Response Assessment After Stereotactic Body Radiation Therapy for Spine and Non-spine Bone Metastases: Results From a Single Institutional Study

Response Assessment After Stereotactic Body Radiation Therapy for Spine and Non-spine Bone Metastases: Results From a Single Institutional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Response Assessment After Stereotactic Body Radiation Therapy for Spine and Non-spine Bone Metastases: Results From a Single Institutional Study Dora Correia, Barbara Moullet, Jennifer Cullmann, Rafael Heiss, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-995077/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Feb, 2022 Read the published version in Radiation Oncology → Version 1 posted 8 You are reading this latest preprint version Abstract Background The use of stereotactic body radiation therapy (SBRT) for tumor- and pain control in patients with bone metastases is increasing. Here, we report response assessment after bone SBRT using radiological changes through time and clinical examination of patients. Methods We analyzed retrospectively the oligo-metastatic/progressive patients with bony lesions treated with SBRT between 12/2008 and 10/2018 in our institution. Radiological data were obtained from imaging modalities used for SBRT planning and follow-up (FU) purposes in PACS and assessed by two independent radiologists blind to the time of treatment. Several radiological changes were described. Radiographic response assessment was classified according to University of Texas MD Anderson Cancer Center criteria. Pain response was captured pre- and >= 6 months post-SBRT. Results A total of 35 of the 74 reviewed patients were eligible, presenting 43 bone metastases, with 51.2% (n=22) located in vertebral column. Median age at the time of SBRT was 66 years (range, 38-84), and 77.1% (n=27) were male. Histology was mainly prostate (51.4%, n=18) and breast cancer (14.3%, n=5). Median total radiation dose delivered was 24 Gy (range: 24-42), in three fractions (range: 2-7), prescribed to 70 - 90% isodose-line. After a median FU of 1.8 years (range, 0.1-8.2) for survivors, complete-/ partial response, stable (SD), and progressive disease occurred in 0%, 11.4% (n=4), 68.6% (n=24) and 20.0% (n=7) of the patients respectively. Twenty patients (57.1%) died during the FU time, all from disease progression, yet 70% (n=14) from this population with local SD after SBRT. From patients who were symptomatic and available for FU, almost 50% reported pain reduction after SBRT. Conclusions Eighty percent of the patients showed local control (LC) after SBRT for bone metastases. Pain response was favorable. For more accurate response assessment, comparing current imaging modalities with advanced imaging techniques such as functional MRI and PET-CT is warranted. Trial registration Retrospectively registered. Oncology Spine metastases SBRT Response Assessment Pain Response Figures Figure 1 Figure 2 Figure 3 Background Many patients suffering from solid tumors develop metastatic cancer with single, limited or diffuse metastases. Besides lung and liver, bone is a common site of metastasis 1 . Caused in up to 70% by prostate and breast cancer, bone metastases are a major cause for morbidity 2 . Bone metastases are predominantly located in the vertebral column and it is estimated that over 10% of cancer patients develop symptoms at this site 3 , 4 . The role of radiotherapy to palliating pain for bone metastases is well established 5 . In the past, patients with painful bone metastases have a limited median overall survival (OS) of 7-9 months 6 , 7 , 8 . However, patients show increased OS in recent years due to improved treatment approaches, and therefore it is essential to provide a highly effective local therapy. SBRT is a promising modality to treat bone metastases with locally ablative intent 9 and has been used frequently in daily practice for more than a decade. Nevertheless, the results of prospective randomized trials comparing conventional radiotherapy to SBRT are very recent 10 , 11 , 12 . The pain response is the focus of these prospective randomized trials and none of them has reported the radiological response assessment yet. As the histological confirmation is challenging and costly in case of suspicious tumor progression after SBRT, an accurate radiological assessment is of utter importance and could avoid unnecessary interventions in asymptomatic patients. The SPIne response assessment in Neuro-Oncology (SPINO) group consensus uniforms the various criteria for radiological assessment of therapy response after spinal SBRT 13 . Nevertheless, few studies have evaluated the detailed radiological changes in bone metastases after SBRT 14 , 15 , 16 . For bone metastases, there are specific aspects to consider in interpretation of radiological changes after SBRT, including pseudo-progression, vertebral compression fracture (VCF), epidural progression, changes in bone density depending on the nature of metastasis and altered vascularization. In this retrospective study, we aim to evaluate radiological changes after SBRT to osseous metastases at the last follow-up, thus reporting its oncological outcome with LC and pain response. Methods Patient selection After approval of the study protocol by the institutional review board and ethic committee, patient informed consent was waived. We enrolled 74 adult patients (18 years-old or older) with a total of 103 spine or non-spine bone metastases, treated consecutively with SBRT between 12/2008 and 10/2018 in the radiation oncology department at Bern University Hospital, Switzerland. As shown in Figure 1, the exclusion criteria was the following: soft tissue component (n=1 metastasis), in-field re-irradiation (before or after SBRT, including overlapping of treatment fields) (n=28 metastases), different diagnostic imaging modality pre-/post-SBRT (n=8 metastases), patients with imaging less than six weeks after SBRT (n=17 metastases), and no diagnostic images from the treated site (n=5 metastases). All patients had a histologic diagnosis of malignancy with either synchronous or metachronous bone metastasis. Diagnosis of bone metastasis was established by magnetic resonance imaging (MRI), computer tomography (CT), or less frequently positron emission tomography/computed tomography (PET/CT) and bone scintigraphy. Bone lesions were divided into osteolytic, osteoblastic, or mixed-form. No bone-targeted agents (i.e., denosumab, bisphosphonate, hydroxyapatite derivatives, or radioactive isotope therapy) have been administered. SBRT Technique Similar to what was previously described by Hwang et al. 17 , the SBRT procedure consisted of: 1) image acquisition, 2) patient setup, and 3) SBRT planning and treatment. For planning, high-resolution thin-section MRI images were obtained (1.5 or 3 Tesla MRI). All MRI examinations included both turbo spin echo (TSE) T1-weighted (with and without contrast enhancement) and TSE T2-weighted sequences. For accurate and precise treatment positioning and immobilization, patients were placed in a vacuum bag (BodyFix®). The DICOM data of the MRI and CT were transferred to workstations for stereotactic planning, where the MRI was fused, at the area of interest, onto the CT images. The target volumes for spine metastases were delineated according to international spine radiosurgery guidelines 18 . For non-spine bone metastases, a gross tumor volume/clinical target volume (GTV-CTV) margin of 3-5mm and CTV-planning target volume of 3 mm were applied. Generally, patients with spinal metastases were treated at CyberKnife® using a spine-tracking system (SpineX®). For non-spine metastases, we have treated patients at NovalisTX using daily cone-beam CT. The median total radiation dose was 24 Gy (range 24 - 42 Gy) in median 3 fractions (range 2 - 7 fractions), prescribed to 80% isodose-line (range 70 - 90%). Follow-Up Imaging Evaluation As we analyze a retrospective cohort of patients, different imaging modalities have been used in order to assess the response to SBRT and evaluate the local control. Besides that, the intervals between SBRT and first FU-visit, as well as between following visits are inhomogeneous. For example, most of patients with metastatic prostate cancer were followed-up using prostate specific antigen (PSA) and the diagnostic imaging was done as the PSA raised from baseline after therapy. Despite all these inhomogeneity, we focused on MRI and CT-images and observed their changes through time. This assessment was done by two independent radiologists, blind to the time of treatment. Several radiological changes were described: alterations in mineralization of sclerotic/lytic bone metastases, vertebral compression fracture for spinal metastases, pathologic fracture for non-spine metastases, morphological size progression, and signal alterations on different MRI-sequences. Radiographic response assessment of metastases was classified according to University of Texas MD Anderson Cancer 19 as complete or partial response, and stable or progressive disease, based on the last follow-up imaging. As MRI is the most recommended imaging modality for response assessment after bone SBRT, following changes were particularly observed on different MRI sequences: tumor volume, T2 signal intensity (SI) alterations and contrast enhancement patterns. Considering pre- and post-treatment volumes, we categorized the tumors as decreased (group 1), unchanged (group 2), or increased (group 3). If the volumetric change was within 10% (ratio range 0.9 –1.1), the lesions were regarded as unchanged in volume. In case of absence of post-therapeutic MRI, we compared the volumes of the lesions in pre- and post-therapeutic CT. T2 SI changes of the tumors were categorized into four types: 1) no changes); 2) increase in T2 signal intensity; 3) increase in T2 signal intensity intermixed with dark signal intensity, and 4) totally dark signal intensity, based on the publication from Hwang et al. 17 . Enhancement patterns were divided into two groups: no change in contrast enhancement and decrease of contrast enhancement with or without non-enhancing foci. The SPINO-consensus recommends FU-MRI every 3-6 months after spine-SBRT; however, as mentioned before, our retrospective cohort is inhomogeneous regarding radiological FUs. Besides MRI, computed tomography (CT), positron emission tomography/computed tomography (PET/CT), bone scintigraphy, or single-photon emission computerized tomography (SPECT) were also performed for some patients. Pain response Pain response was assessed before and at least six months after SBRT, using the numerical rating scale (NRS). We also captured the intake of painkillers. Statistical analysis Statistical analysis was performed with SPSS, version 22. Descriptive statistics were presented as means (M) and standard deviations (SD) for quantitative variables and frequencies (n) and percentages (%) for categorical ones. Two-Way repeated measures ANOVA was conducted to evaluate the effect of SBRT on the quantitative parameters, along with the interaction of the effect of SBRT with the follow-up method. We also calculated the effect for the FU method but did not present these results due to lack of significant values. Effect sizes were assessed with eta squared (η2), considering Cohen’s (1988) suggestion: 0.01, 0.06 e 0.14 for weak, moderate and high effect 20 . Then, we computed the difference between the two moments of assessment - i.e. , the last imaging before SBRT took place and the last follow-up imaging after SBRT (ΔSBRT= (after - before SBRT)), and built linear regression models adjusting not only for follow-up method, but also for type of lesion. This was done to reduce to number of estimated parameters and allow the computation of the effects when adjusting for these two variables. We computed unstandardized effect sizes (β), standard errors (SE) and p-values. Residual’s normality was assessed and confirmed with Shapiro-Wilk test (p>0.05). No residuals were found above the threshold Ri> |3|. For assessing the categorical parameters before and after SBRT, we calculated frequencies (n), percentages (%) and Cohen’s kappa measure of agreement to assess the changes between these two moments. Significance was considered for p<0.05. We also considered marginally significant results for p<0.10. Results Population A total of 35 patients, 27 (77.1%) males and 8 (22.9%) females with 43 bone metastases were analysed in this cohort. Metastases were mainly from prostate cancer (n=18, 51.4%), followed by breast cancer (n=5, 14.3%). As shown in Table 1 , the bony lesions are classified as spine (n=22, 51.2%) and non-spine (n=21, 48.8%) metastases. The spinal metastases involve mainly the lumbar spine (n=11, 50%) and non-spinal metastases are mostly located in pelvic/hip bones (n=15, 71.4%). The