Purpose:As screening chest computed tomography for patients at high risk for cancer has become more widely accepted, increasing numbers of patients with early-stage small cell lung cancer (SCLC) are being diagnosed. Although surgery is an accepted option for patients with early-stage SCLC, for patients who decline or cannot undergo surgery, stereotactic body radiation treatment (SBRT) is an alternative. Although prophylactic cranial irradiation (PCI) improves survival in patients with limited-stage SCLC, PCI for early-stage SCLC (stage T1-T2) has not been explored. This study defines survival and recurrence patterns in patients with early-stage SCLC who were treated with surgery or SBRT in the absence of PCI. Methods and Materials:In this single-institution retrospective study, 14 patients diagnosed with early-stage SCLC (stage T1-T2) between July 2015 and May 2021 at a single tertiary care hospital were treated with SBRT or surgery with no PCI. Primary outcomes were locoregional cancer recurrence, distant recurrence, recurrence-free survival, and overall survival. The secondary outcome was development of brain metastasis. Analyses included Cox regression, Kaplan-Meier survival, and log-rank tests. Results:A total of 14 patients (5 women and 9 men) were included in the study: 9 with stage T1 and 5 with stage T2 SCLC. Six patients (43%) received SBRT and 8 (57%) had surgical treatment. All patients except 1 received adjuvant chemotherapy. Median follow-up was 14.3 months (range, 2.4-64.4 months), and the median age at diagnosis was 71.5 years (range, 54-81 years). Cox regression and log-rank tests showed no significant differences in any outcomes between the surgery and SBRT groups, and no patients developed brain metastases during the study period. Conclusions:Data are lacking regarding the benefit of PCI in early-stage SCLC. Although the sample size in this study was too small to draw any conclusions, the findings add to the ongoing dialogue regarding the importance of PCI in this patient population. No difference was identified in survival and cancer recurrence in patients who received either surgery or SBRT in the absence of PCI.

8523 Background: In the landmark PACIFIC trial, adjuvant durvalumab after definitive chemoradiation for unresectable stage III non-small-cell lung cancer (NSCLC) produced a 11% absolute overall survival benefit at two years compared to placebo, and the US Food and Drug Administration approved durvalumab for this indication in February 2018. We investigated the real-world use of adjuvant durvalumab and other immune checkpoint inhibitors (ICI) in a contemporary cohort of patients. Methods: We identified patients with unresectable stage III (AJCC 8th edition) NSCLC treated with definitive chemoradiation from February 2018 to March 2020 from a statewide radiation oncology quality consortium, representing a mix of community (n=22 centers, 336 patients) and academic practice settings (n=5 centers, 64 patients) across the state of Michigan. Use of adjuvant durvalumab or other ICI (atezolizumab, nivolumab, or pembrolizumab) was ascertained at the time of routine three- or six-month follow-up after completion of chemoradiation. Baseline characteristics of patients treated with or without adjuvant ICI were compared with the Chi-squared test for categorical variables and a two-sided t-test for continuous variables. Results: Of 400 patients with unresectable stage III NSCLC treated with definitive chemoradiation, 268 (67%) received adjuvant ICI. Of these, the majority received durvalumab (86%) followed by pembrolizumab (7.5%) and nivolumab (6.0%). The proportion of patients receiving ICI remained stable throughout the study period with no discernable time trends. Eight-five percent of white patients received ICI compared with 77% of black patients (p=0.04), but there were no differences in gender (54.5% male in ICI vs 52.3% no ICI), current smoking (42.2% ICI vs 37.9% no ICI, p=0.68), number of comorbidities (29.5% with 3 or more comorbidities in ICI vs. 26.5% in no ICI, p=0.86), baseline oxygen use (8.9% ICI vs 10.6% no ICI, p=0.59), age (median 66.4 years [IQR 60.3-73.4] for ICI vs. 66.9 years [IQR 61.1-72.2] no ICI, p=0.89), treatment at an academic center (16.0% ICI vs 15.9% no ICI, p=0.97), or ECOG performance status (59.3% ECOG 0 in ICI vs 62.8% no ICI). Conclusions: In a broad range of academic and community-based practices across a state including 27 sites, only two-thirds of potentially eligible stage III NSCLC patients received adjuvant durvalumab or other ICI agents despite a proven overall survival benefit. Receipt of ICI was not strongly associated with baseline demographic or comorbidity variables. Further work will seek to clarify the patient-level reasons behind non-initiation of adjuvant ICI.

