Lung Stereotactic Ablative Radiotherapy Research Articles

Stereotactic ablative radiotherapy (SABR) for patients with lung tumor and severe pulmonary function impairment.

To evaluate clinical outcomes after SABR in a cohort of early-stage non-small cell lung cancer (NSCLC) or pulmonary metastases in chronic obstructive pulmonary disease (COPD) patients with forced expiratory volume in the first second predicted (FEV1) ≤ 50%. Retrospective single-center study was performed to analyze clinical outcomes and toxicities in COPD patients with severe lung dysfunction treated with SABR from 1st June 2015 to 31st October 2022. Thirty four patients (forty locations) were enrolled for analysis. Median follow-up was 2.9years. Median age was 73.5years (range, 65.6-80.1). FEV1 was 38% (range, 28.2-50.0) prior to radiotherapy. Median overall survival (OS) was 41.1months (95% CI 38.9-not reached). OS rates at 2-, 3-, and 5- years were 79%, 71%, and 36%, respectively. Cancer-specific survival rates at 2-, 3-, and 5- years were 96%, 96%, and 68%, respectively. Local control rates at 2-, 3-, and 5- years were 88%, 83%, and 83%, respectively. No grade 4 or 5 toxicity was observed. The most common acute toxicity was pneumonitis (38.2%), of which only 1 patient (2.9%) reported grade 3 acute toxicity. Lung SABR in patients with poor pulmonary function may be effective with acceptable toxicity.

Artificial intelligence-assisted quantitative CT analysis of airway changes following SABR for central lung tumors

IntroductionUse of stereotactic ablative radiotherapy (SABR) for central lung tumors can result in up to a 35% incidence of late pulmonary toxicity. We evaluated an automated scoring method to quantify post-SABR bronchial changes by using artificial intelligence (AI)-based airway segmentation. Materials and methodsCentral lung SABR patients treated at Amsterdam UMC (AUMC, internal reference dataset) and Peter MacCallum Cancer Centre (PMCC, external validation dataset) were identified. Patients were eligible if they had pre- and post-SABR CT scans with ≤ 1 mm resolution. The first step of the automated scoring method involved AI-based airway auto-segmentation using MEDPSeg, an end-to-end deep learning-based model. The Vascular Modeling Toolkit in 3D Slicer was then used to extract a centerline curve through the auto-segmented airway lumen, and cross-sectional measurements were computed along each bronchus for all CT scans. For AUMC patients, airway stenosis/occlusion was evaluated by both visual assessment and automated scoring. Only the automated method was applied to the PMCC dataset. ResultsStudy patients comprised 26 from AUMC, and 33 from PMCC. Visual scoring identified stenosis/occlusion in 8 AUMC patients (31 %), most frequently in the segmental bronchi. After airway auto-segmentation, minor manual edits were needed in 9 % of patients. Segmentation for a single scan averaged 83sec (range 73–136). Automated scoring nearly doubled detected airway stenosis/occlusion (n = 15, 58 %), and allowed for earlier detection in 5/8 patients who had also visually scored changes. Estimated rates were 48 % and 66 % at 1- and 2-years, respectively, for the internal dataset. The automated detection rate was 52 % in the external dataset, with 1- and 2-year risks of 56 % and 61 %, respectively. ConclusionAn AI-based automated scoring method allows for detection of more bronchial stenosis/occlusion after lung SABR, and at an earlier time-point. This tool can facilitate studies to determine early airway changes and establish more reliable airway tolerance doses.

