Prospective Trial of Functional Lung Avoidance Radiation Therapy for Lung Cancer: Quality of Life Report.

PURPOSE: A novel form of lung function imaging has been developed that uses 4-dimensional computed tomography (4DCT) data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side effects. A phase 2, multicenter 4DCT-ventilation functional avoidance clinical trial was completed. The purpose of this work was to quantify changes in patient-reported outcomes (PROs) for patients treated with functional avoidance and determine which metrics are predictive of PRO changes. MATERIALS AND METHODS: Patients with locally advanced lung cancer receiving curative-intent radiation therapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire administered pretreatment; at the end of treatment; and at 3, 6, and 12 months posttreatment. Using the FACT-Trial Outcome Index and the FACT-Lung Cancer Subscale results, the percentage of clinically meaningful declines (CMDs) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. RESULTS: Of the 59 patients who completed baseline PRO surveys. 83% had non-small cell lung cancer, with 75% having stage 3 disease. The median dose was 60 Gy in 30 fractions. CMD FACT-Trial Outcome Index decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-Lung Cancer Subscale decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. Although an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all P > .053). CONCLUSIONS: The current work presents an innovative combination of use of functional avoidance and PRO assessment and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months posttreatment. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance.

Clinical and Dosimetric Impact of 2D kV Motion Monitoring and Intervention in Liver Stereotactic Body Radiation Therapy.

Purpose: Positional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the impact of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose. Methods and Materials: Data from 33 patients treated with 41 courses of liver SBRT were analyzed. During treatment, planar kV images orthogonal to the treatment beam were acquired to determine treatment interventions, namely treatment pauses (ie, adequacy of gating thresholds) or treatment shifts. Patients were shifted if internal markers were >3 mm, corresponding to the PTV margin used, from the expected reference condition. The frequency, duration, and nature of treatment interventions (ie, pause vs shift) were recorded, and the dosimetric impact associated with treatment shifts was estimated using a machine learning dosimetric model. Results: Of all fractions delivered, 39% required intervention, which took on average 1.9 ± 1.6 minutes and occurred more frequently in treatments lasting longer than 7 minutes. The median realignment shift was 5.7 mm in size, and the effect of these shifts on minimum tumor dose in simulated clinical scenarios ranged from 0% to 50% of prescription dose per fraction. Conclusion: Real-time kV-based imaging interventions for liver SBRT minimally affect clinical workflow and dosimetrically benefit patients. This potential solution for addressing positional errors from motion addresses concerns about target accuracy and may enable safe dose escalation and margin reduction in the context of liver SBRT.

2D antiscatter grid and scatter sampling based CBCT method for online dose calculations during CBCT guided radiation therapy of pelvis.

BACKGROUND: Online dose calculations before the delivery of radiation treatments have applications in dose delivery verification, online adaptation of treatment plans, and simulation-free treatment planning. While dose calculations by directly utilizing CBCT images are desired, dosimetric accuracy can be compromised due to relatively lower HU accuracy in CBCT images. PURPOSE: In this work, we propose a novel CBCT imaging pipeline to enhance the accuracy of CBCT-based dose calculations in the pelvis region. Our approach aims to improve the HU accuracy in CBCT images, thereby improving the overall accuracy of CBCT-based dose calculations prior to radiation treatment delivery. METHODS: An in-house developed quantitative CBCT pipeline was implemented to address the CBCT raw data contamination problem. The pipeline combines algorithmic data correction strategies and 2D antiscatter grid-based scatter rejection to achieve high CT number accuracy. To evaluate the effect of the quantitative CBCT pipeline on CBCT-based dose calculations, phantoms mimicking pelvis anatomy were scanned using a linac-mounted CBCT system, and a gold standard multidetector CT used for treatment planning (pCT). A total of 20 intensity-modulated treatment plans were generated for five targets, using 6 and 10 MV flattening filter-free beams, and utilizing small and large pelvis phantom images. For each treatment plan, four different dose calculations were performed using pCT images and three CBCT imaging configurations: quantitative CBCT, clinical CBCT protocol, and a high-performance 1D antiscatter grid (1D ASG). Subsequently, dosimetric accuracy was evaluated for both targets and organs at risk as a function of patient size, target location, beam energy, and CBCT imaging configuration. RESULTS: When compared to the gold-standard pCT, dosimetric errors in quantitative CBCT-based dose calculations were not significant across all phantom sizes, beam energies, and treatment sites. The largest error observed was 0.6% among all dose volume histogram metrics and evaluated dose calculations. In contrast, dosimetric errors reached up to 7% and 97% in clinical CBCT and high-performance ASG CBCT-based treatment plans, respectively. The largest dosimetric errors were observed in bony targets in the large phantom treated with 6 MV beams. The trends of dosimetric errors in organs at risk were similar to those observed in the targets. CONCLUSIONS: The proposed quantitative CBCT pipeline has the potential to provide comparable dose calculation accuracy to the gold-standard planning CT in photon radiation therapy for the abdomen and pelvis. These robust dose calculations could eliminate the need for density overrides in CBCT images and enable direct utilization of CBCT images for dose delivery monitoring or online treatment plan adaptations before the delivery of radiation treatments.

