Spine Stereotactic Body Radiotherapy Research Articles

A Dosimetric Study Comparing Two Beam Arrangement Strategies in Fractionated Thoracic Spine Stereotactic Body Radiotherapy (SBRT) Planning

To compare dosimetric results of two beam arrangement strategies and their robustness to setup uncertainties in fractionated thoracic spine Stereotactic Body Radiotherapy (SBRT) MATERIALS/METHODS: Fifteen patients who received fractionated thoracic spine SBRT were retrospectively studied. All patients received simulation CT scans in body vacuum bag immobilization and multiparametric MRI exams. Clinical target volumes (CTVs) included single vertebral bodies with possible paraspinal space inclusion. Planning target volumes (PTVs) were expanded from CTVs with a 2mm margin but were cropped from spinal cord defined by MRI with a 2mm margin. Two different beam arrangement strategies of volumetric modulated arc therapy planning were studied: 1) 5 full arcs (FA) (360° each arc) with different collimator angles; and 2) 6 partial arcs (PA) (90° each arc) divided into two groups (3 arcs in each group) covering patient left-posterior-oblique (LPO) and right-posterior-oblique (RPO) regions, respectively, with orthogonal collimator angles. Both plans (PlanFA and PlanPA) were calculated as 24 Gy in 3 fractions using 6xFFF photon energy and a high-definition MLC model. During the inverse optimization of each plan for same patient, a same set of dose-volume constraints and optimization settings was used to exhaust parameter space search. Key dosimetric results of PTV as well as dose-volume parameters of relevant organs-at-risk (OARs) including spinal cord, esophagus, heart, lung and liver were evaluated. Dosimetric impact of on-board patient setup uncertainties to both plans were also simulated. All comparison results were analyzed by Wilcoxon signed-rank tests when the statistical power was sufficient.Both PlanFA and PlanPA achieved satisfactory spatial dose distribution. After PTV coverage normalization, PlanPA had better PTV dose uniformity (P = 0.026) and PlanFA had better dose fall-off gradient outside PTV. PlanPA had slightly better (18.1 ± 0.8 Gy vs 18.3 ± 0.9 Gy) cord max dose (D0.035cc) results (P = 0.213) and better cord low dose sparing V12 Gy (P = 0.013) results. PlanPA also achieved lower max dose (D0.035cc) of esophagus (P = 0.003) and heart, and improved low dose sparing (V5 Gy) of lung (P = 0.002) and liver. In plan parameter comparisons, PlanFA demonstrated stronger beam modulation effect (P < 0.001) but PlanPA had smaller MLC apertures (P < 0.001). In the simulated on-board scenarios with setup uncertainties, while both PlanFA and PlanPA had similar cord max dose increases with simulated pitch and/or roll in setup (< 0.1 Gy differences), PlanPA had minimal cord max dose increase (P < 0.001) with simulated anterior body weight loss.For thoracic spine SBRT plans, the beam arrangement in PlanPA might be favored dosimetrically with better OAR sparing results and could be less sensitive to certain patient uncertainties, while the PlanFA could be acceptable with satisfactory dosimetry results.C. Wang: None. Y. Xie: None. Z. Hu: None. F. Yin: Research Grant; Varian Medical Systems. Teaching and mentoring graduate students. Administration of graduate program activities; Duke Kunshan University. Board of Directors Member at Large Members; AAPM. organize activities of the SANTRO; SANTRO.Z. Reitman: None. Y. Cui: None.

Circumferential Stereotactic Body Radiotherapy for Spine Metastasis: The Feasibility, Toxicity and Local Control