Non-coplanar lung SABR treatments delivered with a gantry-mounted x-ray tube

Objective. To create two non-coplanar, stereotactic ablative radiotherapy (SABR) lung patient treatment plans compliant with the radiation therapy oncology group (RTOG) 0813 dosimetric criteria using a simple, isocentric, therapy with kilovoltage arcs (SITKA) system designed to provide low cost external radiotherapy treatments for low- and middle-income countries (LMICs). Approach. A treatment machine design has been proposed featuring a 320 kVp x-ray tube mounted on a gantry. A deep learning cone-beam CT (CBCT) to synthetic CT (sCT) method was employed to remove the additional cost of planning CTs. A novel inverse treatment planning approach using GPU backprojection was used to create a highly non-coplanar treatment plan with circular beam shapes generated by an iris collimator. Treatments were planned and simulated using the TOPAS Monte Carlo (MC) code for two lung patients. Dose distributions were compared to 6 MV volumetric modulated arc therapy (VMAT) planned in Eclipse on the same cases for a Truebeam linac as well as obeying the RTOG 0813 protocols for lung SABR treatments with a prescribed dose of 50 Gy. Main results. The low-cost SITKA treatments were compliant with all RTOG 0813 dosimetric criteria. SITKA treatments showed, on average, a 6.7 and 4.9 Gy reduction of the maximum dose in soft tissue organs at risk (OARs) as compared to VMAT, for the two patients respectively. This was accompanied by a small increase in the mean dose of 0.17 and 0.30 Gy in soft tissue OARs. Significance. The proposed SITKA system offers a maximally low-cost, effective alternative to conventional radiotherapy systems for lung cancer patients, particularly in low-income countries. The system’s non-coplanar, isocentric approach, coupled with the deep learning CBCT to sCT and GPU backprojection-based inverse treatment planning, offers lower maximum doses in OARs and comparable conformity to VMAT plans at a fraction of the cost of conventional radiotherapy.

Intrafraction Imaging Can Replace the Midtreatment Cone Beam Tomography for Lung Stereotactic Ablative Radiation Therapy Patients for Increased Treatment Efficiency

PurposeTo determine the feasibility of replacing the mid-treatment cone beam computed tomography (MT CBCT) image with Intra-fraction Imaging (IFI) acquired concurrently during dose delivery in lung stereotactic ablative radiotherapy (SABR) patients, and thus improve treatment efficiency. Methods and MaterialsA review of departmental imaging data was performed on ten Lung SABR patients treated with dual arc volumetric modulated arc therapy (VMAT) on an Elekta Versa HDTM linear accelerator with XVI imaging software.IFI data was extracted and a database of the translational (TX, TY, TZ) and the rotational (RX, RY, RZ) position errors was created for retrospective comparison, with the values of the MT CBCT for the same patients, treated between March 2021 and March 2022 at our centre. The data was evaluated for correlation between the values in all six degrees of freedom. ResultsThe Inter-Class Correlation (ICC) coefficient for Tx was 0.89 (95%CI: 0.80-0.94), Ty was 0.69 (95%CI: 0.49-0.82), Tz was 0.89 (95%CI: 0.82-0.95) in the translational planes, and Rx was 0.79 (95%CI:0.65-0.88), Ry was 0.79 (95%CI:0.65-0.88), and Rz was 0.91 (95%CI:0.84-0.95) in rotational planes.The Bland-Altman (BA) Statistics for Tx had a bias of -1.22 × 10−3, with an upper limit of agreement (UOA) of 0.07, and a lower limit of agreement (LOA) of -0.07, for Ty the bias was 0.01 (UOA: 0.18, LOA: -0.16), Tz bias was 2.6 × 10−3(UOA:0.10, LOA:-0.09), Rx bias was 0.09 (UOA:0.82, LOA:-0.64), Ry bias was -0.04 (UOA:1.08, LOA:-1.16) and Rz was -0.03 (UOA:0.44, LOA:-0.51). ConclusionsThe ICC was excellent for Tx, Tz, Rx, y, z, and good for Ty. The data demonstrated promising correlation between IFI and MT CBCT values, and therefore supports the use of IFI for clinical decision making and improving treatment efficiency.

What is the predictive value of RECIST criteria following stereotactic lung radiation?

PurposeResponse EvaluationCriteriain Solid Tumors (RECIST) is commonly used to assess response to anti-cancer therapies. However, its application after lung stereotactic ablative radiotherapy (SABR) is complicated by radiation-induced lung changes. This study assesses the frequency of progressive disease (PD) by RECIST following lung SABR and correlates this with actual treatment outcomes as determined by longitudinal follow-up. Methods and MaterialsWe reviewed patients treated with lung SABR for primary lung tumors or oligometastases between 2010 and 2015. Patients were treated with SABR doses of 54–60 Gy in 3–8 fractions. All follow-up scans were assessed and the treated lesion was serially measured over time, with the maximum diameter on axial CT slices used for RECIST calculations. Lesions demonstrating PD by RECIST criteria were identified and subsequently followed for long-term outcomes. The final ‘gold-standard’ assessment of response was based on size changes after PD and, as available, positron emission tomography scan and/or biopsy. ResultsEighty-eight lesions met inclusion criteria. Seventy-five were lung primaries and thirteen were lung metastases. Median follow-up was 52 months (interquartile range: 33–68). Two-thirds (66 %, 58/88) of treated lesions met RECIST criteria for PD; however, local recurrence was only confirmed in 16 % (9/58) of cases. Most lesions that triggered PD by RECIST (47/58, 81 %) were ultimately found not to represent recurrence, while a minority (2/58, 3 %) had an uncertain response. The positive predictive value [PPV] of a RECIST defined PD event was 0.16. If PD was triggered within 12-months post-treatment, PPV was 0.08, compared to 0.21 for lesions triggering PD after 12-months. ConclusionUsing RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, only a minority had recurrence, leading to a poor PPV of RECIST. This highlights the limitations of RECIST in this setting and provides context for physicians when interpreting post-lung SABR imaging.

