassium channels Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1) and Kcnj2 (Kir2.1) was observed. Additionally, Connexin 43 (Cx43) was upregulated. Irradiated cardiomyocytes showed a significant increase in beat rate over time. APD was significantly shortened, with a significantly increased upstroke velocity. Regarding calcium handling, significant upregulations of Ryr2 (RYR2) and Slc8a1 (NCX) transcript and protein level was detected. Additionally, calcium handling properties were altered. Conclusion Our results suggest that acute irradiation effects are associated with electrophysiological remodelling in cardiomyocytes. Changes of cellular ion channel expression and calcium homeostasis lead to normalization and shortening of heart-failure associated APD prolongation. These results reveal new insights into acute antiarrhythmic effects on cardiomyocytes after SBRT-therapy. Funding Acknowledgement Type of funding sources: None.

Bone-only oligometastatic renal cell carcinoma patients treated with stereotactic body radiotherapy: a multi-institutional study.

This study aimed to analyze the prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in patients with bone-only metastatic renal cell carcinoma (RCC) who have five or fewer lesions treated with stereotactic body radiotherapy (SBRT). The clinical data of 54patients with 70bone metastases undergoing SBRT treated between 2013 and 2020 with adose of at least 5 Gy per fraction and abiologically effective dose (BED) of at least 90 Gy were retrospectively evaluated. The majority of lesions were located in the spine (57.4%) and had only one metastasis (64.8%). After amedian follow-up of 22.4months, the 1‑ and 2‑year OS rates were 84.6% and 67.3%, respectively, and median OS was 43.1months. The 1‑ and 2‑year PFS rates and median PFS were 63.0%, 38.9%, and 15.3months, respectively. In SBRT-treated lesions, the 1‑year local control (LC) rate was 94.9%. Age, metastasis localization, and number of fractions of SBRT were significant prognostic factors for OS in univariate analysis. In multivariate analysis, patients with spinal metastasis had better OS compared to their counterparts, and patients who received single-fraction SBRT had better PFS than those who did not. No patient experienced acute or late toxicities of grade3 or greater. Despite excellent LC at the oligometastatic site treated with SBRT, disease progression was observed in nearly half of patients 13months after metastasis-directed local therapy, particularly as distant disease progression other than the treated lesion, necessitating an effective systemic treatment to improve treatment outcomes.

Local Control With Single-Fraction Lung Stereotactic Body Radiotherapy is not influenced by Non-Small Cell Lung Cancer Histologic Subtype

Introduction/BackgroundFor early stage medically inoperable lung cancer treated with fractionated stereotactic body radiotherapy (SBRT), higher local failure is associated with squamous carcinoma (SqC) compared to adenocarcinoma (AC). This study explored whether histology influences single-fraction SBRT local control. Materials and MethodsWe surveyed our prospective data registry from 12/2009 to 12/2019 for SF-SBRT cases with biopsy-proven AC or SqC only. Outcomes of interest included local (LF), nodal (NF), distant (DF) failure rates and overall survival (OS), as well as treatment-related toxicity. ResultsFor the 10-year interval surveyed, 113 patients met study criteria. There was no association between histology and dose received (34 Gy or 30 Gy). Median follow up was 22.9 months. Patient characteristics were balanced between histologic cohorts. Median tumor size was 1.9 cm. Comparing total AC vs. SqC cohorts, 2-year LF rates (%) were 7.3 vs. 9.6, respectively (P = .9805). In %, 2-year LF, NF, DF and OS rates for AC for 30 Gy and 34 Gy, respectively, were 10.8 vs. 6.4; 10.5 vs. 16.2; 15.8 vs. 13.0; 77.9 vs.71.2 (all P = non-significant). In %, 2-year LF, NF, DF, and OS rates for SqC for 30 Gy and 34 Gy, respectively, were 11.8 vs. 8.1; 5.9 vs. 18.0; 23.5 vs. 9.7; 70.6 vs. 77.1 (all P = non-significant). When considering toxicities, there were no grade 4/5 toxicities and no significant differences in any other toxicity rate by histology or dose. ConclusionSF-SBRT local control was not associated with histology, unlike fractionated schedules. This novel finding adds to the evolving understanding of this treatment schedule.

Stereotactic body radiotherapy for spinal metastases: a review.

To evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) in treating spinal metastases. Two reviewers performed independent literature searches of the PubMed database, searching literatures of the efficacy and safety of SBRT in metastatic spinal diseases. A total of 67 studies were included in the review. Regarding SBRT for de novo spinal metastases, the 1- and 2-year local control (LC) rates were 51-100% and 56-96%, respectively. The local failure rate was 10.5-47.5%, with most studies reporting a local failure rate of < 30%. The 1- and 2-year overall survival (OS) rates were 25.7-80% and 25-60.7%, respectively. The pain relief rate was 41.6-100%. In the postoperative scenario, the LC rate was 70-100%, and the local failure rate was 11.7-33%. Regarding the reirradiated setting, the 1-year LC rate was 71-83%, the local failure rate was 6.0-25.5%, and the 1-year OS rate was 28-68%. The pain relief rate was approximately 35.7-77%. Between studies on single- and multi-fraction SBRT, the 1- and 2-year LC rates with single-fraction SBRT were 71-95% and 70-96%, respectively; the 1- and 2-year OS rates with single-fraction SBRT were 43.5-46% and 43.5-49%, respectively. For the management of spinal metastases, it appears that regardless of the clinical scenario in which SBRT is applied, a high rate of LC is achieved, particularly with single-fraction SBRT, regardless of histology. Additionally, spinal SBRT can establish durable pain palliation with acceptable toxicities.

P05.02 Does Non-Small Cell Lung Cancer Histologic Type Influence Outcomes with Single-Fraction Stereotactic Body Radiotherapy?

For early stage medically inoperable Non-Small Cell Lung Cancer (NSCLC) treated with fractionated stereotactic body radiotherapy (SBRT), when compared by biologically equivalent dose (BED) higher rates of local failure have been associated with squamous (SqC) histology compared to adenocarcinoma (AC) for equivalent BEDs. We sought to determine if histology outcomes differed when using single-fraction schedules (SF-SBRT). An IRB-approved prospective lung SBRT data registry was surveyed from 12/2009 till 12/2019 for all patients (pts) receiving SF-SBRT with minimum 6-month follow up with biopsy-proven AC or SqC excluding bronchoalveolar and “NSCLC not-otherwise specified” cases. Doses employed were either 34 Gy, planned per RTOG 0915, or 30 Gy, planned per RPCI-124407. Outcomes of interest included cumulative incidence rates of local (LF), nodal (NF), and distant (DF) failure and overall survival (OS), as well as treatment-related toxicity graded per CTCAE version 3.0. 229 SF-SBRT pts treated over 10 years had a 2-year LF rate of 7.28%. For this analysis 113 (49.3%) met study’s pathology criteria and had a 2-year LF rate of 8.41%. No association was seen between histology type and the SF-SBRT dose given: 65 pts (57.5%) had AC, of these 19 (29.2%) and 46 (70.8%) received 30 Gy and 34 Gy, respectively. Of 48 SqC pts (42.5%), 17 (35.4%) and 31 (64.6%) received 30 Gy and 34 Gy, respectively. Median follow up was 22.9 months. Patient characteristics were balanced between histologies. Median tumor size was 1.9 cm and 2.05 cm for AC and SqC, respectively. When comparing tumor features for each histology or by dose group, there were no significant (NS) differences including specifically tumor distance from the chest wall. Comparing total Ac vs. SqC cohorts, 2-year LF rates in % were 7.32 vs. 9.64, respectively (p=0.9805). In %, 2-year LF, NF, DF and OS rates for AC for 30 Gy and 34 Gy, respectively, were 10.84 vs. 6.41; 10.53 vs. 16.24; 15.79 vs. 13.04; 77.9 vs.71.2 (all NS). In %, 2-year LF, NF, DF, and OS rates for SqC for 30 Gy and 34 Gy, respectively, were 11.76 vs. 8.08; 5.88 vs. 17.94; 23.53 vs. 9.68; 70.6 vs. 77.1 (all NS). There were no grade 4/5 toxicities and NS differences in any other toxicity rate by histology or dose. For AC pts, pneumonitis rates were: 4 pts (6.2%) with grades 1-2; chest wall toxicity rates were: 7pts (10.8%) with grade 1-2 and 1 (1.5%) with grade 3. For SqC, pneumonitis rates were: 4 pts (8.3%) with grade 1-2 rates pneumonitis; chest wall toxicity rates were: 10 (20.8%) with grade 1-2 only. SqC LF rates are similar to AC’s with either SF-SBRT schedule and no significant differences were seen for other outcomes or for toxicity profiles by histology and dose. This suggests equivalent efficacy for SF-SBRT doses independent of NSCLC histology

Clinical and dosimetric risk factors for vertebral compression fracture after single-fraction stereotactic body radiation therapy for spine metastases

