Stereotactic Body Radiotherapy For Lung Cancer Research Articles

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.

Evaluation of Flattening-Filter-Free and Flattening Filter Dosimetric and Radiobiological Criteria for Lung SBRT: A Volume-Based Analysis

The use of volumetric modulated arc therapy (VMAT) with flattening-filter-free (FFF) beams is becoming more prevalent in lung cancer stereotactic body radiotherapy (SBRT). The aim in this study was to assess the impact of dosimetric and radiobiological differences between FFF and flattening filter (FF) beams for lung SBRT based on the target volume. A total of 198 lung stereotactic body radiation therapy treatment plans with FFF beams and FF beams were retrospectively selected for this study. For all plans, the prescribed dose was 50 Gy/5 fractions, and the dose volume histogram (DVH) for the target and organs at risk (OAR) and the normal tissue complication probability (NTCP) of the lung were recorded and compared. Moreover, monitor units (MUs), the beam on-time and the treatment time were evaluated. The study was performed following the Radiation Therapy Oncology Group (RTOG) 0813 and 0915 protocols. No significant differences in D90, coverage rate (CR) or conformity index (CI) of the target were observed between FFF beams and FF beams (p>0.05). The D2, R50% and gradient index (GI) for the target improved with FFF beams compared with FF beams (p<0.05). FFF beams also significantly reduced the dose for the lung, heart, spinal cord, esophagus and NTCP of the lung (p<0.05), compared with FF beams. However, there was no significant difference in sparing of the trachea (p>0.05). The mean MUs, beam on-time and treatment time were 1871±278 MUs, 3.2 ±0.2 min and 3.9 ±0.3 min for FFF beams, and 1890±260 MUs, 4.2±0.3 min and 4.8 ±0.4 min for FF beams, respectively. The FFF beam technique for lung SBRT with VMAT results in a better dose fall-off, better dose-sparing of OAR, lower NTCP of the lung and a shorter beam on-time compared with the FF beam technique. Additionally, the improvement in target and OAR-sparing for FFF beams was increased with increasing target volume.

High Risk Prognostic Factors Predictive of Outcome Following Stereotactic Body Radiation Therapy (SBRT) for Early-Stage Lung Cancer

High risk prognostic factors for outcomes following SBRT for early-stage lung cancer per SWOG/NRG 1914 include: tumor size > 2cm; moderately/poorly/undifferentiated histology; or high metabolic activity on PET/CT defined as SUV > 6.2. The purpose of this IRB approved retrospective study is to assess outcome for stage I lung cancer and to validate SWOG risk stratification in a single community-based radiation department. A total of 132 patients with 139 tumors treated with SBRT between 2014 and 2019 were stratified by SWOG risk group (high vs. low). To assess differences by risk group in estimated overall survival (OS) at the patient level, as well as Freedom from Local Failure (FFLF), Freedom from Regional Failure (FFRF) and Freedom from Distant Failure (FFDF) at the tumor level, Kaplan-Meier methodology and Cox proportional hazards (PH) modeling for correlated data were used. Statistical significance was concluded at the 0.05 level. Median follow-up for the entire group is 56 months. 77% of patients had high risk tumors. The median patient age was 75 years with 57% female. Patients with high-risk tumors were older (p = 0.023) compared to patients with low-risk tumors. At the tumor level, high risk tumors were more likely to have biopsies performed (91% vs 57% p = 0.002) and more likely to experience regional failure (28% vs 7% p = 0.005). High risk tumors were more likely to experience local failure (8% vs 0% p = NS) and distant failure (27% vs 14% p = NS). Median survival was 49 months for the whole group (46.0 months high risk, 65.1 months low risk). Actuarial OS at 5 years is 38% (35% high risk, 51% low risk). Actuarial FFLF at 5 years is 94% (93% high risk, 100% low risk). Actuarial FFRF at 5 years is 77% (72% high risk, 93% low risk). Actuarial FFDF at 5 years is 74% (70% high risk, 88% low risk). Cox PH models revealed no statistically significant differences in FFRF by risk group (p = 0.08). Excellent local control but higher regional and distant failure was demonstrated for high-risk lung tumors as defined by SWOG/NRG 1914. Clinically important decrement in outcomes were consistently noted for high-risk tumors in this sample which did not demonstrate statistical significance due to lack of events and statistical power. However, our data supports the prognostic importance of tumor size/grade and SUV for identifying patients at high risk. Further validation with larger sample sizes would contribute to our knowledge regarding risk stratification for early-stage lung cancer treated with SBRT.

