Clinical Outcomes of Stereotactic Body Radiotherapy for Spinal Metastases with Paraspinal Extension

Clinical Outcomes of Stereotactic Body Radiotherapy for Spinal Metastases with Paraspinal Extension | 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 Case Report Clinical Outcomes of Stereotactic Body Radiotherapy for Spinal Metastases with Paraspinal Extension Dylan Ross, Neil Vuppala, Michael LeCompte, Majid Khan, Ali Bydon, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8730558/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Mar, 2026 Read the published version in Journal of Neuro-Oncology → Version 1 posted 12 You are reading this latest preprint version Abstract Purpose: SBRT for spinal column metastases with paraspinal extension poses a challenge for local control. However, data is limited. The purpose of this study is to better characterize patterns of local recurrence in this patient population with the goal of improving outcomes. Methods: Patients with spinal metastases with paraspinal extension treated with SBRT at a single institution from 2009–2021 were reviewed. Sites with previous surgery and/or radiation were included. Univariate analysis of size, PTV shape, previous fracture, multiple vertebral levels, muscle invasion, organ abutment, and dosimetric variables in relation to time-to-local failure (LF) was performed. Results: Seventy-six paraspinal masses were included in the analysis. Median follow-up period was 11.8 months. Seventy-six percent of thoracic paraspinal masses involved adjacent ribs. Twenty-one percent of paraspinal masses abutted organs, 18% had muscle invasion. The most common prescription for both radiation naive and re-irradiation treatments was 2700 cGy in 3 fractions. The 12-month incidence of local failure (LF) was 30% overall and 29.4% for re-irradiated sites. Forty percent of LFs involved the paraspinal region. No analyzed variables were significantly associated with LF events, PTV > 225cc and PTV shape (donut) trended toward significance (p = 0.08 and 0.07). Conclusion: While clinical and dosimetric variables did not show significant associations with LF, a large portion of LF occurrences were observed within the paraspinal region, suggesting that a generous asymmetrical expansion in the direction of paraspinal disease may help improve outcomes. Nonetheless, this study emphasizes the importance of refining treatment approaches for this population. Figures Figure 1 Figure 2 Figure 3 Introduction The spinal column has a high incidence of metastatic disease, estimated to be involved in 15–20% in patients with solid tumors [ 1 ]. In recent years, management of spine metastases has progressed from exclusively pain control to aggressive multi-disciplinary care with the goal of durable local control, especially in patients with limited sites of disease [ 2 ]-[ 4 ]. In this light, spinal stereotactic body radiotherapy (SBRT) has shown the ability to improve local control (LC) without compromising quality of life (QOL) [ 5 ]. Multiple studies have validated the improved local control and pain control rates seen with SBRT techniques, including a randomized controlled study demonstrating a superior rate of complete pain relief at both 3 and 6 months compared to conventional radiation [ 6 ]-[ 10 ]. Notably, SC.24 compared 24 Gy in 2 fractions with conventional RT in a randomized controlled trial and showed significantly improved complete pain responses at both 3- and 6-months [ 10 ] Meta-analysis suggests that single fraction SBRT boasts local control rates of > 90%, significantly improved from conventional radiation therapy [ 11 ]. Other well-validated reports have summarized local control rates for a variety of fractionated SBRT regimens, all with the ability to achieve LC approaching or surpassing 90% [ 12 ]. Despite this promise, paraspinal extension of spinal metastatic disease has been shown as an important risk factor for worse outcomes in multiple studies [ 13 ]-[ 21 ]. A few retrospective studies have reported outcomes using SBRT in this patient population, however, data is underreported [ 22 ], [ 23 ] The purpose of this study is to better characterize patterns of local recurrence in this patient population with the goal of improving outcomes moving forward. To try to overcome the historically poor local control in this patient population, our institutional practice for clinical target volume delineation in recent years typically involves an approximately 3 mm expansion in the direction of paraspinal involvement. This analysis also aims to explore if this approach impacts local control and patterns of failure relative to prior publications. Materials and Methods Patient Selection Patients with nonhematologic spinal metastases with paraspinal extension treated with SBRT at a single institution from 2009–2021 were retrospectively reviewed. Our Institutional Review Board approved this study. Paraspinal extension was defined as defined as tumor extension beyond the cortex of the bone. Patients with prior surgery and prior radiotherapy to the same vertebral level were included. Radiation Technique SBRT was delivered using a robotic platform or linear accelerator-based system. Gross-tumor-volume (GTV) was delineated using the simulation CT and co-registered MRI sequences, typically T1 pre- and post-contrast, and a T2 variant. Clinical-target-volume (CTV) was based on the consensus contouring guidelines for intact and post-operative spine SBRT [ 24 ], [ 25 ]. However, given the historically poor local control in this patient population, the institutional practice for CTV delineation in recent years typically involves an additional approximately 3 mm expansion in the direction of paraspinal involvement. Planning-target-volume (PTV) expansion was typically 1 mm radially. Prescription dose was selected by the treating radiation oncologist. The spinal cord and neural avoidance elements were delineated on T2 weighted MRI or CT-myelogram in cases of extensive metal artifact from spinal instrumentation. Dose constraints were applied to the spinal cord expanded radially by 2mm or the true cauda equina without expansion. Dose constraints for the neural avoidance structure were according to Sahgal and colleagues[ 26 ]. Constraints for the remainder of organs-at-risk (OARs) were per TG-101 [ 27 ]. In the reirradiation setting, the cord plus 2 mm was allowed a cumulative BED3 of 75 accounting for 25% repair at 6 months after prior RT and 50% repair at 1 year. The cauda equina was allowed a cumulative BED3 of 106 accounting for the same repair factors [ 28 ]. Outcome Measures Outcome Measures The primary outcome of the current study was local failure (LF), defined per Spine response assessment in Neuro-Oncology (SPINO) criteria as unequivocal tumor volume growth or new or progressive epidural disease that persisted beyond 3 months following SBRT and/or on repeat imaging [ 29 ]. LF events were then categorized as involving the vertebra, the epidural space, and/or the paraspinal component. Failures that occurred in multiple regions were included in each category. Patients were generally seen in follow up by a oncology care team provider for clinical evaluation and surveillance imaging at approximately 3-month intervals following SBRT. Pain response was defined using a combination of pain score and analgesic consumption, as is recommended by international consensus guidelines [ 10 ]. Pain response compared a pre-SBRT reference to pain levels at 3-month intervals and was categorized as: (i) complete response defined as a pain level rated as 0; (ii) partial response defined as a pain level that decreased by ≥ 2 with the same or lower analgesic consumption (measured by oral morphine equivalents [OME]), or the same pain level with ≥ 25% decrease in OME; (iii) stable defined as same pain level and OME; (iv) worse pain defined as higher pain level [ 30 ]. Statistical Analysis LF was calculated in months from the end of SBRT to failure event or the last follow up (censored). Cumulative incidence of LF was estimated using Fine and Gray methodology with death as a competing risk. Craniocaudal extent of paraspinal mass, number of