Circumferential spine stereotactic body radiotherapy (CsSBRT) is indicated in selected patients with circumferential vertebral bone/epidural spine metastatic disease. There is a paucity of data on the feasibility, toxicity and outcomes of CsSBRT. This study aimed to determine the feasibility, toxicities and outcomes of CsSBRT treatments.We analyzed sixty-four circumferential treatments from 2013-2019 treated with SBRT in the post-operative and intact spine metastatic setting. Radiotherapy was delivered with 1-5 fractions. We analyzed the local control, side effects and the dose-volume histogram for each treatment.In the sixty-four plans, the median follow-up was 15 months (1-63 months). All images and treatment plans were reviewed by the CNS radiation oncology and neuro-radiology. The most common regimen used was 27 Gy in 3 fractions. The 12-month cumulative incidence of local failure was 15%. In this cohort, there was eight local failures; 5 of them had recurrence in the epidural space, two had disease progression in the vertebral body and one had disease progression in the vertebral body with extension to the right lateral compartment. The planning target volume (PTV) coverage was ≥95% in 60 plans (94%). The median biologically effective dose (BED) for delivered dose, mean dose, minimum dose and D95% were 51.3 Gy, 54.13 Gy, 29.3 Gy and 51.3 Gy, respectively. The median BED max dose to spinal cord and cauda equine were 59 Gy (15-114) and 68 Gy (7.5-136). There were no grade 3 or higher early or late toxicities reported.In this retrospective analysis of patients who received CsSBRT treatments, we were able to achieve excellent local control safely with minimal toxicity. We recommend at least 2-4 mm space between the target and the spinal cord or cauda equine in order to deliver CsSBRT.K. Dibs: None. J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.A. Olausson: None. E. Bourekas: None. D. Boulter: None. A.S. Ayan: None. E.R. Cochran: None. V. Yildiz: None. J.C. Grecula: None. A.L. Arnett: None. R. Raval: None. S. Beyer: None. T. Scharschmidt: None. J.B. Elder: None. A. Chakravarti: None. E. Mendel: None. D.M. Blakaj: None.

Clinical Implementation and Utility of Triggered kV Imaging During Spine Stereotactic Body Radiotherapy for Intrafraction Motion Management

To monitor intrafraction motion during spine stereotactic radiosurgery (SRS) treatment delivery with readily available device, we implemented triggered kV imaging using the on-board imager of the medical linear accelerator advanced imaging package.Triggered kV imaging technique was clinically implemented and applied to 32 spine SBS patients (75 fx, 20 T-spine tumors, 12 L-spine tumors) during VMAT delivery. Currently available trigger options in the medical linear accelerator software package are MU, gantry angle, time, and respiratory gating. Time trigger was selected to acquire kV images every 15 seconds, in an effort to balance temporal resolution with reasonable time for image evaluation. Upon each image acquisition, a 2D projection of the 3D image-guided radiotherapy (IGRT) structures was automatically calculated and updated at arbitrary angles as a qualitative visual guide for patient alignment during treatment delivery. For IGRT structures, patient anatomy (vertebra and spinous process) and orthopedic hardware if present were contoured, with a 1 mm expansion. As the technique depends on visual inspection, decisions could vary depending on interobserver variability. Therefore, a survey of 10 trained physicists (4) and physicians (6) was conducted to evaluate efficiency and accuracy of clinical decision with kV images collected using an anthropomorphic phantom with different CT slice thicknesses and shifts introduced. The survey consisted of 192 sample images. The participants were asked to determine if a shift requiring intervention was observed. Average time per decision was recorded.The robustness of our current patient immobilization system was validated in our clinical implementation. Based on visual inspection of projected IGRT contours on planar kV images, appreciable movement was detected in only one fraction (1.3%). However, in this instance, motion was well beyond PTV/PRV margins (2.4 mm) and treatment was stopped to take a CBCT and correct the displacement, which otherwise would have not been detected. From the survey, the average time spent per decision was 7.5 seconds. In all shift directions, detectability was proportional to the shift size and superior detectability was observed with contours drawn using CT images with 1 mm slice thickness. Shifts smaller than 1 mm are less noticeable (12.6%) compared to 2 mm shifts (42.6%). Participant detection capability was dependent on the level of training.This approach provides an effective, non-invasive intrafraction motion monitoring solution, using the built in triggered-imaging technique of the medical linear accelerator. One of the benefits this technique offers is that it can serve as a quality assurance approach to verify adequacy of a patient immobilization system. An important limitation is that the monitoring result is qualitative and depends on observer visual detection capability. Enhanced precision and utility could be achieved if an automated quantitative evaluation feature is implemented.J. Koo: None. L.Nardella: None. M.Degnan: None. J.Andreozzi: None. H.M. Yu: Honoraria; UpToDate. Speaker's Bureau; BrainLab. Advisory Board; Novocure, AbbVie. J.A.Penagaricano: None. P.A. Johnstone: None. D.E. Oliver: None. K.A. Ahmed: Research Grant; Bristol-Myers Squibb, Genentech. S.Rosenburg: Consulting; Novocure. E.J.Wuthrick: Research Grant; BMS. Honoraria; Regeneron/Sanofi, Varian. Consultant; Regeneron/Sanofi, Varian. R. Diaz: Honoraria; Zeiss; Global Health Outreach. V.Feygelman: None. E.G. Moros: Research Grant; Varian Medical Systems. Promote research in the AAPM; American Association of Physicists in Medicine. Promoting research in the AAPM; American Association of Physicists in Medicine. G.Redler: None.