Deep learning model fusion improves lung tumor segmentation accuracy across variable training-to-test dataset ratios.

This study aimed to investigate the robustness of a deep learning (DL) fusion model for low training-to-test ratio (TTR) datasets in the segmentation of gross tumor volumes (GTVs) in three-dimensional planning computed tomography (CT) images for lung cancer stereotactic body radiotherapy (SBRT). A total of 192 patients with lung cancer (solid tumor, 118; part-solid tumor, 53; ground-glass opacity, 21) who underwent SBRT were included in this study. Regions of interest in the GTVs were cropped based on GTV centroids from planning CT images. Three DL models, 3D U-Net, V-Net, and dense V-Net, were trained to segment the GTV regions. Nine fusion models were constructed with logical AND, logical OR, and voting of the two or three outputs of the three DL models. TTR was defined as the ratio of the number of cases in a training dataset to that in a test dataset. The Dice similarity coefficients (DSCs) and Hausdorff distance (HD) of the 12 models were assessed with TTRs of 1.00 (training data: validation data: test data = 40:20:40), 0.791 (35:20:45), 0.531 (31:10:59), 0.291 (20:10:70), and 0.116 (10:5:85). The voting fusion model achieved the highest DSCs of 0.829 to 0.798 for all TTRs among the 12 models, whereas the other models showed DSCs of 0.818 to 0.804 for a TTR of 1.00 and 0.788 to 0.742 for a TTR of 0.116, and an HD of 5.40 ± 3.00 to 6.07 ± 3.26mm better than any single DL models. The findings suggest that the proposed voting fusion model is a robust approach for low TTR datasets in segmenting GTVs in planning CT images of lung cancer SBRT.

Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience.

The detection rate of early-stage lung cancer with ground-glass opacity (GGO) has increased, and stereotactic body radiotherapy (SBRT) has been suggested as an alternative to surgery in inoperable patients. However, reports on treatment results are limited. Therefore, we performed a retrospective study to investigate the clinical outcome after SBRT in patients with early-stage lung cancer with GGO-predominant tumor lesions at a single institution. This study included 89 patients with 99 lesions who were treated with SBRT for lung cancer with GGO-predominant lesions that had a consolidation-to-tumor ratio of ≤0.5 at Asan Medical Center between July 2016 and July 2021. A median total dose of 56.0 Gy (range, 48.0-60.0) was delivered using 10.0-15.0 Gy per fraction. The overall follow-up period for the study was median 33.0 months (range, 9.9 to 65.9 months). There was 100% local control with no recurrences in any of the 99 treated lesions. Three patients had regional recurrences outside of the radiation field, and three had distant metastasis. The 1-year, 3-year, and 5-year overall survival rates were 100.0%, 91.6%, and 82.8%, respectively. Univariate analysis revealed that advanced age and a low level of diffusing capacity of the lungs for carbon monoxide were significantly associated with overall survival. There were no patients with grade ≥3 toxicity. SBRT is a safe and effective treatment for patients with GGO-predominant lung cancer lesions and is likely to be considered as an alternative to surgery.

