Four-Dimensional Computed Tomography Ventilation Image-Guided Lung Functional Avoidance Radiation Therapy: A Single-Arm Prospective Pilot Clinical Trial.

PURPOSE: The primary objective of this prospective pilot trial was to assess the safety and feasibility of lung functional avoidance radiation therapy (RT) with 4-dimensional (4D) computed tomography (CT) ventilation imaging. METHODS AND MATERIALS: Patients with primary lung cancer or metastatic disease to the lungs to receive conventionally fractionated RT (CFRT) or stereotactic body RT (SBRT) were eligible. Standard-of-care 4D-CT scans were used to generate ventilation images through image processing/analysis. Each patient required a standard intensity modulated RT plan and ventilation image guided functional avoidance plan. The primary endpoint was the safety of functional avoidance RT, defined as the rate of grade ≥3 adverse events (AEs) that occurred ≤12 months after treatment. Protocol treatment was considered safe if the rates of grade ≥3 pneumonitis and esophagitis were <13% and <21%, respectively for CFRT, and if the rate of any grade ≥3 AEs was <28% for SBRT. Feasibility of functional avoidance RT was assessed by comparison of dose metrics between the 2 plans using the Wilcoxon signed-rank test. RESULTS: Between May 2015 and November 2019, 34 patients with non-small cell lung cancer were enrolled, and 33 patients were evaluable (n = 24 for CFRT; n = 9 for SBRT). Median follow-up was 14.7 months. For CFRT, the rates of grade ≥3 pneumonitis and esophagitis were 4.2% (95% confidence interval, 0.1%-21.1%) and 12.5% (2.7%-32.4%). For SBRT, no patients developed grade ≥3 AEs. Compared with the standard plans, the functional avoidance plans significantly (P < .01) reduced the lung dose-function metrics without compromising target coverage or adherence to standard organs at risk constraints. CONCLUSIONS: This study, representing one of the first prospective investigations on lung functional avoidance RT, demonstrated that the 4D-CT ventilation image guided functional avoidance RT that significantly reduced dose to ventilated lung regions could be safely administered, adding to the growing body of evidence for its clinical utility.

Characterization and clinical validation of patient-specific three-dimensional printed tissue-equivalent bolus for radiotherapy of head and neck malignancies involving skin.

PURPOSE: Megavoltage radiotherapy to irregular superficial targets is challenging due to the skin sparing effect. We developed a three-dimensional bolus (3DB) program to assess the clinical impact on dosimetric and patient outcomes. MATERIALS AND METHODS: Planar commercial bolus (PCB) and 3DB density, clarity, and net bolus effect were rigorously evaluated prior to clinical implementation. After IRB approval, patients with cutaneous or locally advanced malignancies deemed to require bolus for radiotherapy treatment were treated with custom 3DB. RESULTS: The mean density of 3DB and PCB was of 1.07 g/cm 3 and 1.12 g/cm3, respectively. 3DB optic clarity was superior versus PCB at any material thickness. Phantom measurements of superficial dose with 3DB and PCB showed excellent bolus effect for both materials. 3DB reduced air gaps compared with PCB - particularly in irregular areas such as the ear, nose, and orbit. A dosimetric comparison of 3DB and PCB plans showed equivalent superficial homogeneity for 3DB and PCB (3DB median HI 1.249, range 1.111-1.300 and PCB median HI 1.165, range 1.094-1.279), but better conformity with 3DB (3DB median CI 0.993, range 0.962-0.993) versus PCB (PCB median CI 0.977, range 0.601-0.991). Patient dose measurements using 3DB confirm the delivered superficial dose was within 1% of the intended prescription (95% CI 97-102%; P = 0.11). CONCLUSIONS: 3DB improves radiotherapy plan conformity, reduces air gap volume in irregular superficial areas which could affect superficial dose delivery, and provides excellent dose coverage to irregular superficial targets.

Clinical feasibility of MR-assisted CT-based cervical brachytherapy using MR-to-CT deformable image registration.

PURPOSE: The purpose of this study is to evaluate the feasibility of using deformable image registration algorithms to improve high-dose-rate high-risk clinical target volume (HR-CTV) delineation between preapplicator implantation MRI (pre-MRI) and postapplicator implantation CT (post-CT) in the treatment of locally advanced cervical cancer (LACC). METHOD AND MATERIALS: Twenty-six patients were identified for the study. Regions of interest were segmented on MRI and CT. A HR-CTV was delineated on pre-MRI and compared with the previously contoured HR-CTV on the post-CT. Two commercially available algorithms, ANACONDA (anatomically constrained) and MORFEUS (biomechanical model based) with various controlling structure settings, including the cervix, uterus, etc., were used to deform pre-MRI to post-CT. MRI-to-CT deformed targets are denoted as HR-CTV'. Quantitative deformation metrics include Dice index, distance to agreement, and center of mass displacement. Qualitative clinical usefulness of deformations was scored based on HR-CTV identification on CT images. RESULTS: For ANACONDA and MORFEUS deformations, using a cervix controlling region of interest resulted in the highest Dice, lowest distance to agreement, and lowest center of mass displacement for HR-CTV'. With MORFEUS deformations, the deformed HR-CTV' proved clinically useful in 23 patients. CONCLUSIONS: Prebrachytherapy implantation MRI can aid target contours for CT-based brachytherapy through ANACONDA or MORFEUS algorithms with appropriate parameter selection for LACC patients.