PURPOSE:To analyze clinical toxicity and quality-of-life (QOL) outcomes among patients with stage I non-small cell lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT) as a function of radiation dose and volume parameters. METHODS AND MATERIALS:In this institutional review board-approved study, 55 patients with stage I NSCLC who received SBRT (12 Gy × 4) and completed QOL forms were analyzed. Clinical symptoms and QOL outcomes were measured at baseline and at 3, 6, 12, 18, 24, and 36 months after SBRT. Clinical toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Lung-Trial Outcome Index (FACT-L-TOI) instrument. Dosimetric parameters including the mean lung radiation dose and the volume of normal lung receiving greater than 5, 10, 13, or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student t tests and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxic effects. The Kaplan-Meier method was used to estimate rates of local control (LC), disease-free survival (DFS), and overall survival (OS). RESULTS:With a median follow-up of 24 months, the 3-year LC, DFS, and OS were 93%, 65%, and 84%, respectively, with a 5.5% rate of grade-3 toxic effects and no grade 4 or 5 toxic effects. Clinically meaningful declines in patient-reported QOL (FACT-L-TOI, lung cancer subscale, physical well-being, and/or functional well-being) posttreatment significantly correlated with increased dosimetric parameters such as V10, V13, and V20. CONCLUSION:Although lung SBRT was associated with excellent LC and minimal clinical toxic effects for early-stage NSCLC, clinically meaningful declines in QOL were significantly correlated with increasing lung dose and volume parameters.

Lung radiation pneumonitis (RP) is one of the major toxicities experienced by lung cancer patients (13%–37%) receiving thoracic radiation therapy (RT) (Kocak Z, et al. Int. J. Radiat. Oncol. Biol. Phys. 2005 and Rodrigues G, et al. Oncol. 2004). Investigation of imaging biomarkers that can predict the incidence of RP can be useful toward reduce the probability of RP development. In this pilot study, we investigated the application of Kohonen Self-Organizing Map (K-SOM; a type of adaptive model that is trained using unsupervised competitive-learning (Kohonen T, Springer 1995)), for analysis of radiomic features extracted from normal lung tissue of non-RP and RP patients. The goal was to build an adaptive model to stratify patients and to reveal dominant characteristics of radiomics features for patient stratification. These characteristics are likely to remain unnoticed using conventional statistical analysis. To perform deep and unsupervised analysis of radiomics features extracted from planning CT images of normal lung tissue for patients with locally advanced, non-small cell lung cancers (NSCLC) to characterize and stratify patients with and without radiation-induced RP. Planning CT images of 41 patients (14 with RP and 27 with no evidence of RP) with stage-III lung cancers, treated with IMRT/3D-CRT, were studied. One hundred sixty eight radiomics features were extracted from the volume of normal lung tissue receiving ≥20 Gy, excluding the ITV, according to the following 8 different classes: Intensity Histogram Based Features (IHBF), Gray Level Run Length (GLRL), Law's Textural information (LAWS), Discrete Orthonormal Stockwell Transform (DOST), Local Binary Pattern (LBP), 2D-Wavelet Transform (2DWT), 2D-Gabor Filter (2DGF), and Gray Level Co-Occurrence Matrix (GLCM). A K-SOM ([9×9]-neurons) was constructed using 168 radiomic features and was trained and evaluated using random-permutation-sampling method (100-iterations, 67% and 33% for modeling and testing respectively). Regions pertaining to the dominant characteristics of the discriminant features were identified in the K-SOM space and used to calculate stratification power of the classifier. The K-SOM revealed 3 dominant regions associated with the RP status: high-certainty-non-RP, high-certainty-RP, and intermediate/uncertain region. The average of AUC, positive predictive and negative predictive values were 76.20%, %71.65, and 82.12% respectively. Correlation-based dissimilarity analysis (r<0.2, p-value<0.05) ranked and revealed the stability and robustness of the 6 discriminant features as follows: Skewness, Entropy, and Moment (3 and 4) from IHBF, Entropy-CA1 from DOST, and Short-Run-Emphasis from GLRL. The results of this pilot study, albeit subject to confirmation in a larger patient population, suggest a potential role for the use of an unsupervised method for radiomics-based stratification and prediction of radiation-induced pneumonitis in patients with locally advanced NSCLC.

The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.

