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Simple Summary: We studied clinical aspects in central vs. peripheral tumors (n = 78 patients) and applied the internal organ at risk volume (IRV) concept (n = 35 patients) in stereotactic body radiation therapy (SBRT) for centrally located non-small cell lung cancer (NSCLC). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central tumors when compared with peripheral tumors. We here provide evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in cases of higher body mass index. Applying the IRV concept (retrospectively, without new optimization), the normal tissue complication probabilities increased >10% for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment. The internal organ at risk volume (IRV) concept might improve toxicity profiles in stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). We studied (1) clinical aspects in central vs. peripheral tumors, (2) the IRV concept in central tumors, (3) organ motion, and (4) associated normal tissue complication probabilities (NTCPs). We analyzed patients who received SBRT for NSCLC (clinical aspects, n = 78; motion management, n = 35). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central vs. peripheral tumors. Organ motion was greater in males and tall patients (bronchial tree), whereas volume changes were lower in patients with a high body mass index (BMI) (esophagus). Applying the IRV concept (retrospectively, without new optimization), we found an absolute increase of >10% in NTCPs for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. There is evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in patients with higher BMI. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: Motion of the prostate may adversely affect the outcome of radiotherapy. Online tracking of the prostate during irradiation is technologically feasible but only available at select institutions. It would be beneficial to be able to identify patients at risk of particularly high prostate intrafraction motion with simpler technology. In this paper, we present a larger inner diameter of the lesser pelvis as an anatomical predictor for high prostate intrafraction motion. It can be measured with a single planning CT, which should always be available. Risk patients identified in this way could then be selected for more rigorous online motion management or benefit from increased safety margins. Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation pneumonitis is a major late complication in radiotherapy (RT) for lung cancer. Respiratory gating radiotherapy and deep inspiration breath hold are representative techniques to protect the normal lung by managing the movement of the tumor. However, these are highly patient-dependent techniques. Continuous positive airway pressure (CPAP) is used as an alternative, but it is unclear how much pressure will be effective. We aimed to determine the optimal pressure of CPAP for RT through changes in the dosimetric parameters and lung volume according to pressure. The air pressure was raised in five steps of 4, 7, 10, 14, and 17 cmH2O and a CT scan was performed at the baseline and at each pressure step, accompanied by contouring and RT planning. CPAP linearly increased lung volume and decreased the dosimetric parameter in the pressure range 7 to 13 cmH2O (p < 0.01). Above 13 cmH2O, V5 of the heart also showed a significant decrease (p < 0.01). We aimed to determine the optimal pressure of continuous positive airway pressure (CPAP) for radiotherapy (RT) through changes in the dosimetric parameters and lung volume according to pressure. Patients with locally advanced lung cancer, who underwent CPAP during computed tomography (CT) simulation, were included. The air pressure was raised in five steps of 4, 7, 10, 14, and 17 cmH2O and a CT scan was performed at the baseline and at each pressure step, accompanied by contouring and RT planning. Paired t- and Wilcoxon signed rank tests were used to compare the volumetric and dosimetric parameters according to pressure and interpressure. A total of 29 patients were selected, and 158 CT datasets were obtained. The lung volume increased significantly at all pressures (p < 0.01). The Dmean of the lung decreased significantly from 7 cmH2O (p < 0.01), the V5, V10, V15, and V20 of the lung decreased significantly from 7 cmH2O with increasing pressure, and the Dmean and V5 of the heart decreased significantly from 14 cmH2O with increasing pressure. The V50 showed no significant differences at any pressure. We recommend the use of at least 7 cmH2O with 14 cmH2O as the optimal pressure to achieve the effect of heart preservation. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung stereotactic body radiotherapy (SBRT) is the standard of care for early-stage lung cancer and oligometastases. For SBRT, motion has to be considered to avoid misdosage. Respiratory phase gating, meaning to irradiate the target volume only in a predefined gating motion phase window, can be applied to mitigate motion-induced effects. The aim of this study was to exploit the clinical benefit of gating for lung SBRT. For the majority of 14 lung tumor patients and various gating windows, we could prove a reduced dose to normal tissue by gating simulation. A normal tissue complication probability (NTCP) model analysis revealed a major reduction of normal tissue toxicity for moderate gating window sizes. The most beneficial effect of gating was found for those patients with the highest prior toxicity risk. The presented results are useful for personalized risk assessment prior to treatment and may help to select patients and optimal gating windows. We investigated the potential of respiratory gating to mitigate the motion-caused misdosage in lung stereotactic body radiotherapy (SBRT). For fourteen patients with lung tumors, we investigated treatment plans for a gating window (GW) including three breathing phases around the maximum exhalation phase, GW40–60. For a subset of six patients, we also assessed a preceding three-phase GW20–40 and six-phase GW20–70. We analyzed the target volume, lung, esophagus, and heart doses. Using normal tissue complication probability (NTCP) models, we estimated radiation pneumonitis and esophagitis risks. Compared to plans without gating, GW40–60 significantly reduced doses to organs at risk without impairing the tumor doses. On average, the mean lung dose decreased by 0.6 Gy (p < 0.001), treated lung V20Gy by 2.4% (p = 0.003), esophageal dose to 5cc by 2.0 Gy (p = 0.003), and maximum heart dose by 3.2 Gy (p = 0.009). The model-estimated mean risks of 11% for pneumonitis and 12% for esophagitis without gating decreased upon GW40–60 to 7% and 9%, respectively. For the highest-risk patient, gating reduced the pneumonitis risk from 43% to 32%. Gating is most beneficial for patients with high-toxicity risks. Pre-treatment toxicity risk assessment may help optimize patient selection for gating, as well as GW selection for individual patients. [ABSTRACT FROM AUTHOR]

Background: Major challenges in the application of intensity-modulated proton therapy (IMPT) for lung cancer patients include the uncertainties associated with breathing motion, its mitigation and its consideration in IMPT optimization. The primary objective of this research was to evaluate the potential of four-dimensional robust optimization (4DRO) methodology to make IMPT dose distributions resilient to respiratory motion as well as to setup and range uncertainties; Methods: The effect of respiratory motion, characterized by different phases of 4D computed tomography (4DCT), was incorporated into an in-house 4DRO system. Dose distributions from multiple setup and range uncertainty scenarios were calculated for each of the ten phases of CT datasets. The 4DRO algorithm optimizes dose distributions to achieve target dose coverage and normal tissue sparing for multiple setup and range uncertainty scenarios as well as for all ten respiratory phases simultaneously. IMPT dose distributions of ten lung cancer patients with different tumor sizes and motion magnitudes were optimized to illustrate our approach and its potential; Results: Compared with treatment plans generated using the conventional planning target volume (PTV)-based optimization and 3D robust optimization (3DRO), plans generated by 4DRO were found to have superior clinical target volume coverage and dose robustness in the face of setup and range uncertainties as well as for respiratory motion. In most of the cases we studied, 4DRO also resulted in more homogeneous target dose distributions. Interestingly, such improvements were found even for cases in which moving diaphragms intruded into the proton beam paths; Conclusion: The incorporation of respiratory motion, along with setup and range uncertainties, into robust optimization, has the potential to improve the resilience of target and normal tissue dose distributions in IMPT plans in the face of the uncertainties considered. Moreover, it improves the optimality of plans compared to PTV-based optimization as well as 3DRO. [ABSTRACT FROM AUTHOR]