A 2D antiscatter grid and scatter sampling based CBCT method for online dose calculations during CBCT guided radiation therapy of pelvis.

Online dose calculations before radiation treatment have applications in dose delivery verification, plan adaptation, and treatment planning. We propose a novel CBCT imaging pipeline to enhance accuracy. Our approach aims to improve HU accuracy in CBCT images for more precise dose calculations. A quantitative CBCT pipeline was implemented, combining data correction strategies and scatter rejection, achieving high CT number accuracy. We evaluated the pipeline's effect using pelvis anatomy phantoms and found that dosimetric errors in quantitative CBCT-based dose calculations were minimal. In contrast, clinical CBCT and high-performance ASG CBCT-based plans showed significant errors. The proposed quantitative CBCT pipeline offers comparable dose calculation accuracy to the gold-standard planning CT, eliminating the need for density overrides and enabling precise dose delivery monitoring or online plan adaptations in radiation therapy.

A simulation study to evaluate the effect of 2D antiscatter grid primary transmission on flat panel detector based CBCT image quality.

Purpose. Two-dimensional antiscatter grids' (2D-ASGs) septal shadows and their impact on primary transmission play a critical role in cone-beam computed tomography (CBCT) image noise and artifact characteristics. Therefore, a numerical simulation platform was developed to evaluate the effect of 2D-ASG's primary transmission on image quality, as a function of grid geometry and CBCT system properties.Methods. To study the effect of 2D-ASG's septal shadows on primary transmission and CBCT image quality, two new methods were introduced; one to simulate projection signal gradients in septal shadows, and the other to simulate septal shadow variations due to gantry flex. Signal gradients in septal shadows were simulated by generating a system point spread function that was directly extracted from projection images of 2D-ASG prototypes in experiments. Variations in septal shadows due to gantry flex were simulated by generating oversampled shadow profiles extracted from experiments. Subsequently, the effect of 2D-ASG's septal shadows on primary transmission and image quality was evaluated.Results.For an apparent septal thickness of 0.15 mm, the primary transmission of 2D-ASG varied between 72%-90% for grid pitches 1-3 mm. In low-contrast phantoms, the effect of 2D-ASG's radiopaque footprint on information loss was subtle. At high spatial frequencies, information loss manifested itself as undersampling artifacts, however, its impact on image quality is subtle when compared to quantum noise. Effects of additive electronic noise and gantry flex induced ring artifacts on image quality varied as a function of grid pitch and septal thickness. Such artifacts were substantially less in lower resolution images.Conclusion. The proposed simulation platform allowed successful evaluation of CBCT image quality variations as a function of 2D-ASG primary transmission properties and CBCT system characteristics. This platform can be potentially used for optimizing 2D-ASG design properties based on the imaging task and properties of the CBCT system.

A quantitative CBCT pipeline based on 2D antiscatter grid and grid-based scatter sampling for image-guided radiation therapy.