Predicting Local Control with Dosimetric Parameters in Patients Receiving Individualized Stereotactic Ablative Radiotherapy for Lung Tumors

Stereotactic ablative radiotherapy (SABR) is an effective treatment option for lung tumors. The individualized lung tumor SABR (iSABR) trial was a phase II single-arm study that personalized lung tumor SABR dose and fractionation based on tumor size, location, and histology with very low rates of local recurrence (LR). A secondary analysis of this trial was conducted to assess for potential dosimetric predictors of LR, in order to help guide future clinical treatment planning. From 2011 to 2018, local, regional and distant recurrence data were prospectively collected from 204 patients (261 lung SABR treatments) enrolled in a prospective trial. Baseline characteristics and treatment details were evaluated. Dosimetric and treatment plan parameters were evaluated for their potential to predict LR, using logistic regression and chi-squared analyses. The majority of treated tumors were peripheral (71%, vs 29% central), primary lesions (76%, versus 24% metastatic), and of adenocarcinoma histology (67%, versus 13% squamous cell carcinoma and 19% other). The median follow-up was 24 months (range 2-95). Twenty-seven (10.3%) LRs occurred, with a median time to LR of 15 months (range 6-81 months). There were no significant associations between the overall cohort and the dosimetric parameters. However, for the multi-fraction cohort, an increased proportion of the PTV receiving 110% and 115% of the prescription dose were associated with lower LR (p = 0.01 and p = 0.01 respectively). Specifically for the 50 Gy in 4 fraction cohort, an increased D1cc, D0.03cc, as well as the proportion of the PTV receiving 110%, 115%, and 120% of the prescription dose were associated with lower LR (p < 0.001, p = 0.001, p = 0.003, p < 0.001, p = 0.004, respectively). There was no association of LR with prescription dose expressed as biologically effective dose using an alpha/beta of 10 Gy (BED10), D99%, or single- versus multi-fraction regimens. SABR for lung tumors using the individualized protocol on this trial showed excellent LR rates. We identified dosimetric parameters that were associated with LR, including V110% and V115% within the multi-fraction cohort, as well as the 50 Gy in 4 fraction cohort the D1cc, D0.03cc, and proportions of the PTV receiving 110%, 115%, and 120% of the prescription dose in the 50 Gy in 4 fraction cohort. Optimal thresholds for these parameters will be identified in further analyses. There did not appear to be an association with LR and BED10, D99%, or comparing single- vs multi-fraction regimens.

Central Lung Tumors Eligible for Stereotactic Ablative Radiotherapy (SABR) Trials: Analysis of a Cohort Treated Using MR-Guided SABR