median age at the time of SBRT was 66 years-old (range: 38 - 84). Table 1 Patient, treatment and follow-up characteristics. Characteristics Value (range) Median follow-up, years 1.8 (<1 - 8.2) Median age at SBRT, years-old 66 (38 - 84) Dose Prescription Median total dose delivered, Gy 24 (24 - 42) Median single dose, Gy 8 (5 - 12) Median number of fractions 3 (2 - 7) Median isodose prescription, % 80 (70 - 90) Imaging Follow-up after SBRT 3 months, range 1.3 - 4.3 6 months, range 5.1 - 9.8 12 months, range 9.3 - 19.3 Nr. of Patients (%) Sex Male 27 (77.1) Female 8 (22.9) Histology (primary tumor) Prostate 18 (51.4) Breast 5 (14.3) Melanoma 3 (8.6) Non-small cell lung cancer 3 (8.6) Other 6 (17.1) Bone Metastases Location Nr. of metastases (%) Non-spine 21 (48.8) Temporal bone 1 (4.8) Scapula 1 (4.8) Sternum 1 (4.8) Rib 2 (9.5) Pelvic/hip bones (6 ileum, 4 ischium, 4 pubis, 1 acetabulum) 15 (71.4) Femur 1 (4.8) Spine 22 (51.2) Cervical 0 (0.0.) Thoracic 9 (40.9) Lumbar 11 (50.0) Sacral 2 (9.1) Radiological response FU radiological assessment was performed with contrast-CT (n=17, 39.5%), MRI (n=26, 60.5%), and PET/CT (n=14, 32.6%), which took place mainly three, six, and 12 months after SBRT. After a median FU of almost 2 years (range: <1 - 8.2), complete-/ and partial response, stable-/ and progressive disease occurred in 0%, 11.4%, 68.6%, and 20% respectively. Twenty patients (57.1%) died, all from disease progression, yet 70% (n=14) with still local stable disease after SBRT. No statistically significant difference on the radiological assessment of two independent radiologists was found. Table 2 presents results for paired comparisons regarding quantitative variables, compared by the imaging method. We found no significant differences for any of the quantitative parameters considering pre or post SBRT. Considering interactions, we found a statistically significant difference between the width parameter and the imaging method (F=6.13 (p=0.004), η2=0.19: increased only in contrast-CT, stable in MRI, while decreased in PET/CT (Figure 2 ). A marginally significant association was seen for the SBRT effect on the depth and height (respectively, F=3.97, p=0.052, η2=0.07 and F=3.05 (p=0.056) η2=0.11). There was a trend (depth: F=3.12, p=0.053, η2=0.11; height: F=3.05 (p=0.056) η2=0.11) to increase after SBRT in the contrast-CT follow-up, whereas it decreased in the PET/CT (Figure 2 ). Despite the absence of significance on the volume (F=2.23, p=0.118), moderate effect size was found (η2=0.08) after SBRT, similarly with a slight increase in contrast-CT, stable results in MRI, and decrease in PET/CT. No significant or marginally significant results were found for the effect of SBRT or its interaction with the imaging method in CT density native (CT-DN). ANOVA test was not done for the CT density contrast enhanced (CT-CE) because results were equal before and after SBRT. For the parameters T2-weighted images signal intensity (T2-SI), T2-weighted images turbo inversion recovery magnitude signal intensity (T2-TSI), T1-weighted images native signal intensity (T1-NSI), and T1-weighted images contrast enhanced signal intensity (T1-CESI) no significant results were found for the effect of SBRT. Table 2 Repeated measures ANOVA for the quantitative parameters compared by the imaging method. CT contrast enhanced MRI PET/CT Total RM ANOVA effects M SD n M SD n M SD n M SD n SBRT Imaging Width Pre-SBRT 21.09 11.73 15 20.58 12.74 26 21.91 14.45 14 21.91 14.45 55 F=2.55 (p=0.116) η2=0.05 F=6.13 (p=0.004)* η2=0.19 Post-SBRT 29.33 15.27 15 21.40 14.31 26 18.84 8.13 14 18.84 8.13 55 Depth Pre-SBRT 20.46 10.26 15 24.03 13.81 26 22.67 14.65 14 22.71 13.02 55 F=3.97 (p=0.052) † η2=0.07 F=3.12 (p=0.053) † η2=0.11 Post-SBRT 25.68 10.99 15 24.76 15.72 26 22.25 11.03 14 24.37 13.30 55 Height Pre-SBRT 17.09 6.07 15 17.66 8.28 26 22.27 17.85 14 18.68 11.07 55 F=0.15 (p=0.701) η2=0.003 F=3.05 (p=0.056) † η2=0.11 Post-SBRT 20.94 5.05 15 18.55 7.85 26 18.83 7.64 14 19.27 7.09 55 Volume Pre-SBRT 9997.74 13068.83 16 12775.66 15571.32 26 29478.44 74682.81 14 16157.66 39201.12 56 F=0.42 (p=0.502) η2=0.01 F=2.23 (p=0.118) η2=0.08 Post-SBRT 17678.62 19147.79 16 14338.71 17120.47 26 10532.05 9453.02 14 14341.30 16164.13 56 CT-DN Pre-SBRT 248.57 307.38 7 - - - 300.64 259.62 14 283.29 269.80 21 F=2.05 (p=0.168) η2=0.10 F=0.08 (p=0.778) η2=0.01 Post-SBRT 300.14 324.13 7 - - - 377.93 337.06 14 352.00 326.76 21 CT-CE Pre-SBRT 263.71 323.85 7 - Post-SBRT 263.71 323.85 7 T2-SI Pre-SBRT - - - 224.71 175.53 19 - - - - - - F=0.01 (p=0.947) η2=0.00 Post-SBRT - - - 222.74 206.11 19 - - - - - - T2-TSI Pre-SBRT - - - 214.82 194.65 8 - - - - - - F=0.06 (p=0.816) η2=0.01 Post-SBRT - - - 225.63 163.17 8 - - - - - - T1-NSI Pre-SBRT - - - 213.76 141.40 21 - - - - - - F=0.01 (p=0.945) η2=0.00 Post-SBRT - - - 215.69 171.15 21 - - - - - - T1-CESI Pre-SBRT 417.03 284.76 20 - - - - - - F=0.01 (p=0.945) η2=0.00 Post-SBRT 357.85 267.84 20 - - - - - - Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/ computed tomography; RM, repeated measures; M, mean; SD, standard deviation; SBRT, stereotactic body radiotherapy; CT-DN, computed tomography density native in Hounsfield units; CT-CE, computed tomography density contrast enhanced in Hounsfield units; T2-SI, T2-weighted images signal intensity; T2-TSI, T2-weighted images turbo inversion recovery magnitude signal intensity; T1-NSI, T1-weighted images native signal intensity; T1-CESI, T1-weighted images contrast enhanced signal intensity. *statistically significant; †p<0.10 η2=0.01 weak, η2=0.06 moderate, η2=0.14 high effect, according to Cohen, J (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Erlbaum. Table 3 shows the results of linear regressions for the difference before and after SBRT (ΔSBRT) adjusted for type of imaging method and type of lesion, not only showing that spinal metastases were associated with increased width (β = 4.89; p=0.031), but also confirming that contrast-CT is associated with increased width (β = 11.82; p<0.001), depth (β = 5.73; p=0.017), height (β = 7.27; p=0.012), and volume (β = 28347.15; p=0.026) compared with PET/CT. Table 3 Linear regressions for the difference before and after SBRT adjusted for the type of imaging method and spinal lesion. ΔSBRT=(After – Before SBRT) Δ Width Δ Depth Δ Height Δ Volume Δ CT-DN Δ T2-SI Δ T2-TSI Δ T1-NSI Δ T1-CESI Imaging CT 11.82 (3.11) p<0.001* 5.73 (2.39) p=0.017* 7.27 (2.90) p=0.012* 28347.15 (12743.88) p=0.026* -25.71 (85.02) p=0.762 - - - - MRI 3.87 (2.76) (p=0.162) 1.14 (2.13) p=0.592 4.34 (2.58) p=0.092 † 20438.88 (11487.83) p=0.075 † - - - - - PET/CT Ref Ref Ref Ref Ref - - - - Spine Yes 4.89 (2.27) p=0.031* 0.93 (1.74) p=0.593 -0.20 (2.11) p=0.926 12841.73 (9358.37) (p=0.170) -40.56 (80.99) p=0.617 19.16 (60.67) (p=0.752) -124.38 (71.00) p=0.080 † 88.54 (51.23) p=0.084 † 112.05 (66.88) p=0.094 † No Ref Ref Ref Ref Ref Ref Ref Ref Ref Abbreviations: SBRT, stereotactic body radiotherapy; CT-DN, computed tomography density native in Hounsfield units; T2-SI, T2-weighted images signal intensity; T2-TSI, T2-weighted images turbo inversion recovery magnitude signal intensity; T1-NSI, T1-weighted images native signal intensity; T1-CESI, T1-weighted images contrast enhanced signal intensity; CT, computed tomography; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/ computed tomography; Ref, reference. *statistically significant; †p<0.10; results presented as unstandardized effect sizes β, standard errors (SE), and p-values. When we assessed the spinal metastases without adjusting for the imaging method (only data for MRI was achievable), marginally significant results were found for their association with the parameters T2-TSI (β=-124.38; p=0.080), T1-NSI (β = 88.54; p=0.084), and T1-CESI (β = 4.89; p=0.031) after SBRT: lower in T2-TSI, while higher in T1-NSI and T1-CESI. On Table 4 , we present the assessment for the categorical variables’ association with pre versus post SBRT, with Cohen’s kappa measure of agreement to assess the changes between these two moments (k). CT appearance (k=0.84), soft component (k=0.72) and T2 turbo inversion recovery magnitude (TIRM) appearance (k=0.67) had moderate to high agreement between the two assessments. For CT appearance, proportion of agreement was 100% for osteolytic, 93.3% for osteoblastic and 71.4% for mixed-type lesions. For soft tissue component, 75% agreement for presence and 94.7% for non-presence were applicable. For SI on T2-TIRM sequence, agreement was 100% for homogenous hyper-intensity, 50% for dark spots, 50% for homogenous hypo-intensity, and 100% for intermediary. The other parameters showed low or very low agreement, with k varying from k=0.14 to k=0.40. Table 4 Agreement of radiological categorical variables before and after SBRT. Before SBRT After SBRT k CT appearance Osteolytic Osteoblastic Mixed Osteolytic 8 (100%) 0 (0.0%) 1 (14.3%) 0.84 Osteoblastic 0 (0.0%) 14 (93.3%) 1 (14.3%) Mixed 0 (0.0%) 1 (6.7%) 5 (71.4%) T2 appearance Homogenous bright Dark spots Totally dark signal intensity Intermediary Homogenous bright 0 (0.0%) 0 (0.0%) 1 (12.5%) 1 (25.0%) - Dark spots 0 (0.0%) 4 (57.1%) 0 (0.0%) 0 (0.0%) Totally dark signal intensity 0 (0.0%) 3 (42.9%) 7 (87.5%) 1 (25.0%) Intermediary 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (50.0%) T2 TIRM appearance Homogenous bright Dark spots Totally dark signal intensity Intermediary Homogenous bright 2 (100.0%) 1 (50.0%) 0 (0.0%) 0 (0.0%) 0.67 Dark spots 0 (0.0%) 1 (50.0%) 0 (0.0%) 0 (0.0%) Totally dark signal intensity 0 (0.0%) 0 (0.0%) 1 (50.0%) 0 (0.0%) Intermediary 0 (0.0%) 0 (0.0%) 1 (50.0%) 2 (100.0%) T1 signal native appearance Homogenous bright Dark spots Totally dark signal intensity Intermediary Homogenous bright 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0.30 Dark spots 0 (0.0%) 1 (33.3%) 1 (7.1%) 0 (0.0%) Totally dark signal intensity 0 (0.0%) 2 (66.7%) 11 (78.6%) 2 (50.0%) Intermediary 0 (0.0%) 0 (0.0%) 2 (14.3%) 2 (50.0%) T1 CE signal appearance No enhancement Slight enhancement Bright enhancement No enhancement 0 (0%) 0 (0%) 0 (0%) 0.14 Slight enhancement 3 (75.0%) 9 (81.8%) 3 (60.0%) Bright enhancement 1 (25.0%) 2 (18.2%) 2 (40.0%) Contrast enhancement Yes No Yes 17 (100.0%) 6 (66.7%) 0.40 No 0 (0.0%) 3 (33.3%) Soft component Yes No Yes 9 (75.0%) 2 (5.3%) 0.72 No 3 (25.0%) 36 (94.7%) Abbreviations: SBRT, stereotactic body radiotherapy; CT, computed tomography; T2 TIRM, T2-weighted. Pain response Considering the pain response, we observed that 22 (62.9%) patients remained asymptomatic on the treated metastases; four (11.4%) patients reported decreased pain (complete and partial); three (8.6%) had stable pain (two without regular analgesia and one stable after SBRT but requiring analgesia after surgery); two (5.7%) complained of increased pain, even though one of them without requiring analgesia; four (11.4%) had no available pain response follow-up, whereas one of them deceased before it was captured. Discussion Results of the current retrospective study present SBRT as an effective treatment for bone metastases. SBRT has been increasingly accepted as a valuable option for selective patients with metastatic disease. Using the appropriate imaging modality for treatment planning, SBRT offers an excellent local control with acceptable toxicity profile 21 . However, response assessment after SBRT is a challenging topic, which is not only limited to the bone, as we confront difficulties to interpret the changes in imaging modalities after stereotactic radiotherapy in other organs, like brain, liver and lung 22 – 24 . Appropriate evaluating of diagnostic images is a critical point in the process of the disease and can prevent the risks of unnecessary interventions. Besides that, pain response should be considered after RT for bone metastases, as pain relief is the most important goal in such patients. In this retrospective study, we report our institutional results regarding imaging-based local control and pain response after SBRT for bone metastases. The SPINO-group published a report in 2015, focusing on response assessment after SBRT for spinal metastases 13 . The consensus is based on an international survey and not yet evaluated in clinical trials. We considered the recommendations from SPINO group for image-based tumor- and pain response, although we analyzed both spine and non-spine bone metastases in our study. The MRI is the preferred modality for response assessment after SBRT; however, we should be aware of some unique aspects such as pseudo-progression (PP) and vertebral compression fracture (VCF) when interpreting the post-SBRT images. PP is a well-known phenomenon after SBRT in different organs. It was first reported for spine metastasis in a case report from 2015 and the authors described PP as subacute, post-radiotherapy reaction that mimics progressive disease (PD) with increased contrast enhancement and ultimate stabilization and regression 25 . Time is an important factor evaluating post-SBRT radiological changes, as PP present few weeks up to 6 months after radiation, in contrast to radio-necrosis (RN) which is a late effect and can occur even years after therapy 25 . Amini et al. did an analysis of osseous pseudo-progression in vertebral body following SBRT in patients from two prospective phase I/II clinical trials 26 . They defined the osseous pseudo-progression as “transient growth in signal abnormality centered at the lesion with a sustained decline on FU MRI that was not attributable to chemotherapy”. They reported the rates of PP and PD of 14% and 24% respectively. Furthermore, there was a significant association between single-fraction SBRT and development of PP 26 . The so far published randomized trials comparing SBRT versus conventional RT have not reported the rates of PP 12 , 27 , 28 . SPINO group defined any new or progressive tumor within the epidural space as local progression 13 , but we have recently published a case report showing clear epidural involvement on radiological images after spine SBRT, however, the histological analysis revealed no tumor cells in epidural space 29 . Therefore, it is critical to distinguish between PP, PD and RN to avoid false patient management. In our study, we observed PP as a common finding after SBRT, however not all patients had MRI shortly after the therapy and therefore it was not possible to report the exact rate of PP. VCF is a well-known and most common complication after spine SBRT. The rate of VCF after single fraction SBRT (SF-SBRT) with 18-24Gy was reported around 39%, and lytic lesions and location below T10 confer a high risk of fracture 30 . The median time to fracture was 25 months and VCF was seen earlier in patients with lytic lesions compared to sclerotic lesions 30 . Sahgal et al. reported 14% of new or progressing VCF after spine SBRT, using different fractionation and considering SINS-score to determine its predictive value 31 . They defined the high dose per fraction, lytic lesion and baseline fracture as significant predictors of VCF 31 . A review from 2017 reported a crude VCF rate of 13.9% 32 . Jawad et al. demonstrated low rates of VCF for 5.7% in their multi-institutional study, using 1-5 fractions for spine SBRT 33 . We report here the rates of new/progressive fractures for spine and non-spine metastases as 4.5% and 4.7% respectively. As half of our cohort had metastatic prostate cancer, one reason for our low rates of fractures could be the sclerotic nature of the metastases. Another reason might be related to our moderate SBRT schema with median total dose of 24Gy in three fractions. As mentioned above, MRI is the most recommended imaging modality for radiological assessment of bone metastasis after SBRT. Hwang et al. reported the MRI changes after SBRT for osteoblastic spinal lesions, as these metastases usually show no obvious radiological volumetric alterations 17 . They classified signal intensity (SI) alterations on T2-MRI sequences as following: 1) no changes in SI; 2) increased SI; 3) increased SI intermixed with dark SI; 4) changed to complete dark SI. Most of our patients had prostate cancer as primary diagnosis; therefore, we assessed the T2 weighted MRI sequences for radiological response evaluation after SBRT for both spine and non-spine bone metastases as described above. According to recommendations from SPINO group, the routine use of contrast-enhanced T1-MRI sequences to visualize spinal metastases is controversial as both normal bone marrow and tumor are enhanced 13 . The interpretation becomes even more difficult after SBRT and therefore we considered the T1-MRI with gadolinium only for delineating the epidural and para-spinal tumor components. Although the patient population was heterogeneous in our cohort, SBRT achieved 80% of LC at almost 2 years. More than 40% of our patients survived and among the population who died in FU time, 40% had still SD at the irradiated sites. These results are in line with data from other studies, showing an excellent rate of LC after SBRT for osseous metastases 21 . Considering pain response, the randomized phase 2 trial from Germany reported significant improved pain values in SBRT group 6 months after the therapy in patients with spinal metastases 12 . However, as they chose the SF-SBRT with 24Gy, the rates of new pathological fracture were high in that study, with 8.7% and 27.8% at 3 and 6 months respectively 12 . Another randomized phase 2 trial from Netherlands compared SBRT versus conventional RT for bone metastases using different fractionations 28 . SBRT group did not show significant pain improve, but because of selective dropout, this trial was underpowered to detect the difference in pain response 28 . The NRG Oncology/RTOG 0631 trial initial results were presented at ASTRO annual meeting in 2019 34 . Randomizing patients with spinal metastases into SBRT and conventional RT groups, this study showed negative results for SBRT arm, as pain control was similar at 3 months between two groups. Finally, the Canadian randomized phase 3 trial compared spine SBRT with 24Gy in two daily fractions with conventional RT at a dose of 20Gy in five fractions 27 . The SBRT was superior to conventional RT and improved the complete pain response at 3 months. Interestingly, the incidence of VCF was equal between two groups, showing the safety of SBRT regimen 27 . In our retrospective study, the majority of patients (62.9%) had no pain prior to SBRT and the indication was mostly local ablation in oligo-metastatic/progressive disease. This group of patients remained asymptomatic after SBRT. In symptomatic group, only two patients experienced pain exacerbation following SBRT with only one of them required analgesic medication. Conclusion In conclusion, our results from a single institutional study show high rates of tumor- and pain control after SBRT for spine and non-spine metastases. We assessed the LC by analyzing the imaging modalities and hope that these results provide a better understanding of radiological changes, mainly on MRI after SBRT. The next step could be the comparison between different imaging modalities for response assessment, especially for solid tumors with specific tumor biomarkers as PSMA for prostate cancer. List Of Abbreviations SBRT Stereotactic Body Radiation Therapy FU Follow-Up SD Stable Disease PD Progressive Disease LC Local Control OS Overall Survival VCF Vertebral Compression Fracture MRI Magnetic Resonance Imaging CT Computed Tomography PET Positron Emission Tomography TSE Turbo Spin Echo PSA Prostate Specific Antigen SI Signal Intensity SPECT Single Photon Emission Computer Tomography NRS Numerical Rating Scale SE Standard Error DN Density Native CE Contrast Enhanced TIRM Turbo Inversion Recovery Magnitude PP Pseudo-Progression RN Radiation Necrosis Declarations Ethics approval: Study protocol was approved by the institutional review board and ethic committee (Berner Kantonale Ethikkommission für die Forschung – Project-ID 2018-01831) Consent for publication: No individual person`data Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Disclosures: None Funding: None Competing interests: None Authors` contributions: J. Cullmann and R. Heiss analyzed the whole imaging modalities as two independent radiologists. D. Correia, B. Moullet and H. Hemmatazad wrote the manuscript. D. Correia made also the tables and figures. D. M. Aebersold and Ekin Ermis did critical review of the manuscript. The project was supervised by H. Hemmatazad. ACKNOWLEDGMENTS: We thank Edgar Mesquita (statistical consultant, Portuguese Institute of Oncology of Porto Francisco Gentil, Portugal) for statistical analysis supervision. References Coleman RE. Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treat Rev . 2001;27(3):165-176. doi:10.1053/CTRV.2000.0210 Cecchini MG, Wetterwald A, van der Pluijm G, Thalmann GN. Molecular and biological mechanisms of bone metastasis. EAU Updat Ser . 2005;3(4):214-226. doi:10.1016/j.euus.2005.09.006 Maccauro G, Spinelli MS, Mauro S, Perisano C, Graci C, Rosa MA. Physiopathology of Spine Metastasis. Int J Surg Oncol . 2011;2011:1-8. doi:10.1155/2011/107969 Galgano M, Fridley J, Oyelese A, et al. Surgical management of spinal metastases. Expert Rev Anticancer Ther . Published online 2018. doi:10.1080/14737140.2018.1453359 Lutz S, Berk L, Chang E, et al. Palliative radiotherapy for bone metastases: An ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys . Published online 2011. doi:10.1016/j.ijrobp.2010.11.026 Steenland E, Leer J, Van Houwelingen H, et al. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol . 1999;52(2):101-109. doi:10.1016/S0167-8140(99)00110-3 Yarnold JR. 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-upOn behalf of the Bone Pain Trial Working Party. Radiother Oncol . 1999;52(2):111-121. doi:10.1016/S0167-8140(99)00097-3 Ratanatharathorn V, Powers WE, Moss WT, Perez CA. Bone metastasis: review and critical analysis of random allocation trials of local field treatment. Int J Radiat Oncol . 1999;44(1):1-18. doi:10.1016/S0360-3016(98)00510-0 Vellayappan BA, Chao ST, Foote M, et al. The evolution and rise of stereotactic body radiotherapy (SBRT) for spinal metastases. Expert Rev Anticancer Ther . Published online 2018. doi:10.1080/14737140.2018.1493381 Ryu S, Deshmukh S, Timmerman RD, et al. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631. Int J Radiat Oncol . 2019;105(1):S2-S3. doi:10.1016/j.ijrobp.2019.06.382 Sahgal A, Myrehaug SD, Siva S, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol . 2021;22(7):1023-1033. doi:10.1016/S1470-2045(21)00196-0 Sprave T, Verma V, Förster R, et al. Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy. Radiother Oncol . 2018;128(2):274-282. doi:10.1016/j.radonc.2018.04.030 Thibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: A report from the SPIne response assessment in Neuro-Oncology (SPINO) group. Lancet Oncol . 2015;16(16):e595-e603. doi:10.1016/S1470-2045(15)00166-7 Soliman M, Taunk NK, Simons RE, et al. Anatomic and functional imaging in the diagnosis of spine metastases and response assessment after spine radiosurgery. Neurosurg Focus . 2017;42(1):E5. doi:10.3171/2016.9.FOCUS16350 Wong E, Howard P, Chan AKM, Atenafu EG, Lu H, Tyrrell P. The Initial Step Towards Establishing a Quantitative , Magnetic Resonance Imaging-Based Framework for. 2021;0(0):1-8. doi:10.1093/neuros/nyab310 O’Sullivan S, McDermott R, Keys M, O’Sullivan M, Armstrong J, Faul C. Imaging response assessment following stereotactic body radiotherapy for solid tumour metastases of the spine: Current challenges and future directions. J Med Imaging Radiat Oncol . 2020;64(3):385-397. doi:10.1111/1754-9485.13032 Hwang YJ, Sohn MJ, Lee BH, et al. Radiosurgery for metastatic spinal tumors: Follow-up MR findings. Am J Neuroradiol . 2012;33(2):382-387. doi:10.3174/ajnr.A2760 Cox BW, Spratt DE, Lovelock M, et al. International spine radiosurgery consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys . 2012;83(5):e597-e605. doi:10.1016/j.ijrobp.2012.03.009 Costelloe CM, Chuang HH, Madewell JE, Ueno NT. J o u r n a l o f C a n c e r Cancer Response Criteria and Bone Metastases : RECIST 1 . 1 , MDA and PERCIST. Published online 2010:80-92. Cohen J. Statistical power analysis for the behavioral sciences. Published online 2013. Cao Y, Chen H, Sahgal A, et al. An international pooled analysis of SBRT outcomes to oligometastatic spine and non-spine bone metastases. Radiother Oncol . Published online 2021. doi:10.1016/j.radonc.2021.08.011 Huang Y, Chen JL, Hsu F, et al. Response Assessment of Stereotactic Body Radiation Therapy Using Dynamic Contrast-Enhanced Integrated MR-PET in Non-Small Cell Lung Cancer Patients. Published online 2017:191-199. doi:10.1002/jmri.25758 Yip C, Cook GJR, Owczarczyk K, Goh V. Challenges in imaging assessment following liver stereotactic body radiotherapy : pitfalls to avoid in clinical practice. 2017;6(Suppl 2):1-9. doi:10.21037/cco.2017.06.06 Sawlani V, Davies N, Patel M, et al. Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature. Clin Oncol . 2019;31(1):41-49. doi:10.1016/j.clon.2018.09.003 Taylor DR, Weaver JA. Tumor pseudoprogression of spinal metastasis after radiosurgery: a novel concept and case reports. 2015;22(May):534-539. doi:10.3171/2014.10.SPINE14444.Disclosure Amini B, Beaman CB, Madewell JE, et al. Osseous pseudoprogression in vertebral bodies treated with stereotactic radiosurgery: A secondary analysis of prospective phase I/II clinical trials. Am J Neuroradiol . 2016;37(2):387-392. doi:10.3174/ajnr.A4528 Sahgal A, Myrehaug SD, Siva S, et al. Articles Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases : an open-label , multicentre , randomised , controlled , phase 2 / 3 trial. Lancet Oncol . 