vertebral segments involved in the lesion, treatment of the entire circumference of the vertebral segment (i.e., a donut), pre-existing compression fracture at the same level, immunotherapy use, radioresistant primary histology, paraspinal involvement of ribs, organ abutment (gastrointestinal structures or kidney), paraspinal muscle invasion, RTOG conformity index (CI), and dosimetric variables were evaluated for associations with time to LF event using univariate cox proportional hazard modelling [ 31 ], [ 32 ]. Any characteristics found to be associated with LF were planned to be included in a multivariate model. Regarding dosimetric data, all fractionation schemes were converted to 3-fraction equivalent doses (3fxED) using the linear quadratic model with an alpha/beta of 3. A p value of less than 0.05 was considered statistically significant. Statistical analyses were completed using STATA v18.0 software (College Station, TX). Results Seventy-six paraspinal masses from 69 patients included in the analysis. Median follow-up was 11.8 months. Fifty-nine sites were radiation naive, and 17 sites received previous radiation to the same levels. Table 1 displays a summary of clinical and dosimetry results. Common primary tumor types were non-small cell lung cancer (n = 13, 17%), sarcoma (n = 12, 16%), and gastrointestinal (n = 12, 16%). Twenty-one percent of paraspinal disease cases spanned 1 vertebral segment, 34% spanned 2 segments, 33% spanned 3 segments, and 12% spanned ≥ 4 segments. Sixty-seven percent of cases occurred in the thoracic region; in this location, 76% of paraspinal masses involved adjacent ribs. Twenty-one percent of paraspinal masses abutted or compressed gastrointestinal organs or the kidney, and 18% had muscle invasion. The median craniocaudal extent of the paraspinal masses was 3.6 cm (1.0–8.8 cm). Two patients experienced grade 3 vertebral compression fractures (VCF) while 0 patients experienced grade 3 myelopathy. The median PTV size was 133 cc (22–753cc). Figure 1 displays a representative case of asymmetric volume expansion. The most common prescriptions for radiation naive patients were 2700 cGy in 3 fractions (22%), 2400 cGy in 2 fractions (12%), and 3000 cGy in 5 fractions (12%). Re-irradiation patients most commonly were prescribed 2700 cGy in 3 fractions (12%), 2500 cGy in 5 fractions (4%), and 3000 cGy in 5 fractions (2.5%). Re-irradiation occurred most commonly after an initial prescription of either conventional 30 Gy in 10 fractions (29.4%) or 27 Gy in 3 fractions (23.5%). Additional prescription details may be found in Table 1 . At 3 months post-SBRT, complete pain response was 39%, and partial pain response was 15%, while at 6 months, complete pain response was 37%, and partial pain response was 14%. The 12-month incidence of LF was 30% ( Fig. 2 ) . In terms of local failure, 50% involved the vertebrae, 47% involved the epidural space, and 40% involved the paraspinal region. These values exceed 100% as 33% of failures involved 2 or more regions. Specifically, 20% with vertebral body and epidural, 3% with vertebral body and paraspinal region, 3% with both epidural and paraspinal, and 7% with all 3 components showing progression ( Fig. 3 ). Seventy-seven percent of LFs included a marginal component. Of the marginal failures, 35% involved the paraspinal component and 57% involved the epidural space. On univariate analysis, clinical and dosimetric data were not significantly associated with LF events. PTV volume of greater than 225cc (75th percentile of our dataset) trended towards significance at p = 0.08 ( Table 2 ) . PTV volume with a shape of a donut (full vertebral body included in PTV with cord PRV subtracted out of the middle) also trended towards significance (p = 0.07) ( Table 2 ). Five of the 17 (29.4%) re-irradiated sites had local failure at a median time of 7.4 months after SBRT. Twenty-six of the 59 (44.1%) of radiation naive sites had local failure at a median time of 4.4 months (p = 0.40, Fisher’s exact). Table 1 Clinical and dosimetric variables. N (%) Primary NSCLC 13 (17.1) Sarcoma 12 (15.8) GI 12 (15.8) Renal 9 (11.8) Uterine 8 (10.5) Prostate 5 (6.6) Thyroid 4 (5.3) Melanoma 3 (3.9) Breast 3 (3.9) Other 7 (9.2) Number of Vertebral Segments 1 16 (21.1) 2 26 (34.2) 3 25 (32.9) 4+ 9 (11.8) Spinal Level Cervical 5 (6.6) Thoracic 51 (67.1) Lumbar 20 (26.3) Paraspinal Involvement Ribs 58 (76.3) Bowel/Kidney abutment 16 (21.1) Muscle invasion 14 (18.4) Size Craniocaudal extent [Range] 3.6 cm [1.0-8.8] Prescription Doses for Radiation Naïve Patients (N = 59) 27 Gy in 3 fractions 17 (28.8) 24 Gy in 2 fractions 9 (15.3) 30 Gy in 5 fractions 9 (15.3) 25 Gy in 5 fractions 6 (10.2) 24 Gy in 3 fractions 3 (5.1) 40 Gy in 5 fractions 3 (5.1) 45 Gy in 5 fractions 3 (5.1) 21 Gy in 3 fractions 2 (3.4) 30 Gy in 3 fractions 2 (3.4) Other 5 (8.5) Prescriptions-Previously Radiated (N = 17) 27 Gy in 3 fractions 9 (53.0) 25 Gy in 5 fractions 3 (17.6) 30 Gy in 5 fractions 2 (11.8) 20 Gy in 5 fractions 1 (5.9) 27.5 Gy in 5 fractions 1 (5.9) 40 Gy in 5 fractions 1 (5.9) Prescriptions of Previous Radiation 30 Gy in 10 fractions 5 (29.4) 27 Gy in 3 fractions 4 (23.5) 24 Gy in 3 fractions 2 (11.8) 30 Gy in 5 fractions 2 (11.8) 15 Gy in 1 fraction 1 (5.9) 24 Gy in 2 fractions 1 (5.9) 20 Gy in 5 fractions 1 (5.9) 35 Gy in 5 fractions 1 (5.9) GTV size [Range] 41.9cm [7.8–170] PTV size [IQR] 133cc [78.1-213.8] Table 2 Univariate analysis of clinical and dosimetric variables for local failure. Data reported as Hazard Ration (95% Confidence Interval) with p-values in separate column. Craniocaudal extent 0.98 (0.75–1.28) p = 0.89 Number of vertebral segments 0.92 (0.6–1.4) p = 0.67 PTV donut shape 1.97 (0.9–4.1) p = 0.07 RTOG CI 0.54 (0.25–1.15) p = 0.11 Pre-existing VCF 1.6 (0.7–3.3) p = 0.24 Immunotherapy treatment 0.63 (0.28–1.41) p = 0.26 Radioresistant histology 3.2 (0.4–26.0) P = 0.27 Rib involvement 1.3 (0.44–3.97) p = 0.63 Organ abutment (GI, kidney) 0.88 (0.37–2.11) p = 0.78 Muscle invasion 1.2 (0.55–2.6) p = 0.66 PTV maximum dose (3 fraction dose) 1.0 (0.97–1.04) p = 0.97 PTV volume > 150cc 1.68 (0.83–3.40) p = 0.15 PTV volume > 225cc 2.03 (0.91–4.51) p = 0.08 Discussion This single institution analysis revealed a radiographic LF rate of 30% one year after SBRT which is lower than expected following SBRT for disease confined to the spinal column [ 12 ], [ 33 ]-[ 37 ]. The radiographic LF rate is much improved, however, compared to historical data of paraspinal extension which reported rates of 55% when spinal disease extended beyond osseous borders [ 38 ]. Our results were corroborated by another recently published series using similar techniques that showed a 12-month LF rate of 19.5% [ 22 ], [ 23 ] When stratified by paraspinal volume of greater or less than 43mL, LF rates at one year increased from 12% to 36.3%. Our study’s univariate analysis did not find significant correlation when stratifying PTV size at thresholds of 150cc and 225cc although hazard ratios were trending towards significance. However, the mean PTV size in our study was much larger than Ong et al, which may contribute to the size correlation discrepancy. Interestingly, the rate of local failure was higher and time to failure earlier in radiation naïve patients. We speculate this may be due to differences in doses received between the LFs compared to the locally controlled patients, however, this was not statistically significant. It appears re-irradiation cumulative doses received to the spinal levels continues to improve control, providing reinforcement that re-irradiation is warranted in cases of LF. Further investigation is needed. The reason for poorer outcomes following SBRT to spinal lesions with paraspinal extension remains unclear. It may be that this reflects baseline poor biology in that only the most aggressive tumors extend beyond the cortex of the bone. However, it is also plausible that the difference represents the difficulty with target delineation in these patients. Incorporation of advanced imaging techniques may be considered to alleviate this challenge. In addition, paraspinal lesions have less anatomic barriers to microscopic spread