SABR for central and ultracentral lung tumors results in increased toxicity. We implemented MR-guided SABR in patients meeting the IASLC classification for central tumors, namely a Gross Tumor Volume (GTV) ≤2cm from trachea, main bronchi, esophagus, heart, brachial plexus, main mediastinal vessels, phrenic or laryngeal nerves and spinal cord. As patient inclusion criteria for ongoing clinical trials varies, we studied the eligibility of MR-SABR patients for inclusion into 3 clinical trials for central tumors. An Ethics approved institutional database was accessed for details of patients treated using multifractionated lung MR-SABR between 2016 and 2022. GTV and Planning Target Volumes (PTV) had been delineated on a breath-hold planning MRI and CT scans. For each tumor meeting the IASLC classification, patient eligibility for HILUS (NCT04917224), STRICT/STARLUNG (NCT05354596) and SUNSET (NCT03306680) trials were examined. Multifraction MR-SABR was performed in 97 central lung lesions meeting IASLC criteria. Of these, 73 patients (75.3%) fulfilled inclusion criteria for at least 1 trial, but inclusion in all 3 trials was possible in just 18.6% of treated lesions. Inclusion in the HILUS, STRICT/STARLUNG and SUNSET trials were possible in 33.0%, 73.2% and 25.8% of MR-SABR patients, respectively. For HILUS-eligible patients, 11 met the HILUS group A classification (GTV ≤1cm from the trachea and main bronchi), and 21 in group B (GTV >1cm from the trachea and main bronchi but ≤1cm from the intermediate and lobar bronchi). Use of STRICT/STARLUNG trial criteria would have defined 13 tumors as ultracentral (GTV ≤0.5cm from the trachea, main bronchi or intermediary bronchus or esophagus), and 58 as central (GTV 0.5cm-2.5cm from previously described structures or ≤0.5cm from the heart, aorta, spinal cord or lobar bronchi). For the SUNSET study, 25 tumors fulfilled criteria for ultracentral location (PTV touching or overlapping the central bronchial tree, esophagus, pulmonary vein or pulmonary artery). Ongoing clinical trials in central or ultracentral lung SABR enroll considerably different patient populations than those selected using the IASLC definition of central tumors. Due to steep dose-fall off in SABR plans, detailed descriptions of the location of tumor and organs-at-risk, as well as dose-distributions achieved, are necessary in order to allow study results to be uniformly extrapolated to clinical practice.

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors

Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. ClinicalTrials.gov Identifier: NCT01463423.

216 Impact of Intra-Fraction Motion Correction on Target and Oar Dosimetry in Single Fraction Lung Stereotactic Ablative Radiation Therapy

216 Impact of Intra-Fraction Motion Correction on Target and Oar Dosimetry in Single Fraction Lung Stereotactic Ablative Radiation Therapy

Radiomic analysis for early differentiation of lung cancer recurrence from fibrosis in patients treated with lung stereotactic ablative radiotherapy.

The development of radiation-induced fibrosis after SABR can obscure follow-up images and delay detection of a local recurrence in early-stage lung cancer patients. The objective of this study was to develop a radiomics model for computer-assisted detection of local recurrence and fibrosis for an earlier timepoint (<1 year) after the SABR treatment.&#xD;&#xD;This retrospective clinical study included CT images (n=107) of 66 patients treated with SABR. A z-score normalization technique was used for radiomic feature standardization across scanner protocols. The training set for the radiomics model consisted of CT images (66 patients; 22 recurrences and 44 fibrosis) obtained at 24 months (median) follow-up. The test set included CT-images of 41 patients acquired at 5-12 months follow-up. Combinations of four widely used machine learning techniques (support vector machines (SVMs), gradient boosting, random forests (RF), and logistic regression (LR)) and feature selection methods (Relief feature scoring, maximum relevance minimum redundancy (MRMR), mutual information maximization (MIM), forward feature selection, and LASSO) were investigated. Pyradiomics was used to extract 106 radiomic features from the CT-images for feature selection and classification. &#xD;&#xD;An RF + LASSO model scored the highest in terms of AUC (0.87) and obtained a sensitivity of 75% and a specificity of 88% in identifying a local recurrence in the test set. In the training set, 86% accuracy was achieved using five-fold cross-validation. Delong's test indicated that AUC achieved by the RF+LASSO is significantly better than 11 other machine learning models presented here. The top three radiomic features: Interquartile Range (first order), Cluster Prominence (GLCM), and Autocorrelation (GLCM), were revealed as differentiating a recurrence from fibrosis with this model.&#xD;&#xD;The radiomics model selected, out of multiple machine learning and feature selection algorithms, was able to differentiate a recurrence from fibrosis in earlier follow-up CT-images with a high specificity rate and satisfactory sensitivity performance. &#xD.

