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INTRODUCTION: Modern radiotherapy with 4-dimensional computed tomographic (4D-CT) image acquisition for non-small cell lung cancer (NSCLC) captures respiratory-mediated tumor motion to provide more accurate target delineation. This study compares conventional 3-dimensional (3D) conformal radiotherapy (3DCRT) plans generated with standard helical free-breathing CT (FBCT) with plans generated on 4D-CT contoured volumes to determine whether target volume coverage is affected. MATERIALS AND METHODS: Fifteen patients with stage I to IV NSCLC were enrolled in the study. Free-breathing CT and 4D-CT data sets were acquired at the same simulation session and with the same immobilization. Gross tumor volume (GTV) for primary and/or nodal disease was contoured on FBCT (GTV_3D). The 3DCRT plans were obtained, and the patients were treated according to our institution's standard protocol using FBCT imaging. Gross tumor volume was contoured on 4D-CT for primary and/or nodal disease on all 10 respiratory phases and merged to create internal gross tumor volume (IGTV)_4D. Clinical target volume margin was 5 mm in both plans, whereas planning tumor volume (PTV) expansion was 1 cm axially and 1.5 cm superior/inferior for FBCT-based plans to incorporate setup errors and an estimate of respiratory-mediated tumor motion vs 8 mm isotropic margin for setup error only in all 4D-CT plans. The 3DCRT plans generated from the FBCT scan were copied on the 4D-CT data set with the same beam parameters. GTV_3D, IGTV_4D, PTV, and dose volume histogram from both data sets were analyzed and compared. Dice coefficient evaluated PTV similarity between FBCT and 4D-CT data sets. RESULTS: In total, 14 of the 15 patients were analyzed. One patient was excluded as there was no measurable GTV. Mean GTV_3D was 115.3 cm³ and mean IGTV_4D was 152.5 cm³ (P = .001). Mean PTV_3D was 530.0 cm³ and PTV_4D was 499.8 cm³ (P = .40). Both gross primary and nodal disease analyzed separately were larger on 4D compared with FBCT. D95 (95% isodose line) covered 98% of PTV_3D and 88% of PTV_4D (P = .003). Mean dice coefficient of PTV_3D and PTV_4D was 84%. Mean lung V20 was 24.0% for the 3D-based plans and 22.7% for the 4D-based plans (P = .057). Mean heart V40 was 12.1% for the 3D-based plans and 12.7% for the 4D-based plans (P = .53). Mean spinal cord Dmax was 2517 and 2435 cGy for 3D-based and 4D-based plans, respectively (P = .019). Mean esophageal dose was 1580 and 1435 cGy for 3D and 4D plans, respectively (P = .13). CONCLUSIONS: IGTV_4D was significantly larger than GTV_3D for both primary and nodal disease combined or separately. Mean PTV_3D was larger than PTV_4D, but the difference was not statistically significant. The PTV_4D coverage with 95% isodose line was inferior, indicating the importance of incorporating the true size and shape of the target volume. Relatively less dose was delivered to spinal cord and esophagus with plans based on 4D data set. Dice coefficient analysis for degree of similarity revealed that 16% of PTVs from both data sets did not overlap, indicating different anatomical positions of the PTV due to tumor/nodal motion during a respiratory cycle. All patients with lung cancer planned for radical radiotherapy should have 4D-CT simulation to ensure accurate coverage of the target volumes. [ABSTRACT FROM AUTHOR]