than those contained within the vertebrae. As such, our institutional practice has been to do a larger expansion in the region of paraspinal disease. Although our data are optimistic compared to the older series by Mizumoto, a real opportunity for improvement persists [ 38 ]. In terms of patterns of failure, Ong et al reported 49% in paraspinal region and 63% in epidural space, which is consistent with our results showing 40% and 47%, respectively. This is unique from intact spine SBRT which recur overwhelmingly in the epidural space, given the need to respect the radiation dose tolerance of the spinal cord [ 19 ], [ 22 ], [ 36 ], [ 39 ]-[ 42 ]. Notably, 77% of recurrences were marginal failures, 35% of which were in the paraspinal region of disease [ 34 ], [ 35 ]. This may be driven by the need to meet normal tissue constraints for adjacent organs such as the bowel or kidney [ 12 ], [ 27 ], [ 43 ], it raises the hypothesis that target contours should be more generous in these cases or include larger CTV expansion in the paraspinal region. An important aspect of our data is the inclusion of previously irradiated patients and vertebral levels. Seventeen such patients were included in our data set with a local failure rate of 29.4%. Detsky et al reported LF rates of 18% for SBRT re-irradiation with paraspinal extension being predictive of LF [ 14 ]. A similar series reported LF rates of 23% with 46% of these failures involving the paraspinal region [ 15 ]. Again, paraspinal involvement was predictive of worse control in the re-irradiation series. LF rates of about 25% in re-irradiation settings using SBRT have been shown in other studies as well [ 44 ], [ 45 ]. Considering the initial involvement of the paraspinal region in all seventeen patients in our series, 29.4% LF rate for SBRT re-irradiation is promising in this limited sample size. In terms of time to progression, we report a high rate of late failures in the limited number of patients evaluable at these late time points. Specifically, 43% of our LFs occur 18 + months after SBRT and 23% were a full 24 months or longer after SBRT. This may be related to the fact that the most common dose fractionation regimens used were 27 Gy in 3 fractions and 30 Gy in 5 fractions, which are much more conservative than dose escalated approaches supported by Hytec that are currently integrated into our institutional practice [ 12 ]. At present, given the challenges meeting normal tissue constraints for large paraspinal masses, we typically deliver fractionated regimens of 40 Gy in 5 fractions to histologies with standard radiosensitivity and 45 Gy in 5 fractions to histologies historically considered radioresistant. Interestingly, in a dose-intensified study of SBRT, paraspinal involvement was not associated with worse outcomes, as it previously was in historical studies, emphasizing the need to further investigate these dose-escalated regimens [ 46 ]. One consideration is the role of histology in driving outcomes in these patients. Our patient population was more heterogenous than Ong et al. whose cohort consisted primarily of kidney and breast tumors. While we did not see a relationship between tumor histology and rate of recurrence, this may be driven by the limited number of patients and power to detect any relationship. Ultimately, more data is needed to better understand if a uniform approach across histologies is suitable or if target delineation should be tailored by tumor type. Interestingly, historical data suggests that pain control following SBRT for spinal metastases with paraspinal extension are superior to radiographic local control, with rates of pain control of 75% or greater [ 47 ]-[ 51 ]. Current reports define local control by SPINO criteria rather than pain response, including our series. However, in regard to modern pain control with SBRT, our analysis yielded complete pain responses consistent with previous data. Specifically, complete pain response was approximately about 35% at both 3 and 6 months which is consistent with the recently published randomized controlled trial, SC-24 [ 10 ]. Given the limited data regarding outcomes following SBRT for paraspinal metastases, this study represents an important contribution to the literature. Nonetheless, there are several limitations including the retrospective nature, small sample size, and biases inherent to its single institution nature. In addition, there is a relatively low percentage of common histologies such as breast (4%) and prostate (3%) and limited patients with evaluable outcomes data at late time points. Furthermore, the majority of patients were treated with doses of RT that are considered overly conservative in the context of an increasing body of literature supporting the importance of dose escalation in optimizing local control. Only a limited number of patients were treated with doses such as 40 Gy in 5 fractions and 45 Gy in 5 fractions (for radioresistant histologies), which represent the current standard practice at our institution. It remains unclear if this will help to improve local control in this patient population as it does in patients with spinal metastases contained within the bone. Conclusions We report high rates of local recurrence following SBRT for spinal metastases with paraspinal extension, albeit markedly lower than the 55% rate reported in older studies. Interestingly, 40% of failures involved the paraspinal region, supporting the potential benefit of larger asymmetric CTV expansions in regions of paraspinal involvement. Future studies will be essential to explore methods to improve outcomes in this patient population such as dose escalation, larger CTV expansions and/or potential combination with ablation. Declarations Corresponding Author Dr. Kristin Redmond, [email protected] Competing Interests KJR: research funding from Accuray, Canon, Icotec, GammaTile and Teleflex; honorarium for speaking engagement from Accuray and Icotec; travel support from Brainlab and Icotec; patent under development with Canon; Data Safety Monitoring Board for BioMimetix DL: Consulting for Globus, Johnson and Johnson, Hemoblast, and research support from Icotec, AO foundation, Premier Inc All other authors of no relevant funding or non-funding competing interests to disclose. Ethics Approval This study was retrospective in nature with no potential harm to those involved. Research took place under an approved IRB from Johns Hopkins University and did not require specific ethical approval. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contribution DR contributed to data collection and analysis, manuscript writing and editing. NV contributed to data collection, data analysis, manuscript writing and editing. MCL contributed to study design, data collected and analysis, manuscript writing and editing. MK, AB, KK, NT, BW, LRK, SHL, and DL contributed to study design and methods, manuscript writing and editing. KJR contributed to study design and methods, data collection and analysis, manuscript writing and editing. Data Availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. 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Available: https://www.redjournal.org/article/S0360- 3016(13)01384-9/fulltext . DOI: 10.1016/j.ijrobp.2013.06.714 Sahgal A et al (2007) Proximity of Spinous/Paraspinous Radiosurgery Metastatic Targets to the Spinal Cord Versus Risk of Local Failure, International Journal of Radiation Oncology, Biology, Physics , vol. 69, (3) , p. S243, Available: https://www.redjournal.org/article/S0360-3016( 07)02521-7/fulltext . DOI: 10.1016/j.ijrobp.2007.07.1240 Nelson JW et al (2009) Stereotactic Body Radiotherapy for Lesions of the Spine and Paraspinal Regions, International Journal of Radiation Oncology*Biology*Physics , vol. 73, (5) , pp. 1369–1375, Available: https://www.sciencedirect.com/science/article/pii/S0360301608031027 . 10.1016/j.ijrobp.2008.06.1949 Soltys SG et al (2021) Stereotactic Body Radiation Therapy for Spinal Metastases: Tumor Control Probability Analyses and Recommended Reporting Standards, International Journal of Radiation Oncology*Biology*Physics , vol. 110, (1) , pp. 112–123, Available: https://www.sciencedirect.com/science/article/pii/S0360301620345430 . 