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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.

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.

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.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 (FEVFifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEVThe 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 FEV

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.

Purpose/Objective(s) Ventilation-perfusion dose-response studies have focused on using functional imaging to characterize a dose-response and to assess whether the dose-response can predict subsequent pulmonary toxicity. Current dose-response studies typically focus on a single modality (ventilation or perfusion) and perform assessments on a population-based basis. There is no work evaluating whether ventilation dose-response differs from perfusion dose-response for individual lung cancer patients. The purpose of this study was to use single photon emission computed tomography (SPECT)-CT ventilation-perfusion imaging to quantitatively and clinically evaluate whether lung cancer patients treated with radiotherapy have differences between their ventilation and perfusion dose-responses. Materials/Methods Twenty patients with biopsy proven lung cancer enrolled on a prospective functional avoidance protocol underwent SPECT-CT perfusion-ventilation scans pre- and 3-month post-radiotherapy. The SPECT-CT, planning CT, and dose distribution were rigidly registered. We calculated the relative changes in pre- to post-treatment ventilation-perfusion in lung regions receiving ≥ 20 Gy (referred to as ΔPV20 for perfusion and ΔVV20 for ventilation). Differences between perfusion-based ΔPV20 and ventilation-based ΔVV20 were assessed and referred to as ΔfV20. A radiologist read each pre- and post-treatment ventilation-perfusion scans using a semi-quantitative scale that assigned a score ranging from 1 to 8 that reflected functional defect and heterogeneity in each lung. The difference between radiologist scores for the pre- and post-treatment scans was calculated for both ventilation and perfusion. Differences between ventilation-based and perfusion-based radiologist scores were assessed. Results Twenty-five percent of patients had a difference of ΔfV20 > 35% between ventilation-perfusion pre- to post-treatment changes (ΔVV20 and ΔPV20) and 20% of patients had opposite directions for ventilation-perfusion pre- to post-treatment changes. Radiologist assessment resulted in 20% of patients having different ventilation-perfusion semi-quantitative change scores for ipsilateral lungs. Conclusion The current work employed quantitative metrics and clinical assessments to evaluate whether ventilation dose-response differs from perfusion dose-response for individual lung cancer patients. Our data showed that ventilation dose-response can differ from perfusion dose-response for 20% to 30% of patients. Our study demonstrates that when evaluating functional dose-response for lung cancer patients, it is insufficient to look at ventilation or perfusion alone for a subset of patients; but rather both modes of functional imaging may be needed when predicting for clinical outcomes.