Dosimetric effects of the custom dose iteration times on stereotactic radiotherapy for lung cancer

PurposeTo evaluate the dosimetric effects of the custom dose iteration function in the Monaco 6.0 planning system on stereotactic radiotherapy for lung cancer. MethodsUsing the custom dose iterative function segment shape optimization (SSO) times in the Monaco 6.0 treatment planning system, the iterative times were set as 3, 5, 8, 10, and 12, respectively. Five volumetric modulated arc stereotactic body radiation therapy (SBRT) plans were made for each patient, and other optimization parameters and optimization functions were kept consistent. The dose volume histogram (DVH) statistical table was used to evaluate the dose of the target area and organs at risk (OAR). Statistical analysis was performed using SPSS 25 software, and the results were statistically different when p < 0.05. ResultsFor the target area dose analysis, SSO8, SSO10, and SSO12 groups showed similar results, significantly better than both SSO3 and SSO5 groups (p < 0.05). With the increase in the times of SSO, the protection of the heart was better, except for SSO3, the maximum dose of the esophagus and V47Gy of great vessels were significantly lower than SSO5 in all groups. The mean dose of heart was significantly lower in SSO10 and SSO12 than SSO5 (p < 0.05). There was no significant difference in other OAR among the groups. The optimization time (OT) of each group was statistically different, the maximum OT exceeded 1000s, the maximum deviation between groups exceeded 600s, and the OT increased significantly with the times of SSO (p < 0.05). There was no statistically significant difference between the 5 groups of monitor unit (MU), and segment was not significantly different between the groups except SSO3 which was significantly higher than SSO5 (p < 0.05). The delivery time (DT) was statistically different between the groups except for SSO3. ConclusionsIn the treatment of left-sided lung cancer patients with volumetric modulated arc SBRT, considering both calculation accuracy and clinical treatment efficiency, SSO times of 8 is recommended for designing SBRT for lung cancer with the Monaco treatment planning system.

Lung Stereotactic Body Radiation Therapy in a Patient with Severe Lung Function Impairment Allowed by Gallium-68 Perfusion PET/CT Imaging: A Case Report

Lung stereotactic body radiotherapy (SBRT) is increasingly proposed, especially for patients with poor lung function who are not eligible for surgery. However, radiation-induced lung injury remains a significant treatment-related adverse event in these patients. Moreover, for patients with very severe COPD, we have very few data about the safety of SBRT for lung cancer. We present the case of a female with very severe chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in one second (FEV1) of 0.23 L (11%), for whom a localized lung tumor was found. Lung SBRT was the only possible treatment. It was allowed and safely performed, based on a pre-therapeutic evaluation of regional lung function with Gallium-68 perfusion lung positron emission tomography combined with computed tomography (PET/CT). This is the first case report to highlight the potential use of a Gallium-68 perfusion PET/CT in order to safely select patients with very severe COPD who can benefit from SBRT.

Comparison of Recurrence Patterns between Adenocarcinoma and Squamous Cell Carcinoma after Stereotactic Body Radiotherapy for Early-Stage Lung Cancer.

We compared recurrence patterns between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) after stereotactic body radiotherapy (SBRT) for early-stage lung cancer. Patients with ADC and SCC histology, who were treated with SBRT for clinical stage IA1-IIA lung cancer at our institution, were included in the analysis. The rates of disease-free survival (DFS), overall survival (OS), local recurrence (LR), lymph node metastasis (LNM), and distant metastasis (DM) were calculated using the Kaplan-Meier method or the cumulative incidence function. Among the 204 patients analyzed, 138 and 66 were in the ADC and SCC groups, respectively. The median follow-up period was 60 months. The five-year DFS and OS rates were 57% vs. 41% and 69% vs. 48% in the ADC and SCC groups, respectively (p = 0.015 and 0.019, respectively). In the multivariate analysis, the histological type was not associated with DFS or OS. Five-year LR, LNM, and DM rates were 10% vs. 24%, 12% vs. 20%, and 25% vs. 27% in the ADC and SCC groups, respectively (p = 0.0067, 0.074, and 0.67, respectively). The multivariate analysis identified the histological type of SCC as an independent factor for LR (hazard ratio, 2.41; 95% confidence interval, 1.21-4.77; p = 0.012). The present results suggest that the risk of LR after SBRT is higher for SCC than for ADC.

