Single-cell sequencing on CD8+ TILs revealed the nature of exhausted T cells recognizing neoantigen and cancer/testis antigen in non-small cell lung cancer.

BACKGROUND: CD8+tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8+ TILs, especially T-cell populations specific for tumor antigens, remain poorly understood. METHODS: High throughput single-cell RNA sequencing and single-cell T-cell receptor (TCR) sequencing were performed on CD8+ TILs from three surgically-resected lung cancer specimens. Dimensional reduction for clustering was performed using Uniform Manifold Approximation and Projection. CD8+ TIL TCR specific for the cancer/testis antigen KK-LC-1 and for predicted neoantigens were investigated. Differentially-expressed gene analysis, Gene Set Enrichment Analysis (GSEA) and single sample GSEA was performed to characterize antigen-specific T cells. RESULTS: A total of 6998 CD8+ T cells was analyzed, divided into 10 clusters according to their gene expression profile. An exhausted T-cell (exhausted T (Tex)) cluster characterized by the expression of ENTPD1 (CD39), TOX, PDCD1 (PD1), HAVCR2 (TIM3) and other genes, and by T-cell oligoclonality, was identified. The Tex TCR repertoire (Tex-TCRs) contained nine different TCR clonotypes recognizing five tumor antigens including a KK-LC-1 antigen and four neoantigens. By re-clustering the tumor antigen-specific T cells (n=140), it could be seen that the individual T-cell clonotypes were present on cells at different stages of differentiation and functional states even within the same Tex cluster. Stimulating these T cells with predicted cognate peptide indicated that TCR signal strength and subsequent T-cell proliferation and cytokine production was variable but always higher for neoantigens than KK-LC-1. CONCLUSIONS: Our approach focusing on T cells with an exhausted phenotype among CD8+ TILs may facilitate the identification of tumor antigens and clarify the nature of the antigen-specific T cells to specify the promising immunotherapeutic targets in patients with NSCLC.

Thoracoscopic Anatomical Sublobar Resection Including Subsegmentectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC. METHODS: We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy. RESULTS: No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups. CONCLUSIONS: Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option.

The beginning of a new era in induction treatment for operable non-small cell lung cancer: a narrative review.

Background and Objective: The survival benefit of induction therapy for non-small cell lung cancer (NSCLC) remains controversial. Recently, the outcomes of systemic therapy for NSCLC have dramatically changed with the advent of molecular target drugs and immune checkpoint inhibitors (ICIs). The present review was conducted to investigate the outcomes of induction therapy with reference to randomized control trials (RCTs). Methods: We reviewed RCTs and ongoing clinical trials between 1990 and 2022 using relevant databases: PubMed, Web of Science, and EMBASE database. We investigated the outcomes of induction therapy. Key Content and Findings: Induction therapy was associated with longer overall survival in comparison to surgery alone in several RCTs for stage III disease. However, its benefit in early-stage (I-II) disease was unclear. Regarding induction chemotherapy and chemoradiotherapy, the safety and survival outcomes did not differ between the two arms. Epidermoid growth factor receptor (EGFR) tyrosine kinase inhibitors as induction therapy in patients with proven EGFR mutations may be a sufficient choice for the improvement of overall survival. In ongoing single arm clinical trials and a randomized control study, the administration of ICIs as induction therapy was associated with a good pathological response and satisfactory safety, which will lead to a better survival outcome. Long-term observation is needed to evaluate the toxicity and survival impact of induction therapy with ICIs. Conclusions: Induction chemotherapy and EGFR-TKIs for stage IIIA NSCLC may contribute to the improvement of survival outcomes although the effect of systemic therapy on stage I-II remains controversial. ICIs may be considered as a valuable treatment option because of their feasibility and safety for induction therapy.

Biological Difference between L858R and Exon 19 Deletion Contributes to Recurrence-Free Survival of Resected Non-Small Cell Lung Cancer.

INTRODUCTION: The differences in biological characteristics among different genotypes of classical EGFR mutations have not been clarified. This study aimed to clarify the clinical and biological differences between L858R and 19 deletion in NSCLC. METHODS: We analyzed a cohort of 191 consecutive cases of surgically resected NSCLC harboring EGFR driver mutations (L858R or 19 deletion) in which curative resection was performed in Aichi Cancer Center Hospital, Nagoya, Japan, from January 2006 to September 2021 and in which recurrence subsequently developed. We also subjected 61 surgically resected NSCLC specimens harboring EGFR driver mutations (L858R or 19 deletion) to an RNA sequencing analysis. RESULTS: In patients with stage I disease, the median time to recurrence did not differ to a statistically significant extent between the types of EGFR mutations; however, among those with stage II and III disease, the median time to recurrence in patients with the L858R genotype tended to be shorter in comparison to those with 19 deletion (log-rank test, p = 0.47 and 0.46, respectively). In comparison to 19 deletion tumors, L858R tumors had higher cytological malignancy (e.g., mitotic ability) and showed stronger immunogenicity. CONCLUSION: L858R and 19 deletion tumors are likely to have a slight difference in the time to recurrence. They suggest that even in EGFR driver tumors, which are treated as the same disease category, the biological characteristics of the tumors are different, which may leave room for innovations in postoperative treatment and treatment at recurrence.

Deep learning-assisted development and validation of an algorithm for predicting the growth of persistent pure ground-glass nodules.