2021;2045(21):1-11. doi:10.1016/S1470-2045(21)00196-0 Pielkenrood BJ, Velden JM Van Der, Linden YM Van Der, et al. Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases d A Phase 2 Randomized Controlled Trial Within a Prospective Cohort. Radiat Oncol Biol . 2021;110(2):358-367. doi:10.1016/j.ijrobp.2020.11.060 Stutz E, Wartenberg M, Hemmatazad H, Hemmatazad H, Hemmatazad H. RAS ONCOLOGY & THERAPY Case Report : Epidural tumor pseudoprogression after spine SBRT : A case report and a mini review of the literature. Published online 2021:1-5. Rose PS, Laufer I, Boland PJ, et al. J OURNAL OF C LINICAL O NCOLOGY Risk of Fracture After Single Fraction Image-Guided Intensity-Modulated Radiation Therapy to Spinal Metastases. 2009;27(30):6-10. doi:10.1200/JCO.2008.19.3508 Sahgal A, Atenafu EG, Chao S, et al. J OURNAL OF C LINICAL O NCOLOGY Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy : A Multi-Institutional Analysis With a Focus on Radiation Dose and the Spinal Instability Neoplastic Score. 2017;31(27):0-5. doi:10.1200/JCO.2013.50.1411 Faruqi S, Whyne C, Alghamdi M, Maralani P. Stereotactic Body Radiation Therapy : A Review of the Pathophysiology and Risk Factors. 2017;0(0):1-9. doi:10.1093/neuros/nyx493 Jawad MS, Fahim DK, Gerszten PC, et al. multinational evaluation. 2016;24(June):928-936. doi:10.3171/2015.10.SPINE141261.928 Ryu S, Deshmukh S, Timmerman RD, et al. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631. Radiat Oncol Biol . 2013;105(1):S2-S3. doi:10.1016/j.ijrobp.2019.06.382 Cite Share Download PDF Status: Published Journal Publication published 21 Feb, 2022 Read the published version in Radiation Oncology → Version 1 posted Editorial decision: Major revision 29 Dec, 2021 Reviews received at journal 05 Nov, 2021 Reviewers invited by journal 05 Nov, 2021 Reviewer # 1 agreed at journal 04 Nov, 2021 Editor assigned by journal 20 Oct, 2021 Submission checks completed at journal 19 Oct, 2021 Editor invited by journal 19 Oct, 2021 First submitted to journal 19 Oct, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-995077","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":58460959,"identity":"a3805d3c-5aa7-4561-874e-10bcaa5aa261","order_by":0,"name":"Dora Correia","email":"","orcid":"","institution":"Department for Radiation Oncology, Bern University Hospital and University of Bern, Switzerland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dora","middleName":"","lastName":"Correia","suffix":""},{"id":58460960,"identity":"c4fd8575-aa16-459c-a40c-d6353ed2d7a3","order_by":1,"name":"Barbara Moullet","email":"","orcid":"","institution":"Department of Radiation Oncology, Bern University Hospital and University of Bern, Switzerland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Barbara","middleName":"","lastName":"Moullet","suffix":""},{"id":58460961,"identity":"d5f75429-7520-4378-a1db-0a1330f3fcbc","order_by":2,"name":"Jennifer Cullmann","email":"","orcid":"","institution":"Department of Radiology, Bern University Hospital and University of Bern, Switzerland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"","lastName":"Cullmann","suffix":""},{"id":58460962,"identity":"48406320-a7ac-47a1-a7f8-2d6d5ff7aa8c","order_by":3,"name":"Rafael Heiss","email":"","orcid":"","institution":"Department of Radiology, Bern University Hospital and University of Bern, Switzerland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"","lastName":"Heiss","suffix":""},{"id":58460963,"identity":"bb79e232-fa00-4763-8906-0c34275c9be2","order_by":4,"name":"Ekin Ermiş","email":"","orcid":"","institution":"Department for Radiation Oncology, Bern University Hospital and University of Bern, Switzerland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ekin","middleName":"","lastName":"Ermiş","suffix":""},{"id":58460964,"identity":"2e1795ad-3ccc-493a-a9f3-a1f86667ca0d","order_by":5,"name":"Daniel Matthias Aebersold","email":"","orcid":"","institution":"Department of Radiation Oncology, Bern University Hospital and University of Bern, Switzerland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"Matthias","lastName":"Aebersold","suffix":""},{"id":58460965,"identity":"98a980f7-4f59-4731-8363-eac697448855","order_by":6,"name":"Hossein Hemmatazad","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIie2RMUvDQBTHHwSS5YWuEUv8Cs/FIpT2qxwE45JIdwed2qH5APotMmUOvCHLdU+poBDoZKHSpcKBXgpFhGtwdLjf8Phz3I/33h2AxfIPoWOln7OoLHXtA+BfFNGWWLQKdivwS0kO+aQy8GbNdjt50WF+k3/uR+PeLPngiRoieIvSpFxn8ursidY6LIplJiInkJucn6cxAt4J42B14jpIrENa1CgcF+o0Z/+REQIks3Lb7FSrvG6KpRIPeFEnb4zqq0MRdA6HLn6xQsGB7guMbnlakXqXjBhJpsWqH1d0KdfE/jRCFxOzUukX2ysOqdLrvw/vx2EVNTtUo7DnSaNyxPAFbtd9i8VisXTyDYdyZXMN8BI3AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-4426-6188","institution":"Inselspital Universitatsspital Bern","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hossein","middleName":"","lastName":"Hemmatazad","suffix":""}],"badges":[],"createdAt":"2021-10-19 12:29:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-995077/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-995077/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13014-022-02004-7","type":"published","date":"2022-02-21T18:56:25+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":14867926,"identity":"8d9d9905-99ff-462a-80bf-b1da9b58296c","added_by":"auto","created_at":"2021-10-25 14:47:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":71288,"visible":true,"origin":"","legend":"Study cohort flow diagram. Abbreviations: Mets, bone metastases; VMAT, volumetric modulated arc therapy. ","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-995077/v1/b0d2693eb324de1c15c0a1ac.jpg"},{"id":14867928,"identity":"1c85596a-8e1d-4b87-8804-0fe5a722d3f1","added_by":"auto","created_at":"2021-10-25 14:47:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":97003,"visible":true,"origin":"","legend":"Quantitative parameters evolution and interaction with the imaging method. Abbreviations: SBRT, radiotherapy; CT w/ contrast, computed tomography contrast enhanced; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/ computed tomography; CT-DN, computed tomography density native in Hounsfield units.","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-995077/v1/cb34238e775bdd94220e41ea.jpg"},{"id":14867927,"identity":"a817656c-baad-4a24-abbf-b4dff933a446","added_by":"auto","created_at":"2021-10-25 14:47:43","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":107970,"visible":true,"origin":"","legend":"Example of radiological changes of a spine metastasis treated with SBRT (stable disease (C), yet initially classified as “pseudoprogression” (B)), and associated SBRT-plan (A1). ","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-995077/v1/1efbd1e8e0153ce9843c15ba.jpg"},{"id":18452961,"identity":"a8747c12-571b-42c8-84d8-40fd70020d45","added_by":"auto","created_at":"2022-02-21 18:56:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":599261,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-995077/v1/63cbe188-f172-4c1f-ad93-f9e85fd93ed2.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eResponse Assessment After Stereotactic Body Radiation Therapy for Spine and Non-spine Bone Metastases: Results From a Single Institutional Study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eMany patients suffering from solid tumors develop metastatic cancer with single, limited or diffuse metastases. Besides lung and liver, bone is a common site of metastasis\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Caused in up to 70% by prostate and breast cancer, bone metastases are a major cause for morbidity\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Bone metastases are predominantly located in the vertebral column and it is estimated that over 10% of cancer patients develop symptoms at this site\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe role of radiotherapy to palliating pain for bone metastases is well established\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. In the past, patients with painful bone metastases have a limited median overall survival (OS) of 7-9 months\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. However, patients show increased OS in recent years due to improved treatment approaches, and therefore it is essential to provide a highly effective local therapy. SBRT is a promising modality to treat bone metastases with locally ablative intent\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e and has been used frequently in daily practice for more than a decade. Nevertheless, the results of prospective randomized trials comparing conventional radiotherapy to SBRT are very recent\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. The pain response is the focus of these prospective randomized trials and none of them has reported the radiological response assessment yet. As the histological confirmation is challenging and costly in case of suspicious tumor progression after SBRT, an accurate radiological assessment is of utter importance and could avoid unnecessary interventions in asymptomatic patients. The SPIne response assessment in Neuro-Oncology (SPINO) group consensus uniforms the various criteria for radiological assessment of therapy response after spinal SBRT\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Nevertheless, few studies have evaluated the detailed radiological changes in bone metastases after SBRT\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. For bone metastases, there are specific aspects to consider in interpretation of radiological changes after SBRT, including pseudo-progression, vertebral compression fracture (VCF), epidural progression, changes in bone density depending on the nature of metastasis and altered vascularization.\u003c/p\u003e \u003cp\u003eIn this retrospective study, we aim to evaluate radiological changes after SBRT to osseous metastases at the last follow-up, thus reporting its oncological outcome with LC and pain response.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003e After approval of the study protocol by the institutional review board and ethic committee, patient informed consent was waived. We enrolled 74 adult patients (18 years-old or older) with a total of 103 spine or non-spine bone metastases, treated consecutively with SBRT between 12/2008 and 10/2018 in the radiation oncology department at Bern University Hospital, Switzerland. As shown in Figure 1, the exclusion criteria was the following: soft tissue component (n=1 metastasis), in-field re-irradiation (before or after SBRT, including overlapping of treatment fields) (n=28 metastases), different diagnostic imaging modality pre-/post-SBRT (n=8 metastases), patients with imaging less than six weeks after SBRT (n=17 metastases), and no diagnostic images from the treated site (n=5 metastases).\u003c/p\u003e \u003cp\u003eAll patients had a histologic diagnosis of malignancy with either synchronous or metachronous bone metastasis. Diagnosis of bone metastasis was established by magnetic resonance imaging (MRI), computer tomography (CT), or less frequently positron emission tomography/computed tomography (PET/CT) and bone scintigraphy. Bone lesions were divided into osteolytic, osteoblastic, or mixed-form. No bone-targeted agents (i.e., denosumab, bisphosphonate, hydroxyapatite derivatives, or radioactive isotope therapy) have been administered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSBRT Technique\u003c/h2\u003e \u003cp\u003eSimilar to what was previously described by Hwang et al.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, the SBRT procedure consisted of: 1) image acquisition, 2) patient setup, and 3) SBRT planning and treatment. For planning, high-resolution thin-section MRI images were obtained (1.5 or 3 Tesla MRI). All MRI examinations included both turbo spin echo (TSE) T1-weighted (with and without contrast enhancement) and TSE T2-weighted sequences.\u003c/p\u003e \u003cp\u003eFor accurate and precise treatment positioning and immobilization, patients were placed in a vacuum bag (BodyFix\u0026reg;). The DICOM data of the MRI and CT were transferred to workstations for stereotactic planning, where the MRI was fused, at the area of interest, onto the CT images.