10.1016/j.ijrobp.2020.11.021 Garg AK et al (2011) Prospective evaluation of spinal reirradiation by using stereotactic body radiation therapy: The University of Texas MD Anderson Cancer Center experience, Cancer , vol. 117, (15) , pp. 3509–3516, Available: https://pubmed.ncbi.nlm.nih.gov/21319143/ . 10.1002/cncr.25918 Myrehaug S et al (2017) Reirradiation spine stereotactic body radiation therapy for spinal metastases: systematic review, J Neurosurg Spine , vol. 27, (4) , pp. 428–435, Available: https://pubmed.ncbi.nlm.nih.gov/28708043/ . 10.3171/2017.2.SPINE16976 Guckenberger M et al (2025) Dose-intensified SBRT for vertebral oligometastases: results from a prospective clinical trial, Radiother Oncol , vol. 208, p. 110940, Available: https://pubmed.ncbi.nlm.nih.gov/40378895/ . 10.1016/j.radonc.2025.110940 Dirk et al Evaluation of Five Radiation Schedules and Prognostic Factors for Metastatic Spinal Cord Compression | Journal of Clinical Oncology, Available: https://ascopubs.org/doi/full/ 10.1200/JCO.2005.04.754 Rades D et al (2007) Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression, International Journal of Radiation Oncology*Biology*Physics , vol. 67, (2) , pp. 525–531, Available: https://www.sciencedirect.com/science/article/pii/S0360301606029944 . 10.1016/j.ijrobp.2006.09.025 van der Linden YM et al (2005) Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy, Cancer , vol. 103, (2) , pp. 320–328, Available: https://pubmed.ncbi.nlm.nih.gov/15593360/ . 10.1002/cncr.20756 van der Linden YM et al (2006) Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: Results on survival in the Dutch Bone Metastasis Study, Radiotherapy and Oncology , vol. 78, (3) , pp. 245–253, Available: https://www.sciencedirect.com/science/article/pii/S0167814006000703 . 10.1016/j.radonc.2006.02.007 Masashi Mizumoto MD et al Prognostic Factors for Local Control and Survival After Radiotherapy of Metastatic Spinal Cord Compression | Journal of Clinical Oncology, Available: https://ascopubs.org/doi/full/ 10.1200/JCO.2005.05.0542 Additional Declarations Competing interest reported. KJR: research funding from Accuray, Canon, Icotec, GammaTile and Teleflex; honorarium for speaking engagement from Accuray and Icotec; travel support from Brainlab and Icotec; patent under development with Canon; Data Safety Monitoring Board for BioMimetix DL: Consulting for Globus, Johnson and Johnson, Hemoblast, and research support from Icotec, AO foundation, Premier Inc All other authors of no relevant funding or non-funding competing interests to disclose. Cite Share Download PDF Status: Published Journal Publication published 24 Mar, 2026 Read the published version in Journal of Neuro-Oncology → Version 1 posted Editorial decision: Revision requested 17 Feb, 2026 Reviews received at journal 11 Feb, 2026 Reviewers agreed at journal 09 Feb, 2026 Reviewers agreed at journal 06 Feb, 2026 Reviews received at journal 06 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers invited by journal 03 Feb, 2026 Editor assigned by journal 03 Feb, 2026 Submission checks completed at journal 03 Feb, 2026 First submitted to journal 29 Jan, 2026 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. 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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-8730558","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":585969273,"identity":"9babcd49-c43a-4532-b894-81a11ccf960d","order_by":0,"name":"Dylan Ross","email":"","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dylan","middleName":"","lastName":"Ross","suffix":""},{"id":585969278,"identity":"b6e063fb-2819-47b3-a60f-b2e14ebe0a32","order_by":1,"name":"Neil Vuppala","email":"","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":false,"prefix":"","firstName":"Neil","middleName":"","lastName":"Vuppala","suffix":""},{"id":585969284,"identity":"00b435b9-9a7b-4f86-9886-21902a37727c","order_by":2,"name":"Michael LeCompte","email":"","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"LeCompte","suffix":""},{"id":585969290,"identity":"d7a6b4a3-7d38-4427-9109-7086eb76b1e4","order_by":3,"name":"Majid Khan","email":"","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":false,"prefix":"","firstName":"Majid","middleName":"","lastName":"Khan","suffix":""},{"id":585969298,"identity":"fba40e53-e29e-48bf-ad14-ce3cb2dff30b","order_by":4,"name":"Ali Bydon","email":"","orcid":"","institution":"Johns Hopkins 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Binbin","middleName":"","lastName":"Wu","suffix":""},{"id":585969320,"identity":"18c85f81-6e7e-4c79-b565-7dd615f36a36","order_by":8,"name":"Lawrence Kleinberg","email":"","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lawrence","middleName":"","lastName":"Kleinberg","suffix":""},{"id":585969323,"identity":"e6930240-7f6b-4591-b94a-a7a8b6c62921","order_by":9,"name":"Sang Lee","email":"","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sang","middleName":"","lastName":"Lee","suffix":""},{"id":585969328,"identity":"84edb644-11fd-47e5-96c0-055c055d1f00","order_by":10,"name":"Daniel Lubelski","email":"","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Lubelski","suffix":""},{"id":585969332,"identity":"ec86df1d-4e1d-4e4f-8bed-9b27712fe52b","order_by":11,"name":"Kristin Redmond","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIie3QMQrCMBiG4T+4VrsmhHqGQiAu0rNUCj2CdIxLR2e9RUFwjgTtEp0rOOjSI0idtKaLdElHh7xLviEPhAC4XH8YBmnOyAcNEAMgMZQkRAwnXaiQXjeshKxU/Wiy24gdzsfiDvOgkBZC4TRjnq4nXF7SKoaUWckUJKcoVyMuNW+JWgwg5ZO8coV2wpC3nVDQHI9bUoAh0k7av11ST6sEm4eFCdvaCK7KPWkyFfkbza9NFgVrGwEsf0dou/7NF/3hcrlcrl4fXulNrkFAOfMAAAAASUVORK5CYII=","orcid":"","institution":"Johns Hopkins Medicine","correspondingAuthor":true,"prefix":"","firstName":"Kristin","middleName":"","lastName":"Redmond","suffix":""}],"badges":[],"createdAt":"2026-01-29 10:58:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8730558/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8730558/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11060-026-05512-8","type":"published","date":"2026-03-24T16:12:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":102182308,"identity":"a2e9bb14-84f4-47ff-8459-fc63cf023062","added_by":"auto","created_at":"2026-02-09 07:28:54","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":452998,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative plan of asymmetric expansion to cover paraspinal disease. \u003c/strong\u003eThis patient is a patient treated to L5 myxoid liposarcoma to 4500 cGy in 5 fractions. At most recent follow up 27 months after treatment there was no evidence of local failure.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8730558/v1/29f4361bcbb053c26f2438ff.jpeg"},{"id":102182307,"identity":"2ef18ab9-a30a-4284-b0dc-14a834b0361a","added_by":"auto","created_at":"2026-02-09 07:28:54","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":138337,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative incidence of local failure over time in months. \u003c/strong\u003eThe 12-month LF rate was 30%.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8730558/v1/ee142113e59575abed04d71d.jpeg"},{"id":102182309,"identity":"37d6f99b-010b-429b-9bc1-08bf2bf7c7c8","added_by":"auto","created_at":"2026-02-09 07:28:55","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":209939,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSchematic representation of locations of local failure. \u003c/strong\u003e19.4% failed in vertebral body only, 26.7% failed in paraspinal region only, and 16.7% failed in epidural space only. 20% failed in vertebral body and epidural space at the same time. 3% failed in the vertebral body and paraspinal region, and 3% also failed in the epidural and paraspinal region at the same time. 7% failed in all 3 components simaltenously.