Stereotactic Body Radiation Therapy Treatment Research Articles

Patient-specific quality assurance in SBRT treatments using 3D polymer gel dosimetry

In stereotactic body radiation therapy (SBRT), patient-specific quality assurance (PSQA) is required due to the complex dose distributions delivered. In this context, polymer gels are considered reliable as a three-dimensional dosimeter. This work used polymer MAGIC-gel sealed in 2 mm thin-wall glass spheres to assess the three-dimensional (3D) dose distribution imparted to patients and compared the results with that provided by the treatment planning system. Four SBRT treatments targeting vertebral, ilium, pelvic lymph node and lung regions were selected for this study. A computed tomography (CT) scan of each glass sphere was obtained, and the patient treatment plan was superimposed on the glass sphere CT image. Thereafter, the spheres were irradiated under similar conditions to the patient using a Varian TrueBeam linear accelerator. A high-spatial resolution optical CT scanner was used to read the glass sphere containing the gel. Planned and delivered 3D dose distributions were compared quantitatively through 3D gamma passing rates at several selected acceptance criteria and qualitatively through the evaluation of dose-profiles, isodose-curves, and dose-volume histograms. We observed that the overall 3D gamma passing rate exceeded 90% at acceptance criteria of 2% dose difference and 2 mm distance-to-agreement for a dose threshold of 20%. The results of this study suggest that the polymer MAGIC-gel sealed in thin-wall glass spheres in conjunction with the optical CT readout method is a suitable PSQA system for SBRT treatments.

Dysfunction of CD8+ T cells around tumor cells leads to occult lymph node metastasis in NSCLC patients.

Occult lymph node metastasis (OLNM) is one of the main causes of regional recurrence in inoperable N0 non-small cell lung cancer (NSCLC) patients following stereotactic ablation body radiotherapy (SABR) treatment. The integration of immunotherapy and SABR (I-SABR) has shown preliminary efficiency in mitigating this recurrence. Therefore, it is necessary to explore the functional dynamics of critical immune effectors, particularly CD8+ T cells in the development of OLNM. In this study, tissue microarrays (TMAs) and multiplex immunofluorescence (mIF) were used to identify CD8+ T cells and functional subsets (cytotoxic CD8+ T cells/predysfunctional CD8+ T cells (CD8+ Tpredys)/dysfunctional CD8+ T cells (CD8+ Tdys)/other CD8+ T cells) among the no lymph node metastasis, OLNM, and clinically evident lymph node metastasis (CLNM) groups. As the degree of lymph node metastasis escalated, the density of total CD8+ T cells and CD8+ Tdys cells, as well as their proximity to tumor cells, increased progressively and remarkably in the invasive margin (IM). In the tumor center (TC), both the density and proximity of CD8+ Tpredys cells to tumor cells notably decreased in the OLNM group compared with the group without metastasis. Furthermore, positive correlations were found between the dysfunction of CD8+ T cells and HIF-1α+CD8 and cancer microvessels (CMVs). In conclusion, the deterioration in CD8+ T cell function and interactive dynamics between CD8+ T cells and tumor cells play a vital role in the development of OLNM in NSCLC. Strategies aimed at improving hypoxia or targeting CMVs could potentially enhance the efficacy of I-SABR.

Treatment planning and delivery practice of lung SBRT: Results of the 2022 ESTRO physics survey

Background and purposeThe use of Stereotactic Body Radiation Therapy (SBRT) in lung cancer is increasing. However, there is no consensus on the most appropriate treatment planning and delivery practice for lung SBRT. To gauge the range of practice, quantify its variability and identify where consensus might be achieved, ESTRO surveyed the medical physics community. Materials and methodsAn online survey was distributed to ESTRO’s physicist membership in 2022, covering experience, dose and fractionation, target delineation, dose calculation and planning practice, imaging protocols, and quality assurance. ResultsTwo-hundred and forty-four unique answers were collected after data cleaning. Most respondents were from Europe the majority of which had more than 5 years’ experience in SBRT. The large majority of respondents deliver lung SBRT with the VMAT technique on C-arm Linear Accelerators (Linacs) employing daily pre-treatment CBCT imaging. A broad spectrum of fractionation schemes were reported, alongside an equally wide range of dose prescription protocols. A clear preference was noted for prescribing to 95% or greater of the PTV. Several issues emerged regarding the dose calculation algorithm: 22% did not state it while 24% neglected to specify the conditions under which the dose was calculated. Contouring was usually performed on Maximum or Average Intensity Projection images while dose was mainly computed on the latter. No clear indications emerged for plan homogeneity, complexity, and conformity assessment. Approximately 40% of the responders participated in inter-centre credentialing of SBRT in the last five years. Substantial differences emerged between high and low experience centres, with the latter employing less accurate algorithms and older equipment. ConclusionThe survey revealed an evident heterogeneity in numerous aspects of the clinical implementation of lung SBRT treatments. International guidelines and codes of practice might promote harmonisation.