Linear Accelerator-Based Radiotherapy Simulation Using On-Board Kilovoltage Cone-Beam Computed Tomography for 3-Dimensional Volumetric Planning and Rapid Treatment in the Palliative Setting.

BACKGROUND: Palliation of advanced disease using radiotherapy can create difficult clinical situations where standard computed tomography simulation and immobilization techniques are not feasible. We developed a linear accelerator-based radiotherapy simulation technique using nonstandard patient positioning for head and neck palliation using on-board kilovoltage cone-beam computed tomography for 3-D volumetric planning and rapid treatment. Material and Methods: We proved cone-beam computed tomography simulation feasibility for semi-upright patient positioning using an anthropomorphic phantom on a clinical Elekta-Synergy linear accelerator. Cone-beam computed tomography imaging parameters were optimized for high-resolution image reconstruction and to ensure mechanical clearance. The patient was simulated using a cone-beam computed tomography-based approach and the cone-beam computed tomography digital imaging and communications in medicine file was imported to the treatment planning software to generate radiotherapy target volumes. Rapid planning was achieved by using a 3-level bulk density correction for air, soft tissue, and bone set at 0, 1.0, and 1.4 g/cm3, respectively. RESULTS: Patient volumetric imaging was obtained through cone-beam computed tomography simulation and treatment was delivered as planned without incident. Bulk density corrections were verified against conventionally simulated patients where differences were less than 1%. Conclusion: We successfully developed and employed a semi-upright kilovoltage cone-beam computed tomography-based head and neck simulation and treatment planning method for 3-D conformal radiotherapy delivery. This approach provides 3-D documentation of the radiotherapy plan and allows tabulation of quantitative spatial dose information which is valuable if additional palliative treatments are needed in the future. This is a potentially valuable technique that has broad clinical applicability for benign and palliative treatments across multiple disease sites-particularly where standard supine simulation and immobilization techniques are not possible.

Converting Treatment Plans From Helical Tomotherapy to L-Shape Linac: Clinical Workflow and Dosimetric Evaluation.

This work evaluated a commercial fallback planning workflow designed to provide cross-platform treatment planning and delivery. A total of 27 helical tomotherapy intensity-modulated radiotherapy plans covering 4 anatomical sites were selected, including 7 brain, 5 unilateral head and neck, 5 bilateral head and neck, 5 pelvis, and 5 prostate cases. All helical tomotherapy plans were converted to 7-field/9-field intensity-modulated radiotherapy and volumetric-modulated radiotherapy plans through fallback dose-mimicking algorithm using a 6-MV beam model. The planning target volume (PTV) coverage ( D1, D99, and homogeneity index) and organs at risk dose constraints were evaluated and compared. Overall, all 3 techniques resulted in relatively inferior target dose coverage compared to helical tomotherapy plans, with higher homogeneity index and maximum dose. The organs at risk dose ratio of fallback to helical tomotherapy plans covered a wide spectrum, from 0.87 to 1.11 on average for all sites, with fallback plans being superior for brain, pelvis, and prostate sites. The quality of fallback plans depends on the delivery technique, field numbers, and angles, as well as user selection of structures for organs at risk. In actual clinical scenario, fallback plans would typically be needed for 1 to 5 fractions of a treatment course in the event of machine breakdown. Our results suggested that <1% dose variance can be introduced in target coverage and/or organs at risk from fallback plans. The presented clinical workflow showed that the fallback plan generation typically takes 10 to 20 minutes per case. Fallback planning provides an expeditious and effective strategy for transferring patients cross platforms, and minimizing the untold risk of a patient missing treatment(s).

Changes in Regional Ventilation During Treatment and Dosimetric Advantages of CT Ventilation Image Guided Radiation Therapy for Locally Advanced Lung Cancer.