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8730558/v1/2884413ec92ab4601b25a225.jpeg"},{"id":105755024,"identity":"4616b0a7-e187-4640-a5f0-86abe44efe36","added_by":"auto","created_at":"2026-03-30 16:24:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1578404,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8730558/v1/cf724ef2-d8f3-4e79-a22a-6d05b1f34571.pdf"}],"financialInterests":"Competing interest reported. KJR: research funding from Accuray, Canon, Icotec, GammaTile and Teleflex; honorarium for speaking engagement from Accuray and Icotec; travel support from Brainlab and Icotec; patent under development with Canon; Data Safety Monitoring Board for BioMimetix \n\nDL: Consulting for Globus, Johnson and Johnson, Hemoblast, and research support from Icotec, AO foundation, Premier Inc \n\nAll other authors of no relevant funding or non-funding competing interests to disclose.","formattedTitle":"Clinical Outcomes of Stereotactic Body Radiotherapy for Spinal Metastases with Paraspinal Extension","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe spinal column has a high incidence of metastatic disease, estimated to be involved in 15\u0026ndash;20% in patients with solid tumors [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In recent years, management of spine metastases has progressed from exclusively pain control to aggressive multi-disciplinary care with the goal of durable local control, especially in patients with limited sites of disease [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]-[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In this light, spinal stereotactic body radiotherapy (SBRT) has shown the ability to improve local control (LC) without compromising quality of life (QOL) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultiple studies have validated the improved local control and pain control rates seen with SBRT techniques, including a randomized controlled study demonstrating a superior rate of complete pain relief at both 3 and 6 months compared to conventional radiation [\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]-[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Notably, SC.24 compared 24 Gy in 2 fractions with conventional RT in a randomized controlled trial and showed significantly improved complete pain responses at both 3- and 6-months [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Meta-analysis suggests that single fraction SBRT boasts local control rates of \u0026gt;\u0026thinsp;90%, significantly improved from conventional radiation therapy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Other well-validated reports have summarized local control rates for a variety of fractionated SBRT regimens, all with the ability to achieve LC approaching or surpassing 90% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite this promise, paraspinal extension of spinal metastatic disease has been shown as an important risk factor for worse outcomes in multiple studies [\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]-[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. A few retrospective studies have reported outcomes using SBRT in this patient population, however, data is underreported [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] The purpose of this study is to better characterize patterns of local recurrence in this patient population with the goal of improving outcomes moving forward. To try to overcome the historically poor local control in this patient population, our institutional practice for clinical target volume delineation in recent years typically involves an approximately 3 mm expansion in the direction of paraspinal involvement. This analysis also aims to explore if this approach impacts local control and patterns of failure relative to prior publications.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Selection\u003c/h2\u003e \u003cp\u003ePatients with nonhematologic spinal metastases with paraspinal extension treated with SBRT at a single institution from 2009\u0026ndash;2021 were retrospectively reviewed. Our Institutional Review Board approved this study. Paraspinal extension was defined as defined as tumor extension beyond the cortex of the bone. Patients with prior surgery and prior radiotherapy to the same vertebral level were included.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRadiation Technique\u003c/h3\u003e\n\u003cp\u003eSBRT was delivered using a robotic platform or linear accelerator-based system. Gross-tumor-volume (GTV) was delineated using the simulation CT and co-registered MRI sequences, typically T1 pre- and post-contrast, and a T2 variant. Clinical-target-volume (CTV) was based on the consensus contouring guidelines for intact and post-operative spine SBRT [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. However, given the historically poor local control in this patient population, the institutional practice for CTV delineation in recent years typically involves an additional approximately 3 mm expansion in the direction of paraspinal involvement. Planning-target-volume (PTV) expansion was typically 1 mm radially. Prescription dose was selected by the treating radiation oncologist. The spinal cord and neural avoidance elements were delineated on T2 weighted MRI or CT-myelogram in cases of extensive metal artifact from spinal instrumentation. Dose constraints were applied to the spinal cord expanded radially by 2mm or the true cauda equina without expansion. Dose constraints for the neural avoidance structure were according to Sahgal and colleagues[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Constraints for the remainder of organs-at-risk (OARs) were per TG-101 [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In the reirradiation setting, the cord plus 2 mm was allowed a cumulative BED3 of 75 accounting for 25% repair at 6 months after prior RT and 50% repair at 1 year. The cauda equina was allowed a cumulative BED3 of 106 accounting for the same repair factors [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eOutcome Measures\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eOutcome Measures\u003c/div\u003e \u003cp\u003eThe primary outcome of the current study was local failure (LF), defined per Spine response assessment in Neuro-Oncology (SPINO) criteria as unequivocal tumor volume growth or new or progressive epidural disease that persisted beyond 3 months following SBRT and/or on repeat imaging [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. LF events were then categorized as involving the vertebra, the epidural space, and/or the paraspinal component. Failures that occurred in multiple regions were included in each category. Patients were generally seen in follow up by a oncology care team provider for clinical evaluation and surveillance imaging at approximately 3-month intervals following SBRT. Pain response was defined using a combination of pain score and analgesic consumption, as is recommended by international consensus guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Pain response compared a pre-SBRT reference to pain levels at 3-month intervals and was categorized as: (i) complete response defined as a pain level rated as 0; (ii) partial response defined as a pain level that decreased by \u0026ge;\u0026thinsp;2 with the same or lower analgesic consumption (measured by oral morphine equivalents [OME]), or the same pain level with \u0026ge;\u0026thinsp;25% decrease in OME; (iii) stable defined as same pain level and OME; (iv) worse pain defined as higher pain level [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eLF was calculated in months from the end of SBRT to failure event or the last follow up (censored). Cumulative incidence of LF was estimated using Fine and Gray methodology with death as a competing risk. Craniocaudal extent of paraspinal mass, number of vertebral segments involved in the lesion, treatment of the entire circumference of the vertebral segment (i.e., a donut), pre-existing compression fracture at the same level, immunotherapy use, radioresistant primary histology, paraspinal involvement of ribs, organ abutment (gastrointestinal structures or kidney), paraspinal muscle invasion, RTOG conformity index (CI), and dosimetric variables were evaluated for associations with time to LF event using univariate cox proportional hazard modelling [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Any characteristics found to be associated with LF were planned to be included in a multivariate model. Regarding dosimetric data, all fractionation schemes were converted to 3-fraction equivalent doses (3fxED) using the linear quadratic model with an alpha/beta of 3. A p value of less than 0.05 was considered statistically significant. Statistical analyses were completed using STATA v18.0 software (College Station, TX).