Cyclotron and linear accelerator generated scanning proton beams for lung cancer SBRT: Interplay effects and mitigations.

Pencil beam scanning (PBS) proton therapy for moving targets is known to be impacted by interplay effects between the scanning beam and organ motion. While respiratory motion in the thoracic region is the major cause for organ motion, interplay effects depend on the delivery characteristics of proton accelerators. To evaluate the impact of different types of PBS proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for Stereotactic Body Radiation Therapy (SBRT) treatment of non-small cell lung cancer (NSCLC). Twenty NSCLC patients treated with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes (median: 0.6cm with abdominal compression) for this retrospective study. For each patient, plans were created using: (1) cyclotron-generated proton beams (CPB) with spot sizes of σ=2.7-7.0mm; (2) linear accelerator proton beams (LPB) (σ=2.9-5.5mm); and (3) linear accelerator proton minibeams (LPMB) (σ=0.9-3.9mm). The energy switching time is one second for CPB, and 0.005 s for LPMB and LPB. Plans were robustly optimized on the gross tumor volume (GTV) using each individual phase of four-dimensional computed tomography (4DCT) scans. Initially, single-field optimization (SFO) plans were evaluated; if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparisons. For each patient, all plans were normalized to have the same dose received by 99% of the GTV. Interplay effects were evaluated by computing the dose on 10 breathing phases, based on the spot distribution. Volumetric repainting (VR) was performed 2-6 times for each plan. We compared volume receiving 100% of the prescribed dose (V100%RX) of the GTV, and normal lung V20Gy. Twelve of 20 plans can be optimized sufficiently with SFO. SFO plans were less sensitive to the interplay effect compared to MFO plans in terms of target coverage for both LPB and LPMB. The following comparisons showed results utilizing the MFO technique. In the interplay evaluation without repainting, the mean V100%RX of the GTV were 99.42±0.6%, 97.52±3.9%, and 94.49±7.3% for CPB, LPB, and LPMB plans, respectively. Following VR (2 × for CPB; 3 × for LPB; 5 × for LPMB), V100%RX of the GTV were improved (on average) by 0.13%, 1.84%, and 4.63%, respectively, achieving the acceptance criteria of V100%RX>95%. Because of fast energy switch in linear accelerator proton machines, the delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 min longer than CPB plans. The advantage of small spot machines was better sparing in normal lung V20Gy, even when VR was applied. In the absence of repainting, proton machines with large spot sizes generated more robust plans against interplay effects. The number of VR increased with decreasing spot sizes to achieve the acceptance criteria. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.

Comparison between Volumetric Modulated arc Therapy based Coplanar and Noncoplanar Planning for Stereotactic Body Radiation Therapy of Liver

The study aims to investigate potential dosimetric benefits between non-coplanar and coplanar beam arrangements of Volumetric-Modulated Arc Therapy (VMAT) plans for liver stereotactic body radiotherapy (SBRT). Thirteen patients who had undergone liver SBRT treatment in our department were chosen retrospectively for the study. Two sets of SBRT-VMAT plans namely, non-coplanar (NC-VMAT) and Coplanar (C-VMAT) were generated in Monaco(v5.11) planning system for Elekta Versa HD Linac using unflatten 6MV photon. The NC-VMAT plans were created by two/three non-coplanar partial arcs with couch rotation of ±150 and had an arc span of 1300 to 1600 whereas the C-VMAT plans consisted of a full arc. Both plans were compared by statistically analyzing various dosimetric and technical parameters. There is no statistically significant difference observed between the C-VMAT and NC-VMAT plans for planning target volume (PTV) coverage. However, the spine dose (D1cc) was much less in the NC-VMAT plan compared to the C-VMAT plan, with mean values of 6.127 ± 3.08Gy and 9.058 ± 4.76Gy, respectively (p-value=0.002). The low dose spillage to the healthy tissue was compared by the volume receiving 5Gy (V5Gy) and 10Gy (V10Gy). V5Gy of the NC-VMAT plan was 2399.23±1870.76cc while that of C-VMAT plans was 2835.36±1930.20cc with the p-value <0.001. Moreover, the monitor units(MU) were less with NC-VMAT than with C-VMAT SBRT plans (p=0.015). The plan quality of NC-VMAT plans was favorable compared to C-VMAT plans for liver SBRT especially in reducing spine dose, low dose spillage to healthy tissue, and MU.