\u003c/p\u003e \u003cp\u003eThe target volumes for spine metastases were delineated according to international spine radiosurgery guidelines\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. For non-spine bone metastases, a gross tumor volume/clinical target volume (GTV-CTV) margin of 3-5mm and CTV-planning target volume of 3 mm were applied. Generally, patients with spinal metastases were treated at CyberKnife\u0026reg; using a spine-tracking system (SpineX\u0026reg;). For non-spine metastases, we have treated patients at NovalisTX using daily cone-beam CT. The median total radiation dose was 24 Gy (range 24 - 42 Gy) in median 3 fractions (range 2 - 7 fractions), prescribed to 80% isodose-line (range 70 - 90%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eFollow-Up Imaging Evaluation\u003c/h2\u003e \u003cp\u003eAs we analyze a retrospective cohort of patients, different imaging modalities have been used in order to assess the response to SBRT and evaluate the local control. Besides that, the intervals between SBRT and first FU-visit, as well as between following visits are inhomogeneous. For example, most of patients with metastatic prostate cancer were followed-up using prostate specific antigen (PSA) and the diagnostic imaging was done as the PSA raised from baseline after therapy. Despite all these inhomogeneity, we focused on MRI and CT-images and observed their changes through time. This assessment was done by two independent radiologists, blind to the time of treatment. Several radiological changes were described: alterations in mineralization of sclerotic/lytic bone metastases, vertebral compression fracture for spinal metastases, pathologic fracture for non-spine metastases, morphological size progression, and signal alterations on different MRI-sequences. Radiographic response assessment of metastases was classified according to University of Texas MD Anderson Cancer\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e as complete or partial response, and stable or progressive disease, based on the last follow-up imaging.\u003c/p\u003e \u003cp\u003eAs MRI is the most recommended imaging modality for response assessment after bone SBRT, following changes were particularly observed on different MRI sequences: tumor volume, T2 signal intensity (SI) alterations and contrast enhancement patterns.\u003c/p\u003e \u003cp\u003eConsidering pre- and post-treatment volumes, we categorized the tumors as decreased (group 1), unchanged (group 2), or increased (group 3). If the volumetric change was within 10% (ratio range 0.9 \u0026ndash;1.1), the lesions were regarded as unchanged in volume. In case of absence of post-therapeutic MRI, we compared the volumes of the lesions in pre- and post-therapeutic CT. T2 SI changes of the tumors were categorized into four types: 1) no changes); 2) increase in T2 signal intensity; 3) increase in T2 signal intensity intermixed with dark signal intensity, and 4) totally dark signal intensity, based on the publication from Hwang et al.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Enhancement patterns were divided into two groups: no change in contrast enhancement and decrease of contrast enhancement with or without non-enhancing foci.\u003c/p\u003e \u003cp\u003eThe SPINO-consensus recommends FU-MRI every 3-6 months after spine-SBRT; however, as mentioned before, our retrospective cohort is inhomogeneous regarding radiological FUs. Besides MRI, computed tomography (CT), positron emission tomography/computed tomography (PET/CT), bone scintigraphy, or single-photon emission computerized tomography (SPECT) were also performed for some patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePain response\u003c/h2\u003e \u003cp\u003ePain response was assessed before and at least six months after SBRT, using the numerical rating scale (NRS). We also captured the intake of painkillers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed with SPSS, version 22. Descriptive statistics were presented as means (M) and standard deviations (SD) for quantitative variables and frequencies (n) and percentages (%) for categorical ones.\u003c/p\u003e \u003cp\u003eTwo-Way repeated measures ANOVA was conducted to evaluate the effect of SBRT on the quantitative parameters, along with the interaction of the effect of SBRT with the follow-up method. We also calculated the effect for the FU method but did not present these results due to lack of significant values. Effect sizes were assessed with eta squared (η2), considering Cohen\u0026rsquo;s (1988) suggestion: 0.01, 0.06 e 0.14 for weak, moderate and high effect \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThen, we computed the difference between the two moments of assessment - \u003cem\u003ei.e.\u003c/em\u003e, the last imaging before SBRT took place and the last follow-up imaging after SBRT (ΔSBRT= (after - before SBRT)), and built linear regression models adjusting not only for follow-up method, but also for type of lesion. This was done to reduce to number of estimated parameters and allow the computation of the effects when adjusting for these two variables. We computed unstandardized effect sizes (β), standard errors (SE) and p-values. Residual\u0026rsquo;s normality was assessed and confirmed with Shapiro-Wilk test (p\u0026gt;0.05). No residuals were found above the threshold Ri\u0026gt; |3|.\u003c/p\u003e \u003cp\u003eFor assessing the categorical parameters before and after SBRT, we calculated frequencies (n), percentages (%) and Cohen\u0026rsquo;s kappa measure of agreement to assess the changes between these two moments.\u003c/p\u003e \u003cp\u003eSignificance was considered for p\u0026lt;0.05. We also considered marginally significant results for p\u0026lt;0.10.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003ePopulation\u003c/h2\u003e\n\u003cp\u003eA total of 35 patients, 27 (77.1%) males and 8 (22.9%) females with 43 bone metastases were analysed in this cohort. Metastases were mainly from prostate cancer (n=18, 51.4%), followed by breast cancer (n=5, 14.3%). As shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, the bony lesions are classified as spine (n=22, 51.2%) and non-spine (n=21, 48.8%) metastases. The spinal metastases involve mainly the lumbar spine (n=11, 50%) and non-spinal metastases are mostly located in pelvic/hip bones (n=15, 71.4%). The median age at the time of SBRT was 66 years-old (range: 38 - 84).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePatient, treatment and follow-up characteristics.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eValue (range)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian follow-up, years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.8 (\u0026lt;1 - 8.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian age at SBRT, years-old\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66 (38 - 84)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDose Prescription\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian total dose delivered, Gy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24 (24 - 42)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian single dose, Gy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (5 - 12)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian number of fractions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (2 - 7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian isodose prescription, %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e80 (70 - 90)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eImaging Follow-up after SBRT\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 months, range\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.3 - 4.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 months, range\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.1 - 9.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 months, range\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.3 - 19.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNr. of Patients (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (77.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (22.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHistology (primary tumor)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProstate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (51.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMelanoma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (8.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNon-small cell lung cancer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (8.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOther\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (17.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBone Metastases Location\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNr. of metastases (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNon-spine\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (48.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTemporal bone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eScapula\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSternum\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRib\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (9.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePelvic/hip bones (6 ileum, 4 ischium, 4 pubis, 1 acetabulum)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (71.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemur\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSpine\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22 (51.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCervical\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0.)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eThoracic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (40.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLumbar\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSacral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003eRadiological response\u003c/h2\u003e\n\u003cp\u003eFU radiological assessment was performed with contrast-CT (n=17, 39.5%), MRI (n=26, 60.5%), and PET/CT (n=14, 32.6%), which took place mainly three, six, and 12 months after SBRT. After a median FU of almost 2 years (range: \u0026lt;1 - 8.2), complete-/ and partial response, stable-/ and progressive disease occurred in 0%, 11.4%, 68.6%, and 20% respectively. Twenty patients (57.1%) died, all from disease progression, yet 70% (n=14) with still local stable disease after SBRT.\u003c/p\u003e\n\u003cp\u003eNo statistically significant difference on the radiological assessment of two independent radiologists was found. Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e presents results for paired comparisons regarding quantitative variables, compared by the imaging method. We found no significant differences for any of the quantitative parameters considering pre or post SBRT. Considering interactions, we found a statistically significant difference between the width parameter and the imaging method (F=6.13 (p=0.004), \u0026eta;2=0.19: increased only in contrast-CT, stable in MRI, while decreased in PET/CT (Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). A marginally significant association was seen for the SBRT effect on the depth and height (respectively, F=3.97, p=0.052, \u0026eta;2=0.07 and F=3.05 (p=0.056) \u0026eta;2=0.11). There was a trend (depth: F=3.12, p=0.053, \u0026eta;2=0.11; height: F=3.05 (p=0.056) \u0026eta;2=0.11) to increase after SBRT in the contrast-CT follow-up, whereas it decreased in the PET/CT (Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Despite the absence of significance on the volume (F=2.23, p=0.118), moderate effect size was found (\u0026eta;2=0.08) after SBRT, similarly with a slight increase in contrast-CT, stable results in MRI, and decrease in PET/CT. No significant or marginally significant results were found for the effect of SBRT or its interaction with the imaging method in CT density native (CT-DN). ANOVA test was not done for the CT density contrast enhanced (CT-CE) because results were equal before and after SBRT. For the parameters T2-weighted images signal intensity (T2-SI), T2-weighted images turbo inversion recovery magnitude signal intensity (T2-TSI), T1-weighted images native signal intensity (T1-NSI), and T1-weighted images contrast enhanced signal intensity (T1-CESI) no significant results were found for the effect of SBRT.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eRepeated measures ANOVA for the quantitative parameters compared by the imaging method.