Lung Stereotactic Body Radiation Therapy Research Articles

Prognostic evaluation using radiomics after stereotactic body radiotherapy in early-stage lung cancer

Non-small cell lung cancer (NSCLC), the leading cause of cancer-related deaths, is the most common subtype of lung cancer with an incidence of 85%. Stereotactic body radiotherapy (SBRT) is a curative treatment option for patients with early-stage NSCLC who cannot undergo surgery due to medical reasons or who refuse surgery. Radiomics non-invasively extracts advanced imaging features invisible to the human eye from medical images. Radiomics has prognostic value in predicting oncological outcomes after lung SBRT. Although studies on this subject are available in the literature, they are quite heterogeneous. There is a need for large-scale multicenter studies in which standard imaging techniques are used to obtain radiomic features, artificial intelligence-based segmentations are used to eliminate differences between contours, and SBRT dose schemes with appropriate therapeutic indexes are applied. This review aimed to interpret the existing studies and emphasize the clinical importance of radiomics, which can contribute to personalized treatment. A comprehensive literature search was conducted through the PubMed database using a wide range of keywords, which yielded 11 peer-reviewed articles published between 2017 and 2024. Seven articles evaluated computed tomography radiomics, and four evaluated fluorodeoxyglucose positron emission tomography-computed tomography radiomics. Oncological outcomes are not always identical in patients with a similar history receiving similar treatments at the same stage and age. Clinical, demographic, or treatment-related data are insufficient to predict prognosis and determine personalized treatment. Incorporating radiomics to these data can help establish models with higher accuracy and achieve personalized treatment.

Optimization of image reconstruction technique for respiratory-gated lung stereotactic body radiotherapy treatment planning using four-dimensional CT: a phantom study.

Patient respiration is characterized by respiratory parameters, such as cycle, amplitude, and baseline drift. In treatment planning using four-dimensional computed tomography (4DCT) images, the target dose may be affected by variations in image reconstruction techniques and respiratory parameters. This study aimed to optimize 4DCT image reconstruction techniques for the treatment planning of lung stereotactic body radiotherapy (SBRT) based on respiratory parameters using respiratory motion phantom. We quantified respiratory parameters using 30 respiratory motion datasets. The 4DCT images were acquired, and the phase- and amplitude-based reconstruction images (RI) were created. The target dose was calculated based on these reconstructed images. Statistical analysis was performed using Pearson's correlation coefficient (r) to determine the relationship between respiratory parameters and target dose in each reconstructed technique and respiratory region. In the inhalation region of phase-based RI, r of the target dose and baseline drift was -0.52. In particular, the target dose was significantly reduced for respiratory parameters with a baseline drift of 0.8mm/s and above. No other respiratory parameters or respiratory regions were significantly correlated with target dose in phase-based RI. In amplitude-based RI, there were no significant differences in the correlation between all respiratory parameters and target dose in the exhalation or inhalation regions. These results showed that the target dose of the amplitude-based RI did not depend on changes in respiratory parameters or respiratory regions, compared to the phase-based RI. However, it is possible to guarantee the target dose by considering respiratory parameters during the inhalation region of the phase-based RI.

Dosimetric comparison of gamma knife and linear accelerator (VMAT and IMRT) plans of SBRT of Lung tumours