Evaluation of flattening-filter-free and flattening filter dosimetric and radiobiological criteria for lung SBRT: A volume-based analysis.

The use of volumetric modulated arc therapy (VMAT) with flattening-filter-free (FFF) beams is becoming more prevalent in lung cancer stereotactic body radiotherapy (SBRT). The aim in this study was to assess the impact of dosimetric and radiobiological differences between FFF and flattening filter (FF) beams for lung SBRT based on the target volume. A total of 198 lung stereotactic body radiation therapy treatment plans with FFF beams and FF beams were retrospectively selected for this study. For all plans, the prescribed dose was 50 Gy/5 fractions, and the dose volume histogram (DVH) for the target and organs at risk (OAR) and the normal tissue complication probability (NTCP) of the lung were recorded and compared. Moreover, monitor units (MUs), the beam on-time and the treatment time were evaluated. The study was performed following the Radiation Therapy Oncology Group (RTOG) 0813 and 0915 protocols. No significant differences in D90, coverage rate (CR) or conformity index (CI) of the target were observed between FFF beams and FF beams (p>0.05). The D2, R50% and gradient index (GI) for the target improved with FFF beams compared with FF beams (p<0.05). FFF beams also significantly reduced the dose for the lung, heart, spinal cord, esophagus and NTCP of the lung (p<0.05), compared with FF beams. However, there was no significant difference in sparing of the trachea (p>0.05). The mean MUs, beam on-time and treatment time were 1871 ± 278 MUs, 3.2 ± 0.2min and 3.9 ± 0.3min for FFF beams, and 1890 ± 260 MUs, 4.2 ± 0.3min and 4.8 ± 0.4min for FF beams, respectively. The FFF beam technique for lung SBRT with VMAT results in a better dose fall-off, better dose-sparing of OAR, lower NTCP of the lung and a shorter beam on-time compared with the FF beam technique. Additionally, the improvement in target and OAR-sparing for FFF beams was increased with increasing target volume.

Angiotensin receptor blockade and stereotactic body radiation therapy for early stage lung cancer ARB & SBRT for early stage lung cancer

ABSTRACT Stereotactic body radiotherapy (SBRT) demonstrates excellent local control in early stage lung cancer, however a quarter of patients develop recurrence or distant metastasis. Transforming growth factor-beta (TGF-β) supports metastasis and treatment resistance, and angiotensin receptor blockade (ARB) indirectly suppresses TGF-β signaling. This study investigates whether patients taking ARBs while undergoing SBRT for early stage lung cancer exhibited improved overall survival (OS) or recurrence free survival (RFS) compared to patients not taking ARBs. This was a single institution retrospective analysis of 272 patients treated with SBRT for early stage lung cancer between 2009 and 2018. Patient health data was abstracted from the electronic medical record. OS and RFS were assessed using Kaplan–Meier method. Log-rank test was used to compare unadjusted survival between groups. Univariable and multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Of 247 patients analyzed, 24 (10%) patients took ARBs for the duration of radiotherapy. There was no difference in mean age, median tumor diameter, or median biologic effective dose between patients taking ARBs or not. Patients taking ARBs exhibited increased OS (ARB = 96.7 mo.; no ARB = 43.3 mo.; HR = 0.25 [95% CI: 0.10 to 0.62, P = .003]) and increased RFS (median RFS, ARB = 64.3 mo.; No ARB = 35.1 mo.; HR = 0.26 [95% CI: 0.10 to 0.63, P = .003]). These effects were not seen in patients taking angiotensin converting enzyme inhibitors (ACEIs) or statins. ARB use while undergoing SBRT for early stage lung cancer may increase OS and RFS, but ACEI use does not show the same effect.

Simulation of dosimetric consequences of intrafraction variation of tumor drift in lung cancer stereotactic body radiotherapy.