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eCT contrast enhanced\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eMRI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003ePET/CT\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRM ANOVA effects\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImaging\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eWidth\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=2.55 (p=0.116) \u0026eta;2=0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=6.13 \u003cstrong\u003e(p=0.004)*\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026eta;2=0.19\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDepth\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.81\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.71\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=3.97 (p=0.052)\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e \u0026eta;2=0.07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=3.12 (p=0.053)\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e \u0026eta;2=0.11\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.76\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHeight\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=0.15 (p=0.701) \u0026eta;2=0.003\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=3.05 (p=0.056)\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e \u0026eta;2=0.11\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.94\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eVolume\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9997.74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13068.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12775.66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15571.32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29478.44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e74682.81\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16157.66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39201.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=0.42 (p=0.502) \u0026eta;2=0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=2.23 (p=0.118) \u0026eta;2=0.08\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17678.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19147.79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14338.71\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17120.47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10532.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9453.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14341.30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16164.13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCT-DN\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e248.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e307.38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e300.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e259.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e283.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e269.80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=2.05 (p=0.168) 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align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e352.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e326.76\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCT-CE\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e263.71\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e323.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e263.71\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e323.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT2-SI\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e224.71\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e175.53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=0.01 (p=0.947) \u0026eta;2=0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e222.74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e206.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT2-TSI\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e214.82\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e194.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=0.06 (p=0.816) \u0026eta;2=0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e163.17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT1-NSI\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e213.76\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e141.40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=0.01 (p=0.945) \u0026eta;2=0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e215.69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e171.15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT1-CESI\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e417.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e284.76\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eF=0.01 (p=0.945) \u0026eta;2=0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePost-SBRT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e357.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e267.84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"15\"\u003eAbbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/ computed tomography; RM, repeated measures; M, mean; SD, standard deviation; SBRT, stereotactic body radiotherapy; CT-DN, computed tomography density native in Hounsfield units; CT-CE, computed tomography density contrast enhanced in Hounsfield units; T2-SI, T2-weighted images signal intensity; T2-TSI, T2-weighted images turbo inversion recovery magnitude signal intensity; T1-NSI, T1-weighted images native signal intensity; T1-CESI, T1-weighted images contrast enhanced signal intensity.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"15\"\u003e*statistically significant; \u0026dagger;p\u0026lt;0.10\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"15\"\u003e\u0026eta;2=0.01 weak, \u0026eta;2=0.06 moderate, \u0026eta;2=0.14 high effect, according to Cohen, J (1988). \u003cem\u003eStatistical power analysis for the behavioral sciences\u003c/em\u003e (2nd ed.). Hillsdale, NJ: Erlbaum.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the results of linear regressions for the difference before and after SBRT (\u0026Delta;SBRT) adjusted for type of imaging method and type of lesion, not only showing that spinal metastases were associated with increased width (\u0026beta;\u0026thinsp;=\u0026thinsp;4.89; p=0.031), but also confirming that contrast-CT is associated with increased width (\u0026beta;\u0026thinsp;=\u0026thinsp;11.82; p\u0026lt;0.001), depth (\u0026beta;\u0026thinsp;=\u0026thinsp;5.73; p=0.017), height (\u0026beta;\u0026thinsp;=\u0026thinsp;7.27; p=0.012), and volume (\u0026beta;\u0026thinsp;=\u0026thinsp;28347.15; p=0.026) compared with PET/CT.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLinear regressions for the difference before and after SBRT adjusted for the type of imaging method and spinal lesion.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"9\" align=\"left\"\u003e\n\u003cp\u003e\u0026Delta;SBRT=(After \u0026ndash; Before SBRT)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta; Width\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta; Depth\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta; Height\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta; Volume\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta;\u0026nbsp;CT-DN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta; T2-SI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta; T2-TSI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta; T1-NSI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026Delta;\u0026nbsp;T1-CESI\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eImaging\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.82 (3.11)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ep\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.73 (2.39)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ep=0.017*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.27 (2.90)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ep=0.012*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28347.15 (12743.88)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ep=0.026*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-25.71 (85.02)\u003c/p\u003e\n\u003cp\u003ep=0.762\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMRI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.87 (2.76)\u003c/p\u003e\n\u003cp\u003e(p=0.162)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.14 (2.13)\u003c/p\u003e\n\u003cp\u003ep=0.592\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.34 (2.58)\u003c/p\u003e\n\u003cp\u003ep=0.092\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20438.88 (11487.83)\u003c/p\u003e\n\u003cp\u003ep=0.075\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePET/CT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSpine\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.89 (2.27)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ep=0.031*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.93 (1.74)\u003c/p\u003e\n\u003cp\u003ep=0.593\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.20 (2.11)\u003c/p\u003e\n\u003cp\u003ep=0.926\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12841.73 (9358.37)\u003c/p\u003e\n\u003cp\u003e(p=0.170)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-40.56 (80.99)\u003c/p\u003e\n\u003cp\u003ep=0.617\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.16 (60.67)\u003c/p\u003e\n\u003cp\u003e(p=0.752)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-124.38 (71.00)\u003c/p\u003e\n\u003cp\u003ep=0.080\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e88.54 (51.23)\u003c/p\u003e\n\u003cp\u003ep=0.084\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e112.05 (66.88)\u003c/p\u003e\n\u003cp\u003ep=0.094\u003cstrong\u003e\u0026dagger;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRef\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"10\"\u003eAbbreviations: SBRT, stereotactic body radiotherapy; CT-DN, computed tomography density native in Hounsfield units; T2-SI, T2-weighted images signal intensity; T2-TSI, T2-weighted images turbo inversion recovery magnitude signal intensity; T1-NSI, T1-weighted images native signal intensity; T1-CESI, T1-weighted images contrast enhanced signal intensity; CT, computed tomography; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/ computed tomography; Ref, reference.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"10\"\u003e*statistically significant; \u0026dagger;p\u0026lt;0.10; results presented as unstandardized effect sizes \u0026beta;, standard errors (SE), and p-values.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhen we assessed the spinal metastases without adjusting for the imaging method (only data for MRI was achievable), marginally significant results were found for their association with the parameters T2-TSI (\u0026beta;=-124.38; p=0.080), T1-NSI (\u0026beta;\u0026thinsp;=\u0026thinsp;88.54; p=0.084), and T1-CESI (\u0026beta;\u0026thinsp;=\u0026thinsp;4.89; p=0.031) after SBRT: lower in T2-TSI, while higher in T1-NSI and T1-CESI.\u003c/p\u003e\n\u003cp\u003eOn Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, we present the assessment for the categorical variables\u0026rsquo; association with pre versus post SBRT, with Cohen\u0026rsquo;s kappa measure of agreement to assess the changes between these two moments (k). CT appearance (k=0.84), soft component (k=0.72) and T2 turbo inversion recovery magnitude (TIRM) appearance (k=0.67) had moderate to high agreement between the two assessments. For CT appearance, proportion of agreement was 100% for osteolytic, 93.3% for osteoblastic and 71.4% for mixed-type lesions. For soft tissue component, 75% agreement for presence and 94.7% for non-presence were applicable. For SI on T2-TIRM sequence, agreement was 100% for homogenous hyper-intensity, 50% for dark spots, 50% for homogenous hypo-intensity, and 100% for intermediary. The other parameters showed low or very low agreement, with k varying from k=0.14 to k=0.40.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eAgreement of radiological categorical variables before and after SBRT.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBefore SBRT\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eAfter SBRT\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003ek\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCT appearance\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOsteolytic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOsteoblastic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMixed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOsteolytic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (14.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.84\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOsteoblastic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14 (93.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (14.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMixed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (6.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (71.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT2 appearance\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHomogenous bright\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDark spots\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotally dark\u003c/p\u003e\n\u003cp\u003esignal intensity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntermediary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHomogenous bright\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDark spots\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (57.