Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver ...metastases treated with SBRT from a multi-center, international patient registry.
Patients with liver metastases treated with SBRT were identified in the RSSearch® Patient Registry. Patient, tumor and treatment characteristics associated with treatment outcomes were assessed. Dose fractionations were normalized to BED
. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test.
The study included 427 patients with 568 liver metastases from 25 academic and community-based centers. Median age was 67 years (31-91 years). Colorectal adenocarcinoma (CRC) was the most common primary cancer. 73% of patients received prior chemotherapy. Median tumor volume was 40 cm
(1.6-877 cm
), median SBRT dose was 45 Gy (12-60 Gy) delivered in a median of 3 fractions 1-5. At a median follow-up of 14 months (1-91 months) the median overall survival (OS) was 22 months. Median OS was greater for patients with CRC (27 mo), breast (21 mo) and gynecological (25 mo) metastases compared to lung (10 mo), other gastro-intestinal (GI) (18 mo) and pancreatic (6 mo) primaries (p < 0.0001). Smaller tumor volumes (< 40 cm
) correlated with improved OS (25 months vs 15 months p = 0.0014). BED
≥ 100 Gy was also associated with improved OS (27 months vs 15 months p < 0.0001). Local control (LC) was evaluable in 430 liver metastases from 324 patients. Two-year LC rates was better for BED
≥ 100 Gy (77.2% vs 59.6%) and the median LC was better for tumors < 40 cm
(52 vs 39 months). There was no difference in LC based on histology of the primary tumor.
In a large, multi-institutional series of patients with liver metastasis treated with SBRT, reasonable LC and OS was observed. OS and LC depended on dose and tumor volume, while OS varied by primary tumor. Future prospective trials on the role of SBRT for liver metastasis from different primaries in the setting of multidisciplinary management including systemic therapy, is warranted.
Clinicaltrials.gov: NCT01885299 .
In this review a summary of the published literature pertaining to the stereotactic body radiation therapy multiplanning comparison, data sharing strategies, and implementation of benchmark planning ...cases to improve the skills and knowledge of the participating centers was investigated. A total of 30 full-text articles were included. The studies were subdivided in 3 categories: multiplanning studies on dosimetric variability, planning harmonization before clinical trials, and technical and methodologic studies. The methodology used in the studies were critically analyzed to find common and original elements with the pros and cons. Multicenter planning studies have played a key role in improving treatment plan harmonization, treatment plan compliance, and even clinical practices. This review has highlighted that some fundamental steps should be taken to transform a simple treatment planning comparison study into a potential credentialing method for stereotactic body radiation therapy accreditation. In particular, prescription and general requirements should always be well defined; data analysis should be performed with independent dose volume histogram or dose calculations; quality score indices should be constructed; feedback and correction strategies should be provided; and a simple web-based collaboration platform should be used. The results reported clearly showed that a crowd-based replanning approach is a viable method for achieving harmonization and standardization of treatment planning among centers using different technologies.
Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain metastases with high local control rates. However, data about local re-irradiation in case of local ...failure after SRS (re-SRS) are rare. We evaluated the feasibility, efficacy and patient selection characteristics in treating locally recurrent metastases with a second course of SRS.
We retrospectively evaluated patients with brain metastases treated with re-SRS for local tumor progression between 2011 and 2017. Patient and treatment characteristics as well as rates of tumor control, survival and toxicity were analyzed.
Overall, 32 locally recurrent brain metastases in 31 patients were irradiated with re-SRS. Median age at re-SRS was 64.9 years. The primary histology was breast cancer and non-small-cellular lung cancer (NSCLC) in respectively 10 cases (31.3%), in 5 cases malignant melanoma (15.6%). In the first SRS-course 19 metastases (59.4%) and in the re-SRS-course 29 metastases (90.6%) were treated with CyberKnife® and the others with Gamma Knife. Median planning target volume (PTV) for re-SRS was 2.5 cm3 (range, 0.1-37.5 cm3) and median dose prescribed to the PTV was 19 Gy (range, 12-28 Gy) in 1-5 fractions to the median 69% isodose (range, 53-80%). The 1-year overall survival rate was 61.7% and the 1-year local control rate was 79.5%. The overall rate of radiological radio-necrosis was 16.1% and four patients (12.9%) experienced grade ≥ 3 toxicities.