The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during stereotactic body radiotherapy (SBRT) for lung cancer. Intensity-modulated radiation therapy (IMRT) plans were designed based on average computed tomography (AVG CT) utilizing the planning target volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Variation was simulated by shifting the nominal plan isocenter along six directions from 0.5mm to 4.5mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan. Dose indices, including ΔD99 for internal target volume (ITV) and gross tumor volume (GTV), were adopted as endpoint samples. The mean dose discrepancy was calculated under the 3-dimensional space distribution. We found that motion can lead to serious dose degradation of the target and ITV in lung SBRT, especially during SBRT with PTV surrounding the lower isodose line. Lower isodose line may lead to larger dose discrepancy, while make steeper dose fall-off gradient. This phenomenon was compromised when 3-dimensional space distribution was considered. This result may provide a prospective reference for target dose degradation due to motion during lung SBRT treatment.

Difference in failure patterns after stereotactic body radiotherapy for lung cancer according to clinical Tstage based on 4D computed tomography.

Stereotactic body radiotherapy (SBRT) is atreatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical Tstage. Atotal of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. Median follow-up time was 27.5months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8months, respectively. The 3‑year PFS and OS rates were 50.7% and 60.3%, respectively. Asignificant difference was observed in PFS according to the clinical Tstage (p = 0.001). No significant differences were observed in OS according to the clinical Tstage (p = 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (p = 0.010). Clinical Tstage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to Tstage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.

Impact of Systemic Autoimmune Diseases on Treatment Outcomes and Radiation Toxicities in Patients with Stage I Non-Small Cell Lung Cancer Receiving Stereotactic Body Radiation Therapy: A Matched Case-Control Analysis.

We aimed to evaluate the impact of systemic autoimmune diseases (SADs) on treatment outcomes and radiation toxicities following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We queried an institution-based database on patients with SADs treated with SBRT for lung cancer between 2001 and 2016 (SAD group). Each patient was matched to three controls without SADs. The primary outcomes of interest were the overall survival (OS) and local control rate (LCR). The secondary outcomes were radiation toxicities of grades ≥2 (≥G2). Twelve patients with SADs were matched to 36 controls. The median follow-up duration was 3.6 years. There was a significant intergroup difference in the OS (hazard ratio [HR]: 4.11, 95% confidence incidence [CI]: 1.82−9.27, p < 0.001) and LCR (HR: 15.97, 95% CI: 2.89−88.29, p < 0.001). However, there were no significant intergroup differences in the odds of acute (odds ratio [OR]: 0.38, 95% CI: 0.02−8.91, p = 0.550) and late (OR: 2.20, 95% CI: 0.32−15.10, p = 0.422) ≥G2 radiation pneumonitis. No other ≥G2 toxicities were identified. In conclusion, although radiation toxicities are not enhanced by SADs, SADs are risk factors of poor prognosis following SBRT for stage I NSCLC.

Dosimetric and biological comparisons of single planning and double plannings for bilateral lung cancer SBRT planning based on the Cyber-Knife system.

The aim is to investigate the influence of single planning (Plan S) and double plannings (Plan D) on bilateral lung cancer stereotactic body radiation therapy planning from the perspective of dosimetry and biology respectively. Methods Cases with bilateral lung cancer patients who had undergone SBRT with the Cyber-Knife were enrolled, and a single planning and double plannings were designed in the Multiplan@4.2 treatment planning system equipped with the Cyber-Knife system. The single plan was to optimize the two target volumes in a separate plan, while the dual plan is to optimize two target volumes respectively in two separate plans, then perform dose superposition. Then based on the dosimetric results, the biological parameters were calculated. Thus the quality of SBRT plans for those bilateral lung cancer designed by the two methods were compared and evaluated according to the dosimetric and biological results. The dose distribution of both planning target volumes and surrounding organs at risk in Plan S and Plan D could meet the clinical prescription requirements. The target conformity index and the new conformity index of PTV were closer to 1 in the Double plannings, and the dose gradient GI in the Plan D was smaller than Plan S. For organs at risks, the doses received by the Plan D were relatively small. In terms of biological models, for the equivalent uniform dose of normal lung tissue, heart and esophagus, the Plan D was 6.51% (P=0.045), 19.8% (P=0.022), 27.08% (P>0.05) lower than Plan S respectively. The results showed that the equivalent uniform dose of normal tissue in the Plan D was lower relative to Plan S. Dosimetric and biological results show that both the use of Plan D have an advantage of protecting normal tissues, and it was suggested that to design double plannings for bilateral lung cancer stereotactic body radiation therapy planning based on Cyber-Knife in the clinical practice.

