Purpose: To investigate the ability of four-dimensional computed tomography (4D CT)-derived ventilation images to identify regions of highly functional lung for avoidance in intensitymodulated radiotherapy (IMRT) planning in locally advanced non-small cell lung cancer (NSCLC). Methods and Materials:The treatment planning records from 21 patients with stage III NSCLC were selected. Ventilation images were generated from the 4D CT sets, and each was imported into the treatment-planning system. Ninety percentile functional volumes (PFV90), constituting the 10% of the lung volume where the highest ventilation occurs, were generated. Baseline IMRT plans were generated using the lung volume constraint on V20 (<35%), and two additional plans were generated using constraints on the PFV90 without a volume constraint. Dose-volume (DVH) and dose-function (DFH) histograms were generated and used to evaluate the PTV coverage, lung volume, and functional parameters for comparison of the plans. Results:The mean dose to the PFV90 was reduced by 2.9 Gy, and the DFH at 5 Gy (F5) was reduced by 9.6% (SE=2.03%). The F5, F10, V5, and V10 were all significantly reduced from the baseline values. We identified a favorable subset of patients for whom there was a further significant improvement in the mean lung dose.Conclusions: 4D CT-derived ventilation regions were successfully utilized as avoidance structures to reduce the DVH and DFH at 5 Gy in all the cases. In a subset, there was also a Conflict of Interest NotificationThe authors have no commercial or financial interests related to this study to disclose.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

Purpose To analyze dosimetric variables and outcomes after adaptive replanning of radiotherapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. Results At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm3 adaptive and 86.4 cm3 non-adaptive; median changes in volume, 25.3% adaptive and 1.2% non-adaptive; p<0.01). The median number of fractions delivered using adaptive planning was 13 (range, 4–22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V70, 1.8%; range, 0–22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0–13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs. 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, versus non-adaptive plans.

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