Assessment of minimum target dose as a predictor of local failure after spine SBRT

ObjectivesMetastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. MethodsSpine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20–24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27–36 Gy and 21–24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. Results522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3–54.4). The cumulative incidence of local failure was 10.5 % (7.4–13.4) at 1 year and 16.3 % (12.6–19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 – 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6–9.4) vs. 14.2 % (8.3–19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). ConclusionsSpine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14–15.3 Gy with single fraction SBRT is recommended whenever possible.

Intra-fractional geometric and dose/volume metric variations of magnetic resonance imaging-guided stereotactic radiotherapy of prostate bed after radical prostatectomy

Background and purposeMagnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment. Materials and methodsNineteen patients who received 30–34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05. ResultsBladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9–76.8 %) and a median MDA of 5.1 mm (IQR 3.4–7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0–4.8 %). DSC was 0.97 (IQR 0.94–0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V32.5 Gy and mean dose. The CTV V95% changed from 99.9 % (IQR 98.8–100 %) to 99.6 % (IQR 93.9–100 %). ConclusionDespite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed.

Abstract 4781: Evaluation of a TP53 biomarker for lung cancer risk in nasal brushings and peripheral blood

Abstract Background and Purpose: Early detection of lung cancer through annual screening with low-dose computed tomography (LDCT) scans enables potentially curative surgical or stereotactic body radiation therapy (SBRT) treatment and thereby significantly reduces mortality. However, LDCT screening among those currently eligible based primarily on age and smoking criteria yields a large number of false-positive findings and many lung cancers occur among individuals who currently are ineligible. A biomarker that identifies lung cancer risk independent from that caused by age and cigarette smoking might increase specificity and increase the number of people eligible for LDCT screening. Recently we demonstrated that a biomarker measuring TP53 somatic mutations in bronchial brush biopsy specimens from grossly normal airway epithelium was significantly associated with cancer status independent of age and smoking status. Additionally, the TP53 biomarker was synergistic with traditional risk score models (e.g. PLCOM2012 risk score). The goal of this pilot study was to test the TP53 biomarker in nasal brush biopsy specimens, a potential surrogate tissue obtained using less invasive collection methods. Methods: Nasal brushings from 10 lung cancer and 11 control subjects were collected at the University of Toledo and Vanderbilt University Medical Center under approved institutional protocols. Genomic DNA (gDNA) was extracted with the Qiagen AllPrep DNA/RNA kit using a modified protocol. Amplifiable copies of gDNA were measured using quantitative PCR. For each test a sample comprising 25,000 amplifiable copies of gDNA was combined with 50,000 copies of a TP53 internal standard and a complexity control, then PCR amplified, purified and barcoded. Samples were pooled to create two NGS libraries, each with approximately equal numbers of cases and controls, and sequenced on an Illumina MiSeq (Two V3 flow cells, 2 x 250 paired-end). Bioinformatic analysis was conducted using Qiagen CLC Workbench. Variants were called using the Basic Variant Detection Tool. Poisson Exact Test was utilized to determine the significance of endogenous variants relative to internal standard variants at the same base position and a Bonferroni correction was applied to minimize false discovery. Comparison of variant numbers between cases and controls was conducted using an f-test followed by a paired t-test. Results and Conclusions: Consistent with previous results in airway epithelium, in this pilot study the TP53 mutation biomarker measured in nasal brushing was associated with lung cancer (p=0.0085). Measurement of the TP53 biomarker in nasal brush specimens in a larger case-control study currently is underway along with a pilot study in gDNA from peripheral blood. Citation Format: Erin L. Crawford, Daniel J. Craig, Patrick T. Gorman, Mohamed Omballi, Rami Ahmad, Eric L. Grogan, Stephen A. Deppen, James C. Willey. Evaluation of a TP53 biomarker for lung cancer risk in nasal brushings and peripheral blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4781.

