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 (V 20 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 heart ), and dose received by 33% of the heart (D33 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. C 2016 American Association of Physicists in Medicine. [http://dx

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Purpose: To assess the efficacy of intensity modulated radiotherapy (IMRT) optimization for lung cancer based on dose‐to‐structure mass objectives. Methods: Three patient cases are planned for two radiotherapy deliveries; each optimized using either dose‐volume histogram (DVH) constraints or dose‐mass histogram (DMH) constraints. An inhale‐phase optimization simulates breath hold (BH) treatment; an average CT (aCT) optimization simulates treatment under free breathing. DVH plan objectives include 70 Gy to 98% of the PTV while minimizing lung V20, esophagus V25, heart V30. DMH optimization utilizes the same beam angles with corresponding objectives; 70 Gy to 98% of the PTV mass and minimum dose to relative mass of risk structures. Relative mass at objective dose levels are compared for DVH and DMH optimization. Results: For BH plans, DMH optimization maintains or improves target‐mass coverage (up to 2% increase in mass at 70 Gy) and decreases lung mass by up to 2%, heart mass by up to 4%, and esophagus mass by up to 2% at the objective dose levels. The DMH plans optimized on aCT increase target mass coverage by <:1% in all cases and do not improve risk structure mass sparing compared to DVH based plans. The DVH to DMH optimization differences are patient and radiation path dependent. For a complete set of voxels composing a given volume, irradiated voxels are a subset which can have a different mean density than the entire set. This leads to variations in DVH and DMH solutions for the PTV, lungs, esophagus, and heart. Preferred (reduced) radiation path‐lengths through regions of lower density lung are observed in BH‐DMH optimization. Conclusions: DMH optimization has the potential to improve the therapeutic ratio on well‐defined geometry (for example during BH‐RT). This may have advantages in the heart, however, functional lung sub‐units must be further investigated. Support: P01CA11602 and Philips Medical Systems

Purpose To present a novel method for generating nonuniform lesion‐specific rotational margins for targets remote from isocenter, as encountered in single isocenter multiple metastasis radiotherapy. Methods Target contours are rotated using a large series of 3D rotations, corresponding to a given range of rotational uncertainty, and combined to create a rotational envelope that encompasses potential motion. A set of artificial spherical targets ranging from 0.5 to 2.0 cm in diameter, and residing a distance of 1 – 15 cm from isocenter, is used to generate rotational envelopes assuming uncertainties of 0.5–3.0°. Computing time and number of samples are reported for simulated scenarios. Hausdorff distances (HD) between rotational envelopes and original target structures are calculated to represent the magnitude of uniform expansion required to encompass potential rotation. Volume differences between uniform expansions (based on HD) and rotational envelopes are reported to articulate potential advantages. Results Median time to generate rotational envelopes was 60 s (31–974 s). Median required samples was 86 (61–851). Maximum HD for all targets located 10 cm from isocenter was 1.5 mm, 3.0 mm, 5.8 mm, and 8.6 mm assuming 0.5°, 1.0°, 2.0°, and 3.0° of rotational uncertainty, respectively. At 5 cm from isocenter and assuming 0.5° of rotational uncertainty, volumes were decreased by 0.07 cc (60%), 0.24 cc (39%), and 1.08 cc (19%) for 5 mm, 10 mm, and 20 mm targets respectively. At 10 cm from isocenter and 1.0° of uncertainty, volumes decreased by 0.42 cc (58%), 2.0 cc (40%), and 2.5 cc (27%). On average target volumes decreased 45% (SD = 17%) when compared with uniform expansions based on HD. Conclusion Rotational margins may be generated by sampling a set of 3D rotations. Resulting margins explicitly account for target shape, distance from isocenter, and magnitude of rotational uncertainty, while reducing treated volumes when compared with uniform expansions.