Purpose To investigate the differences between internal target volumes (ITVs) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT) and determine the dose delivered on 4D planning technique. Methods For nine patients, 4DCBCTs were acquired before each fraction to assess tumor motion. An ITV was contoured on each phase of the 4DCBCT and a union of the 10 ITVs was used to create a composite ITV. Another ITV was drawn on the average 3DCBCT (avgCBCT) to compare with current clinical practice. The Dice coefficient, Hausdorff distance, and center of mass (COM) were averaged over four fractions to compare the ITVs contoured on the 4DCT, avgCBCT, and 4DCBCT for each patient. Planning was done on the average CT, and using the online registration, plans were calculated on each phase of the 4DCBCT and on the avgCBCT. Plan dose calculations were tested by measuring ion chamber dose in the CIRS lung phantom. Results The Dice coefficients were similar for all three comparisons: avgCBCT-to-4DCBCT (0.7 +/- 0.1), 4DCT-to-avgCBCT (0.7 +/- 0.1), and 4DCT-to-4DCBCT (0.7 +/- 0.1); while the mean COM differences were also comparable (2.6 +/- 2.2mm, 2.3 +/- 1.4mm, and 3.1 +/- 1.1mm, respectively). The Hausdorff distances for the comparisons with 4DCBCT (8.2 +/- 2.9mm and 8.1 +/- 3.2mm) were larger than the comparison without (6.5 +/- 2.5mm). The differences in ITV D95% between the treatment plan and avgCBCT calculations were 4.3 +/- 3.0% and -0.5 +/- 4.6%, between treatment plan and 4DCBCT plans, respectively, while the ITV V100% coverages were 99.0 +/- 1.9% and 93.1 +/- 8.0% for avgCBCT and 4DCBCT, respectively. Conclusion There is great potential for 4DCBCT to evaluate the extent of tumor motion before treatment, but image quality challenges the clinician to consistently delineate lung target volumes.

Stereotactic body radiation therapy (SBRT) is an appropriate treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates. As these patients often present with significant co-morbidities, quality of life (QOL) outcomes are especially important. To use a validated patient reported quality of life (QOL) assessment tool to measure clinical toxicity and patient reported quality of life (QOL) outcomes up to 36 months after SBRT in stage I NSCLC patients based on pre-treatment dosimetric parameters and tumor volumes. Fifty-six stage I NSCLC patients treated with SBRT (12 Gy x 4) were prospectively monitored for symptoms including cough, dyspnea, fatigue, and pneumonitis. Symptoms were measured at baseline (before treatment), immediately after treatment and 3, 6, 12, 18, 24, and 36 months post-treatment. Toxicity was graded from zero to five following the Charlson comorbidity and toxicity index. Quality of life was determined using the previously-validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) Lung questionnaire which incorporated three subscale endpoints: lung subscale (LSC), physical well-being (PWB) and functional well-being (FWB). Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving at least 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were obtained from the treatment plan. Pearson correlation and student t-test analyses were used to measure correlations and distinguish between lung metrics with QOL and clinical toxicities. SBRT produced minimal toxicities. QOL (TOI, LSC, PWB, or FWB) at 3, 6, 12 and 24 months post-treatment were significantly correlated with V5, V10, V13, V20, or MLD. Radiation pneumonitis showed mild positive but statistically significant (P < 0.05) correlation with V20. Moreover, FWB at 3 months showed mild negative correlation with dyspnea. Lung SBRT treatment for patients with NSCLC, using a 12 Gy x 4 dose regimen, was well tolerated with minimal toxicity observed. A validated patient related quality of life assessment tool was used to identify the dosimetric parameters most crucial for treatment planning. Further follow-up is recommended.

Background: Functional image guided radiotherapy allows for the delivery of an equivalent dose to tumor targets while sparing high ventilation lung tissues. In this study, we investigate whether radiation dose to functional lung is associated with clinical outcome for stereotactic body radiation therapy (SBRT) patients. Methods: Four-dimensional computed tomography (4DCT) images were used to assess lung function. Deformable image registration (DIR) was performed from the end-inhale phase to the end-exhale phase with resultant displacement vectors used to calculate ventilation maps. In addition to the Jacobian-based ventilation we introduce a volumetric variation method (Rv) based on a biomechanical finite element method (FEM), to assess lung ventilation. Thirty NSCLC patients, treated with SBRT, were evaluated in this study. 4DCT images were used to calculate both Jacobian and Rv-based ventilation images. Areas under the receiver operating characteristic curve (AUC) were used to assess the predictive power of functional metrics. Metrics were calculated over the whole lung as well as high and low ventilated regions. Results: Ventilation in dose regions between 1 and 5 Gy had higher AUC values compared to other dose regions. Rv based ventilation imaging method also showed to be less spatially variant and less heterogeneous, and the resultant Rv metrics had higher AUC values for predicting grade 2 + dyspnea. Conclusions: Low dose delivered to high ventilation areas may also increase the risk of compromised pulmonary function. Rv based ventilation images could be useful for the prediction of clinical toxicity for lung SBRT patients.