PURPOSE: Lung functional image guided radiation therapy (RT) that avoids irradiating highly functional regions has potential to reduce pulmonary toxicity following RT. Tumor regression during RT is common, leading to recovery of lung function. We hypothesized that computed tomography (CT) ventilation image-guided treatment planning reduces the functional lung dose compared to standard anatomic image-guided planning in 2 different scenarios with or without plan adaptation. METHODS AND MATERIALS: CT scans were acquired before RT and during RT at 2 time points (16-20 Gy and 30-34 Gy) for 14 patients with locally advanced lung cancer. Ventilation images were calculated by deformable image registration of four-dimensional CT image data sets and image analysis. We created 4 treatment plans at each time point for each patient: functional adapted, anatomic adapted, functional unadapted, and anatomic unadapted plans. Adaptation was performed at 2 time points. Deformable image registration was used for accumulating dose and calculating a composite of dose-weighted ventilation used to quantify the lung accumulated dose-function metrics. The functional plans were compared with the anatomic plans for each scenario separately to investigate the hypothesis at a significance level of 0.05. RESULTS: Tumor volume was significantly reduced by 20% after 16 to 20 Gy (P = .02) and by 32% after 30 to 34 Gy (P < .01) on average. In both scenarios, the lung accumulated dose-function metrics were significantly lower in the functional plans than in the anatomic plans without compromising target volume coverage and adherence to constraints to critical structures. For example, functional planning significantly reduced the functional mean lung dose by 5.0% (P < .01) compared to anatomic planning in the adapted scenario and by 3.6% (P = .03) in the unadapted scenario. CONCLUSIONS: This study demonstrated significant reductions in the accumulated dose to the functional lung with CT ventilation image-guided planning compared to anatomic image-guided planning for patients showing tumor regression and changes in regional ventilation during RT.

Cardiac Dose and Survival After Stereotactic Body Radiotherapy for Early-stage Non-Small-cell Lung Cancer.

INTRODUCTION: Recent analyses have identified cardiac dose as an important predictor of overall survival (OS) after chemoradiation for locally advanced non-small-cell lung cancer (NSCLC). However, the survival influence of the cardiac dose after stereotactic body radiotherapy (SBRT) is unknown. We performed a dose-volume histogram (DVH) analysis of patients treated with SBRT for early stage NSCLC to examine survival and cardiac toxicity. MATERIALS AND METHODS: We reviewed the medical records of patients who had undergone SBRT for early-stage NSCLC from June 2007 to June 2015 and documented the cardiac DVH parameters, including the maximum and mean dose and percentage of volume receiving >5, >10, >20, and >30 Gy (V5, V10, V20, and V30, respectively). The biologically effective doses and 2-Gy equivalent doses were also calculated. The DVH parameters were assessed as predictors of OS using Cox regression analysis. RESULTS: We identified 102 patients with 118 treated tumors. At a median follow-up period of 27.2 months (range, 9.8-72.5 months), the 2-year OS estimate was 70.4%. The cardiac DVH parameters were as follows: maximum dose, median, 14.2 Gy (range, 0.3-77.8 Gy); mean dose, median, 1.6 Gy (range, 0-12.6 Gy); and V5, median, 8.7% (range, 0%-96.4%). We identified no correlation between OS and any cardiac dose parameter. No patient developed acute (within 3 months) cardiac toxicity. Four patients died of cardiac causes; all had had preexisting heart disease. CONCLUSION: In our cohort, cardiac dose was not a predictor of OS after lung SBRT, despite a subset of patients receiving high maximum cardiac doses. The findings from our limited cohort showed that high doses to small volumes of the heart appear safe. Analyses of larger patient cohorts with longer follow-up durations are needed to better delineate the safe cardiac DVH constraints for SBRT.

Workflow efficiency for the treatment planning process in CT-guided high-dose-rate brachytherapy for cervical cancer.

PURPOSE: To investigate process efficiency, we present a prospective investigation of the treatment planning phase of image-guided brachytherapy (BT) for cervical cancer using a specific checklist. METHODS AND MATERIALS: From October 2012 to January 2014, 76 BT procedures were consecutively performed. Prospective data on the CT-based treatment planning process was collected using a specific checklist which details the following steps: (1) dosimetry planning, (2) physician review start, (3) physician review time, (4) dosimetry processing, (5) physics review start, (6) physics review, and (7) procedural pause. Variables examined included the use of a pre-BT MRI, clinic duty conflicts, resident teaching, and the use of specific BT planners. Analysis was performed using descriptive statistics, t-test, and analysis of variance. RESULTS: Seventy-five prospectively gathered checklists comprised this analysis. The mean time for treatment planning was 95 minutes (med 94, std 18). The mean intervals in the above steps were (1) = 42, (2) = 5, (3) = 19, (4) = 10, (5) = 6, (6) = 13, and (7) = 26 minutes. There was no statistical difference in patients who had a pre-BT MRI. Resident teaching did not influence time, p = 0.17. Treatment planning time was decreased with a specific planner, p = 0.0015. CONCLUSIONS: A skillful team approach is required for treatment planning efficiency in image-guided BT. We have found that the specific BT planners can have a significant effect on the overall planning efficiency. We continue to examine clinical and workflow-related factors that will enhance our safety and workflow process with BT.