BACKGROUND: Quantitative accuracy is critical for expanding the role of cone beam CT (CBCT) imaging from target localization to quantitative treatment monitoring and plan adaptations in radiation therapy. Despite advances in CBCT image quality improvement methods, quantitative accuracy gap between CBCT and multi-detector CT (MDCT) remains. PURPOSE: In this work, a physics-driven approach was investigated that combined robust scatter rejection, raw data correction and iterative image reconstruction to further improve CBCT image quality and quantitative accuracy, referred to as quantitative CBCT (qCBCT). METHODS: QCBCT approach includes tungsten 2D antiscatter grid hardware, residual scatter correction with grid-based scatter sampling, image lag, and beam hardening correction for offset detector geometry linac-mounted CBCT. Images were reconstructed with iterative image reconstruction to reduce image noise. qCBCT was evaluated using a variety of phantoms to investigate the effect of object size and its composition on image quality, and image quality was benchmarked against clinical CBCT and gold standard MDCT images used for treatment planning. RESULTS: QCBCT provided statistically significant improvement in CT number accuracy and reduced image artifacts when compared to clinical CBCT images. When compared to gold standard MDCT, mean HU errors in qCBCT and clinical CBCT were 17 ± 9 and 38 ± 29 HU, respectively. Magnitude of phantom size dependent HU variations were comparable between MDCT and qCBCT images. With iterative reconstruction, contrast-to-noise ratio improved by 25% when compared to clinical CBCT protocols. CONCLUSIONS: Combination of novel scatter suppression techniques and other data correction methods in qCBCT provided CT number accuracy comparable to gold standard MDCT used for treatment planning. This approach may potentially improve CBCT's promise in fulfilling the tasks that demand high quantitative accuracy, such as online dose calculations and treatment response assessment, in image guided radiation therapy.

2D antiscatter grid and scatter sampling based CBCT pipeline for image guided radiation therapy.

Poor tissue visualization and quantitative accuracy in CBCT is a major barrier in expanding the role of CBCT imaging from target localization to quantitative treatment monitoring and plan adaptations in radiation therapy sessions. To further improve image quality in CBCT, 2D antiscatter grid based scatter rejection was combined with a raw data processing pipeline and iterative image reconstruction. The culmination of these steps was referred as quantitative CBCT, qCBCT. qCBCT data processing steps include 2D antiscatter grid implementation, measurement based residual scatter, image lag, and beam hardening correction for offset detector geometry CBCT with a bow tie filter. Images were reconstructed with iterative image reconstruction to reduce image noise. To evaluate image quality, qCBCT acquisitions were performed using a variety of phantoms to investigate the effect of object size and its composition on image quality. qCBCT image quality was benchmarked against clinical CBCT and MDCT images. Addition of image lag and beam hardening correction to scatter suppression reduced HU degradation in qCBCT by 10 HU and 40 HU, respectively. When compared to gold standard MDCT, mean HU errors in qCBCT and clinical CBCT were 10 HU and 27 HU, respectively. HU inaccuracy due to change in phantom size was 22 HU and 85 HU in qCBCT and clinical CBCT images, respectively. With iterative reconstruction, contrast to noise ratio improved by a factor of 1.25 when compared to clinical CBCT protocols. Robust artifact and noise suppression in qCBCT images can reduce the image quality gap between CBCT and MDCT, improving the promise of qCBCT in fulfilling the tasks that demand high quantitative accuracy, such as CBCT based dose calculations and treatment response assessment in image guided radiation therapy.

Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A Comprehensive PENTEC Genitourinary Review.

PURPOSE: Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. METHODS AND MATERIALS: We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. RESULTS: The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and <3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a <5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. CONCLUSIONS: In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure.

Evaluation of variables predicting PFT changes for lung cancer patients treated on a prospective 4DCT-ventilation functional avoidance clinical trial.