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotally dark signal intensity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (42.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (87.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntermediary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT2 TIRM appearance\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHomogenous bright\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDark spots\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotally dark\u003c/p\u003e\n\u003cp\u003esignal intensity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntermediary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHomogenous bright\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (100.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e0.67\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDark spots\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotally dark signal intensity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntermediary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (100.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT1 signal native appearance\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHomogenous bright\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDark spots\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotally dark\u003c/p\u003e\n\u003cp\u003esignal intensity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntermediary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHomogenous bright\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e0.30\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDark spots\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (33.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (7.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotally dark signal intensity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (66.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (78.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntermediary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (14.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (50.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eT1 CE signal appearance\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo enhancement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSlight\u0026nbsp;enhancement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBright enhancement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo enhancement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.14\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSlight enhancement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (75.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (81.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (60.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBright enhancement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (18.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (40.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eContrast enhancement\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (100.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (66.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.40\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (33.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSoft component\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (75.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (5.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.72\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36 (94.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003eAbbreviations: SBRT, stereotactic body radiotherapy; CT, computed tomography; T2 TIRM, T2-weighted.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003ePain response\u003c/h2\u003e\n\u003cp\u003eConsidering the pain response, we observed that 22 (62.9%) patients remained asymptomatic on the treated metastases; four (11.4%) patients reported decreased pain (complete and partial); three (8.6%) had stable pain (two without regular analgesia and one stable after SBRT but requiring analgesia after surgery); two (5.7%) complained of increased pain, even though one of them without requiring analgesia; four (11.4%) had no available pain response follow-up, whereas one of them deceased before it was captured.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eResults of the current retrospective study present SBRT as an effective treatment for bone metastases. SBRT has been increasingly accepted as a valuable option for selective patients with metastatic disease. Using the appropriate imaging modality for treatment planning, SBRT offers an excellent local control with acceptable toxicity profile\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, response assessment after SBRT is a challenging topic, which is not only limited to the bone, as we confront difficulties to interpret the changes in imaging modalities after stereotactic radiotherapy in other organs, like brain, liver and lung\u003csup\u003e\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Appropriate evaluating of diagnostic images is a critical point in the process of the disease and can prevent the risks of unnecessary interventions. Besides that, pain response should be considered after RT for bone metastases, as pain relief is the most important goal in such patients. In this retrospective study, we report our institutional results regarding imaging-based local control and pain response after SBRT for bone metastases.\u003c/p\u003e \u003cp\u003eThe SPINO-group published a report in 2015, focusing on response assessment after SBRT for spinal metastases\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. The consensus is based on an international survey and not yet evaluated in clinical trials. We considered the recommendations from SPINO group for image-based tumor- and pain response, although we analyzed both spine and non-spine bone metastases in our study. The MRI is the preferred modality for response assessment after SBRT; however, we should be aware of some unique aspects such as pseudo-progression (PP) and vertebral compression fracture (VCF) when interpreting the post-SBRT images.\u003c/p\u003e \u003cp\u003ePP is a well-known phenomenon after SBRT in different organs. It was first reported for spine metastasis in a case report from 2015 and the authors described PP as subacute, post-radiotherapy reaction that mimics progressive disease (PD) with increased contrast enhancement and ultimate stabilization and regression\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Time is an important factor evaluating post-SBRT radiological changes, as PP present few weeks up to 6 months after radiation, in contrast to radio-necrosis (RN) which is a late effect and can occur even years after therapy\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Amini et al. did an analysis of osseous pseudo-progression in vertebral body following SBRT in patients from two prospective phase I/II clinical trials\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. They defined the osseous pseudo-progression as \u0026ldquo;transient growth in signal abnormality centered at the lesion with a sustained decline on FU MRI that was not attributable to chemotherapy\u0026rdquo;. They reported the rates of PP and PD of 14% and 24% respectively. Furthermore, there was a significant association between single-fraction SBRT and development of PP\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. The so far published randomized trials comparing SBRT versus conventional RT have not reported the rates of PP\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. SPINO group defined any new or progressive tumor within the epidural space as local progression\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, but we have recently published a case report showing clear epidural involvement on radiological images after spine SBRT, however, the histological analysis revealed no tumor cells in epidural space\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Therefore, it is critical to distinguish between PP, PD and RN to avoid false patient management. In our study, we observed PP as a common finding after SBRT, however not all patients had MRI shortly after the therapy and therefore it was not possible to report the exact rate of PP.\u003c/p\u003e \u003cp\u003eVCF is a well-known and most common complication after spine SBRT. The rate of VCF after single fraction SBRT (SF-SBRT) with 18-24Gy was reported around 39%, and lytic lesions and location below T10 confer a high risk of fracture\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. The median time to fracture was 25 months and VCF was seen earlier in patients with lytic lesions compared to sclerotic lesions\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Sahgal et al. reported 14% of new or progressing VCF after spine SBRT, using different fractionation and considering SINS-score to determine its predictive value\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. They defined the high dose per fraction, lytic lesion and baseline fracture as significant predictors of VCF\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. A review from 2017 reported a crude VCF rate of 13.9%\u003csup\u003e32\u003c/sup\u003e. Jawad et al. demonstrated low rates of VCF for 5.7% in their multi-institutional study, using 1-5 fractions for spine SBRT\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. We report here the rates of new/progressive fractures for spine and non-spine metastases as 4.5% and 4.7% respectively. As half of our cohort had metastatic prostate cancer, one reason for our low rates of fractures could be the sclerotic nature of the metastases. Another reason might be related to our moderate SBRT schema with median total dose of 24Gy in three fractions.\u003c/p\u003e \u003cp\u003eAs mentioned above, MRI is the most recommended imaging modality for radiological assessment of bone metastasis after SBRT. Hwang et al. reported the MRI changes after SBRT for osteoblastic spinal lesions, as these metastases usually show no obvious radiological volumetric alterations\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. They classified signal intensity (SI) alterations on T2-MRI sequences as following: 1) no changes in SI; 2) increased SI; 3) increased SI intermixed with dark SI; 4) changed to complete dark SI. Most of our patients had prostate cancer as primary diagnosis; therefore, we assessed the T2 weighted MRI sequences for radiological response evaluation after SBRT for both spine and non-spine bone metastases as described above. According to recommendations from SPINO group, the routine use of contrast-enhanced T1-MRI sequences to visualize spinal metastases is controversial as both normal bone marrow and tumor are enhanced\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. The interpretation becomes even more difficult after SBRT and therefore we considered the T1-MRI with gadolinium only for delineating the epidural and para-spinal tumor components. Although the patient population was heterogeneous in our cohort, SBRT achieved 80% of LC at almost 2 years. More than 40% of our patients survived and among the population who died in FU time, 40% had still SD at the irradiated sites. These results are in line with data from other studies, showing an excellent rate of LC after SBRT for osseous metastases\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eConsidering pain response, the randomized phase 2 trial from Germany reported significant improved pain values in SBRT group 6 months after the therapy in patients with spinal metastases\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. However, as they chose the SF-SBRT with 24Gy, the rates of new pathological fracture were high in that study, with 8.7% and 27.8% at 3 and 6 months respectively\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Another randomized phase 2 trial from Netherlands compared SBRT versus conventional RT for bone metastases using different fractionations\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. SBRT group did not show significant pain improve, but because of selective dropout, this trial was underpowered to detect the difference in pain response\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The NRG Oncology/RTOG 0631 trial initial results were presented at ASTRO annual meeting in 2019\u003csup\u003e34\u003c/sup\u003e. Randomizing patients with spinal metastases into SBRT and conventional RT groups, this study showed negative results for SBRT arm, as pain control was similar at 3 months between two groups. Finally, the Canadian randomized phase 3 trial compared spine SBRT with 24Gy in two daily fractions with conventional RT at a dose of 20Gy in five fractions\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. The SBRT was superior to conventional RT and improved the complete pain response at 3 months. Interestingly, the incidence of VCF was equal between two groups, showing the safety of SBRT regimen\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. In our retrospective study, the majority of patients (62.9%) had no pain prior to SBRT and the indication was mostly local ablation in oligo-metastatic/progressive disease. This group of patients remained asymptomatic after SBRT. In symptomatic group, only two patients experienced pain exacerbation following SBRT with only one of them required analgesic medication.