A second course of SRS for locally recurrent brain metastases after prior local SRS appears to be feasible with acceptable toxicity and can be considered as salvage treatment option for selected patients with high performance status. Furthermore, this is the first study utilizing robotic radiosurgery for this indication, as an additional option for frameless fractionated treatment.
Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in ...SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS).
A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS.
Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval CI 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively (P=.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers (P≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC.
Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center.
Highlights • SBRT for inoperable pulmonary metastases achieved excellent LC and promising OS. • LC was mainly influenced by BED at both isocenter and periphery. • Important prognostic factors were ...identified for selecting patients for SBRT treatment. • Important prognostic factors for OS were performance status, metastasis diameter and tumor histology. • OS was further significantly affected by number of metastases and time interval between primary tumor diagnosis and SBRT treatment.
Abstract Purpose A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with ...adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. Results For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation ( p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation ( p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.
Abstract Background and purpose To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and ...between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. Materials and methods A retrospective multi-institutional ( n = 22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. Results After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose–response relationship was observed in the primary NSCLC and metastatic cohort but dose–response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151–223) and 160 Gy (123–237) (n.s.), respectively. The dose–response relationship was not influenced by the primary cancer site within the metastatic cohort. Conclusions Dose–response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.
Although the metric precision of robotic stereotactic body radiation therapy in the presence of breathing motion is widely known, we investigated the dosimetric implications of breathing ...phase-related residual tracking errors.
In 24 patients (28 liver metastases) treated with the CyberKnife, we recorded the residual correlation, prediction, and rotational tracking errors from 90 fractions and binned them into 10 breathing phases. The average breathing phase errors were used to shift and rotate the clinical tumor volume (CTV) and planning target volume (PTV) for each phase to calculate a pseudo 4-dimensional error dose distribution for comparison with the original planned dose distribution.
The median systematic directional correlation, prediction, and absolute aggregate rotation errors were 0.3 mm (range, 0.1-1.3 mm), 0.01 mm (range, 0.00-0.05 mm), and 1.5° (range, 0.4°-2.7°), respectively. Dosimetrically, 44%, 81%, and 92% of all voxels differed by less than 1%, 3%, and 5% of the planned local dose, respectively. The median coverage reduction for the PTV was 1.1% (range in coverage difference, -7.8% to +0.8%), significantly depending on correlation (P=.026) and rotational (P=.005) error. With a 3-mm PTV margin, the median coverage change for the CTV was 0.0% (range, -1.0% to +5.4%), not significantly depending on any investigated parameter. In 42% of patients, the 3-mm margin did not fully compensate for the residual tracking errors, resulting in a CTV coverage reduction of 0.1% to 1.0%.
For liver tumors treated with robotic stereotactic body radiation therapy, a safety margin of 3 mm is not always sufficient to cover all residual tracking errors. Dosimetrically, this translates into only small CTV coverage reductions.
Electrical isolation of the pulmonary veins (PVs) has been established in clinical routine as a curative treatment for atrial fibrillation (AF). While catheter ablation carries procedural risks, ...radiosurgery might be able to non-invasively induce lesions at the PV ostia to block veno-atrial electrical conduction. This porcine feasibility and dose escalation study determined the effect of radiosurgery on electrophysiologic properties of the left atrial-PV junction.
Eight adult Goettingen mini-pigs underwent electrophysiological voltage mapping in the left atrium and the upper right PV. Radiation was delivered with a conventional linear accelerator. A single homogeneous dose ranging from 22.5 to 40 Gy was applied circumferentially to the target vein antrum. Six months after radiosurgery, electrophysiological mapping was repeated and a histological examination performed. Voltage mapping consistently showed electrical potentials in the upper right PV at baseline. Pacing the target vein prompted atrial excitation, thus proving veno-atrial electrical conduction. After 6 months, radiation had reduced PV electrogram amplitudes. This was dose dependent with a mean interaction effect of -5.8%/Gy. Complete block of atrio-venous electrical conduction occurred after 40 Gy dose application. Histology revealed transmural scarring of the targeted PV musculature with doses >30 Gy. After 40 Gy, it spanned the entire circumference in accordance with pulmonary vein isolation.
Pulmonary vein isolation to treat AF can be achieved by radiosurgery with a conventional linear accelerator. Yet, it requires a high radiation dose which might limit clinical applicability.
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