PURPOSE: Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. A phase-II, multi-center, prospective study of 4DCT-ventilation functional avoidance was completed. Pre and post-treatment pulmonary function tests (PFTs) were acquired and assessed pulmonary function change. This study aims to evaluate which clinical, dose and dose-function factors predict PFT changes for patients treated with 4DCT-ventilation functional avoidance radiotherapy. MATERIALS AND METHODS: 56 patients with locally advanced lung cancer receiving radiotherapy were accrued. PFTs were obtained at baseline and three months following radiotherapy and included forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), and FEV1/FVC. The ability of patient, clinical, dose (lung and heart), and dose-function metrics (metrics that combine dose and 4DCT-ventilation-based function) to predict PFT changes were evaluated using univariate and multivariate linear regression. RESULTS: Univariate analysis showed that only dose-function metrics and the presence of chronic obstructive pulmonary disease (COPD) were significant (p<0.05) in predicting FEV1 decline. Multivariate analysis identified a combination of clinical (immunotherapy status, presence of thoracic comorbidities, smoking status, and age), along with lung dose, heart dose, and dose-function metrics in predicting FEV1 and FEV1/FVC changes. CONCLUSION: The current work evaluated factors predicting PFT changes for patients treated in a prospective functional avoidance radiotherapy study. The data revealed that lung dose- function metrics could predict PFT changes, validating the significance of reducing the dose to the functional lung to mitigate the decline in pulmonary function and providing guidance for future clinical trials.

Is individual perfusion dose-response different than ventilation dose-response for lung cancer patients treated with radiotherapy?

OBJECTIVE: Current ventilation and perfusion dose-response studies focus on single-modalities (ventilation or perfusion) and perform pulmonary-toxicity assessment related to radiotherapy on a population-based basis. This study aims at quantitative and clinical evaluation of intrapatient differences between ventilation and perfusion dose-responses among lung cancer patients treated with radiotherapy. METHODS: 20 patients enrolled on a prospective functional avoidance protocol underwent single photon emission computed tomography-CT ventilation and perfusion scans pre- and post-radiotherapy. Relative changes in pre- to post-treatment ventilation and perfusion in lung regions receiving ≥20 Gy were calculated. In addition, the slopes of the linear fit to the relative ventilation and perfusion changes in regions receiving 0-60 Gy were calculated. A radiologist read and assigned a functional defect score to pre- and post-treatment ventilation/perfusion scans. RESULTS: 25% of patients had a difference >35% between ventilation and perfusion pre- to post-treatment changes and 20-30% of patients had opposite directions for ventilation and perfusion pre- to post-treatment changes. Using a semi-quantitative scale, radiologist assessment showed that 20% of patients had different pre- to post-treatment ventilation changes when compared to pre- to post-treatment perfusion changes. CONCLUSION: Our data showed that ventilation dose-response can differ from perfusion dose-response for 20-30% of patients. Therefore, when performing thoracic dose-response in cancer patients, it is insufficient to look at ventilation or perfusion alone; but rather both modes of functional imaging may be needed when predicting for clinical outcomes. ADVANCES IN KNOWLEDGE: The significance of this study can be highlighted by the differences between the intrapatient dose-response assessments of this analysis compared to existing population-based dose-response analyses. Elucidating intrapatient ventilation and perfusion dose-response differences may be valuable in predicting pulmonary toxicity in lung cancer patients post-radiotherapy.

Characterizing Pulmonary Function Test Changes for Patients With Lung Cancer Treated on a 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial.

Purpose: Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy. Methods and Materials: Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months after chemoradiation. Differences for PFT metrics are reported, including diffusing capacity for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). PFT metrics were compared for patients who did and did not experience grade 2 or higher pneumonitis. Results: Fifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEV1, and FVC was -11.6% ± 14.2%, -5.6% ± 16.9%, and -9.0% ± 20.1%, respectively. The mean change in DLCO was -15.4% ± 14.4% for patients with grade 2 or higher radiation pneumonitis and -10.8% ± 14.1% for patients with grade <2 radiation pneumonitis (P = .37). The mean change in FEV1 was -14.3% ± 22.1% for patients with grade 2 or higher radiation pneumonitis and -3.9% ± 15.4% for patients with grade <2 radiation pneumonitis (P = .09). Conclusions: The current work is the first to quantitatively characterize PFT changes for patients with lung cancer treated on a prospective functional avoidance radiation therapy study. In comparison with patients treated with standard thoracic radiation planning, the data qualitatively show that functional avoidance resulted in less of a decline in DLCO and FEV1. The presented data can help elucidate the potential pulmonary function improvement with functional avoidance radiation therapy.