Reduction of inter-observer differences in the delineation of the target in spinal metastases SBRT using an automatic contouring dedicated system

BackgroundApproximately one third of cancer patients will develop spinal metastases, that can be associated with back pain, neurological symptoms and deterioration in performance status. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have been offered in clinical practice mainly for the management of oligometastatic and oligoprogressive patients, allowing the prescription of high total dose delivered in one or few sessions to small target volumes, minimizing the dose exposure of normal tissues. Due to the high delivered doses and the proximity of critical organs at risk (OAR) such as the spinal cord, the correct definition of the treatment volume becomes even more important in SBRT treatment, thus making it necessary to standardize the method of target definition and contouring, through the adoption of specific guidelines and specific automatic contouring tools. An automatic target contouring system for spine SBRT is useful to reduce inter-observer differences in target definition. In this study, an automatic contouring tool was evaluated.MethodsSimulation CT scans and MRI data of 20 patients with spinal metastases were evaluated. To evaluate the advantage of the automatic target contouring tool (Elements SmartBrush Spine), which uses the identification of different densities within the target vertebra, we evaluated the agreement of the contours of 20 spinal target (2 cervical, 9 dorsal and 9 lumbar column), outlined by three independent observers using the automatic tool compared to the contours obtained manually, and measured by DICE similarity coefficient.ResultsThe agreement of GTV contours outlined by independent operators was superior with the use of the automatic contour tool compared to manually outlined contours (mean DICE coefficient 0.75 vs 0.57, p = 0.048).ConclusionsThe dedicated contouring tool allows greater precision and reduction of inter-observer differences in the delineation of the target in SBRT spines. Thus, the evaluated system could be useful in the setting of spinal SBRT to reduce uncertainties of contouring increasing the level of precision on target delivered doses.

Evaluation of inter- and intra-fraction 6D motion for stereotactic body radiation therapy of spinal metastases: influence of treatment time

BackgroundThe objective of this study was to analyze the amplitude of translational and rotational movements occurring during stereotactic body radiotherapy (SBRT) of spinal metastases in two different positioning devices. The relevance of intra-fractional imaging and the influence of treatment time were evaluated.MethodsTwenty patients were treated in the supine position either (1) on a body vacuum cushion with arms raised and resting on a clegecel or (2) on an integrated SBRT solution consisting of a SBRT table top, an Orfit™ AIO system, and a vacuum cushion. Alignments between the cone beam computed tomography (CBCT) and the planning computed tomography allowed corrections of inter- and intra-fraction positional shifts using a 6D table. The absolute values of the translational and rotational setup errors obtained for 329 CBCT were recorded. The translational 3D vector, the maximum angle, and the characteristic times of the treatment fractions were calculated.ResultsAn improvement in the mean (SD) inter-fraction 3D vector (mm) from 7.8 (5.9) to 5.9 (3.8) was obtained by changing the fixation devices from (1) to (2) (p < 0.038). The maximum angles were less than 2° for a total of 87% for (1) and 96% for (2). The mean (SD) of the intra-fraction 3D vectors (mm) was lower for the new 1.1 (0.8) positioning fixation (2) compared to the old one (1) 1.7 (1.7) (p = 0.004). The angular corrections applied in the intra-fraction were on average very low (0.4°) and similar between the two systems. A strong correlation was found between the 3D displacement vector and the fraction time for (1) and (2) with regression coefficients of 0.408 (0.262–0.555, 95% CI) and 0.069 (0.010–0.128, 95% CI), respectively. An accuracy of 1 mm would require intra-fraction imaging every 5 min for both systems. If the expected accuracy was 2 mm, then only system (2) could avoid intra-fractional imaging.ConclusionsThis study allowed us to evaluate setup errors of two immobilization devices for spine SBRT. The association of inter- and intra-fraction imaging with 6D repositioning of a patient is inevitable. The correlation between treatment time and corrections to be applied encourages us to move toward imaging modalities which allow a reduction in fraction time.