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eSeventy-six paraspinal masses from 69 patients included in the analysis. Median follow-up was 11.8 months. Fifty-nine sites were radiation naive, and 17 sites received previous radiation to the same levels. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e displays a summary of clinical and dosimetry results. Common primary tumor types were non-small cell lung cancer (n\u0026thinsp;=\u0026thinsp;13, 17%), sarcoma (n\u0026thinsp;=\u0026thinsp;12, 16%), and gastrointestinal (n\u0026thinsp;=\u0026thinsp;12, 16%). Twenty-one percent of paraspinal disease cases spanned 1 vertebral segment, 34% spanned 2 segments, 33% spanned 3 segments, and 12% spanned\u0026thinsp;\u0026ge;\u0026thinsp;4 segments. Sixty-seven percent of cases occurred in the thoracic region; in this location, 76% of paraspinal masses involved adjacent ribs. Twenty-one percent of paraspinal masses abutted or compressed gastrointestinal organs or the kidney, and 18% had muscle invasion. The median craniocaudal extent of the paraspinal masses was 3.6 cm (1.0\u0026ndash;8.8 cm). Two patients experienced grade 3 vertebral compression fractures (VCF) while 0 patients experienced grade 3 myelopathy.\u003c/p\u003e \u003cp\u003eThe median PTV size was 133 cc (22\u0026ndash;753cc). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e displays a representative case of asymmetric volume expansion. The most common prescriptions for radiation naive patients were 2700 cGy in 3 fractions (22%), 2400 cGy in 2 fractions (12%), and 3000 cGy in 5 fractions (12%). Re-irradiation patients most commonly were prescribed 2700 cGy in 3 fractions (12%), 2500 cGy in 5 fractions (4%), and 3000 cGy in 5 fractions (2.5%). Re-irradiation occurred most commonly after an initial prescription of either conventional 30 Gy in 10 fractions (29.4%) or 27 Gy in 3 fractions (23.5%). Additional prescription details may be found in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eAt 3 months post-SBRT, complete pain response was 39%, and partial pain response was 15%, while at 6 months, complete pain response was 37%, and partial pain response was 14%. The 12-month incidence of LF was 30% \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. In terms of local failure, 50% involved the vertebrae, 47% involved the epidural space, and 40% involved the paraspinal region. These values exceed 100% as 33% of failures involved 2 or more regions. Specifically, 20% with vertebral body and epidural, 3% with vertebral body and paraspinal region, 3% with both epidural and paraspinal, and 7% with all 3 components showing progression \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Seventy-seven percent of LFs included a marginal component. Of the marginal failures, 35% involved the paraspinal component and 57% involved the epidural space. On univariate analysis, clinical and dosimetric data were not significantly associated with LF events. PTV volume of greater than 225cc (75th percentile of our dataset) trended towards significance at p\u0026thinsp;=\u0026thinsp;0.08 \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. PTV volume with a shape of a donut (full vertebral body included in PTV with cord PRV subtracted out of the middle) also trended towards significance (p\u0026thinsp;=\u0026thinsp;0.07) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Five of the 17 (29.4%) re-irradiated sites had local failure at a median time of 7.4 months after SBRT. Twenty-six of the 59 (44.1%) of radiation naive sites had local failure at a median time of 4.4 months (p\u0026thinsp;=\u0026thinsp;0.40, Fisher\u0026rsquo;s exact).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and dosimetric variables. N (%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNSCLC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (17.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (15.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (15.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (10.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (5.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMelanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (9.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of Vertebral Segments\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (21.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (34.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (32.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpinal Level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThoracic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (67.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLumbar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (26.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParaspinal Involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRibs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (76.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBowel/Kidney abutment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (21.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscle invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (18.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSize\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniocaudal extent [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.6 cm [1.0-8.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrescription Doses for Radiation Na\u0026iuml;ve Patients (N\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27 Gy in 3 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (28.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 Gy in 2 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (15.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (15.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (10.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 Gy in 3 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21 Gy in 3 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30 Gy in 3 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (8.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrescriptions-Previously Radiated (N\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27 Gy in 3 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (53.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (17.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27.5 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrescriptions of Previous Radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30 Gy in 10 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (29.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27 Gy in 3 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (23.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 Gy in 3 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15 Gy in 1 fraction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 Gy in 2 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35 Gy in 5 fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGTV size [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.9cm [7.8\u0026ndash;170]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTV size [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133cc [78.1-213.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis of clinical and dosimetric variables for local failure. Data reported as Hazard Ration (95% Confidence Interval) with p-values in separate column.