Cardiac metabolic changes on 18 F-positron emission tomography after thoracic radiotherapy predict for overall survival in esophageal cancer patients.

PURPOSE: Heart doses have been shown to be predictive of cardiac toxicity and overall survival (OS) for esophageal cancer patients. There is potential for functional imaging to provide valuable cardiac information. The purpose of this study was to evaluate the cardiac metabolic dose-response using 18 F-deoxyglucose (FDG)-PET and to assess whether standard uptake value (SUV) changes in the heart were predictive of OS. METHODS: Fifty-one patients with esophageal cancer treated with radiation who underwent pre- and post-treatment FDG-PET scans were retrospectively evaluated. Pre- and post-treatment PET-scans were rigidly registered to the planning CT for each patient. Pre-treatment to post-treatment absolute mean SUV (SUVmean) changes in the heart were calculated to assess dose-response. A dose-response curve was generated by binning each voxel in the heart into 10 Gy dose-bins and analyzing the SUVmean changes in each dose-bin. Multivariate cox proportional hazard models were used to assess whether pre-to-post treatment cardiac SUVmean changes predicted for OS. RESULTS: The cardiac dose-response curve demonstrated a trend of increasing cardiac SUV changes as a function of dose with an average increase of 0.044 SUV for every 10 Gy dose bin. In multivariate analysis, disease stage and SUVmean change in the heart were predictive (p < 0.05) for OS. CONCLUSIONS: Changes in pre- to post-treatment cardiac SUV were predictive of OS with patients having a higher pre- to post-treatment cardiac SUV change surviving longer.

Concurrent kilovoltage CBCT imaging and megavoltage beam delivery: suppression of cross-scatter with 2D antiscatter grids and grid-based scatter sampling.

Objective. The concept of using kilovoltage (kV) and megavoltage (MV) beams concurrently has potential applications in cone beam computed tomography (CBCT) guided radiation therapy, such as single breath hold scans, metal artifact reduction, and simultaneous imaging during MV treatment delivery. However, MV cross-scatter generated during MV beam delivery degrades CBCT image quality. To address this, a 2D antiscatter grid and a cross-scatter correction method were investigated in the context of high dose MV treatment delivery.Approach. A 3D printed, tungsten 2D antiscatter grid prototype was utilized in kV CBCT scans to reduce MV cross-scatter fluence during concurrent MV beam delivery. Remaining cross-scatter in projections was corrected by using the 2D grid itself as a cross-scatter intensity sampling device, referred to as grid-based scatter sampling (GSS). To test this approach, kV CBCT acquisitions were performed while delivering 6 and 10 MV beams, mimicking high dose rate treatment delivery scenarios. kV and MV beam deliveries were not synchronized to eliminate MV beam delivery interruption. MV cross-scatter suppression performance of the proposed approach was evaluated in projections and CBCT images of phantoms.Main results. 2D grid reduced the intensity of MV cross-scatter in kV projections by a factor of 3 on the average, when compared to conventional antiscatter grid. Remaining cross scatter as measured by the GSS method was within 7% of measured reference intensity values, and subsequently corrected. CBCT image quality was improved substantially during concurrent kV-MV beam delivery. Median Hounsfield Unit (HU) inaccuracy was up to 182 HU without our methods, and it was reduced to a median 6.5 HU with our 2D grid and scatter correction approach. Our methods provided a factor of 2-6 improvement in contrast-to-noise ratio.Significance. This investigation demonstrates the utility of 2D antiscatter grids and grid-based scatter sampling in suppressing MV cross-scatter. Our approach successfully minimized the effects of MV cross-scatter in concurrent kV CBCT imaging and high dose MV treatment delivery scenarios. Hence, robust MV cross-scatter suppression is potentially feasible without MV beam delivery interruption or compromising kV image acquisition rate.

Results of a Multi-Institutional Phase 2 Clinical Trial for 4DCT-Ventilation Functional Avoidance Thoracic Radiation Therapy.

