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Introduction: Curatively intended chemo-radio-immunotherapy for non-small cell lung cancer (NSCLC) stage III may lead to post-therapeutic pulmonary function (PF) impairment. We hypothesized that the decrease in global PF corresponds to the increase in tissue density in follow-up CTs. Hence, the study aim was to correlate the dynamics in radiographic alterations to carbon monoxide diffusing capacity (DL<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mi>CO</mi></msub></semantics></math></inline-formula>) and FEV<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mn>1</mn></msub></semantics></math></inline-formula>, which may contribute to a better understanding of radiation-induced lung disease. Methods: Eighty-five patients with NSCLC III were included. All of them received two cycles of platinum-based induction chemotherapy followed by high dose radiation. Thereafter, durvalumab was administered for one year in 63/85 patients (74%). Pulmonary function tests (PFTs) were performed three months and six months after completion of radiotherapy (RT) and compared to baseline. At the same time points, patients underwent diagnostic CT (dCT). These dCTs were matched to the planning CT (pCT) using RayStation^® Model Based Segmentation and deformable image registration. Differential volumes defined by specific isodoses were generated to correlate them with the PFTs. Results: In general, significant correlations between PFTs and differential volumes were found in the mid-dose range, especially for the volume of the lungs receiving between 65% and 45% of the dose prescribed (V<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mn>65</mn><mo>−</mo><mn>45</mn><mo>%</mo></mrow></msub></semantics></math></inline-formula>) and DL<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mi>CO</mi></msub></semantics></math></inline-formula> (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo><</mo><mn>0.01</mn></mrow></semantics></math></inline-formula>). This volume range predicted DL<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mi>CO</mi></msub></semantics></math></inline-formula> after RT (<i>p</i>-value 0.03) as well. In multivariate analysis, DL<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mi>CO</mi></msub></semantics></math></inline-formula> (<i>p</i>-value 0.040) and FEV<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mn>1</mn></msub></semantics></math></inline-formula> (<i>p</i>-value 0.014) predicted pneumonitis. Conclusions: The current analysis revealed a strong relation between the dynamics of DL<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mi>CO</mi></msub></semantics></math></inline-formula> and CT morphology changes in the mid-dose range, which convincingly indicates the importance of routinely used PFTs in the context of a curative treatment approach.