We will conduct a prospective clinical study involving up to 40 non-Small Cell Lung Cancer (nSCLC) patients to determine dose thresholds for central and peripheral BSS elements. The workflow is illustrated in Fig. 4. all imaging will be performed under motion control (e.g., with or without abdominal compression) defined as breathing with a resultant motion \[LessThanorequalTo\]5mm by fluoroscopy. Before 4DCT simulation, fluoroscopy using a stand-alone system is used to assess motion under free-breathing conditions. For those with inherent motion \[LessThanorequalTo\]5mm, no motion manipulation is required (ie, motion is controlled). For those with \[Greater Than\]5mm motion, it is customary to use progressively tighter abdominal compression applied via commercially available device or a pneumatic belt, until respiration-induced tumor motion, as seen under fluoroscopy, is \[LessThanorequalTo\] 5mm. Subsequently, a 4DCT scan is acquired with motion control.

in this study, a high-resolution breath-hold CT scan (BHCT) will be acquired from each patient immediately before or after the 4DCT scan. using LungPoint, a virtual bronchoscopy software, individual BSS will be auto-segmented from the BHCT, labeled based on a nomenclature described by netter and exported as Digital imaging and Communications in Medicine radiation Therapy (DiCoMRT) objects to the planning system. The BHCT will be deformably registered to each phase of the 4DCT to create ten high-resolution CT volumes corresponding to ten respiratory phases. acquiring both, the BHCT and the 4DCT, under motion control will ensure that the anatomy is consistently deformed so as to minimize image registration errors. The automatically deformed contours, especially for smaller BSS elements, will be manually verified by a radiation oncologist, and corrected if necessary. a high-resolution maximum intensity projection (MiP) image will be created from the deformed BHCT volumes so as to encompass the extent of respiration-induced motion for each structure in the lung. The high spatial resolution of the MiP will ensure that respiratory motion of smaller, more peripheral BSS segments is captured accurately. The dose to BSS elements from the clinical SabR plan (created without considering BSS) will be computed from the hi-res MiP using the acuros dose calculation algorithm. This algorithm accurately accounts for dose to small structures and tissue inhomogeneities, and has been extensively validated for lung radiotherapy.

a follow-up high resolution BHCT (also under motion control) will be acquired from each patient 8-12 months post-SabR, and BSS elements will be segmented in LungPointRT. a radiation oncologist will compare the pre- and post-SabR contours to determine segmental collapse. univariate and multivariate stepwise generalized estimating equation (Gee) analyses will be conducted to identify significant factors contributing to BSS collapse, accounting for intra-patient correlation within each nSCLC patient. The insights obtained from these analyses will be used to formulate dose-thresholds for BSS segments. For each segment, we will compute the probability of segmental collapse as a function of dose, Cs(D) and also assign a weight \[and\] #955;s. This weight will be based on the findings of aim 2 and will be proportional to the functional lung volume \[Quote\]served\[Quote\] by that segment. This weighting scheme will ensure that the dose-thresholds (DT) are set more conservatively, i.e., with relatively lower Cs(DT) for the more critical BSS segments and vice versa.