Thecal Sac Contouring as a Surrogate for the Cauda Equina and Intracanal Spinal Nerve Roots for Spine Stereotactic Body Radiation Therapy (SBRT): Contour Variability and Recommendations for Safe Practice

To present interobserver variability in thecal sac (TS) delineation based on contours generated by 8 radiation oncologists experienced in spine stereotactic body radiation therapy and to propose contouring recommendations to standardize practice. In the setting of a larger contouring study that reported target volume delineation guidelines specific to sacral metastases, 8 academically based radiation oncologists with dedicated spine stereotactic body radiation therapy programs independently contoured the TS as a surrogate for the cauda equina and intracanal spinal nerve roots. Uniform treatment planning simulation computed tomography datasets fused with T1, T2, and T1 post gadolinium magnetic resonance imaging for each case were distributed to each radiation oncologist. All contours were analyzed and agreement was calculated using both Dice similarity coefficient and simultaneous truth and performance level estimation with kappa statistics. A fair level of simultaneous truth and performance level estimation agreement was observed between practitioners, with a mean kappa agreement of 0.38 (range, 0.210.55) and the mean Dice similarity coefficient (± standard deviation, with range) was 0.43 (0.36 ± 0.1 to -0.53 ±0.1). Recommendations for a reference TS contour, accounting for the variations in practice observed in this study, include contouring the TS to encompass all the intrathecal spinal nerve roots, and caudal to the termination of the TS, the bony canal can be contoured as a surrogate for the extra thecal nerves roots that run within it. This study shows that even among high-volume practitioners, there is a lack of uniformity when contouring the TS. Further modifications may be required once dosimetric data on nerve tolerance to ablative doses, and pattern of failure analyses of clinical data sets using these recommendations, become available. The contouring recommendations were designed as a guide to enable consistent and safe contouring across general practice.

Calculation algorithms and penumbra: Underestimation of dose in organs at risk in dosimetry audits.

The aim of this study is to investigate overdose to organs at risk (OARs) observed in dosimetry audits in Monte Carlo (MC) algorithms and Linear Boltzmann Transport Equation (LBTE) algorithms. The impact of penumbra modeling on OAR dose was assessed with the adjustment of MC modeling parameters and the clinical relevance of the audit cases was explored with a planning study of spine and head and neck (H&N) patient cases. Dosimetric audits performed by the Australian Clinical Dosimetry Service (ACDS) of 43 anthropomorphic spine plans and 1318 C-shaped target plans compared the planned dose to doses measured with ion chamber, microdiamond, film, and ion chamber array. An MC EGSnrc model was created to simulate the C-shape target case. The electron cut-off energy Ecut(kinetic) was set at 500, 200, and 10keV, and differences between 1 and 3mm voxel were calculated. A planning study with 10 patient stereotactic body radiotherapy (SBRT) spine plans and 10 patient H&N plans was calculated in both Acuros XB (AXB) v15.6.06 and Anisotropic Analytical Algorithm (AAA) v15.6.06. The patient contour was overridden to water as only the penumbral differences between the two different algorithms were under investigation. The dosimetry audit results show that for the SBRT spine case, plans calculated in AXB are colder than what is measured in the spinal cord by 5%-10%. This was also observed for other audit cases where a C-shape target is wrapped around an OAR where the plans were colder by 3%-10%. Plans calculated with Monaco MC were colder than measurements by approximately 7% with the OAR surround by a C-shape target, but these differences were not noted in the SBRT spine case. Results from the clinical patient plans showed that the AXB was on average 7.4% colder than AAA when comparing the minimum dose in the spinal cord OAR. This average difference between AXB and AAA reduced to 4.5% when using the more clinically relevant metric of maximum dose in the spinal cord. For the H&N plans, AXB was cooler on average than AAA in the spinal cord OAR (1.1%), left parotid (1.7%), and right parotid (2.3%). The EGSnrc investigation also noted similar, but smaller differences. The beam penumbra modeled by Ecut(kinetic) =500keV was steeper than the beam penumbra modeled by Ecut(kinetic) =10keV as the full scatter is not accounted for, which resulted in less dose being calculated in a central OAR region where the penumbra contributes much of the dose. The dose difference when using 2.5mm voxels of the center of the OAR between 500 and 10keV was 3%, reducing to 1% between 200 and 10keV. Lack of full penumbral modeling due to approximations in the algorithms in MC based or LBTE algorithms are a contributing factor as to why these algorithms under-predict the dose to OAR when the treatment volume is wrapped around the OAR. The penumbra modeling approximations also contribute to AXB plans predicting colder doses than AAA in areas that are in the vicinity of beam penumbra. This effect is magnified in regions where there are many beam penumbras, for example in the spinal cord for spine SBRT cases.

Long-term outcomes of spinal SBRT. Is it important to select the treatment time?