ObjectivesThis analysis was performed to evaluate the incidence of vertebral compression fracture (VCF) and determine the contributing factors for VCF in patients undergoing single-fraction stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM). MethodsA retrospective review of medical records was conducted for patients undergoing SBRT for SBM at our institution between January 2010 and December 2018. Patients who had undergone neither pre-SBRT surgical excision nor post-SBRT prophylactic fixation were included. The effects of clinical and dosimetric parameters were analyzed with respect to VCF risk. The following dosimietric parameters of the planning target volume (PTV) were calculated: mean/minimum/maximum dose, radiation dose to 10–90% volume, and irradiated volume receiving more than 10–25 Gy (PTV_V10 – 25 Gy). ResultsAmong 163 patients (179 vertebrae), 21 (12.8%) experienced VCF. The 1-year and 2-year VCF rates were 12.1% and 13.2%, respectively. Among dosimetric parameters, PTV_V15 Gy was the most significant for VCF prediction. In a univariate analysis, breast or prostate primary, no vertebral body collapse, and PTV_V15 Gy ≤42 cm3 were significantly associated with a lower incidence rate of VCF. In a multivariate analysis, PTV_V15 Gy was the only significant factor for VCF risk. The 1-year VCF rate was 3.8% in patients with PTV_V15 Gy ≤42 cm3, while it was 22.1% in those with PTV_V15 Gy > 42 cm3 (p < 0.01). ConclusionsSBRT-related VCF was found in 12% of patients in our institution. The PTV_V15 Gy is a significant factor for VCF prediction.

A multi-institutional analysis of fractionated versus single-fraction stereotactic body radiotherapy (SBRT) in the treatment of primary lung tumors: a comparison between two antipodal fractionations

Stereotactic body radiotherapy (SBRT) is a consolidate treatment for inoperable early-stage lung tumors, usually delivered in single or multi-fraction regimens. We aimed to compare these two approaches in terms of local effectiveness, safety and survival. Patients affected by medically inoperable early-stage lung tumor were treated at two Institutions with two different schedules: 70Gy in ten fractions (TF) (BED10: 119Gy) or 30Gy in single fraction (SF) (BED10: 120Gy). 73 patients were treated with SBRT delivered with two biological equivalent schedules: SF (44) and TF (29). The median follow-up was 34months (range 3-81months). Three-year Overall survival (OS) was 57.9%, 3-year cancer-specific survival (CSS) was 77.2%, with no difference between treatment groups. Three-year progression-free survival (LPFS) was 88.9% and did not differs between SF and TF. Overall, four cases (5.4%) of acute grade ≥ 3 pneumonitis occurred. No differences in acute and late toxicity between the two groups were detected. SF and TF seems to be equally safe and effective in the treatment of primary inoperable lung tumors especially for smaller lesion. The SF may be preferentially offered to reduce patient access to hospital with no negative impact on tumor control and survival.

Single-fraction prostate stereotactic body radiotherapy: Dose reconstruction with electromagnetic intrafraction motion tracking

PurposeTo reconstruct the dose delivered during single-fraction urethra-sparing prostate stereotactic body radiotherapy (SBRT) accounting for intrafraction motion monitored by intraprostatic electromagnetic transponders (EMT). MethodsWe 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. ResultsThe 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 D98% and D2%, respectively. The clinical target volume remained sufficiently covered with a median D98% 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. ConclusionsThe 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.

RADT-21. NATIONAL PRACTICE PATTERNS AND OUTCOMES OF STEREOTACTIC BODY RADIOTHERAPY VS. CONVENTIONAL EXTERNAL BEAM RADIOTHERAPY FOR SPINAL METASTASES