This study evaluates dosimetric differences in Stereotactic Body Radiation Therapy (SBRT) for lung tumors using plans of Gamma Knife, and Volumetric Modulated Arc Therapy (VMAT), Intensity-Modulated Radiation Therapy (IMRT) plans based on Linear Accelerator, aiming to inform the reader of appropriate treatment strategy selection. Ten patients with 23 lung tumor lesions treated with SBRT at Zhongshan Hospital of Dalian University were analyzed. Plans of Gamma Knife, and VMAT, IMRT plans based on Linear Accelerator were created for each lesion, totaling 18 plans per type. Lesions were treated with 30–50 Gy in 5–10 fractions. Dosimetric parameters, including gradient index (GI), heterogeneity index (HI), conformity index (CI), and doses to the plan target volumes (PTVs), the gross tumor volumes (GTVs) and organs at risk (OARs) were compared. Plans of Gamma Knife showed superior HI and GI, higher PTV and GTV doses, and reduced doses to the ipsilateral and contralateral lungs, esophagus, spinal cord, and heart compared to VMAT and IMRT plans (p < 0.05). However, Plans of Gamma Knife required longer delivery times. When comparing VMAT and IMRT plans, VMAT plans had shorter delivery times than IMRT plans, but required more monitor units (MUs). Additionally, IMRT plans delivered a lower mean dose to the ipsilateral lung compared to VMAT plans. Gamma Knife SBRT plans achieves steeper dose falloff and minimizes radiation to normal lung tissue compared to VMAT and IMRT plans, but with longer delivery times. VMAT and IMRT plans displayed similar dose distributions for lung SBRT.

P4.07G.05 Prediction of Quality-of-Life Results after Lung Stereotactic Body Radiotherapy Using Functional Mapping on Gallium-68 Perfusion PET/CT

P4.07G.05 Prediction of Quality-of-Life Results after Lung Stereotactic Body Radiotherapy Using Functional Mapping on Gallium-68 Perfusion PET/CT

Lung SBRT: Dose gradient optimization based on target size

This study investigated optimization settings that steepen the dose gradient as a function of target size for lung stereotactic body radiation therapy (SBRT). Sixty-eight lung SBRT patients with planning target volumes (PTVs) ranging from 2-203 cc were categorized into small (<20 cc), medium (20-50 cc), and large (>50 cc) groups. VMAT plans were generated using the normal tissue objective (NTO) to penalize the dose gradient at progressively steeper NTO fall-off values (0.1, 0.2, 0.3, 0.4, 0.5 mm-1). Dose was calculated using the AcurosXB algorithm and was normalized so the prescription dose covered 95% of the PTV. Mann-Whitney, Kruskal-Wallis and ANOVA tests were used to assess for statistical differences in the Conformity Index at the 50% isodose level (CI50%), global maximum dose (Dmax), and monitor units (MU) across the various NTO settings. All plans adhered to institutional criteria and met the guidelines of the Radiation Therapy Oncology Group 0813. Steeper NTO fall-off values significantly increased Dmax and MUs across all groups (p < 0.05). CI50% significantly differed with fall-off values in small (0.3 mm-1) and medium (0.2 mm-1) targets, indicating steeper NTO fall-off values improve CI50% for small and medium targets (p < 0.05). Large targets showed no significant CI50% difference across these fall-off values. As target size increases, the importance of fall-off values in achieving an acceptable CI50% diminishes. Smaller targets benefit from steeper fall-off values despite increased Dmax and MUs. Consideration of fall-off value relative to target size is crucial to limit dose spillage outside the target.

A lung SBRT treatment planning technique to focus high dose on gross disease

This study investigated a straightforward treatment planning technique for definitive stereotactic body radiation therapy (SBRT) for patients with early-stage lung cancer aimed at increasing dose to gross disease by strategically penalizing the normal tissue objective (NTO) in the EclipseTM treatment planning system. Twenty-five SBRT cases were replanned to 50 Gy in 5 fractions using static and dynamic NTO methods (50 plans total). The NTO had a start dose of 100% at the target border, end dose of 20%, fall-off rate of 0.4/mm, and a priority of 150. For the static NTO plans, a lower planning target volume (PTV) objective was placed at 52 Gy with a priority of 100. Maximum dose was not penalized. Optimization was performed without user interaction. In contrast, the planner incrementally increased the priority of the NTO on the dynamic NTO plans until 95% of the target volume was covered by the prescription dose. Further, the dynamic NTO plans used both PTV lower and upper objectives at 63-64 Gy with priorities of 50. Maximum dose was penalized to ensure that the hot spot was within ± 2% of the static NTO global maximum dose. Following optimization, all plans were normalized so that the prescription dose covered 95% of the PTV. Plans were scored based on RTOG 0813 criteria, and dose to the internal target volume (ITV) and PTV was evaluated. The Wilcoxon signed-rank test (threshold = 0.05) was used to evaluate differences between the static and dynamic NTO plans. All plans met RTOG 0813 planning guidelines. In comparison to the static NTO plans, the dynamic NTO plans exhibited statistically significant increases in PTV mean dose, ITV mean dose, and PTV-ITV mean dose. Notably, the dynamic NTO plans more effectively concentrated the high dose on gross disease at the center of the PTV. As compared to the static NTO plans, the mean dose was 4.6 Gy higher in the ITV while only 1.3 Gy higher in the PTV-ITV rind of the dynamic NTO plans. Global maximum doses were similar. There were some small yet statistically significant differences in dose conformity between plan types. Furthermore, the dynamic NTO plans demonstrated a significant reduction in total monitor units (MU). This study demonstrated an efficient optimization strategy for lung SBRT plans that concentrates the highest dose in the gross disease, which may improve local control.