Local control and toxicity after magnetic resonance imaging (MR)-guided single fraction lung stereotactic ablative radiotherapy

PurposeMagnetic resonance imaging (MR)-guided radiotherapy permits continuous intrafraction visualization and use of automatic triggered beam delivery, with use of smaller planning target volumes (PTV). We report on long-term clinical outcomes following MR-guided single fraction (SF) lung SABR on a 0.35 T linac. Materials and MethodsDetails of patients treated with SF-SABR for lung tumors were accessed from an ethics approved institutional database. A breath-hold 3D MR simulation scan was performed using a true FISP sequence, followed by a breath-hold 3D CT scan. The gross tumor volume (GTV) was first contoured on the breath-hold CT scan, which was then compared with contours on the 3D MR scan, before the GTV was finalized. SABR plans used step-and-shoot IMRT beams to a PTV derived by adding a 5 mm margin to the breath-hold GTV, and a 3 mm gating window was used. SABR was delivered during repeated breath-holds, using automatic beam gating with continuous visualization of the GTV in a sagittal MR plane. ResultsBetween 2018–2022, 50 consecutive patients were treated, and 69% had a primary non-small cell lung cancer. Median PTV was 11.2 cc (range 3.9–53.5); 80% of GTV’s were located ≤2.5 cm from the chest wall. Prescribed doses were 34 Gy (in 58%), 30 Gy (32%), or between 20–28 Gy (10%). After a median follow-up of 18.1 months (95% CI 12.8–23.5), the 2-year survival was 82% (89% for primary NSCLC and 62% for metastases). After a median follow-up of 16.1 months (95% CI 11.2–21.1), local recurrences developed in 2 patients (4%). The 3-year local control rate was 97%, and just 1 patient developed grade ≥3 toxicity (chest wall pain). ConclusionMR-guided SF-SABR delivery to lung tumors on a 0.35 T linac, using repeated breath-holds with automatic beam gating, achieves good tumor control and low toxicity.

Predicting cancer relapse following lung stereotactic radiotherapy: an external validation study using real-world evidence.

For patients receiving lung stereotactic ablative radiotherapy (SABR), evidence suggests that high peritumor density predicts an increased risk of microscopic disease (MDE) and local-regional failure, but only if there is low or heterogenous incidental dose surrounding the tumor (GTV). A data-mining method (Cox-per-radius) has been developed to investigate this dose-density interaction. We apply the method to predict local relapse (LR) and regional failure (RF) in patients with non-small cell lung cancer. 199 patients treated in a routine setting were collated from a single institution for training, and 76 patients from an external institution for validation. Three density metrics (mean, 90th percentile, standard deviation (SD)) were studied in 1mm annuli between 0.5cm inside and 2cm outside the GTV boundary. Dose SD and fraction of volume receiving less than 30Gy were studied in annuli 0.5-2cm outside the GTV to describe incidental MDE dosage. Heat-maps were created that correlate with changes in LR and RF rates due to the interaction between dose heterogeneity and density at each distance combination. Regions of significant improvement were studied in Cox proportional hazards models, and explored with and without re-fitting in external data. Correlations between the dose component of the interaction and common dose metrics were reported. Local relapse occurred at a rate of 6.5% in the training cohort, and 18% in the validation cohort, which included larger and more centrally located tumors. High peritumor density in combination with high dose variability (0.5 - 1.6cm) predicts LR. No interactions predicted RF. The LR interaction improved the predictive ability compared to using clinical variables alone (optimism-adjusted C-index; 0.82 vs 0.76). Re-fitting model coefficients in external data confirmed the importance of this interaction (C-index; 0.86 vs 0.76). Dose variability in the 0.5-1.6cm annular region strongly correlates with heterogeneity inside the target volume (SD; ρ = 0.53 training, ρ = 0.65 validation). In these real-world cohorts, the combination of relatively high peritumor density and high dose variability predicts increase in LR, but not RF, following lung SABR. This external validation justifies potential use of the model to increase low-dose CTV margins for high-risk patients.

A strategy to reduce fraction number in peripheral lung stereotactic ablative body radiotherapy

Hypo-fractionated lung Stereotactic Ablative Body Radiotherapy (SABR) has often been avoided when tumours are close to the chest wall. Our strategic objective was the reduction of fraction number, while maintaining target biological effective dose coverage without increasing chest wall toxicity (CWT) predictors. Twenty previously treated lung SABR patients were stratified into four cohorts according to distance from PTV to the chest wall, <1 cm, <0.5cm, overlapping up to 0.5cm and 1.0cm. For each patient, four plans were created; a chest wall optimised plan for 54Gy in 3 fractions, the clinical plan re-prescribed for 55Gy in 5, 48Gy in 3 and 45Gy in 3 fractions. For a PTV distance of 0.5-0.0cm, a reduction of the median (range) Dmax from 55.7 (57.5-54.1) Gy to 40.0 (37.1-42.0Gy) Gy was observed for the chest wall optimised plans. The median V30Gy decreased from 18.9 (9.7-25.6) cm3 to 3.1 (1.8-4.5) cm3. For a PTV overlap of up to 0.5cm, the Dmax reduced from 66.5 (64.1-70) Gy to 53.2 (50.6-55.1) Gy. The V30Gy decreased from 21.5 (16.5-29.5) cm3 to 14.9 (11.3-20.2) cm3. For the cohort with up to 1.0cm overlap, there was a reduction in Dmax values of 9.9Gy. The V30Gy for clinical plans, at 66.8 (18.7-188.8) cm3, decreased to 55.3 (15.5-149) cm3. When PTVs are within 0.5cm of chest wall, lung SABR dose heterogeneity can be used to reduce fraction number without increasing CWT predictors.