Abstract INTRODUCTION Up to 10% of cancer patients experience spinal cord compression from metastatic disease. Palliation and local control were traditionally pursued with conventional external beam radiotherapy (cEBRT), but advancements in image-guidance and intensity-modulation for stereotactic body radiotherapy (SBRT) have dramatically changed the management of these lesions. Herein we evaluate the national practice patterns and outcomes associated with cEBRT vs. SBRT. METHODS U.S. patients newly diagnosed with metastatic cancer necessitating RT to the spine were identified from the National Cancer Database (2004-2016), stratified by RT modality and cancer type, and evaluated using multivariable logistic regression and Cox proportional hazards. RESULTS 34,759 U.S. patients required spinal RT within 3 months of initial stage 4 cancer presentation, primarily for lung adenocarcinoma (25%), lung small cell carcinoma (14%), and prostatic (12%) metastases. Patients overwhelming received cEBRT (30Gy/10; 50%), followed by hypo-fractionated SBRT (15-30Gy/2-6; 11%) and single-fraction SBRT (i.e. stereotactic radiosurgery, SRS; 15-24Gy/1; 0.9%); whereas 38% received another regimen (e.g. 30-37.5Gy/12-15 or 40Gy/20). From 2004→2016, the rates of single-fraction SRS (0.4→1.9%) and hypo-fractionated SBRT (13.1→23.6%) increased, whereas cEBRT (86.5→74.4%) decreased. SBRT was significantly more likely to be utilized at academic hospitals as compared to cEBRT (OR 0.57; 95% CI: 0.49-0.66; p&amp;lt; 0.01). SBRT was more likely utilized for elderly or high comorbidity patients and varied across cancer types. Survival analysis indicated that across all cancer types, single-fraction SRS, was independently associated with improved overall survival compared to cEBRT (HR 1.51; 95%CI: 1.31-1.74; p&amp;lt; 0.01) after adjusting for patient characteristics, care setting, tumor type and systemic treatment. CONCLUSIONS Through analysis of cancer registry data, we found that practice patterns of RT for spinal metastases have been evolving nationally, with an increase in the use of SBRT. Single-fraction SBRT was associated with improved adjusted OS. Notably, we found that utilization of SBRT lags in the community setting.

Linear accelerator-based single-fraction stereotactic body radiotherapy for symptomatic vertebral body hemangiomas: The Mayo Clinic experience

Symptomatic vertebral hemangiomas (SVHs) are rare benign tumors that when symptomatic require procedural intervention or radiotherapy (RT). Although conventionally-fractionated RT has been an alternative to surgical resection, there is very little data on stereotactic body radiotherapy (SBRT) for SVHs. Six consecutively treated patients with SVHs underwent definitive single-fraction SBRT from 2010 to 2018 at our institution. The RT planning parameters, treatment, outcome, and toxicities are reported for 6 patients with 6 total SVHs treated with single-fraction SBRT. Each patient presented with back pain and received single-fraction SBRT to a thoracic vertebral body hemangioma. One patient had received radiofrequency ablation prior to SBRT. The median SBRT dose was 18 Gy (range, 13–20). Following SBRT, 4 (67%) patients reported improvement in presenting symptoms and 2 patients (33%) were refractory. There were no acute or chronic toxicities associated with SBRT including esophagitis, vertebral compression fractures, or myelopathy. To date, this is the largest series of single-fraction SBRT for SVHs. Single fraction SBRT appears to be a feasible option for SVHs. Further studies are needed to confirm our preliminary findings and optimize dose fractionation.

Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases

Stereotactic body radiotherapy (SBRT) is an effective treatment of spinal metastases in the vertebral body. However, variation has existed between practitioners regarding the appropriate target delineation. As such, we compared the tumor control, rates of compression fractures, and pain control for patients who had undergone SBRT for spinal metastases to either the lesion only (LO) or the full vertebral body (FVB). A total of 126 spinal metastases in 84 patients had received single-fraction SBRT from January 2009 to February 2015. Of the 126 lesions, 36 (29%) were in the FVB group and 90 were in the LO group. The SBRT plans were reviewed to determine the treatment volume. Odds ratios were used to compare the rates of compression fracture and local failure. Regression analysis was performed to identify the predictors of outcome. A total of 5 failures had occurred in the FVB group and 14 in the LO group; however, the difference was not statistically significant (P= 0.5). No difference was found in pain reduction between the 2 groups (P= 0.9). Seven post-treatment compression fractures occurred in the LO group and four in the FVB group; however, the difference was not statistically significant (P= 0.6). The minimum dose to the planning target volume, patient age, and planning target volume size were the only significant factors predicting for local failure, vertebral body fracture, and pain control, respectively. Given that we found no difference in tumor control, pain reduction, or fracture rate between patients treated to the FVB versus the. LO, it might be reasonable to consider SBRT to the LO for select patients.

Efficacy and safety of different fractions in stereotactic body radiotherapy for spinal metastases: A systematic review.