Purpose: To describe a custom-built, web-based MR Quality Control QC database, and to make a preliminary assessment of its impact on the Quality Assurance QA process in a large U.S. hospital.Methods: The MR QC database was built with Microsoft Access 2010 and published on a Microsoft Sharepoint website owned and maintained by the authors' institution.Authorized users can access the database remotely with mainstream web browsers.QC technologists were granted access to add, review, and print daily and weekly QC records.Qualified medical physicists (QMPs) were granted additional access to edit, review, and approve existing QC records, and to change tolerance limits.A macro was utilized to conduct an automatic weekly review of QC status, and to email the results to a QMP.This web-based QC database was implemented on five clinical MRIs at the authors' institution.Weekly ACR QC findings within five months before and after implementation were compared.Results: Retrospective review of the conventional QC records before implementation revealed 26 QC issues.After the adoption of the new web database, the number of QC issues reduced by 38% to 16.Since only a small fraction of these issues were reported at the time of occurrence, the web-based database permitted the QMPs to more quickly identify a QC issue (before/after: 7.6 ± 7.5/ 1 ± 0 weeks, P = 0.0002).Among the 26 QC issues occurred before the implementation, 8 issues (31%) would have been handled differently had they been identified earlier.The time to corrective actions was also found to be slightly shorter with the web-based system, although the difference is not statistically significant (before/after: 3.2 ± 2.7/1.7 ± 2.1 weeks, P = 0.3).Conclusion: The web-based QC database provides a positive impact on our MR QA process.It enables early detection and facilitates resolution of potential issues that may affect the quality of clinical MRI studies.

Objective: The objective of the study is to present our experience of treating adrenal metastases using stereotactic body radiation therapy (SBRT). Materials and Methods: We retrospectively reviewed patients with adrenal metastases treated using SBRT from 2001 to 2014. Response Evaluation Criteria in Solid Tumors v1.1 was used. Maximum tumor response was defined as the greatest percentage tumor reduction noted on two or more post-SBRT CT scans. Results: We identified 44 patients (median age 61.3 years, range: 25.8–85), with 54 adrenal metastases; primary diagnoses include non-small cell lung cancer (28 patients and 38 lesions), small cell lung cancer (1 patient), hepatocellular carcinoma (6 patients), and other (9 patients). Treatment was delivered in single (16 lesions, median dose 18 Gy [14–18]) or multiple fractions (38 lesions, median dose 30 Gy [16–40]). Median planning target volume was 49.65cc (3.21–984.54). Median response at first post-SBRT follow-up (median 1.65 months (m) (0.33–5.37), n = 46 lesions) was 10.8% with 91.3% local control. Median maximum tumor response was 31.8% (n = 32 lesions) at median follow-up of 5.4 m (0.9–44.8) with 96.6% local control. The response was comparable regardless of tumor histology or treatment fractionation. No patients experienced Grade 3/4 acute toxicities. One patient with a history of naproxen use required suturing with omental patch placement for perforated pyloric ulcer 14 m post-SBRT (18 Gy in single fraction) to the right adrenal metastasis; this region received <5 Gy. Ten patients treated for pain with available follow-up obtained relief. Conclusions: SBRT is a safe and efficacious treatment for adrenal metastases, demonstrating local tumor control. Further study of the impact on survival and quality of life is warranted.

Tumor response to radiation treatment (RT) can be evaluated from changes in metabolic activity between two positron emission tomography (PET) images. Activity changes at individual voxels in pre-treatment PET images (PET1), however, cannot be derived until their associated PET-CT (CT1) images are appropriately registered to during-treatment PET-CT (CT2) images. This study aimed to investigate the feasibility of using deformable image registration (DIR) techniques to quantify radiation-induced metabolic changes on PET images. Five patients with non-small-cell lung cancer (NSCLC) treated with adaptive radiotherapy were considered. PET-CTs were acquired two weeks before RT and 18 fractions after the start of RT. DIR was performed from CT1 to CT2 using B-Spline and diffeomorphic Demons algorithms. The resultant displacements in the tumor region were then corrected using a hybrid finite element method (FEM). Bitmap masks generated from gross tumor volumes (GTVs) in PET1 were deformed using the four different displacement vector fields (DVFs). The conservation of total lesion glycolysis (TLG) in GTVs was used as a criterion to evaluate the quality of these registrations. The deformed masks were united to form a large mask which was then partitioned into multiple layers from center to border. The averages of SUV changes over all the layers were 1.0  ±  1.3, 1.0  ±  1.2, 0.8  ±  1.3, 1.1  ±  1.5 for the B-Spline, B-Spline  +  FEM, Demons and Demons  +  FEM algorithms, respectively. TLG changes before and after mapping using B-Spline, Demons, hybrid-B-Spline, and hybrid-Demons registrations were 20.2%, 28.3%, 8.7%, and 2.2% on average, respectively. Compared to image intensity-based DIR algorithms, the hybrid FEM modeling technique is better in preserving TLG and could be useful for evaluation of tumor response for patients with regressing tumors.