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our results from a single institutional study show high rates of tumor- and pain control after SBRT for spine and non-spine metastases. We assessed the LC by analyzing the imaging modalities and hope that these results provide a better understanding of radiological changes, mainly on MRI after SBRT. The next step could be the comparison between different imaging modalities for response assessment, especially for solid tumors with specific tumor biomarkers as PSMA for prostate cancer.\u003c/p\u003e"},{"header":"List Of Abbreviations ","content":"\u003cp\u003e\u003cstrong\u003eSBRT \u003c/strong\u003eStereotactic Body Radiation Therapy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFU \u003c/strong\u003eFollow-Up\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSD \u003c/strong\u003eStable Disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePD \u003c/strong\u003eProgressive Disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLC \u003c/strong\u003eLocal Control\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOS \u003c/strong\u003eOverall Survival\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVCF \u003c/strong\u003eVertebral Compression Fracture\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRI \u003c/strong\u003eMagnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCT \u003c/strong\u003eComputed Tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePET \u003c/strong\u003ePositron Emission Tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTSE \u003c/strong\u003eTurbo Spin Echo\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePSA \u003c/strong\u003eProstate Specific Antigen\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSI \u003c/strong\u003eSignal Intensity\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSPECT \u003c/strong\u003eSingle Photon Emission Computer Tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNRS \u003c/strong\u003eNumerical Rating Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSE \u003c/strong\u003eStandard Error\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDN \u003c/strong\u003eDensity Native\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCE \u003c/strong\u003eContrast Enhanced\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTIRM \u003c/strong\u003eTurbo Inversion Recovery Magnitude\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePP \u003c/strong\u003ePseudo-Progression\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRN \u003c/strong\u003eRadiation Necrosis\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval: Study protocol was approved by the institutional review board and ethic committee (Berner Kantonale Ethikkommission f\u0026uuml;r die Forschung \u0026ndash; Project-ID 2018-01831)\u003c/p\u003e\n\u003cp\u003eConsent for publication: No individual person`data\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eDisclosures: None\u003c/p\u003e\n\u003cp\u003eFunding: None\u003c/p\u003e\n\u003cp\u003eCompeting interests: None\u003c/p\u003e\n\u003cp\u003eAuthors` contributions: J. Cullmann and R. Heiss analyzed the whole imaging modalities as two independent radiologists. D. Correia, B. Moullet and H. Hemmatazad wrote the manuscript. D. Correia made also the tables and figures. D. M. Aebersold and Ekin Ermis did critical review of the manuscript. The project was supervised by H. Hemmatazad.\u003c/p\u003e\n\u003cp\u003eACKNOWLEDGMENTS: We thank Edgar Mesquita (statistical consultant, Portuguese Institute of Oncology of Porto Francisco Gentil, Portugal) for statistical analysis supervision.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eColeman RE. Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. \u003cem\u003eCancer Treat Rev\u003c/em\u003e. 2001;27(3):165-176. doi:10.1053/CTRV.2000.0210\u003c/li\u003e\n \u003cli\u003eCecchini MG, Wetterwald A, van der Pluijm G, Thalmann GN. 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The evolution and rise of stereotactic body radiotherapy (SBRT) for spinal metastases. \u003cem\u003eExpert Rev Anticancer Ther\u003c/em\u003e. Published online 2018. doi:10.1080/14737140.2018.1493381\u003c/li\u003e\n \u003cli\u003eRyu S, Deshmukh S, Timmerman RD, et al. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631. \u003cem\u003eInt J Radiat Oncol\u003c/em\u003e. 2019;105(1):S2-S3. doi:10.1016/j.ijrobp.2019.06.382\u003c/li\u003e\n \u003cli\u003eSahgal A, Myrehaug SD, Siva S, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. \u003cem\u003eLancet Oncol\u003c/em\u003e. 2021;22(7):1023-1033. doi:10.1016/S1470-2045(21)00196-0\u003c/li\u003e\n \u003cli\u003eSprave T, Verma V, F\u0026ouml;rster R, et al. 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Response Assessment of Stereotactic Body Radiation Therapy Using Dynamic Contrast-Enhanced Integrated MR-PET in Non-Small Cell Lung Cancer Patients. Published online 2017:191-199. doi:10.1002/jmri.25758\u003c/li\u003e\n \u003cli\u003eYip C, Cook GJR, Owczarczyk K, Goh V. Challenges in imaging assessment following liver stereotactic body radiotherapy : pitfalls to avoid in clinical practice. 2017;6(Suppl 2):1-9. doi:10.21037/cco.2017.06.06\u003c/li\u003e\n \u003cli\u003eSawlani V, Davies N, Patel M, et al. Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature. \u003cem\u003eClin Oncol\u003c/em\u003e. 2019;31(1):41-49. doi:10.1016/j.clon.2018.09.003\u003c/li\u003e\n \u003cli\u003eTaylor DR, Weaver JA. 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Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases d A Phase 2 Randomized Controlled Trial Within a Prospective Cohort. \u003cem\u003eRadiat Oncol Biol\u003c/em\u003e. 2021;110(2):358-367. doi:10.1016/j.ijrobp.2020.11.060\u003c/li\u003e\n \u003cli\u003eStutz E, Wartenberg M, Hemmatazad H, Hemmatazad H, Hemmatazad H. RAS ONCOLOGY \u0026amp; THERAPY Case Report : Epidural tumor pseudoprogression after spine SBRT : A case report and a mini review of the literature. Published online 2021:1-5.\u003c/li\u003e\n \u003cli\u003eRose PS, Laufer I, Boland PJ, et al. J OURNAL OF C LINICAL O NCOLOGY Risk of Fracture After Single Fraction Image-Guided Intensity-Modulated Radiation Therapy to Spinal Metastases. 2009;27(30):6-10. doi:10.1200/JCO.2008.19.3508\u003c/li\u003e\n \u003cli\u003eSahgal A, Atenafu EG, Chao S, et al. J OURNAL OF C LINICAL O NCOLOGY Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy : A Multi-Institutional Analysis With a Focus on Radiation Dose and the Spinal Instability Neoplastic Score. 2017;31(27):0-5. doi:10.1200/JCO.2013.50.1411\u003c/li\u003e\n \u003cli\u003eFaruqi S, Whyne C, Alghamdi M, Maralani P. Stereotactic Body Radiation Therapy : A Review of the Pathophysiology and Risk Factors. 2017;0(0):1-9. doi:10.1093/neuros/nyx493\u003c/li\u003e\n \u003cli\u003eJawad MS, Fahim DK, Gerszten PC, et al. multinational evaluation. 2016;24(June):928-936. doi:10.3171/2015.10.SPINE141261.928\u003c/li\u003e\n \u003cli\u003eRyu S, Deshmukh S, Timmerman RD, et al. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631. \u003cem\u003eRadiat Oncol Biol\u003c/em\u003e. 2013;105(1):S2-S3. doi:10.1016/j.ijrobp.2019.06.382\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"radiation-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"raon","sideBox":"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)","snPcode":"13014","submissionUrl":"https://submission.nature.com/new-submission/13014/3","title":"Radiation Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Spine metastases, SBRT, Response Assessment, Pain Response","lastPublishedDoi":"10.21203/rs.3.rs-995077/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-995077/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThe use of stereotactic body radiation therapy (SBRT) for tumor- and pain control in patients with bone metastases is increasing. Here, we report response assessment after bone SBRT using radiological changes through time and clinical examination of patients. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eWe analyzed retrospectively the oligo-metastatic/progressive patients with bony lesions treated with SBRT between 12/2008 and 10/2018 in our institution. Radiological data were obtained from imaging modalities used for SBRT planning and follow-up (FU) purposes in PACS and assessed by two independent radiologists blind to the time of treatment. Several radiological changes were described. Radiographic response assessment was classified according to University of Texas MD Anderson Cancer Center criteria. Pain response was captured pre- and \u0026gt;= 6 months post-SBRT.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA total of 35 of the 74 reviewed patients were eligible, presenting 43 bone metastases, with 51.2% (n=22) located in vertebral column. Median age at the time of SBRT was 66 years (range, 38-84), and 77.1% (n=27) were male. Histology was mainly prostate (51.4%, n=18) and breast cancer (14.3%, n=5). Median total radiation dose delivered was 24 Gy (range: 24-42), in three fractions (range: 2-7), prescribed to 70 - 90% isodose-line. After a median FU of 1.8 years (range, 0.1-8.2) for survivors, complete-/ partial response, stable (SD), and progressive disease occurred in 0%, 11.4% (n=4), 68.6% (n=24) and 20.0% (n=7) of the patients respectively. Twenty patients (57.1%) died during the FU time, all from disease progression, yet 70% (n=14) from this population with local SD after SBRT. From patients who were symptomatic and available for FU, almost 50% reported pain reduction after SBRT.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eEighty percent of the patients showed local control (LC) after SBRT for bone metastases. Pain response was favorable. For more accurate response assessment, comparing current imaging modalities with advanced imaging techniques such as functional MRI and PET-CT is warranted.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eRetrospectively registered.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Response Assessment After Stereotactic Body Radiation Therapy for Spine and Non-spine Bone Metastases: Results From a Single Institutional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-10-25 14:47:42","doi":"10.21203/rs.3.rs-995077/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-12-29T06:58:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-11-05T11:57:37+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-11-05T10:20:37+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-11-05T00:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2021-10-21T01:08:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-10-19T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-10-19T23:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Radiation Oncology","date":"2021-10-19T08:29:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"radiation-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"raon","sideBox":"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)","snPcode":"13014","submissionUrl":"https://submission.nature.com/new-submission/13014/3","title":"Radiation Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bd41b727-59c1-4aa9-928b-33c12fdcef4e","owner":[],"postedDate":"October 25th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":8079549,"name":"Oncology"}],"tags":[],"updatedAt":"2022-02-21T18:56:25+00:00","versionOfRecord":{"articleIdentity":"rs-995077","link":"https://doi.org/10.1186/s13014-022-02004-7","journal":{"identity":"radiation-oncology","isVorOnly":false,"title":"Radiation Oncology"},"publishedOn":"2022-02-21 18:56:25","publishedOnDateReadable":"February 21st, 2022"},"versionCreatedAt":"2021-10-25 14:47:42","video":"","vorDoi":"10.1186/s13014-022-02004-7","vorDoiUrl":"https://doi.org/10.1186/s13014-022-02004-7","workflowStages":[]},"version":"v1","identity":"rs-995077","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-995077","identity":"rs-995077","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}