BackgroundIn the treatment of spinal metastases, stereotactic body radiotherapy (SBRT) delivers precise, high‐dose radiation to the target region while sparing the spinal cord. A range of doses and fractions had been reported; however, the optimal prescribed scheme remains unclear.MethodsTwo reviewers performed independent literature searches of the PubMed, EMBASE, Cochrane Database, and Web of Science databases. Articles were divided into one to five fractions groups. The Methodological Index for Non‐randomized Studies (MINORS) was used to assess the quality of studies. Local control (LC) and overall survival (OS) were presented for the included studies and a pooled value was calculated by the weighted average.ResultsThe 38 included studies comprised 3,754 patients with 4,731 lesions. The average 1‐year LCs for the one to five fractions were 92.7%, 84.6%, 86.8%, 82.6%, and 80.6%, respectively. The average 1‐year OS for the one to five fractions were 53.0%, 70.4%, 60.1%, 48%, and 80%, respectively. The 24 Gy/single fraction scheme had a higher 1‐year LC (98.1%) than those of 24 Gy/two fractions (85.4%), 27 Gy/three fractions (84.9%), and 24 Gy/three fractions (89.0%). The incidence of vertebral compression fracture was 10.3%, with 10.7% in the single‐fraction group and 10.1% in the multi‐fraction group. The incidence of radiation‐induced myelopathy was 0.19%; three and two patients were treated with single‐fraction and multi‐fraction SBRT, respectively. The incidence of radiculopathy was 0.30% and all but one patient were treated with multi‐fraction SBRT.ConclusionsSBRT provided satisfactory efficacy and acceptable safety for spinal metastases. Single‐fraction SBRT demonstrated a higher local control rate than those of the other factions, especially the 24 Gy dose. The risk of vertebral compression fracture (VCF) was slightly higher in single‐fraction SBRT and more patients developed radiculopathy after multi‐fraction SBRT.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

BackgroundBone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic.MethodsThis is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24–48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode.DiscussionIf a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures.Trial registrationThe Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov (NCT03831243) on February 5th 2019.

Single Fraction Urethra-Sparing Prostate Cancer SBRT: Phase I Results of a Multicenter, Single Arm, Phase I/II Trial

To present the phase I results of a single fraction urethra-sparing stereotactic body radiotherapy (SBRT) schedule for localized prostate cancer (PCa) from the single arm, multicenter phase I/II ONE SHOT trial. From 08/2017 through 12/2018, 6 patients from two among the 5 participating institutions with low- and intermediate-risk localized PCa (cT1c-2cN0M0, Gleason ≤3+4, PSA ≤15 ng/ml, with ≤70 cc prostate volume and without significant tumor in the transitional zone) were recruited and treated with a 19 Gy single fraction to the prostate ± seminal vesicles (PTV= CTV + 5 mm isotropic expansion, except 3 mm posteriorly) using a VMAT technique and intrafractional motion control using intraprostatic electromagnetic transponders. The prostatic urethra, with a surrounding margin of 2 mm, received a lesser dose of 17 Gy. Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.03 grading scale), IPSS, IIEF-25 and QOL scores (EPIC) were assessed at baseline, at 5 days (D5), 6th (W6) and 12th weeks (W12) (acute toxicity) since SBRT. Primary endpoint of the phase I was safety as assessed by occurrence of Grade ≥3 acute side effects during the first 3 months in a "3 + 3” cohort-based. Median age and PSA at SBRT were 75 years old and 8.1 ng/ml. All patients underwent SBRT without interruption and doses constraints were respected for all plans. The toxicity stopping rule was never triggered, with no Grade ≥3 acute side effects observed during the first 3 months. Patients experienced mostly grade 1 or 2 GU toxicities (frequency/urgency) resolving from W6 (50% of grade 2 GU) with no grade 2 GI side effects and no rectal toxicity at W12 (33% of grade 1 GI). IPSS increased from baseline to D5 and W6 (mean, from 3.5 to 13.2 and 16.2, respectively) decreasing progressively at W12 (mean, 7.2). The EPIC urinary domain mean score was 92 pretreatment, 73 at D5, 79 at W6 and 87 at W12, while the EPIC bowel domain mean score remained overall stable over weeks (95, 91, 85, 90 at the four endpoints). No impact of SBRT was observed on IIEF-25 scores and the EPIC sexual domain between baseline and W12 (mean, from 10 to 9 and from 46 to 44, respectively). The PSA values showed a bounce at D5 (mean, from 7.9 to 18.3 ng/ml) decreasing successively up to a value of 3.3 ng/ml at W12. 19 Gy single-fraction SBRT irradiation of the whole prostate with urethra sparing to 17 Gy was feasible and well tolerated. This trial represents the first multicenter phase I/II trial assessing the efficacy and safety of a single-fraction SBRT monotherapy in the exclusive treatment of localized disease.