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniocaudal extent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98 (0.75\u0026ndash;1.28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.89\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of vertebral segments\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.92 (0.6\u0026ndash;1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTV donut shape\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.97 (0.9\u0026ndash;4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRTOG CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.54 (0.25\u0026ndash;1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-existing VCF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.6 (0.7\u0026ndash;3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunotherapy treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.63 (0.28\u0026ndash;1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadioresistant histology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.2 (0.4\u0026ndash;26.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRib involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.3 (0.44\u0026ndash;3.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrgan abutment (GI, kidney)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.88 (0.37\u0026ndash;2.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscle invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.2 (0.55\u0026ndash;2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTV maximum dose (3 fraction dose)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0 (0.97\u0026ndash;1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTV volume \u0026gt;\u0026thinsp;150cc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.68 (0.83\u0026ndash;3.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTV volume \u0026gt;\u0026thinsp;225cc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.03 (0.91\u0026ndash;4.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis single institution analysis revealed a radiographic LF rate of 30% one year after SBRT which is lower than expected following SBRT for disease confined to the spinal column [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], [\u003cspan additionalcitationids=\"CR34 CR35 CR36\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]-[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The radiographic LF rate is much improved, however, compared to historical data of paraspinal extension which reported rates of 55% when spinal disease extended beyond osseous borders [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Our results were corroborated by another recently published series using similar techniques that showed a 12-month LF rate of 19.5% [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] When stratified by paraspinal volume of greater or less than 43mL, LF rates at one year increased from 12% to 36.3%. Our study\u0026rsquo;s univariate analysis did not find significant correlation when stratifying PTV size at thresholds of 150cc and 225cc although hazard ratios were trending towards significance. However, the mean PTV size in our study was much larger than Ong et al, which may contribute to the size correlation discrepancy.\u003c/p\u003e \u003cp\u003eInterestingly, the rate of local failure was higher and time to failure earlier in radiation na\u0026iuml;ve patients. We speculate this may be due to differences in doses received between the LFs compared to the locally controlled patients, however, this was not statistically significant. It appears re-irradiation cumulative doses received to the spinal levels continues to improve control, providing reinforcement that re-irradiation is warranted in cases of LF. Further investigation is needed.\u003c/p\u003e \u003cp\u003eThe reason for poorer outcomes following SBRT to spinal lesions with paraspinal extension remains unclear. It may be that this reflects baseline poor biology in that only the most aggressive tumors extend beyond the cortex of the bone. However, it is also plausible that the difference represents the difficulty with target delineation in these patients. Incorporation of advanced imaging techniques may be considered to alleviate this challenge. In addition, paraspinal lesions have less anatomic barriers to microscopic spread than those contained within the vertebrae. As such, our institutional practice has been to do a larger expansion in the region of paraspinal disease. Although our data are optimistic compared to the older series by Mizumoto, a real opportunity for improvement persists [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn terms of patterns of failure, Ong et al reported 49% in paraspinal region and 63% in epidural space, which is consistent with our results showing 40% and 47%, respectively. This is unique from intact spine SBRT which recur overwhelmingly in the epidural space, given the need to respect the radiation dose tolerance of the spinal cord [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], [\u003cspan additionalcitationids=\"CR40 CR41\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]-[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Notably, 77% of recurrences were marginal failures, 35% of which were in the paraspinal region of disease [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This may be driven by the need to meet normal tissue constraints for adjacent organs such as the bowel or kidney [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], it raises the hypothesis that target contours should be more generous in these cases or include larger CTV expansion in the paraspinal region.\u003c/p\u003e \u003cp\u003eAn important aspect of our data is the inclusion of previously irradiated patients and vertebral levels. Seventeen such patients were included in our data set with a local failure rate of 29.4%. Detsky et al reported LF rates of 18% for SBRT re-irradiation with paraspinal extension being predictive of LF [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A similar series reported LF rates of 23% with 46% of these failures involving the paraspinal region [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Again, paraspinal involvement was predictive of worse control in the re-irradiation series. LF rates of about 25% in re-irradiation settings using SBRT have been shown in other studies as well [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Considering the initial involvement of the paraspinal region in all seventeen patients in our series, 29.4% LF rate for SBRT re-irradiation is promising in this limited sample size.\u003c/p\u003e \u003cp\u003eIn terms of time to progression, we report a high rate of late failures in the limited number of patients evaluable at these late time points. Specifically, 43% of our LFs occur 18\u0026thinsp;+\u0026thinsp;months after SBRT and 23% were a full 24 months or longer after SBRT. This may be related to the fact that the most common dose fractionation regimens used were 27 Gy in 3 fractions and 30 Gy in 5 fractions, which are much more conservative than dose escalated approaches supported by Hytec that are currently integrated into our institutional practice [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. At present, given the challenges meeting normal tissue constraints for large paraspinal masses, we typically deliver fractionated regimens of 40 Gy in 5 fractions to histologies with standard radiosensitivity and 45 Gy in 5 fractions to histologies historically considered radioresistant. Interestingly, in a dose-intensified study of SBRT, paraspinal involvement was not associated with worse outcomes, as it previously was in historical studies, emphasizing the need to further investigate these dose-escalated regimens [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOne consideration is the role of histology in driving outcomes in these patients. Our patient population was more heterogenous than Ong et al. whose cohort consisted primarily of kidney and breast tumors. While we did not see a relationship between tumor histology and rate of recurrence, this may be driven by the limited number of patients and power to detect any relationship. Ultimately, more data is needed to better understand if a uniform approach across histologies is suitable or if target delineation should be tailored by tumor type.