Analysis of intra-fractional positioning correction performed by cone beam computed tomography in SBRT treatments

PurposeThis study aims to evaluate the positioning correction extracted from Intra-fraction Cone Beam (IF-CBCT) images obtained during Stereotactic Body Radiotherapy (SBRT) treatments, and to assess whether its magnitude justifies its acquisition. In addition, the results obtained in lung, liver, and pancreas SBRTs with two deep inspiration breath-hold systems (DIBH), and for prostate with/without ultrasound (US) monitoring were compared. Methods1449 treatments, performed with two linear accelerators (LINACs) were retrospectively analyzed. DIBH were performed either with a spirometry-based device or a surface-guidance system and one LINAC was equipped with US monitoring system for prostate. Significance tests were used to account for differences between units. ResultsGroup systematic error (M) was approximately –0.7 mm for DIBH treatments in superior-inferior (SI) direction with no difference (p > 0.7) between LINACs. Moreover, there was a SI difference of 0.5 mm for prostate treatments (p = 0.008), in favor of the US monitored one. In anterior-posterior (AP) direction, only liver treatments exhibited differences between LINACs, with the spirometer-based system being 0.8 mm inferior (p = 0.003). M<0.4 mm in left–right (LR) direction was found for all locations and LINACs. The spirometer-based system resulted in lower standard deviation of systematic and random errors in most components and locations, with a greater effect observed in liver SBRTs. ConclusionsThe corrections made with IF-CBCT during SBRT treatments were not negligible. Both DIBH systems were effective in managing respiratory movements. However, the spirometry-based system was slightly more accurate. In addition, US monitoring of the prostate appeared to be useful in reducing target shift.

Quantitative assessment of intertarget position variations based on 4D-CT and 4D-CBCT simulations in single-isocenter multitarget lung stereotactic body radiation therapy

BackgroundIn single-isocenter multitarget stereotactic body radiotherapy (SBRT), geometric miss risks arise from uncertainties in intertarget position. However, its assessment is inadequate, and may be interfered by the reconstructed tumor position errors (RPEs) during simulated CT and cone beam CT (CBCT) acquisition. This study aimed to quantify intertarget position variations and assess factors influencing it.MethodsWe analyzed data from 14 patients with 100 tumor pairs treated with single-isocenter SBRT. Intertarget position variation was measured using 4D-CT simulation to assess the intertarget position variations (ΔD) during routine treatment process. Additionally, a homologous 4D-CBCT simulation provided RPE-free comparison to determine the impact of RPEs, and isolating purely tumor motion induced ΔD to evaluate potential contributing factors.ResultsThe median ΔD was 4.3 mm (4D-CT) and 3.4 mm (4D-CBCT). Variations exceeding 5 mm and 10 mm were observed in 31.1% and 5.5% (4D-CT) and 20.4% and 3.4% (4D-CBCT) of fractions, respectively. RPEs necessitated an additional 1–2 mm safety margin. Intertarget distance and breathing amplitude variability showed weak correlations with variation (Rs = 0.33 and 0.31). The ΔD differed significantly by locations (upper vs. lower lobe and right vs. Left lung). Notably, left lung tumor pairs exhibited the highest risk.ConclusionsThis study provide a reliable way to assess intertarget position variation by using both 4D-CT and 4D-CBCT simulation. Consequently, single-isocenter SBRT for multiple lung tumors carries high risk of geometric miss. Tumor motion and RPE constitute a substantial portion of intertarget position variation, requiring correspondent strategies to minimize the intertarget uncertainties.