This prospective clinical study focused on the hypothesis that there would be no difference in survival or QOL based on race or income when patients with stage I NSCLC are treated with lung SBRT in a center with a multidisciplinary approach. This IRB-approved study was designed to evaluate changes in QOL using the following validated instruments: EuroQOL-EQ-5D index, EQ-5D-Visual Analog Scale (EQ-5D VAS), and FACT Trial-Outcome-Index (FACT-TOI). Responses at baseline, immediately post-treatment, and at 3 and 6 months post-SBRT were available for analysis. Median household income (MHHI) was estimated at the census tract group level. Changes in QOL across time points were calculated using paired t-tests. Survival was assessed using Kaplan-Meier analysis. 54 patients (36 T1; 18 T2) had at least 6 month follow-up and were included for analysis. Median follow-up was 1.34 years. African Americans (AA) represented 33% of the study cohort, 67% of patients were Caucasians. Most common fractionation was 12 Gy x 4 fractions. MHHI of the cohort was $32,328 and was used to stratify high vs low income. The calculated EQ-5D index, EQ-5D VAS, and FACT-TOI for the entire cohort of patients showed that there was no difference relative to baseline for each of the QOL scores at any of the time points (immediately post-treatment and at 3 and 6 months). Similar comparisons, after stratifying by race and MHHI, again failed to identify any significant differences. Kaplan-Meier analysis showed no differences in OS when stratified by race (p=0.18) or by median household income (p=0.26). The overall survival was excellent (91% at 1-year and 78% at 3-years) with no significant decline in QOL over the first 6 months post-SBRT. In this multidisciplinary care setting, OS and QOL were not influenced by race or income at any timepoint in the 6 months following lung SBRT.

To compare retrospectively generated gated plans to conventional internal target volume (ITV)-based plans and to evaluate whether gated radiotherapy provides clinically relevant dosimetric improvements to organs-at-risk (OARs).

BACKGROUND:This study investigates the effect of gantry speed on 4DCBCT image quality and dose for the Varian On-Board Imager®.METHODS:A thoracic 4DCBCT protocol was designed using a 125 kVp spectrum. Image quality parameters were evaluated for 4DCBCT acquisition using Catphan® phantom with real-time position management™ system for gantry speeds varying between 1.0 to 6.0°/s. Superior-inferior motion of the phantom was executed using a sinusoidal waveform with five second period. Scans were retrospectively sorted into 4 phases (CBCT-4 ph) and 10 phases (CBCT-10 ph); average 4DCBCT (CBCT-ave), using all image data from the 4DCBCT acquisitions was also evaluated. The 4DCBCT images were evaluated using the following image quality metrics: spatial resolution, contrast-to-noise ratio (CNR), and uniformity index (UI). Additionally, Hounsfield unit (HU) sensitivity compared to a baseline CBCT and percent differences and RMS errors (RMSE) of excursion were also determined. Imaging dose was evaluated using an IBA CC13 ion chamber placed within CIRS Thorax phantom using the same sinusoidal motion and image acquisition settings as mentioned above.RESULTS:Spatial resolution decreased linearly from 5.93 to 3.82 lp/cm as gantry speed increased from 1.0 to 6.0°/s. CNR decreased linearly from 4.80 to 1.82 with gantry speed increasing from 1.0 to 6.0°/s, respectively. No noteworthy variations in UI, HU sensitivity, or excursion metrics were observed with changes in gantry speed. Ion chamber dose rates measured ranged from 2.30 (lung) to 5.18 (bone) E-3 cGy/mAs.CONCLUSIONS:A quantitative analysis of the Varian OBI's 4DCBCT capabilities was explored. Changing gantry speed changes the number of projections used for reconstruction, affecting both image quality and imaging dose if x-ray tube current is held constant. From the results of this study, a gantry speed between 2 and 3°/s was optimal when considering image quality, dose, and reconstruction time. The future of 4DCBCT clinical utility relies on further investigation of image acquisition and reconstruction optimization.