\u003c/p\u003e \u003cp\u003eInterestingly, historical data suggests that pain control following SBRT for spinal metastases with paraspinal extension are superior to radiographic local control, with rates of pain control of 75% or greater [\u003cspan additionalcitationids=\"CR48 CR49 CR50\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]-[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Current reports define local control by SPINO criteria rather than pain response, including our series. However, in regard to modern pain control with SBRT, our analysis yielded complete pain responses consistent with previous data. Specifically, complete pain response was approximately about 35% at both 3 and 6 months which is consistent with the recently published randomized controlled trial, SC-24 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the limited data regarding outcomes following SBRT for paraspinal metastases, this study represents an important contribution to the literature. Nonetheless, there are several limitations including the retrospective nature, small sample size, and biases inherent to its single institution nature. In addition, there is a relatively low percentage of common histologies such as breast (4%) and prostate (3%) and limited patients with evaluable outcomes data at late time points. Furthermore, the majority of patients were treated with doses of RT that are considered overly conservative in the context of an increasing body of literature supporting the importance of dose escalation in optimizing local control. Only a limited number of patients were treated with doses such as 40 Gy in 5 fractions and 45 Gy in 5 fractions (for radioresistant histologies), which represent the current standard practice at our institution. It remains unclear if this will help to improve local control in this patient population as it does in patients with spinal metastases contained within the bone.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe report high rates of local recurrence following SBRT for spinal metastases with paraspinal extension, albeit markedly lower than the 55% rate reported in older studies. Interestingly, 40% of failures involved the paraspinal region, supporting the potential benefit of larger asymmetric CTV expansions in regions of paraspinal involvement. Future studies will be essential to explore methods to improve outcomes in this patient population such as dose escalation, larger CTV expansions and/or potential combination with ablation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCorresponding Author\u003c/h2\u003e \u003cp\u003eDr. Kristin Redmond, [email protected]\u003c/p\u003e \u003c/p\u003e\u003cp\u003e\u003ch2\u003eCompeting Interests\u003c/h2\u003e\u003cp\u003eKJR: research funding from Accuray, Canon, Icotec, GammaTile and Teleflex; honorarium for speaking engagement from Accuray and Icotec; travel support from Brainlab and Icotec; patent under development with Canon; Data Safety Monitoring Board for BioMimetix DL: Consulting for Globus, Johnson and Johnson, Hemoblast, and research support from Icotec, AO foundation, Premier Inc All other authors of no relevant funding or non-funding competing interests to disclose.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e \u003ch2\u003eEthics Approval\u003c/h2\u003e \u003cp\u003eThis study was retrospective in nature with no potential harm to those involved. Research took place under an approved IRB from Johns Hopkins University and did not require specific ethical approval.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDR contributed to data collection and analysis, manuscript writing and editing. NV contributed to data collection, data analysis, manuscript writing and editing. MCL contributed to study design, data collected and analysis, manuscript writing and editing. MK, AB, KK, NT, BW, LRK, SHL, and DL contributed to study design and methods, manuscript writing and editing. 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class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\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":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8730558/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8730558/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e \u003cp\u003eSBRT for spinal column metastases with paraspinal extension poses a challenge for local control. However, data is limited. The purpose of this study is to better characterize patterns of local recurrence in this patient population with the goal of improving outcomes.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003ePatients with spinal metastases with paraspinal extension treated with SBRT at a single institution from 2009\u0026ndash;2021 were reviewed. Sites with previous surgery and/or radiation were included. Univariate analysis of size, PTV shape, previous fracture, multiple vertebral levels, muscle invasion, organ abutment, and dosimetric variables in relation to time-to-local failure (LF) was performed.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eSeventy-six paraspinal masses were included in the analysis. Median follow-up period was 11.8 months. Seventy-six percent of thoracic paraspinal masses involved adjacent ribs. Twenty-one percent of paraspinal masses abutted organs, 18% had muscle invasion. The most common prescription for both radiation naive and re-irradiation treatments was 2700 cGy in 3 fractions. The 12-month incidence of local failure (LF) was 30% overall and 29.4% for re-irradiated sites. Forty percent of LFs involved the paraspinal region. No analyzed variables were significantly associated with LF events, PTV \u0026gt;\u0026thinsp;225cc and PTV shape (donut) trended toward significance (p\u0026thinsp;=\u0026thinsp;0.08 and 0.07).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eWhile clinical and dosimetric variables did not show significant associations with LF, a large portion of LF occurrences were observed within the paraspinal region, suggesting that a generous asymmetrical expansion in the direction of paraspinal disease may help improve outcomes. Nonetheless, this study emphasizes the importance of refining treatment approaches for this population.\u003c/p\u003e","manuscriptTitle":"Clinical Outcomes of Stereotactic Body Radiotherapy for Spinal Metastases with Paraspinal Extension","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 07:28:50","doi":"10.21203/rs.3.rs-8730558/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-17T12:36:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-11T07:19:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"234717101737712864446410160054715133117","date":"2026-02-09T06:10:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"82612903765607351336392166483093903350","date":"2026-02-06T07:37:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-06T06:23:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"208563590776824850153079300626107110342","date":"2026-02-06T03:12:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T10:44:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"275208275926684842554008609475398715650","date":"2026-02-04T12:37:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-03T17:55:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-03T17:48:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-03T17:48:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neuro-Oncology","date":"2026-01-29T09:55:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"83e3b0c2-3caa-4fd3-9204-85698ce56410","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T16:19:25+00:00","versionOfRecord":{"articleIdentity":"rs-8730558","link":"https://doi.org/10.1007/s11060-026-05512-8","journal":{"identity":"journal-of-neuro-oncology","isVorOnly":false,"title":"Journal of Neuro-Oncology"},"publishedOn":"2026-03-24 16:12:45","publishedOnDateReadable":"March 24th, 2026"},"versionCreatedAt":"2026-02-09 07:28:50","video":"","vorDoi":"10.1007/s11060-026-05512-8","vorDoiUrl":"https://doi.org/10.1007/s11060-026-05512-8","workflowStages":[]},"version":"v1","identity":"rs-8730558","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8730558","identity":"rs-8730558","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}