Moving towards single fraction peripheral lung stereotactic body radiation therapy: patient care during and after the global COVID-19 pandemic

Moving towards single fraction peripheral lung stereotactic body radiation therapy: patient care during and after the global COVID-19 pandemic

Lung and Liver Stereotactic Body Radiation Therapy During Mechanically Assisted Deep Inspiration Breath-Holds: A Prospective Feasibility Trial

PurposeRadiation therapy of tumours subject to breathing-related motion during breath-holds (BH) has the potential to substantially reduce the irradiated volume. Mechanically-assisted and non-invasive ventilation (MANIV) could ensure the target repositioning accuracy during each BH while facilitating treatment feasibility through oxygen supplementation and a perfectly replicated mechanical support. However, there is currently no clinical evidence substantiating the use of MANIV-induced BH for moving tumours. The aim of this work was therefore to evaluate the technique performances under real treatment conditions. Methods and MaterialsPatients eligible for lung or liver stereotactic body radiotherapy were prospectively included in a single-arm trial. The primary endpoint corresponded to the treatment feasibility with MANIV. Secondary outcomes comprised intrafraction geometrical uncertainties extracted from real-time imaging, tolerance to BH and treatment time. ResultsTreatment was successfully delivered in 92.9% (13/14) of patients: one patient with a liver tumour was excluded due to a mechanically-induced gastric insufflation displacing the liver cranially by more than 1 cm. In the Left-right/Anteroposterior/Craniocaudal directions, the recalculated safety margins based on intrafraction positional data were 4.6 mm / 5.1 mm / 5.6 mm and 4.7 mm / 7.3 mm / 5.9 mm for lung and liver lesions, respectively. Compared to the free-breathing internal target volume and mid-position approaches, the average reduction in the planning target volume with MANIV reached -47.2±15.3 %, p<0.001 and -29.4±19.2 %, p=0.007 for intra-thoracic tumours and -23.3±12.4 %, p<0.001 and -9.3±15.3 %, p=0.073 for upper abdominal tumours, respectively. For one liver lesion, large caudal drifts of occasionally more than one centimetre were measured. The total slot time was 53.1 ± 10.6 minutes with a BH comfort level of 80.1±10.6%. ConclusionsMANIV enables high treatment feasibility within a non-selected population. Accurate intrafraction tumour repositioning is achieved for lung tumours. Due to occasional intra-BH caudal drifts, pre-treatment assessment of BH stability for liver lesions is however recommended.

Evaluation of the performance of both machine learning models using PET and CT radiomics for predicting recurrence following lung stereotactic body radiation therapy: A single-institutional study.

Predicting recurrence following stereotactic body radiotherapy (SBRT) for non-small cell lung cancer provides important information for the feasibility of the individualized radiotherapy and allows to select the appropriate treatment strategy based on the risk of recurrence. In this study, we evaluated the performance of both machine learning models using positron emission tomography (PET) and computed tomography (CT) radiomic features for predicting recurrence after SBRT. Planning CT and PET images of 82 non-small cell lung cancer patients who performed SBRT at our hospital were used. First, tumors were delineated on each CT and PET of each patient, and 111 unique radiomic features were extracted, respectively. Next, the 10 features were selected using three different feature selection algorithms, respectively. Recurrence prediction models based on the selected features and four different machine learning algorithms were developed, respectively. Finally, we compared the predictive performance of each model for each recurrence pattern using the mean area under the curve (AUC) calculated following the 0.632+ bootstrap method. The highest performance for local recurrence, regional lymph node metastasis, and distant metastasis were observed in models using Support vector machine with PET features (mean AUC=0.646), Naive Bayes with PET features (mean AUC=0.611), and Support vector machine with CT features (mean AUC=0.645), respectively. We comprehensively evaluated the performance of prediction model developed for recurrence following SBRT. The model in this study would provide information to predict the recurrence pattern and assist in making treatment strategies.