SBRT (stereotactic body radiation therapy) is widely used as a curative treatment in tumoral lesions and has become a fundamental tool for the treatment of spine metastasis. In this study, we present survival and toxicity outcomes of spine SBRT after a 2-year follow-up. Data from spine SBRT treatments performed at our institution between March 2012 and February 2020 was collected. Medical records, including demographic, primary tumor, and treatment characteristics were reviewed. Patient follow-up included clinical evaluation, imaging, and blood tests. Toxicity was recorded according to CTCAE v4.0. We analyzed 73 consecutive spine SBRT treatments in 60 patients. 39.7% of the cases had primary breast cancer and 23.3% had prostate cancer. Most cases (87.7%) were treated with a single SBRT fraction of 16Gy. Median follow-up was 26.1months (range 1.7-78.6), and 1- and 2-year overall survival (OS) rates were 96.9% and 84.2%, respectively. Local control (LC) rates at 1- and 2-years were 76.3% and 70.6%, respectively. Multivariate analysis identified histology as a prognostic factor for both OS and LC. Patients who underwent spine SBRT 6months after the spinal lesion diagnosis had LC at 2years of 88%, vs 61.7% for those who underwent SBRT before this period. No grade III or higher toxicity was reported. The vertebral compression fracture (VCF) rate was 4.1%. Spine SBRT at our institution showed a 2-year LC of 70.6%, without G3 toxicities. Delaying SBRT at least 6months to administer systemic treatment was related to an improvement in local control.

A Volumetric Dosimetry Analysis of Vertebral Body Fracture Risk After Single Fraction Spine Stereotactic Body Radiation Therapy

PurposeVertebral compression fractures (VCF) are a common and severe complication of spine stereotactic body radiation therapy (SBRT). We sought to analyze how volumetric dosimetry and clinical factors were associated with the risk of VCF. Methods and MaterialsWe evaluated 173 spinal segments that underwent single fraction SBRT in 85 patients from a retrospective database. Vertebral bodies were contoured and dosimetric values were calculated. Competing risk models were used to evaluate the effect of clinical and dosimetry variables on the risk of VCF. ResultsOur primary endpoint was development of a post-SBRT VCF. New or progressive fractures were noted in 21/173 vertebrae (12.1%); the median time to fracture was 322 days. Median follow-up time was 426 days. Upon multivariable analysis, the percentages of vertebral body volume receiving >20 Gy and >24 Gy were significantly associated with increased risk of VCF (hazard ratio, 1.036, 1.104; P = .029, .044, respectively). No other patient or treatment factors were found to be significant on multivariable analysis. Sensitivity analysis revealed that the percentages of vertebral body volume receiving >20 Gy and >24 Gy required to obtain 90% sensitivity for predicting vertebral body fracture were 24% and 0%, respectively. ConclusionsVCF is a common complication after SBRT, with a crude incidence of 12.1%. Treatment plans that permit higher volumes receiving doses >20 Gy and >24 Gy to the vertebral body are associated with increased risk of VCF. To achieve 90% sensitivity for predicting VCF post-SBRT, the percentage of vertebral volume receiving >20 Gy should be <24% and maximum point dose should be <24 Gy. These results may help guide clinicians when evaluating spine SBRT treatment plans to minimize the risk of developing posttreatment VCF.

Evaluation of the setup discrepancy between 6D ExacTrac and cone beam computed tomography in spine stereotactic body radiation therapy.

The objective of this study was to analyze the difference in residual setup errors between 6D ExacTrac and 3D cone-beam computed tomography (CBCT) image-guided systems in spinal stereotactic body radiation therapy (SBRT). We investigated 76 patients with spinal tumors who received SBRT using Novalis Tx at our institution between January 2013 and September 2020. A Vac-lok (EZ-FIX®, Arlico Medical Company, South Korea) fixture and an assistive device, based on the region involved, were used to immobilize patients and to increase the inter-fractional setup reproducibility. The difference in the root mean square (RMS) between the 6D ExacTrac and 3D CBCT was -0.75 mm, 0.45 mm, 0.16 mm, and -0.03°; the RMS value was 1.31 mm, 1.06 mm, 0.87 mm, and 0.64°; and the standard deviation was 0.80 mm, 0.72 mm, 0.62 mm, and 0.44° for lateral, longitudinal, vertical, and yaw directions, respectively. The difference in the average RMS between ExacTrac and CBCT was <1.03 mm in the translation direction and <0.47° in the rotational direction; the results were statistically significant in the lateral, longitudinal, and vertical directions, but not in the yaw direction. Thus, it is necessary to verify the ExacTrac image according to the CBCT image.