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy

IntroductionStereotactic ablative radiation therapy (SABR) is the standard of care for inoperable early-stage non-small-cell lung cancer. Although the probability of grade ≥ II toxicities is low, many patients present radiological subclinical toxicities usually associated with long-term patient management challenges. We evaluated radiological changes and correlated them with the received Biological Equivalent Dose (BED). MethodsWe retrospectively analyzed chest CT scans of 102 patients treated with SABR. An experienced radiologist evaluated the radiation-related changes 6 months and 2 years after SABR. The presence of consolidation, ground-glass opacities, organizing pneumonia pattern, atelectasis and the extent of affected lung were recorded. Dose-volume histograms of the lung healthy tissue were transformed to BED. Clinical parameters such as age, smoking habits, and previous pathologies were registered and correlations between BED and radiological toxicities were drawn. ResultsWe observed a positive and statistically significant correlation between lung BED over 300 Gy and the presence of organizing pneumonia pattern, the degree of lung affectation and the 2-year prevalence and/or increase of these radiological changes. Radiological changes in patients receiving BED > 300 Gy to a healthy lung volume ≥ 30 cc increased or remained in the 2 years follow-up scan. We found no correlation between radiological changes and the analyzed clinical parameters. ConclusionsThere seems to be a clear correlation between BEDs higher than 300 Gy and radiological changes both short and long term. If confirmed in an independent patient cohort, these findings could lead to the first radiotherapy dose constraints for grade I pulmonary toxicity.

Analysis of the interplay effect in lung stereotactic ablative radiation therapy based on both breathing motion and plan characteristics

Abstract Introduction: Stereotactic ablative radiotherapy (SABR) is susceptible to challenges for tumours affected by intrafraction organ motion. This study aims to investigate the effect of breathing characteristics and plan complexity on the interplay effect. Methods: A patient-specific interplay effect evaluation was performed using in-house software with an alpha version of the treatment planning verification software Verisoft (PTW-Freiburg, Germany) on VMAT plans. The OCTAVIUS 4D phantom was used to acquire the static dose distribution, and the simulation approach was utilised to generate the moving dose distribution. The influence of plan complexity, PTV size, number of breaths, and motion amplitudes on the interplay effect were examined. The dose distribution of two extreme phases—end-inhale and end-exhale—was considered using the gamma criteria of 2%/2 mm for the interplay effect evaluation. Results: A strong correlation was found between the motion amplitude (p &lt; 0.001) and the NBs (p &lt; 0.001) with the gamma-passing rate. No correlation was found between the gamma-passing rate and the PTV size or plan complexity. Conclusion: The simulation tool allowed the analysis of a large number of breathing traces, demonstrating how free-breathing patients, suspected of high interplay, could be selected for other motion management solutions. The simulated cases showed strong interplay effects for long breathing periods with extended motion amplitudes in a small group of patients.

Volumetric modulated arc therapy (VMAT) comparison to 3D-conformal technique in lung stereotactic ablative radiotherapy (SABR).