Delta radiomics to track radiation response in lung tumors receiving stereotactic magnetic resonance-guided radiotherapy

Background and purposeLung cancer is a leading cause of cancer-related mortality, and stereotactic body radiotherapy (SBRT) has become a standard treatment for early-stage lung cancer. However, the heterogeneous response to radiation at the tumor level poses challenges. Currently, standardized dosage regimens lack adaptation based on individual patient or tumor characteristics. Thus, we explore the potential of delta radiomics from on-treatment magnetic resonance (MR) imaging to track radiation dose response, inform personalized radiotherapy dosing, and predict outcomes. Materials and methodsA retrospective study of 47 MR-guided lung SBRT treatments for 39 patients was conducted. Radiomic features were extracted using Pyradiomics, and stability was evaluated temporally and spatially. Delta radiomics were correlated with radiation dose delivery and assessed for associations with tumor control and survival with Cox regressions. ResultsAmong 107 features, 49 demonstrated temporal stability, and 57 showed spatial stability. Fifteen stable and non-collinear features were analyzed. Median Skewness and surface to volume ratio decreased with radiation dose fraction delivery, while coarseness and 90th percentile values increased. Skewness had the largest relative median absolute changes (22 %–45 %) per fraction from baseline and was associated with locoregional failure (p = 0.012) by analysis of covariance. Skewness, Elongation, and Flatness were significantly associated with local recurrence-free survival, while tumor diameter and volume were not. ConclusionsOur study establishes the feasibility and stability of delta radiomics analysis for MR-guided lung SBRT. Findings suggest that MR delta radiomics can capture short-term radiographic manifestations of the intra-tumoral radiation effect.

Quantitative analysis of interstitial lung abnormalities on computed tomography to predict symptomatic radiation pneumonitis after lung stereotactic body radiotherapy

Background and purposeSymptomatic radiation pneumonitis (SRP) is a complication of thoracic stereotactic body radiotherapy (SBRT). As visual assessments pose limitations, artificial intelligence-based quantitative computed tomography image analysis software (AIQCT) may help predict SRP risk. We aimed to evaluate high-resolution computed tomography (HRCT) images with AIQCT to develop a predictive model for SRP. Materials and methodsAIQCT automatically labelled HRCT images of patients treated with SBRT for stage I lung cancer according to lung parenchymal pattern. Quantitative data including the volume and mean dose (Dmean) were obtained for reticulation + honeycombing (Ret + HC), consolidation + ground-glass opacities, bronchi (Br), and normal lungs (NL). After associations between AIQCT’s quantified metrics and SRP were investigated, we developed a predictive model using recursive partitioning analysis (RPA) for the training cohort and assessed its reproducibility with the testing cohort. ResultsOverall, 26 of 207 patients developed SRP. There were significant between-group differences in the Ret + HC, Br-volume, and NL-Dmean in patients with and without SRP. RPA identified the following risk groups: NL-Dmean ≥ 6.6 Gy (high-risk, n = 8), NL-Dmean < 6.6 Gy and Br-volume ≥ 2.5 % (intermediate-risk, n = 13), and NL-Dmean < 6.6 Gy and Br-volume < 2.5 % (low-risk, n = 133). The incidences of SRP in these groups within the training cohort were 62.5, 38.4, and 7.5 %; and in the testing cohort 50.0, 27.3, and 5.0 %, respectively. ConclusionAIQCT identified CT features associated with SRP. A predictive model for SRP was proposed based on AI-detected Br-volume and the NL-Dmean.

Robust optimization of the Gross Tumor Volume compared to conventional Planning Target Volume-based planning in photon Stereotactic Body Radiation Therapy of lung tumors.

