Weiss, Elisabeth | Search NASA

DOE OSTI2016

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency

Purpose: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. Methods: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a “no-adapt” scenario that simulates delivery of an initial plan throughout treatment, (2) a “midadapt” scenario that implements a single replan for fraction 18, (3) a “weekly adapt” scenario that simulates weekly adaptations, and (4) a “full-adapt” scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Results: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20{sub lung}) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66{sub heart}), and dose received by 33% of the heart (D33{sub heart}), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). Conclusions: Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

Measuring interfraction and intrafraction lung function changes during radiation therapy using four-dimensional cone beam CT ventilation imaging

Purpose: Adaptive ventilation guided radiation therapy could minimize the irradiation of healthy lung based on repeat lung ventilation imaging (VI) during treatment. However the efficacy of adaptive ventilation guidance requires that interfraction (e.g., week-to-week), ventilation changes are not washed out by intrafraction (e.g., pre- and postfraction) changes, for example, due to patient breathing variability. The authors hypothesize that patients undergoing lung cancer radiation therapy exhibit larger interfraction ventilation changes compared to intrafraction function changes. To test this, the authors perform the first comparison of interfraction and intrafraction lung VI pairs using four-dimensional cone beam CT ventilation imaging (4D-CBCT VI), a novel technique for functional lung imaging. Methods: The authors analyzed a total of 215 4D-CBCT scans acquired for 19 locally advanced non-small cell lung cancer (LA-NSCLC) patients over 4–6 weeks of radiation therapy. This set of 215 scans was sorted into 56 interfraction pairs (including first day scans and each of treatment weeks 2, 4, and 6) and 78 intrafraction pairs (including pre/postfraction scans on the same-day), with some scans appearing in both sets. VIs were obtained from the Jacobian determinant of the transform between the 4D-CBCT end-exhale and end-inhale images after deformable image registration. All VIs were deformably registered to their corresponding planning CT and normalized to account for differences in breathing effort, thus facilitating image comparison in terms of (i) voxelwise Spearman correlations, (ii) mean image differences, and (iii) gamma pass rates for all interfraction and intrafraction VI pairs. For the side of the lung ipsilateral to the tumor, we applied two-sided t-tests to determine whether interfraction VI pairs were more different than intrafraction VI pairs. Results: The (mean ± standard deviation) Spearman correlation for interfraction VI pairs was r{sup -}{sub Inter}=0.52±0.25, which was significantly lower than for intrafraction pairs (r{sup -}{sub Intra}=0.67±0.20, p = 0.0002). Conversely, mean absolute ventilation differences were larger for interfraction pairs than for intrafraction pairs, with |ΔV{sup -}{sub Inter}|=0.42±0.65 and |ΔV{sup -}{sub Intra}|=0.32±0.53, respectively (p < 10{sup −15}). Applying a gamma analysis with ventilation/distance tolerance of 25%/10 mm, we observed mean pass rate of (69% ± 20%) for interfraction VIs, which was significantly lower compared to intrafraction pairs (80% ± 15%, with p ∼ 0.0003). Compared to the first day scans, all patients experienced at least one subsequent change in median ipsilateral ventilation ≥10%. Patients experienced both positive and negative ventilation changes throughout treatment, with the maximum change occurring at different weeks for different patients. Conclusions: The authors’ data support the hypothesis that interfraction ventilation changes are larger than intrafraction ventilation changes for LA-NSCLC patients over a course of conventional lung cancer radiation therapy. Longitudinal ventilation changes are observed to be highly patient-dependent, supporting a possible role for adaptive ventilation guidance based on repeat 4D-CBCT VIs. We anticipate that future improvement of 4D-CBCT image reconstruction algorithms will improve the capability of 4D-CBCT VI to resolve interfraction ventilation changes.

60 APPLIED LIFE SCIENCES↗