Clinical Outcomes of Stereotactic Body Radiation Therapy across Treatment Platforms Employing Varied Approaches to Respiratory Management at a Single Institution

<h3>Purpose/Objective(s)</h3> Stereotactic Body Radiation Therapy (SBRT) has been the standard of care for early-stage non-small cell lung cancer patients who do not undergo surgery since soon after the publication of RTOG 0236. Since then, various linear accelerator platforms have been employed with a variety of approaches to respiratory management, treatment planning and treatment delivery. Comparisons of local control and survival end points using a variety of treatment platforms in addition to respiratory management techniques have not been reported. Here, we present the results of our analysis of clinical outcomes at a single institution across multiple treatment platforms representative of the available technology since the widespread adoption of SBRT for early-stage lung cancer. <h3>Materials/Methods</h3> Consecutive patients who underwent SBRT for early-stage lung cancer between 2011 and 2018 at a single institution were retrospectively analyzed. Treatments were planned and delivered with standardized simulation, dose and fractionation per institutional guidelines. Overall Survival (OS), Local Control (LC), Distant Metastasis Free Survival (DMFS), and Progression Free Survival (PFS) were calculated for the entire cohort. Log rank comparisons of all survival endpoints were then calculated by treatment platform: stereoscopic orthogonal kV x-ray localization with conventional Linac (Linac1), volumetric cone beam CT localization with conventional Linac (Linac2), and megavoltage CT with helical tomotherapy (Linac3). Comparisons were also performed by respiratory management technique: free breath (FB), breath hold (BH) or end expiration respiratory gating (RG). <h3>Results</h3> A total of 240 patients were included in the analysis. Treatment platform utilization was well balanced in the group: 28% on Linac1, 32% on Linac2, and 40% on Linac3. The majority of patients were treated with FB, 72%. Median OS for the entire cohort was 50 months. The crude rate of local recurrence was 7%. Kaplan-Meier estimate of LC for the entire cohort was 94% at 3 years. The median time to local recurrence was not reached. LC was not impacted by treatment platform, p = 0.897, or respiratory management technique, p = 0.623. Comparisons by treatment platform and respiratory management technique revealed no significant differences in OS, DMFS, and PFS. <h3>Conclusion</h3> Irrespective of treatment platform or approach to respiratory management, SBRT remains highly effective at providing durable LC in patients with early-stage lung cancer. Differences in treatment delivery platform and respiratory management do not significantly influence other disease control and survival outcomes.

Recurrence Risk and Survival Following SBRT for Lung Cancer: Impact of Prognostic Factors Used for Patient Selection in a Randomized Trial