Robust optimization has been suggested as an approach to reduce the irradiated volume in lung Stereotactic Body Radiation Therapy (SBRT). We performed a retrospective planning study to investigate the potential benefits over Planning Target Volume (PTV)-based planning. Thirty-nine patients had additional plans using robust optimization with 5-mm isocenter shifts of the Gross Tumor Volume (GTV) created in addition to the PTV-based plan used for treatment. The optimization included the mid-position phase and the extreme breathing phases of the 4D-CT planning scan. The plans were compared for tumor coverage, isodose volumes, and doses to Organs At Risk (OAR). Additionally, we evaluated both plans with respect to observed tumor motion using the peak tumor motion seen on the planning scan and cone-beam CTs. Statistically significant reductions in irradiated isodose volumes and doses to OAR were achieved with robust optimization, while preserving tumor dose. The reductions were largest for the low-dose volumes and reductions up to 188 ccm was observed. The robust evaluation based on observed peak tumor motion showed comparable target doses between the two planning methods. Accumulated mean GTV-dose was increased by a median of 4.46 Gy and a non-significant increase of 100 Monitor Units (MU) was seen in the robust optimized plans. The robust plans required more time to prepare, and while it might not be a feasible planning strategy for all lung SBRT patients, we suggest it might be useful for selected patients.

Performance of cone-beam computed tomography imaging during megavoltage beam irradiation under phase-gated conditions

PurposeTarget positions should be acquired during beam delivery for accurate lung stereotactic body radiotherapy. We aimed to perform kilovoltage (kV) imaging during beam irradiation (intra-irradiation imaging) under phase-gated conditions and evaluate its performance. MethodsCatphan 504 and QUASAR respiratory motion phantoms were used to evaluate image quality and target detectability, respectively. TrueBeam STx linac and the Developer Mode was used. The imaging parameters were 125 kVp and 1.2 mAs/projection. Flattened megavoltage (MV) X-ray beam energies 6, 10 and 15 MV and un-flattened beam energies 6 and 10 MV were used with field sizes of 5 × 5 and 15 × 15 cm2 and various frame rates for intra-irradiation imaging. In addition, using a QUASAR phantom, intra-irradiation imaging was performed during intensity-modulated plan delivery. The root-mean-square error (RMSE) of the CT-number for the inserted rods, image noise, visual assessment, and contrast-to-noise ratio (CNR) were evaluated. ResultsThe RMSEs of intra-irradiation cone-beam computed tomography (CBCT) images under gated conditions were 50–230 Hounsfield Unit (HU) (static < 30 HU). The noise of the intra-irradiation CBCT images under gated conditions was 15–35 HU, whereas that of the standard CBCT images was 8.8–27.2 HU. Lower frame rates exhibited large RMSEs and noise; however, the iterative reconstruction algorithm (IR) was effective at improving these values. Approximately 7 fps with the IR showed an equivalent CNR of 15 fps without the IR. The target was visible on all the gated intra-irradiation CBCT images. ConclusionSeveral image quality improvements are required; however, intra-irradiated CBCT images showed good visual target detection.

Predictive power of PTV volume for choosing manual or automatic planning in lung stereotactic body radiotherapy

PurposeThis study investigated the role of Planning Target Volume (PTV) in determining the suitability of manual and automatic Stereotactic Body Radiation Therapy (SBRT) planning for lung cancer patients. MethodsWe retrospectively created manual and automatic lung SBRT plans for ninety-eight patients using the Pinnacle 16.2 Treatment Planning System (TPS). The superior plan, whether manual or automatic, was selected for each patient through a combined index. Receiver Operating Characteristic (ROC) analysis was used to assess the predictive potential of the PTV volume in determining the superior plan and to establish a cutoff value. Patients were then stratified into two groups based on this value, and dosimetric variances were evaluated. ResultsThe ROC analysis highlighted the PTV volume's proficiency in predicting the superior choice between manual and automatic lung SBRT plans (Area Under Curve (AUC): 0.918, p = 0.005). The delineated cutoff value was set at 22.675 cc. For PTV volumes below this threshold, automatic plans surpassed manual plans in the Conformity Index (CI), Gradient Index (GI), and lung doses. Conversely, for PTV volumes exceeding 22.675 cc, manual plans exhibited improved results in the Heterogeneity Index (HI), GI, and dosimetric metric of heart and lung. ConclusionThe PTV volume is a significant determinant in guiding the optimal selection between manual and automatic lung SBRT plans with the Pinnacle TPS. Automatic plans are recommended for patients with PTV volumes below 22.675 cc, and manual plans for those above this threshold.