The purpose of this study was to describe the development of a clinical model for lung cancer patients treated with stereotactic body radiotherapy (SBRT) within a knowledge‐based algorithm for treatment planning, and to evaluate the model performance and applicability to different planning techniques, tumor locations, and beam arrangements. 105 SBRT plans for lung cancer patients previously treated at our institution were included in the development of the knowledge‐based model (KBM). The KBM was trained with a combination of IMRT, VMAT, and 3D CRT techniques. Model performance was validated with 25 cases, for both IMRT and VMAT. The full KBM encompassed lesions located centrally vs. peripherally (43:62), upper vs. lower (62:43), and anterior vs. posterior (60:45). Four separate sub‐KBMs were created based on tumor location. Results were compared with the full KBM to evaluate its robustness. Beam templates were used in conjunction with the optimizer to evaluate the model's ability to handle suboptimal beam placements. Dose differences to organs‐at‐risk (OAR) were evaluated between the plans generated by each KBM. Knowledge‐based plans (KBPs) were comparable to clinical plans with respect to target conformity and OAR doses. The KBPs resulted in a lower maximum spinal cord dose by compared to clinical plans, Sub‐KBMs split according to tumor location did not produce significantly better DVH estimates compared to the full KBM. For central lesions, compared to the full KBM, the peripheral sub‐KBM resulted in lower dose to 0.035 cc and 5 cc of the esophagus, both by , For all lesions, compared to the full KBM, the posterior sub‐KBM resulted in higher dose to 0.035 cc, 0.35 cc, and 1.2 cc of the spinal cord by , Plans using template beam arrangements met target and OAR criteria, with an increase noted in maximum heart dose (, ) and GI (, ) for the nine‐field plans relative to KBPs planned with custom beam angles. A knowledge‐based model for lung SBRT consisting of multiple treatment modalities and lesion locations produced comparable plan quality to clinical plans. With proper training and validation, a robust KBM can be created that encompasses both IMRT and VMAT techniques, as well as different lesion locations.PACS number(s): 87.55de, 87.55kh, 87.53Ly

This study evaluates respiratory excursions and their impact on patient setup and dosimetric coverage with and without the use of cone-beam computed tomography (CBCT) for localization in stereotactic ablative radiotherapy. The datasets of 150 non-small cell lung cancer patients were assessed. Four groups of patients were evaluated based on their tumor location: upper lobe (UL)-peripheral (N = 39), UL-chest-wall seated (CWS, N = 37), lower lobe (LL)-peripheral (N = 48), and LL-CWS (N = 26). Tumor excursion and setup error were quantified and correlated. Treatment planning margins were derived based on the van Herk formalism. A dosimetric study investigated the dose coverage with and without the use of CBCT for localization. The percentage of patients showing >5 mm tumor respiratory excursion for UL-peripheral/LL-peripheral was 10.0/42.9%, and was 4.2/46.7% for UL-CWS/LL-CWS. Planning margin magnitudes averaged over all patients were Mresidual(2.7, 3.2, 3.7) mm and Minterfxn(9.0, 14.0, 10.0) mm, respectively with and without the use of CBCT for image guidance. Comparatively, the planning margins for the patients with LL tumors exhibiting the largest motion and setup errors were MresidualLL(2.8, 3.6, 4.4). Pearson correlation coefficients (for LL-peripheral tumors in the S/I direction) between tumor excursion and, respectively, inter-fraction and residual setup errors were 0.62 and 0.32. Based on skin tattoo setup, the overall average difference in D95 dose to the planning target volume (PTV) between the delivered and planned doses was 14.1 ± 9.2%. The use of CBCT for localization reduced the overall average ΔD95 to less than 2%. This analysis is suggestive that: (a) patients with LL tumors undergo the largest respiratory-induced motion, and experience larger setup errors relative to UL tumors; (b) the use of CBCT-based image guidance significantly reduces residual setup errors; planning margins of the order of 5 mm appear to be adequate for proper PTV dose coverage; (c) CBCT image guidance reduces the correlation between respiratory-induced motion and setup errors, implying that there is much less variation in the setup uncertainty between tumors undergoing respiratory motion of varying magnitudes, relative to the variation without CBCT.