Stereotactic ablative radiotherapy (SABR) can be a curative option for non-small cell lung cancer (NSCLC) and oligometastatic lung disease. Volumetric modulated arc therapy (VMAT) has offered further advancements in terms of radiation dose shaping without compromising treatment times however there is potential for greater low-dose exposure to the lung. This study was to assess whether VMAT lung SABR would result in any increase to the dosimetry parameters compared with three-dimensional conformal radiotherapy (3D-CRT) that could confer increased risk of radiation pneumonitis. A total of 53 and 30 3D-CRT treatment plans of patients treated with 48 Gy in 4 fractions were compared. No statistically significant difference in planning target volumes between the VMAT 29.9 cc (range 12.4-58.5 cc) and 3D-CRT 31.2 cc (range 12.3-58.3 cc) P=0.79. The mean of total lung V5, ipsilateral lung V5 and contralateral lung V5 all showed a trend of being smaller in the VMAT treatment group- 14% versus 15.8%, 25.6% versus 30.4% and 1.6% versus 2.2%, respectively, but all were not statistically significant differences. Mean of the mean lung dose MLD, again showed a trend of being lower in the VMAT treatments but was also non-significant, 2.6 Gy versus 3.0 Gy, P=1.0. Mean V20 was the same in both cohorts, 3.3%. The dosimetry for 3D-CRT and VMAT plans were not significantly different including V5, and therefore we conclude that VMAT treatment is unlikely to be associated with an increased risk of radiation pneumonitis.

Assessing Treatment Response after Lung SABR: An Evaluation of the Predictive Value of RECIST Criteria

<h3>Purpose/Objective(s)</h3> Response Evaluation Criteria In Solid Tumors (RECIST) – version 1.1 is a commonly used framework to assess treatment response. However, response assessment after lung stereotactic ablative radiotherapy (SABR) can be difficult due to radiation-induced lung changes. The goal of this study was to assess how frequently lung lesions treated with SABR triggered RECIST criteria for recurrence and to correlate RECIST findings with actual treatment outcomes. <h3>Materials/Methods</h3> We reviewed patients who were treated with lung SABR between 2010-2015. Prescribed dose was 54-60 Gy in 3-8 fractions. Both primary lung and metastatic lesions were included. All lesion measurements were based on maximum diameter on CT axial slices. After treatment, progressive disease (PD) by RECIST was based on strict RECIST criteria and defined as: 1) increase of ≥ 20% compared to post-treatment minimum and 2) ≥ 5 mm absolute increase. The final assessment of recurrence was based on subsequent changes in lesions size after PD by RECIST and, when available, PET scan and/or pathology. When assessing subsequent changes in lesion size, stability (≤ 20% change) in size for at least one year or a decrease (> 20%) in size indicated no recurrence, while subsequent growth (> 20%) indicated recurrence. The assessment of lesion response by the treating radiation oncologist (RO) in the clinical record was also recorded when available. <h3>Results</h3> A total of 85 patients, with 88 lesions, met inclusion criteria. 75 of these lesions were lung primaries, the remainder were metastases. Median patient age was 79 years (IQR: 73-85) and mean lesion size was 2.1 ± 0.9 cm. Median follow-up was 52 months (IQR: 33-68). 66% (58/88) of treated lesions met criteria for PD by RECIST. However, on final assessment only 10% (9/88) were found to have recurrence. The positive predictive value (PPV) of RECIST criteria was 0.16. In the subset of patients with primary lung tumors only, 64% (48/75) were classified as PD by RECIST, but only 12% (9/75) were categorized as recurrence on final assessment. PPV was 0.19. The predictive value of RECIST was lower when PD by RECIST was triggered ≤ 12 vs. > 12 months post-treatment (PPV 0.08 vs. PPV 0.21). Median time to PD by RECIST was 19 months (IQR: 12-27) for those with recurrence vs. 15 months (IQR: 8-24) for those without recurrence on final assessment (p=0.13). Assessment by treating RO was only available for 57% (50/88) of cases, but concordance with final study assessment was 0.85, translating to an overall predictive accuracy of 94% (47/50). <h3>Conclusion</h3> Using strict RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, on further follow-up only a minority of these patients were felt to have recurrence, leading to a poor PPV for RECIST criteria in this setting. Further work is needed to develop validated criteria for designation of recurrence after lung SABR.

Initial Clinical Experience of CBCT-Based Adaptive Online Radiotherapy for SAbR of Thoracic Malignancies

