We aimed to develop a deep learning (DL) model for predicting high-grade patterns in lung adenocarcinomas (ADC) and to assess the prognostic performance of model in advanced lung cancer patients who underwent neoadjuvant or definitive concurrent chemoradiation therapy (CCRT). We included 275 patients with 290 early lung ADCs from an ongoing prospective clinical trial in the training dataset, which we split into internal–training and internal–validation datasets. We constructed a diagnostic DL model of high-grade patterns of lung ADC considering both morphologic view of the tumor and context view of the area surrounding the tumor (MC3DN; morphologic-view context-view 3D network). Validation was performed on an independent dataset of 417 patients with advanced non-small cell lung cancer who underwent neoadjuvant or definitive CCRT. The area under the curve value of the DL model was 0.8 for the prediction of high-grade histologic patterns such as micropapillary and solid patterns (MPSol). When our model was applied to the validation set, a high probability of MPSol was associated with worse overall survival (probability of MPSol >0.5 vs. <0.5; 5-year OS rate 56.1% vs. 70.7%), indicating that our model could predict the clinical outcomes of advanced lung cancer patients. The subgroup with a high probability of MPSol estimated by the DL model showed a 1.76-fold higher risk of death (HR 1.76, 95% CI 1.16–2.68). Our DL model can be useful in estimating high-grade histologic patterns in lung ADCs and predicting clinical outcomes of patients with advanced lung cancer who underwent neoadjuvant or definitive CCRT.

Background: Prognostic considerations for non-predominant patterns are necessary because most lung adenocarcinomas (ADCs) have a mixed histologic pattern, and the spectrum of actual prognosis varies widely even among lung ADCs with the same most predominant pattern. We aimed to identify prognostic stratification by second most predominant pattern of lung ADC and to more accurately assess prognostic factors with CT imaging analysis, particularly enhancing non-predominant but high-grade pattern. Methods: In this prospective study, patients with early-stage lung ADC undergoing curative surgery underwent preoperative dual-energy CT (DECT) and positron emission tomography (PET)/CT. Histopathology of ADC, the most predominant and second most predominant histologic patterns, and preoperative imaging parameters were assessed and correlated with patient survival. Results: Among the 290 lung ADCs included in the study, 231 (79.7%) were mixed-pathologic pattern. When the most predominant histologic pattern was intermediate-grade, survival curves were significantly different among the three second most predominant subgroups (p = 0.004; low, lepidic; intermediate, acinar and papillary; high, micropapillary and solid). When the second most predominant pattern was high-grade, recurrence risk increased by 4.2-fold compared with the low-grade group (p = 0.005). To predict a non-predominant but high-grade pattern, the non-contrast CT value of tumor was meaningful with a lower HU value associated with the histologic combination of lower grade (low-grade as most predominant and intermediate-grade as second most predominant pattern, OR = 6.15, p = 0.005; intermediate-grade as most predominant and high-grade as second most predominant pattern, OR = 0.10, p = 0.033). SUVmax of the tumor was associated with the non-predominant but high-grade pattern, especially in the histologic combination of intermediate-high grade (OR = 1.14, p = 0.012). Conclusions: The second most predominant histologic pattern can stratify lung ADC patients according to prognosis. Thus, predicting the malignant potential and establishing treatment policies should not rely only on the most predominant pattern. Moreover, imaging parameters of non-contrast CT value and SUVmax could be useful in predicting a non-predominant but high-grade histologic pattern.