Technical note: Cryostat transmission characterization for MR linac - temporal stability, clinical impact and change implementation.

In the Unity MR linac (Elekta AB, Stockholm, Sweden), the radiation beam traverses the cryostat and the coil support structure. The resulting beam attenuation must be considered for output calibration and its variation with gantry angle must be characterized in the treatment planning system (TPS). The aim of this work was to investigate the impact of a change of the cryostat transmission characterization (CTC) curve, due to the helium level modification, on clinical treatment plan dosimetry and to report on the experience with the CTC curve update. Twenty stereotactic body radiotherapy (SBRT) treatment plans: 10 prostate and 10 oligo-metastatic cancer plans, prepared with a beam model incorporating the CTC curve acquired at installation time, were re-calculated using the model implementing CTC curve post helium top-up. To account for the CTC change as well as to align our system to the recent reference conditions recommendations, the new model was commissioned with the emphasis on the specifics associated with the treatment plan adaptation and the existence of the offline and online TPS components. Average CTV mean dose reduction by 0.45% in prostate cases and average GTV mean dose reduction by 0.22% in oligo-metastatic cases was observed. Updated model validation showcased good agreement between measurements and TPS calculations. The agreement between CTC measurements demonstrates its temporal constancy and robustness of the measurement method employed. A helium fill level change was shown to affect the CTC and led to a small but systematic dose calculation inaccuracy. Finally, model validation and end-to-end testing results presented, underscore the minimal impact of transitioning to the new beam model and new reference conditions.

Outcomes of extracranial stereotactic body radiation therapy for induced oligometastatic non-small cell lung cancer on novel systemic therapy.

Stereotactic body radiation therapy (SBRT) is often delivered in patients with oligometastatic disease (OMD). However, the specific subset of patients with polymetastatic non-small cell lung cancer (NSCLC) on novel systemic therapies who develop induced oligopersistant disease (OpersisD) or oligoprogressive disease (OprogD), as defined by the European Organisation for Research and Treatment of Cancer (EORTC) OMD classification, has not been well described. This study explores the outcomes of patients treated with this strategy. Patients with stage IV NSCLC being treated with osimertinib or immune checkpoint inhibitors (ICIs) who received extracranial SBRT for OpersisD or OprogD were identified in our retrospective analysis. Outcomes reported include progression-free survival (PFS), time to change of systemic treatment (TTCST), overall survival (OS), local control (LC) and treatment-related toxicity. Forty-nine patients received SBRT for OpersisD (34.7%) or OprogD (65.3%) at a median of 5.8 and 15.3 months after start of systemic therapy, respectively. 55.1% received concurrent osimertinib and 44.9% received ICI. Seventy-seven extracranial lesions were treated with various fractionation schemas. At a median of 18.8 months follow-up from first SBRT, LC was achieved in 92.2% of total lesions treated (71). The 1-year OS was 91.7% for OpersisD and 83.3% for OprogD. OpersisD compared to OprogD had a longer median PFS (18.3 vs. 6.1 months) and longer median TTCST (23.6 vs. 13.5 months), median OS was not reached for either cohort. On multivariate analysis, patients treated with osimertinib had shorter PFS (HR: 2.20; 95% CI: 1.01-4.82; P=0.048) and shorter TTCST (HR: 2.83; 95% CI: 1.09-7.33; P=0.032). One patient (2%) experienced grade 3 pneumonitis after SBRT, and no grade 4-5 toxicities were reported with SBRT treatment. This study indicates that SBRT for OpersisD or OprogD in Stage IV NSCLC patients on osimertinib or ICIs is safe, very well tolerated, and may prolong the time before needing a shift in systemic therapy. Further prospective research is needed to validate and expand upon these findings.

The Status and Challenges for Prostate Stereotactic Body Radiation Therapy Treatments in United States Proton Therapy Centers: An NRG Oncology Practice Survey

PurposeTo report the current practice pattern of the proton stereotactic body radiation therapy (SBRT) for prostate treatments. Materials and MethodsA survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in February, 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and image-guided radiation therapy (IGRT) methods. ResultsWe received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited 3 primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and magnetic resonance imaging (MRI) for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35 to 40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. ConclusionProstate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma

Purpose or ObjectiveProspective evaluation of stereotactic body radiotherapy (SBRT) with Robotic Radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and MethodsPatients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function (up to Child Pugh B7) were accrued after ethical and scientific committee approval [CTRI: 2022/01/050234] for treatment on Robotic Radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring and gross tumor volume (GTV) included contrast enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22- 50Gy in 5 fractions) while achieving the constraints of mean liver dose <15Gy, 800 cc liver <8Gy and the duodenum max of <24 Gy). Response assessment done at 2 months follow up for recanalization. Patient and treatment related factors evaluated for influence in survival function. ResultsBetween Jan 2017 till May 2022, 317 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score 5-7 90%, mean age 63 years (38-85yrs), CLIP <3: 84 (40%), 3-6 117 (56%), infective etiology 9.5%, Performance status (PS) 0-37%; 1-56%]. Among 209 consecutive patients after accrual SBRT treatment done (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow up). At mean follow up of 10.2 months (SD 8.43), 88 (63%) patients expired and 51 (36%) were alive. 82 (59%) patients had recanalization of PVT (response), 57 (41%) pts did not recanalize, 28 (17%) had progressive disease had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival in responders and non-responders were 18.4 (SE 2.52) and 9.34 month (SE 0.81) respectively (p<0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (p- 0.019) respectively. Overall survival (OS) in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1, 30.3 months respectively (p-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification (BCLC) stage, gender, age, RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (p-0.019). OS in patients with response to treatment, no response to treatment, fit but not accrued and not suitable patients were 18.4, 9.34, 5.9, 2.6 months respectively (p-<0.001). 36/139 patients (24%) had RILD [10 (7.2%) had Classic Radiation induced liver disease (RILD) & 26 (19%) had non-classic RILD]. Derangement in Child Pugh Score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after Robotic Radiosurgery. 18 (13%) had unplanned admissions, two patients required embolization due to fiducial related bleeding, 20 (14%) had ascites of which 9 (6%) patients required abdominocentesis. ConclusionPVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Efficacious patient-specific QA for Vertebra SBRT using a high-resolution detector array SRS MapCHECK: AAPM TG-218 analysis.

Patient-specific quality assurance (PSQA) for vertebra stereotactic body radiation therapy (SBRT) presents challenges due to highly modulated small fields with high-dose gradients between the target and spinal cord. This study aims to explore the use of the SRS MapCHECK® (SRSMC) for vertebra SBRT PSQA. Twenty vertebra SBRT treatment plans including prescriptions 20Gy/1 fraction and 24Gy/2 fractions were selected for each of Millennium (M)-Multileaf Collimator (MLC), and high-definition (HD)-MLC. All 40 plans were measured using Gafchromic EBT3 film (film) and SRSMC, using the StereoPHAN phantom. Plan complexity was assessed using modulation complexity score (MCS), edge metric (EM) (mm-1 ), modulation factor (MU/cGy), and average leaf pair opening (ALPO) (mm) and its correlation with gamma-pass rate was investigated. The high dose gradient between the target and the spinal cord was analyzed for film and SRSMC and compared against the treatment planning system (TPS). Applying the methodology proposed by AAPM TG-218, action and tolerance values specific to the SRSMC for vertebra SBRT were determined for β values ranging from 5 to 8. Film and SRSMC gamma-pass rates showed no correlation (p>0.05). A moderate negative correlation (R=-0.57, p=0.01) is present between EM and SRSMC 3%/1mm gamma-pass rate for HD-MLC plans. Both film and SRSMC accurately measured high dose gradients between the target and the spinal cord (R2 >0.86, p ≤ 0.05). Notably, dose-gradient of HD-MLC plans is 22% steeper and has a smaller standard deviation to M-MLC plans (p ≤ 0.05). Applying TG-218, the film tolerance limit was 96% with action limit 95% for 5%/1mm (β=6) and for the SRSMC tolerance limit was 97% with an action limit of 96% for 4%/1mm (β=6). Our findings suggest that universal TG-218 limits may not be suitable for vertebra SBRT PSQA. This study demonstrates that SRSMC is a viable tool for vertebra SBRT PSQA, supported by TG-218 implementation of process-based tolerance and action limits.