PURPOSE: Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis. METHODS AND MATERIALS: Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy. RESULTS: Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria. CONCLUSIONS: 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.

Report of AAPM Task Group 219 on independent calculation-based dose/MU verification for IMRT.

Independent verification of the dose per monitor unit (MU) to deliver the prescribed dose to a patient has been a mainstay of radiation oncology quality assurance (QA). We discuss the role of secondary dose/MU calculation programs as part of a comprehensive QA program. This report provides guidelines on calculation-based dose/MU verification for intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) provided by various modalities. We provide a review of various algorithms for "independent/second check" of monitor unit calculations for IMRT/VMAT. The report makes recommendations on the clinical implementation of secondary dose/MU calculation programs; on commissioning and acceptance of various commercially available secondary dose/MU calculation programs; on benchmark QA and periodic QA; and on clinically reasonable action levels for agreement of secondary dose/MU calculation programs.

Characterizing spatial differences between SPECT-ventilation and SPECT-perfusion in patients with lung cancer undergoing radiotherapy.

This study investigates agreement between ventilation and perfusion for lung cancer patients undergoing radiotherapy. Ventilation-perfusion scans of nineteen patients with stage III lung cancer from a prospective protocol were compared using voxel-wise Spearman correlation-coefficients. The presented results show in about 25% of patients, ventilation and perfusion exhibit lower agreement.

Evaluation of scatter rejection and correction performance of 2D antiscatter grids in cone beam computed tomography.

PURPOSE: We have been investigating two-dimensional (2D) antiscatter grids (2D ASGs) to reduce scatter fluence and improve image quality in cone beam computed tomography (CBCT). In this work, two different aspects of 2D ASGs, their scatter rejection and correction capability, were investigated in CBCT experiments. To correct residual scatter transmitted through the 2D ASG, it was used as a scatter measurement device with a novel method: grid-based scatter sampling. METHODS: Three focused 2D ASG prototypes with grid ratios of 8, 12, and 16 were developed for linac-mounted offset detector CBCT geometry. In the first phase, 2D ASGs were used as a scatter rejection device, and the effect of grid ratio on CT number accuracy and contrast-to-noise ratio (CNR) evaluated in CBCT images. In the second phase, a grid-based scatter sampling method which exploits the signal modulation characteristics of the 2D ASG's septal shadows to measure and correct residual scatter transmitted through the grid was implemented. To evaluate CT number accuracy, the percent change in CT numbers was measured by changing the phantom from head to pelvis size and configuration. RESULTS: When 2D ASG was used as a scatter rejection device, CT number accuracy increased and the CT number variation due to change in phantom dimensions was reduced from 23% to 2-6%. A grid ratio of 16 yielded the lowest CT number variation. All three 2D ASGs yielded improvement in CNR, up to a factor of two in pelvis-sized phantoms. When 2D ASG prototypes were used for both scatter rejection and correction, CT number variations were reduced further, to 1.3-2.6%. In comparisons with a clinical CBCT system and a high-performance radiographic ASG, 2D ASG provided higher CT number accuracy under the same imaging conditions. CONCLUSIONS: When 2D ASG is used solely as a scatter rejection device, substantial improvement in CT number accuracy can be achieved by increasing the grid ratio. Two-dimensional ASGs also provided significant CNR improvement even at lower grid ratios. Two-dimensional ASGs used in conjunction with the grid-based scatter sampling method provided further improvement in CT number accuracy, irrespective of the grid ratio, while preserving 2D ASGs' capacity to improve CNR. The combined effect of scatter rejection and residual scatter correction by 2D ASG may accelerate implementation of new techniques in CBCT that require high quantitative accuracy, such as radiotherapy dose calculation and dual energy CBCT.

Local Control After Stereotactic Body Radiation Therapy for Liver Tumors.

PURPOSE: To quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen. METHODS AND MATERIALS: We identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy10 vs >100 Gy10). Comparisons were made using log-rank testing. RESULTS: Thirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log-rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy10 (3-year local control 65%, P < .001). CONCLUSIONS: Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy10 are utilized.