Predicting radiation-induced immune suppression in lung cancer patients treated with stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) is known to modulate the immune system and contribute to the generation of anti-tumor T cells and stimulate T cell infiltration into tumors. Radiation-induced immune suppression (RIIS) is a side effect of radiation therapy that can decrease immunological function by killing naive T cells as well as SBRT-induced newly created effector T cells, suppressing the immune response to tumors and increasing susceptibility to infections. RIIS varies substantially among patients and it is currently unclear what drives this variability. Models that can accurately predict RIIS in near real time based on treatment plan characteristics would allow treatment planners to maintain current protocol specific dosimetric criteria while minimizing immune suppression. In this paper, we present an algorithm to predict RIIS based on a model of circulating blood using early stage lung cancer patients treated with SBRT. This Python-based algorithm uses DICOM data for radiation therapy treatment plans, dose maps, patient CT data sets, and organ delineations to stochastically simulate blood flow and predict the doses absorbed by circulating lymphocytes. These absorbed doses are used to predict the fraction of lymphocytes killed by a given treatment plan. Finally, the time dependence of absolute lymphocyte count (ALC) following SBRT is modeled using longitudinal blood data up to a year after treatment. This model was developed and evaluated on a cohort of 64 patients with 10-fold cross validation. Our algorithm predicted post-treatment ALC with an average error of cells/L with 89% of the patients having a prediction error below 0.5×109 cells/L. The accuracy was consistent across a wide range of clinical and treatment variables. Our model is able to predict post-treatment ALC<0.8 (grade 2 lymphopenia), with a sensitivity of 81% and a specificity of 98%. This model has a ∼38-s end-to-end prediction time of post treatment ALC. Our model performed well in predicting RIIS in patients treated using lung SBRT. With near-real time model prediction time, it has the capability to be interfaced with treatment planning systems to prospectively reduce immune cell toxicity while maintaining national SBRT conformity and plan quality criteria.

Evaluating intra-fractional tumor motion in lung stereotactic radiotherapy with deep inspiration breath-hold.

To evaluate the intra-fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath-hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins. Twenty-eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty-three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post-treatment gated cone-beam computed tomography (CBCT) was acquired to quantify the intra-fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5mm margin in anterior-posterior (AP) and right-left (RL) directions and 8mm in superior-inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (Tbeam_DIBH) was compared with the beam delivery time without DIBH (Tbeam_wo_DIBH) for the corresponding SBRT plan. A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0±1.9mm, 0.1±1.5mm, and -0.5±3.7mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4mm in AP, RL, and SI directions, respectively. The average Tbeam_wo_DIBH and Tbeam_DIBH were 2.4±0.4 min and 3.6±1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3±7.9 min. Intra-fractional tumor motion is the predominant source of treatment uncertainties in CBCT-guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of Tbeam_DIBH, relative to the treatment slot, is not clinically significant.

Technical note: Dosimetry and FLASH potential of UHDR proton PBS for small lung tumors: Bragg-peak-based delivery versus transmission beam and IMPT.