Stereotactic body radiotherapy of central lung tumours using a 1.5 T MR-linac: First clinical experiences

BackgroundMRI-guidance may aid better discrimination between Organs at Risk (OARs) and target volumes in proximity of the mediastinum. We report the first clinical experiences with Stereotactic Body Radiotherapy (SBRT) of (ultra)central lung tumours on a 1.5 T MR-linac. Materials and MethodsPatients with an (ultra)central lung tumour were selected for MR-linac based SBRT treatment. A T2-weighted 3D sequence MRI acquired during free breathing was used for daily plan adaption. Prior to each fraction, contours of Internal Target Volume (ITV) and OARs were deformably propagated and amended by a radiation oncologist. Inter-fractional changes in volumes and coverage of target volumes as well as doses in OARs were evaluated in offline and online treatment plans. ResultsTen patients were treated and completed 60 Gy in 8 or 12 fractions. In total 104 fractions were delivered. The median time in the treatment room was 41 min with a median beam-on time of 8.9 min. No grade ≥3 acute toxicity was observed. In two patients, the ITV significantly decreased during treatment (58 % and 37 %, respectively) due to tumour shrinkage. In the other patients, 81 % of online ITVs were within ±15 % of the volume of fraction 1. Comparison with the pre-treatment plan showed that ITV coverage of the online plan was similar in 52 % and improved in 34 % of cases. Adaptation to meet OAR constraints, led to decreased ITV coverage in 14 %. ConclusionsWe describe the workflow for MR-guided Radiotherapy and the feasibility of using 1.5 T MR-linac for SBRT of (ultra) central lung tumours.

Stereotactic Body Radiotherapy for Treatment of Spinal Metastasis: A Systematic Review of the Literature

Abstract Advances in local and systemic therapies continue to improve overall survival for patients with cancer, resulting in an increase in the incidence of spine metastases. Metastases to the spine are the most common bony metastasis. Up to 15% of patients with solid tumors develop spinal metastases. Spinal metastases can be particularly devastating for quality of life given the potential pain, neurological deficits from spinal cord compression or cauda equina syndrome, spinal instability, and pathological fractures that may result. Stereotactic body radiotherapy (SBRT) with or without the addition of less invasive surgical techniques for stabilization or separation has gained favor. SBRT uses smaller, more precise treatment volumes, allowing for higher doses per fracture, thus increasing ablative abilities. In this systematic review we discuss the literature regarding SBRT’s effectiveness in providing local control and pain control for patients with metastatic disease to the spine. This remains true for patients with spinal cord compression managed with surgical separation followed by postoperative spine SBRT. While not all patients are appropriate candidates for SBRT, careful consideration of appropriate frameworks which take into account the patient’s overall prognosis can guide a multidisciplinary team towards the patients who will benefit the most from this treatment modality.

Using standardized workflows and quantitative data-driven management to reduce time interval from simulation to treatment initiation.

External beam radiotherapy is a complex process, involving timely coordination among multiple teams. The aim of this study is to report our experience of establishing a standardized workflow and using quantitative data and metrics to manage the time-to-treatment initiation (TTI). Starting in 2014, we established a standard process in a radiation oncology-specific electronic medical record system (RO-EMR) for patients receiving external beam radiation therapy in our department, aiming to measure the time interval from simulation to treatment initiation, defined as TTI, for radiation oncology. TTI data were stratified according to the following treatment techniques: three-dimensional (3D) conformal therapy, intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy (SBRT). Statistical analysis was performed with the Mann-Whitney test for the respective metrics of aggregate data for the initial period 2012- 2015 (PI) and the later period 2016-2019 (PII). Over 8 years, the average annual number of treatments for PI and PII were 1760 and 2357 respectively, with 3D, IMRT, and SBRT treatments accounting for 53, 29, 18% and 44, 34, 22%, respectively, of the treatment techniques. The median TTI for 3D, IMRT, and SBRT for PI and PII were 1, 6, 7, and 1, 5, 7 days, respectively, while the 90th percentile TTI for the three techniques in both periods were 5, 9, 11 and 4, 9, 10 days, respectively. From the aggregate data, the TTI was significantly reduced (p=0.0004, p<0.0001, p<0.0001) from PI to PII for the three treatment techniques. Establishing a standardized workflow and frequently measuring TTI resulted in shortening the TTI during the early years (in PI) and maintaining the established TTI in the subsequent years (in PII).

Meta-Analysis of STereotactic body radiothERapy in non-spine BONE metastaseS (MASTER-BONES).