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) is the standard treatment for early stage, medically inoperable non-small cell lung cancer (NSCLC), attaining excellent local control. However, rates of regional and distant recurrence are relatively high. Current randomized phase 3 trials are investigating the addition of immunotherapy to SBRT in this setting to improve disease control and survival, with varying patient selection criteria. We investigate the influence of the high-risk factors used for patient selection on the ongoing randomized phase 3 SWOG/NRG trial (tumor size ≥2 cm, SUV ≥6.2, and grade 2-3) on disease control and survival in a single institution cohort and hypothesize that patients with high-risk features will have increased rates of recurrence and death. <h3>Materials/Methods</h3> Following IRB approval, we retrospectively analyzed patients treated with SBRT for early stage (T1-3N0M0) NSCLC between 2007 and 2019 at a single institution. Patient and disease specific characteristics and oncologic outcomes were documented. Risk factors including size ≥2 cm, SUV ≥6.2, and grade 2-3 histology were documented for each patient, and total number of high-risk features for each patient was calculated. In-field control (IFC), distant control (DC) and overall survival (OS) were calculated using the Kaplan Meier method, and the influence of high-risk factors was assessed with the log-rank method. <h3>Results</h3> We identified 217 courses of SBRT performed for early-stage NSCLC. All cases had tumor diameter available, 196 had SUV_max prior to SBRT available, and 68 had histologic grade available. Median patient age was 76.2 years (range 48.9-93.1) and median follow up was 35.1 months (range: 1.6-145-3). Tumors were treated to a median of 50 Gy (range: 40 - 60 Gy) in a median of 4 (range: 3-8) fractions. OS decreased with increasing number of risk factors, with 3-year OS of 73.7%, 72.2%, 50.7%, and 44.4% for patients with 0, 1, 2, and 3 high risk factors, respectively (p<0.001). Patients with 0-1 risk factors had 3-year OS of 73.2% as compared to 48.3% for those with 2-3 risk factors (p<0.001). This appeared to be driven by distant, rather than local recurrence: patients with 0-1 high risk factors had 3-year DC of 85.3% as compared to 73.3% P=0.006), but the assessed risk factors were not predictive of IFC. Individually, size ≥2 cm was the most robust risk factor, with 3-year DC of 72.7% versus 89.2% and OS of 61% versus 70.2% for tumors ≥2 cm and <2 cm, respectively. <h3>Conclusion</h3> High-risk features used for patient selection for an ongoing phase 3 trial testing the addition of immunotherapy to SBRT in early-stage NSCLC were highly predictive in aggregate for DC and OS but not LC in a single institution cohort of patients. Several ongoing randomized trials will determine whether immunotherapy reduces recurrence and improves OS in medically inoperable NSCLC treated with SBRT.

End-to-end test of respiratory gating radiation therapy for lung stereotactic body radiation therapy treatments.

In this paper, a dosimetric end-to-end test of respiratory gated radiation therapy (RGRT) applied in lung cancer stereotactic body radiation therapy (SBRT) was performed. The test was performed from treatment simulation to treatment delivery using a QUASAR phantom, for regular, slightly irregular and irregular breathing patterns in phase- and amplitude-gated modes. A mechanical and dosimetric verification was performed to evaluate all steps of the proposed treatment workflow. Dose measurements were performed using a PinPoint ion chamber and GafChromic EBT3 films. Mechanical verification confirmed good function of the chosen systems. Dosimetric verification showed good agreement between planned and measured doses, for the phase-gated versus amplitude-gated modes: 1.4 ± 0.4% versus 1.2 ± 0.2% for regular, 2.8 ± 0.3% versus 3.0 ± 0.3% for slightly irregular, and 6.2 ± 0.7% versus 7.4 ± 0.5% for irregular breathing patterns. The gamma passing rates for 3%/3mm and 2%/2mm criteria, comparing phase- versus amplitude-gated modes, were 99.0 ± 0.3% versus 99.5 ± 0.2% and 95.2 ± 0.2% versus 96.1 ± 0.2% for the regular, 97.4 ± 0.8% versus 98.0 ± 0.6% and 91.7 ± 0.5% versus 92.4 ± 0.4% for the slightly irregular, and 96.4 ± 0.5% versus 95.3 ± 0.7% and 86.4 ± 0.5% versus 84.6 ± 0.7% for the irregular breathing patterns, respectively. It is concluded that using equipment and workflow for the treatment of lung cancer by means of SBRT in RGRT mode is safe and efficient, for regular and slightly irregular breathing patterns.