Prognostic Factors Associated With Surviving Less Than 3 Months vs Greater Than 3 Years Specific to Spine Stereotactic Body Radiotherapy and Late Adverse Events.

BACKGROUNDPatient selection is critical for spine stereotactic body radiotherapy (SBRT) given potential for serious adverse effects and the associated costs.OBJECTIVETo identify prognostic factors associated with dying within 3 mo, or living greater than 3 yr, following spine SBRT, to better inform patient selection.METHODSPatients living ≤3 mo after spine SBRT and >3 yr after spine SBRT were identified, and multivariable regression analyses were performed. We report serious late toxicities observed, including vertebral compression fractures (VCF) and plexopathy.RESULTSA total of 605 patients (1406 spine segments) were treated from 2009 to 2018. A total of 51 patients (8.4%) lived ≤3 mo, and 79 patients (13%) survived >3 yr. Significant differences in baseline features were observed. On multivariable analysis, nonbreast/prostate primaries (odds ratio [ORs]: 28.8-104.2, P = .0004), eastern cooperative oncology group (ECOG) ≥2 (OR: 23.7, 95% CI: 3.2-177, P = .0020), polymetastatic disease (OR: 6.715, 95% CI: 1.89-23.85, P = .0032), painful lesions (OR: 3.833-8.898, P = .0118), and paraspinal disease (OR: 2.874, 95% CI: 1.118-7.393, P = .0288) were prognostic for ≤3 mo survival. The 3- and 5-yr rates of VCF were 10.4% and 14.4%, respectively, and 3- and 5-yr rates of plexopathy were 2.2% and 5.1%, respectively. A single duodenal perforation was observed, and there was no radiation myelopathy events.CONCLUSIONShorter survival after spine SBRT was seen in patients with less radiosensitive histologies (ie, not breast or prostate), ECOG ≥2, and polymetastatic disease. Pain and paraspinal disease were also associated with poor survival. Fractionated spine SBRT confers a low risk of late serious adverse events.

Guidelines for Palliative Treatment of Spinal Metastases: Choosing Between Stereotactic Body Radiation Therapy and Conventional Fractionation

Symptomatic spinal metastasis is a frequent complication of cancer that had been treated, until relatively recently, with primitive techniques to modest radiation dose levels, with a baseline assumption of limited survival and poor patient performance in that setting. In the era of targeted and personalized therapies, many patients are living longer and more functionally and are able to manage their disease on the model of chronic illness. Given these developments, an attractive option is the use of stereotactic body radiation therapy (SBRT) to deliver high biologically effective doses of radiation conformally to maximize the palliative gains of treatment. However, randomized data to guide practice are scarce. We review the extant literature and present an algorithmic approach to selecting patients with metastatic disease for palliative spinal SBRT favoring the results of available randomized studies and remaining within the safety constraints supported by evidence from randomized trials.

Stereotactic Body Radiation Therapy for Spinal Metastases: Tumor Control Probability Analyses and Recommended Reporting Standards

We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions. PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose. Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions. Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data.

Local control and patterns of failure for "Radioresistant" spinal metastases following stereotactic body radiotherapy compared to a "Radiosensitive" reference.

The concept of a radioresistant (RR) phenotype has been challenged with use of stereotactic body radiotherapy (SBRT). We compared outcomes following SBRT to RR spinal metastases to a radiosensitive cohort. Renal cell, melanoma, sarcoma, gastro-intestinal, and thyroid spinal metastases were identified as RR and prostate cancer (PCA) as radiosensitive. The primary endpoint was MRI-based local failure (LF). Secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF). From a prospectively maintained database of 1394 spinal segments in 605 patients treated with spine SBRT, 173 patients/395 RR spinal segments were compared to 94 patients/185 PCA segments. Most received 24-28Gy in 2 fractions (68.9%) and median follow-up was 15.5months (range, 1.4-84.2months). 1- and 2-year LF rates were 19.2% and 22.4% for RR metastases, respectively, which were significantly greater (p < 0.001) than PCA (3.2% and 8.4%, respectively). Epidural disease (HR: 2.47, 95% CI 1.65-3.71, p < 0.001) and RR histology (HR: 2.41, 95% CI 1.45-3.99, p < 0.001) predicted for greater LF. Median OS was 17.4 and 61.0months for RR and PCA cohorts, respectively. Lung/liver metastases, polymetastatic disease and epidural disease predicted for worse OS. 2-year VCF rates were ~ 13% in both cohorts. Coverage of the CTV V90 (clinical target volume receiving 90% of prescription dose) by ≥ 87% (HR: 2.32, 95% CI 1.29-4.18, p = 0.005), no prior spine radiotherapy (HR: 1.96, 95% CI 1.09-3.55, p = 0.025), and a greater Spinal Instability Neoplasia Score (p = 0.013) predicted for VCF. Higher rates of LF were observed after spine SBRT in RR metastases. Optimization strategies include dose escalation and aggressive management of epidural disease.