The efficacy and safety of stereotactic body radiation (SBRT) for patients with non-spine bone metastases (NSBM) remains in question. A systematic review and meta-analysis was performed to evaluate SBRT treatment outcomes in NSBM. Eligible studies were retrieved from Medline, Embase, Scielo, the Cochrane Library, and annual meeting proceedings until July 6, 2023. We adhered to the PRISMA and MOOSE guideline recommendations. Quantitative synthesis was performed using a random effects model. Seven retrospective studies, with a total of 807 patients (1048 lesions) treatedwith stereotactic body radiation were included, with median follow-up ranging from 7.6-26.5 months. The most common stereotactic body radiation sites were pelvis (39.2%), ribs (25.8%), femur (16.7%), and humerus/shoulder region (8.7%). At 1-year, the LF and FR were 7% (95%CI 5.5-8.5%; I2=0, n= 75/1048), and 5.3% (95%CI 3-7.5%;I2=0, n= 65/1010). The 2-year cumulative LF incidence was 12.1% (95% CI: 10-15.5%). The OS and PFS at 1-year were 82% (95%CI 75-88%;I2=82%, n= 746/867), and 33.5%(95%CI 26-41%;I2=0%, n= 51/152), with a median of 20.2 months (95%CI: 10.9-49.1 months) and 8.3 months (95% CI: 6.3-10.3%) for OS and PFS, respectively. Meta-regression analysis revealed a significant relationship between planning target volume and fracture rate (p<0.05). Ribs 2.5%followed by the femur 1.9% (95%CI:0-6.1%) were the most common fracture sites. The occurrence of pain flare, fatigue and dermatitis were 7 %, 5.4 %, and 0.65 %, respectively. Stereotactic body radiation proves both safety and efficacy for non-spine bone metastases and serious complications (grade 3) are infrequent. Careful consideration of target volume is crucial due to its link with a higher fracture risk.

Multi-omics integrative modelling for stereotactic body radiotherapy in early-stage non-small cell lung cancer: clinical trial protocol of the MONDRIAN study

BackgroundCurrently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics.MethodsMONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building.DiscussionThanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients.Trial registrationThe study was prospectively registered at clinicaltrials.gov (NCT05974475).

Stereotactic body radiotherapy with volumetric intensity-modulated arc therapy and flattening filter-free beams: dosimetric considerations.

The present study comparatively evaluates the impact of energy-matched flattening filter-free (FFF) photon beams with different energy levels on the physical-dosimetric quality of lung and liver stereotactic body radiotherapy (SBRT) treatment plans. For this purpose, 54different lung and liver lesions from 44patients who had already received SBRT combined with volumetric modulated arc therapy (VMAT) were included in this retrospective planning study. Planning computed tomography scans already available were used for the renewed planning with 6MV, 6MV-FFF, 10MV, and 10MV-FFF under constant planning objectives. The treatment delivery data, dosimetric distributions, and dose-volume histograms as well as parameters such as the conformity index and gradient indices were the basis for the evaluation and comparison of treatment plans. Asignificant reduction of beam-on time (BOT) was achieved due to the high dose rates of FFF beams. In addition, we showed that for FFF beams compared to flattened beams of the same energy level, smaller planning target volumes (PTV) require fewer monitor units (MU) than larger PTVs. An equal to slightly superior target volume coverage and sparing of healthy tissue as well as organs at risk in both lung and liver lesions were found. Significant differences were seen mainly in the medium to lower dose range. We found that FFF beams together with VMAT represent an excellent combination for SBRT of lung or liver lesions with shortest BOT for 10MV-FFF but significant dose savings for 6MV-FFF in lung lesions.

A novel lung SBRT treatment planning: Inverse VMAT plan with leaf motion limitation to ensure the irradiation reproducibility of a moving target

This study exposed the implementation of a novel technique (VMATLSL) for the planning of moving targets in lung stereotactic body radiation therapy (SBRT). This new technique has been compared to static conformal radiotherapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and dynamic conformal arc (DCA). The rationale of this study was to lower geometric complexity (54.9% lower than full VMAT) and hence ensure the reproducibility of the treatment delivery by reducing the risk for interplay errors induced by respiratory motion. Dosimetry metrics were studied with a cohort of 30 patients. Our results showed that leaf speed limitation provided conformal number (CN) close to the VMAT (median CN of VMATLSL is 0.78 vs 0.82 for full VMAT) and was a significant improvement on 3D-CRT and DCA with segment-weight optimized (respectively 0.55 and 0.57). This novel technique is an alternative to VMAT or DCA for lung SBRT treatments, combining independence from the patient's breathing pattern, from the size and amplitude of the lesion, free from interplay effect, and with dosimetry metrics close to the best that could be achieved with full VMAT.