Practical usefulness of partial-range 4-dimensional computed tomography in the simulation process of lung stereotactic body radiation therapy

PurposeFour-dimensional computed tomography (4DCT) scans to cover the entire lungs often fail due to changes in the patient's respiratory cycle, highlighting the need for an improved method that can facilitate successful 4DCT for lung stereotactic body radiation therapy (SBRT). This study aimed to present partial-range 4DCT (PR-4DCT) as a new simulation method to increase the success rate of 4DCT and to verify the practical usefulness of PR-4DCT. Methods & materialsWe retrospectively analyzed 230 consecutive patients (270 tumors) who underwent SBRT for primary lung cancer or pulmonary metastasis between January 2014 and December 2021. We developed a new CT simulation method (PR-4DCT) in 2019 that scans only a partial-range around the tumor. To verify the usability of PR-4DCT, CT simulation methods were compared by period. ResultsUntil 2018, before the PR-4DCT method was introduced, the rate of 4DCT implementation was less than 40%. However, the proportion has continued to increase since then, and rate of implementation of 4DCT improved to approximately 94% in 2021. Moreover, 4DCT could be performed on almost all lower-lobe tumors after the introduction of PR-4DCT. In particular, the success rate increased dramatically after using the PR-4DCT method in patients who had decided to try 4DCT, and in 2021, PR-4DCT was successful in all of these patients. ConclusionPR-4DCT is a very simple method that can be used immediately in any institution currently performing 4DCT, and it is an effective solution to increase the success rate of 4DCT in patients with an irregular respiratory cycle.

Percutaneous local tumor ablation vs. stereotactic body radiotherapy for early-stage non-small cell lung cancer: a systematic review and meta-analysis.

Background:Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).Methods:PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.Results:Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87–1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71–1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25–1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR = 1.32, 95% CI: 1.14–1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64–1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63–6.07, P = 0.25) between the LTA group and SBRT group.Conclusions:Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.INPLASY Registration Number:INPLASY202160099

Dosimetric parameters related to occurrence of distant metastases and regional nodal relapse after SBRT for early-stage non-small cell lung cancer

PurposePrevious studies have suggested that the dose immediately outside the PTV may impact the incidence of distant metastases after stereotactic body radiation therapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC). In particular, Diamant et al. [1,2] reported a correlation between the mean EQD2 of a 30 mm shell around the PTV and both local control and the rate of distant metastases. In this study, we assess this parameter and others in a series of patients with radiographically presumed or biopsy-proven early-stage NSCLC treated at our institution with stereotactic body radiotherapy (SBRT) between 2017 and 2019. Materials/MethodsWe reviewed the dosimetry, local control, regional nodal relapse, and rate of distant metastases for 304 patients with 325 lesions treated with SBRT at our institution. Dosimetric parameters investigated include the prescribed dose, minimum and mean doses to the PTV, conformity index, and the mean EQD2 to a 30 mm shell around the PTV. Time to each event was defined from date of last fraction of SBRT to date of event, with event-free patients censored at last radiographic follow-up. Univariate (UVA) Cox regression analysis was performed on the collected parameters to assess for correlation with regional nodal relapse and rate of distant metastases. ResultsThere was no significant correlation between the mean EQD2 dose to a 30 mm shell around the PTV and the rate of distant metastases. On UVA Cox proportional hazards analysis, positive predictors of reduced incidence of distant metastases were PTV <22 cc (vs. ≥22 cc, p = 0.01) and GTV <10 cc (vs. ≥10 cc, p < 0.01), with GTV <10 cc also being a positive predictor of reduced incidence of regional nodal relapse (p < 0.01). In the subset of patients treated with 4–5 fractions, mean EQD2 dose to the 30 mm shell around the PTV ≥21 Gy was associated with increased incidence of distant metastases (HR 2.42, 95% CI 1.06–5.53, p = 0.04), differing from prior data from Diamant et al. ConclusionsWe did not observe a correlation between the rate of distant metastases and dose outside the PTV, as reported by other groups; rather, we noted an opposite trend in patients treated with 4–5 fractions. Our data show additional correlations between distant metastases and tumor size.