High-energy transmission beams (TBs) are currently the main delivery method for proton pencil beam scanning ultrahigh dose-rate (UHDR) FLASH radiotherapy. TBs place the Bragg-peaks behind the target, outside the patient, making delivery practical and achievement of high dose-rates more likely. However, they lead to higher integral dose compared to conventional intensity-modulated proton therapy (IMPT), in which Bragg-peaks are placed within the tumor. It is hypothesized that, when energy changes are not required and high beam currents are possible, Bragg-peak-based beams can not only achieve more conformal dose distributions than TBs, but also have more FLASH-potential. This works aims to verify this hypothesis by taking three different Bragg-peak-based delivery techniques and comparing them with TB and IMPT-plans in terms of dosimetry and FLASH-potential for single-fraction lung stereotactic body radiotherapy (SBRT). For a peripherally located lung target of various sizes, five different proton plans were made using "matRad" and inhouse-developed algorithms for spot/energy-layer/beam reduction and minimum monitor unit maximization: (1) IMPT-plan, reference for dosimetry, (2) TB-plan, reference for FLASH-amount, (3) pristine Bragg-peak plan (non-depth-modulated Bragg-peaks), (4) Bragg-peak plan using generic ridge filter, and (5) Bragg-peak plan using 3D range-modulated ridge filter. Bragg-peak-based plans are able to achieve sufficient plan quality and high dose-rates. IMPT-plans resulted in lowest OAR-dose and integral dose (also after a FLASH sparing-effect of 30%) compared to both TB-plans and Bragg-peak-based plans. Bragg-peak-based plans vary only slightly between themselves and generally achieve lower integral dose than TB-plans. However, TB-plans nearly always resulted in lower mean lung dose than Bragg-peak-based plans and due to a higher amount of FLASH-dose for TB-plans, this difference increased after including a FLASH sparing-effect. This work indicates that there is no benefit in using Bragg-peak-based beams instead of TBs for peripherally located, UHDR stereotactic lung radiotherapy, if lung dose is the priority.

Feasibility of a Single-Fraction Stereotactic Dose of 30 Gy to Solitary Lung Lesions on Halcyon.

Purpose We sought to explore the feasibility of using the current co-planar Halcyon ring delivery system (RDS) with a novel multileaf collimator (MLC) aperture shape controller in delivering a single high dose of 30 Gy to solitary lung lesions via stereotactic body radiotherapy (SBRT). Materials and methods Thirteen non-small-cell lung cancer (NSCLC) patients previously treated with a single dose of 30 Gy to lung lesions via SBRT on the TrueBeam (6MV-FFF) using non-coplanar volumetric modulated arc therapy (VMAT) arcs were anonymized and replanned onto the Halcyon RDS (6MV-FFF) following RTOG-0915 single-fraction criteria. The Halcyon plans utilized a novel dynamic conformal arc (DCA)-based MLC-fitting approach before VMAT optimization with a user-defined aperture shape controller option. The clinical TrueBeam and Halcyon plans were compared via their protocol compliance, target conformity, gradient index, and dose to organs-at-risk (OAR). Treatment delivery efficacy and accuracy were assessed through end-to-end quality assurance (QA) tests on Halcyon and independent dose verification via in-house Monte Carlo (MC) second-check validation. Results All Halcyon lung SBRT plans met RTOG-0915 protocol's requirements for target coverage, conformity, and gradient indices, and maximum dose 2 cm away from the target (D2cm) while being statistically insignificant (p > 0.05) when compared to clinical TrueBeam plans. Additionally, Halcyon provided a similar dose to OAR except for the ribs, where Halcyon demonstrated a lower maximum dose (15.22 Gy vs 17.01 Gy, p < 0.001). However, Halcyon plans required a higher total monitor unit (8892 MU vs 7413 MU, p < 0.001), resulting in a higher beam modulation factor (2.96 MU/cGy vs 2.47 MU/cGy, p < 0.001) and an increase in beam-on time by a factor of 2.1 (11.11 min vs 5.3 min, p < 0.005). End-to-end QA measurements demonstrate that Halcyon plans were clinically acceptable with an average gamma passing rate of 99.8% for 2%/2mm criteria and independent MC 2nd checks within ±2.86%. Conclusion Our end-to-end testing and validation study demonstrates that by utilizing a DCA-based MLC aperture shape controller before VMAT optimization, Halcyon can be used for delivering a single dose of lung SBRT treatment. However, future improvements of Halcyon RDS are recommended to allow higher output rates, rotational couch corrections, and an integrated intrafraction motion management system that will further enhance Halcyon's capability for site-specific single dosage of SBRT.