Epidural tumor pseudoprogression after spine SBRT: A case report and a mini review of the literature

Introduction: Stereotactic body radiotherapy (SBRT) to the spine is becoming a more common form of treatment. Response assessment is challenging because pseudoprogression (PP) is difficult to distinguish from true tumor progression (TTP). Methods: We report the case of a patient with anaplastic thyroid carcinoma and a bony metastasis to T-7. The MRI 22 months after the first SBRT to this location showed radiological tumor progression to the epidural space resulting in a re-SBRT. The three and six months MRI after re-SBRT showed again progressive epidural growth. After T-7 vertebrectomy, obtained tissue specimens were histopathologically evaluated. Results: Although the MRI sequences after second SBRT were highly suspicious of tumor progression into epidural space, only a small cluster of carcinoma cells of 1mm diameter was found within the bony structure near the disc, not belonging to the radiologically highly suspicious epidural mass. Conclusion: To our knowledge, we report the first case of a radiographic tumor progression to the epidural space following primary SBRT and re-SBRT, which histopathologically revealed a PP after spine surgery. Based on the “epidural progression criterion” from the SPINO-consensus, the first and the second progression after SBRT should have been classified as TTP. Due to the challenge in distinguishing TTP from PP, reporting of such cases are essential to share experiences and thereby improve the understanding of PP after spine SBRT.

Time Dependence of Intra-fractional Motion in Spinal Stereotactic Body Radiotherapy.

Positional uncertainty in spinal stereotactic body radiotherapy (SBRT) may cause fatal error, therefore, we investigated the intra-fractional spinal motion during SBRT and its time dependency. Thirty-one patients who received SBRT using CyberKnife were enrolled in the study. 2D kV X-ray spine images in two directions were taken before and during treatment. Image acquisition intervals during treatment were set at 35-60 sec. Automatic image matchings were performed between the reference digital reconstructed radiography (DRR) and live images, and the spinal position displacements were logged in six translational and rotational directions. If the displacements exceeded 2 mm or 1 degree, the treatment beam delivery was interrupted and the patient position was corrected by moving couch, and the couch adjustments were also logged. Based on the information, the time-dependent accumulated translational and rotational displacements without any couch adjustments were calculated. Spinal position displacements in all translational and rotational directions were correlated with elapsed treatment time. Especially, Right-Left displacements of >1 mm and >2 mm were observed at 4-6 and 8-10 min after treatment initiation, respectively. Rotational displacements in the Yaw direction >1° were observed at 10-15 min after treatment initiation. The translational and rotational displacements systematically increased with elapsed treatment time. It is suggested that the spine position should be checked at least every 4-6 min or the treatment time should be limited within 4-6 minutes to ensure the irradiation accuracy within the millimeter or submillimeter range.

Triggered kV Imaging During Spine SBRT for Intrafraction Motion Management.

Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.

Disparities in Patterns of Conventional Versus Stereotactic Body Radiotherapy in the Treatment of Spine Metastasis in the United States.

The improved survival of patients even with metastatic cancer has led to an increase in the incidence of spine metastases, suggesting the need for a more aggressive palliative treatment than conventional external beam radiation therapy (cEBRT). Consequently, spinal stereotactic body radiation therapy (SBRT) has increased in popularity over the past decade. However, there has been no comparison of patterns of usage of cEBRT versus SBRT in the treatment of spinal metastases in the US. The National Cancer Data Base (NCDB) from 2004-2013 was used for analysis. cEBRT was defined as 30 Gy in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in 1 fraction. SBRT was defined as 25-32 Gy infive5 fractions, 24-32 Gy in 4 fractions, 20-32 Gy in three fractions, 14-32 Gy in 2 fractions, or 14-24 Gy in 1 fraction. Single and multivariable associations between patient demographic and cancer characteristics and type of radiation were performed. From 2004-2013, 23,181 patients with spinal metastases in the United States received cEBRT, while 1,030 received SBRT as part of their first course of treatment. Most patients (88%) received 10 fractions of radiation. Multivariable analysis suggested that non-Medicare or private insurance (adjusted OR 0.4-0.7), African-American race (adjusted OR = 0.8, 95%CI = 0.7-1.0), age 65+ (adjusted OR = 0.8), living in a region with lower population (adjusted OR 0.7), earlier year of diagnosis (OR = 0.9), and receiving treatment in a non-academic/research facility (adjusted OR 0.6) were associated with cEBRT. After controlling for other variables, regional education level was no longer significantly associated with cEBRT. Most patients with spine metastases were treated with cEBRT, usually with 10 fractions. Receipt of SBRT was significantly associated with race, insurance, geography, population, type of treatment facility, and year of diagnosis, even after controlling for other factors. These findings raise questions about disparities in access to and delivery of care that deserve further investigation.