<h3>Purpose/Objective(s)</h3> There has been an increasing trend in the availability and utilization of cone beam computed tomography (CBCT)-based adaptive online radiotherapy (AORT) in radiation oncology clinics. In this study, we report our initial experience of utilizing AORT to deliver stereotactic ablative radiation therapy (SAbR) for either early-stage non-small cell lung cancers (NSCLCs) or metastases to the thorax. <h3>Materials/Methods</h3> We recruited 18 patients treated with daily AORT whose tumors were treated with a total prescribed dose ranging from 33-60Gy treated over 3-5 fractions. During the AORT fraction, the physician contoured an ITV and critical OARs on the CBCT and two plans were created for the physician to choose from, a scheduled plan and an adaptive plan. The scheduled plan was a re-calculation of the reference plan based on the anatomy of the patient on that day's fraction while the adaptive plan was a re-optimization of the reference plan. For each scheduled and adaptive plan, we recorded PTV and ITV coverage (V100%), dose conformality (R50 and R100), and the maximum dose (D_max) received by the esophagus, bronchus, trachea, heart, and spinal cord. Timing data for each fraction from CBCT acquisition to approved plan and patient ready for treatment were also recorded. Dosimetric data between the scheduled and adaptive plans were compared relative to the scheduled plan. Paired t-tests were used to evaluate differences between the scheduled and adaptive plans. <h3>Results</h3> Among the 68 fractions analyzed, there was a reduction in ITV volume over the course of the adaptive treatments in 54.4% of cases (range: 0.7%-82.4%, mean: 24.3%), with physicians selecting the adaptive over scheduled plan 88.2% of the time. Relative to scheduled plans, mean difference in PTV and ITV coverage was 2.99% (p=0.009) and 1.07% (p=0.005) higher, respectively. Dose conformality, R50 and R100, were improved in 62.5% (p=0.05) and 66.7% (p=0.098) of adaptive compared to the scheduled plans. Mean difference in D_max relative to the scheduled plan for critical OARs ranged from -5.62% to 4.03%, only heart and spinal cord showing significance (p=0.004, p=0.023). Timing data demonstrated an average of 9 min spent on contouring, 5 min on plan optimization, and 5 min for online quality assurance. <h3>Conclusion</h3> A significant proportion of the patients in our SAbR-treated CBCT-adaptive therapy cohort demonstrated ITV volume changes during overall course of treatment. AORT-based lung SAbR treatments significantly improved PTV/ITV prescription coverage (compared to scheduled plan deliveries), dose conformity, and OAR sparing, with <15 min added to the overall treatment time for online contour and reoptimization. Overall, CBCT based-AORT is a robust approach to offer high quality online reoptimized plans for SAbR treatment of thoracic malignancies.

Same-day consultation, simulation and lung Stereotactic Ablative Radiotherapy delivery on a Magnetic Resonance-linac.

Magnetic resonance-guided radiotherapy (MRgRT) with real-time intra-fraction tumor motion monitoring allows for high precision Stereotactic Ablative Radiotherapy (SABR). This study aimed to investigate the clinical feasibility, patient satisfaction and delivery accuracy of single-fraction MR-guided SABR in a single day (one-stop-shop, OSS). Ten patients with small lung tumors eligible for single fraction treatments were included. The OSS procedure consisted of consultation, treatment simulation, treatment planning and delivery. Following SABR delivery, patients completed a reported experience measure (PREM) questionnaire. Prescribed doses ranged 28-34Gy. Median GTV was 2.2cm3 (range 1.3-22.9cm3). A gating boundary of 3mm, and PTV margin of 5mm around the GTV, were used with auto-beam delivery control. Accuracy of SABR delivery was studied by analyzing delivered MR-cines reconstructed from machine log files. All 10 patients completed the OSS procedure in a single day, and all reported satisfaction with the process. Median time for the treatment planning step and the whole procedure were 2.8h and 6.6h, respectively. With optimization of the procedure, treatment could be completed in half a day. During beam-on, the 3mm tracking boundary encompassed between 78.0 and 100% of the GTV across all patients, with corresponding PTV values being 94.4-100% (5th-95th percentiles). On average, system-latency for triggering a beam-off event comprised 5.3% of the delivery time. Latency reduced GTV coverage by an average of -0.3 %. Duty-cycles during treatment delivery ranged from 26.1 to 64.7%. An OSS procedure with MR-guided SABR for lung cancer led to good patient satisfaction. Gated treatment delivery was highly accurate with little impact of system-latency.

EP02.02-007 Correlation between Biological Equivalent Dose and Radiological Changes after Lung Stereotactic Ablative Radiation Therapy

Stereotactic ablative radiation therapy (SABR) is the standard of care for inoperable early-stage NSCLC offering excellent local control. Although the related probability of grade ≥2 toxicities is low, 60-100% of the patients present radiological toxicities. Even though these changes may not lead to direct clinical consequences, some are associated with future clinical toxicities and long-term patient management challenges. In this study, we evaluated radiological changes after SABR and correlated them with the received Biological Equivalent Dose (BED).