Technical Note: Synthetic treatment beam imaging for motion monitoring during spine SBRT treatments - a phantom study.

One of the biggest challenges in applying megavoltage (MV) treatment beam imaging for monitoring spine motion in stereotactic body radiotherapy (SBRT) is the small beam apertures in the images due to strong beam modulations in IMRT planning. The purpose of this study is to investigate the feasibility of a markerless motion tracking method in spine SBRT delivery using a novel enhanced synthetic treatment beam (ESTB) imaging technique. Three clinical spine SBRT plans using 6XFFF beams and sliding window IMRT technique were transferred to a thorax phantom and delivered by a TrueBeam machine. Before delivery, the phantom was aligned to the plan isocenter using CBCT setup and verified with a second CBCT, and then, 2mm shifts were introduced in both the craniocaudal (CC) and the left-right (LR) directions with the couch. During beam delivery, MV images were continuously taken with an electronic portal imaging device (EPID) and automatically grabbed by Varian iTools Capture software with a frame rate of 11.6Hz. After preprocessing for scatter correction and beam intensity compensation, every 50 frames of MV images were combined to generate a series of ESTB images for each beam. The ESTB images were then registered to the projections of the verification CBCT at the matched beam angles to detect the 2mm shifts. Compared to snapshot MV images, the ESTB images had significantly enlarged fields of view (FOVs) and improved image quality. Based on two-dimensional (2D) rigid registration, the ESTB image to CBCT projection matching showed submillimeter accuracy in detecting motion. Specifically, the root mean square errors in detecting the LR/CC shifts were 0.35/0.28, 0.32/0.35, 0.63/0.44, 0.55/0.51, and 0.69/0.42mm at gantry angles 180, 160, 140, 120, and 100, respectively. Our results in the phantom study suggest that ESTB images from a sliding window IMRT plan can be used to detect spine motion, with submillimeter precision in the 2D plane perpendicular to the beam.

The Dancing Cord: Inherent Spinal Cord Motion and Its Effect on Cord Dose in Spine Stereotactic Body Radiation Therapy

BACKGROUNDSpinal cord dose limits are critically important for the safe practice of spine stereotactic body radiotherapy (SBRT). However, the effect of inherent spinal cord motion on cord dose in SBRT is unknown.OBJECTIVETo assess the effects of cord motion on spinal cord dose in SBRT.METHODSDynamic balanced fast field echo (BFFE) magnetic resonance imaging (MRI) was obtained in 21 spine metastasis patients treated with SBRT. Planning computed tomography (CT), conventional static T2-weighted MRI, BFFE MRI, and dose planning data were coregistered. Spinal cord from the dynamic BFFE images (corddyn) was compared with the T2-weighted MRI (cordstat) to analyze motion of corddyn beyond the cordstat (Dice coefficient, Jaccard index), and beyond cordstat with added planning organ at risk volume (PRV) margins. Cord dose was compared between cordstat, and corddyn (Wilcoxon signed-rank test).RESULTSDice coefficient (0.70-0.95, median 0.87) and Jaccard index (0.54-0.90, median 0.77) demonstrated motion of corddyn beyond cordstat. In 62% of the patients (13/21), the dose to corddyn exceeded that of cordstat by 0.6% to 13.8% (median 4.3%). The corddyn spatially excursed outside the 1-mm PRV margin of cordstat in 9 patients (43%); among these dose to corddyn exceeded dose to cordstat >+ 1-mm PRV margin in 78% of the patients (7/9). Corddyn did not excurse outside the 1.5-mm or 2-mm PRV cord cordstat margin.CONCLUSIONSpinal cord motion may contribute to increases in radiation dose to the cord from SBRT for spine metastasis. A PRV margin of at least 1.5 to 2 mm surrounding the cord should be strongly considered to account for inherent spinal cord motion.