Background: The prediction of the persistent pure ground-glass nodule (pGGN) growth is challenging and limited by subjective assessment and variation across radiologists. A chest computed tomography (CT) image-based deep learning classification model (DLCM) may provide a more accurate growth prediction. Methods: This retrospective study enrolled consecutive patients with pGGNs from January 2010 to December 2020 from two independent medical institutions. Four DLCM algorithms were built to predict the growth of pGGNs, which were extracted from the nodule areas of chest CT images annotated by two radiologists. All nodules were assigned to either the study, the inner validation, or the external validation cohort. Accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curves, and areas under the ROC curve (AUROCs) were analyzed to evaluate our models. Results: A total of 286 patients were included, with 419 pGGN. In total, 197 (68.9%) of the patients were female and the average age was 59.5±12.0 years. The number of pGGN assigned to the study, the inner validation, and the external validation cohort were 193, 130, and 96, respectively. The follow-up time of stable pGGNs for the primary and external validation cohorts were 3.66 (range, 2.01-10.08) and 4.63 (range, 2.00-9.91) years, respectively. Growth of the pGGN occurred in 166 nodules [83 (43%), 39 (30%), and 44 (45%) in the study, inner and external validation cohorts respectively]. The best-performing DLCM algorithm was DenseNet_DR, which achieved AUROCs of 0.79 [95% confidence interval (CI): 0.70, 0.86] in predicting pGGN growth in the inner validation cohort and 0.70 (95% CI: 0.60, 0.79) in the external validation cohort. Conclusions: DLCM algorithms that use chest CT images can help predict the growth of pGGNs.

Three-Arm Robotic Lung Resection via the Open-Thoracotomy-View Approach Using Vertical Port Placement and Confronting Monitor Setting: Focusing on Segmentectomy.

To perform robotic lung resections with views similar to those in thoracotomy, we devised a vertical port placement and confronting upside-down monitor setting: the three-arm, robotic "open-thoracotomy-view approach (OTVA)". We described the robotic OTVA experiences focusing on segmentectomy and its technical aspects. We retrospectively reviewed 114 consecutive patients who underwent robotic lung resections (76 lobectomies and 38 segmentectomies) with OTVA using the da Vinci Xi Surgical System between February 2019 and June 2022. To identify segmental boundaries, we administered indocyanine green intravenously and used the robotic fluorescence imaging system (Firefly). In all procedures, cranial-side intrathoracic structures, which are often hidden in the conventional look-up-view method, were well visualized. The mean durations of surgery and console operation were 195 and 140 min, respectively, and 225 and 173 min, for segmentectomy and lobectomy, respectively. In segmentectomy, console operation was significantly shorter (approximately 30 min, p < 0.001) and two more staplers (8.2 ± 2.3) were used compared with lobectomy (6.6 ± 2.6, p = 0.003). In both groups, median postoperative durations of chest tube placement and hospitalization were 0 and 3 days, respectively. This three-arm robotic OTVA setting offers natural thoracotomy views and can be an alternative for segmentectomy and lobectomy.

Association of the KRAS genotype and clinicopathologic findings of resected non-small-cell lung cancer: A pooled analysis of 179 patients.

BACKGROUND: This study assessed the clinicopathological background of early-stage KRAS-mutated non-small-cell lung cancer and analyzed the biological process of KRAS-mutated tumor using an RNA sequencing procedure. PATIENTS AND METHODS: We used a cohort of consecutive series of 179 surgically resected early-stage non-small-cell lung cancers harboring KRAS mutations and analyzed the clinicopathological features, including the KRAS genotypes, affecting the recurrence-free survival and prognosis. Consequently, we performed RNA sequencing to determine the gene expression profiles of nineteen KRAS-mutated non-small-cell cancers. RESULTS: The most common KRAS genotype was p.G12C (57; 31.8%). A high p-stage (hazard ratio [HR], 4.181; P < 0.0001) and solid predominant adenocarcinoma histology (HR, 2.343; P = 0.0076) were significant independent prognostic factors for the recurrence-free survival. A high p-stage (HR, 3.793; P < 0.0001), solid predominant adenocarcinoma histology (HR, 2.373; P = 0.0147), and KRAS p.G12V genotype (HR, 1.975; P = 0.0407) were significant independent prognostic factors for the overall survival. A gene expression analysis of the two factors revealed the p.G12V genotype to be closer to those of stem cells, and the traits of e an enhanced fatty acid and amino acid metabolism. as well as And a solid predominant phenotype were shown to an acquired a trait that can withstand hypoxia and the effect of prostaglandin-endoperoxide synthase. CONCLUSION: The KRAS p.G12V genotype and solid predominant adenocarcinoma phenotype may be independent predictive factors of a poor clinical course in resected early-stage non-small-cell lung cancers, possibly due to the differentiation tendency observed in stem cells, the trait of an enhanced fatty acid and amino acid metabolism, and the effect of prostaglandin-endoperoxide synthase.

New evaluation of the tumor immune microenvironment of non-small cell lung cancer and its association with prognosis.

BACKGROUND: A better understanding of the tumor immune microenvironment (TIME) will facilitate the development of prognostic biomarkers and more effective therapeutic strategies in patients with lung cancer. However, little has been reported on the comprehensive evaluation of complex interactions among cancer cells, immune cells, and local immunosuppressive elements in the TIME. METHODS: Whole-exome sequencing and RNA sequencing were carried out on 113 lung cancers. We performed single sample gene set enrichment analysis on TIME-related gene sets to develop a new scoring system (TIME score), consisting of T-score (tumor proliferation), I-score (antitumor immunity) and S-score (immunosuppression). Lung cancers were classified according to a combination of high or low T-score, I-score, and S-scores (eight groups; G1-8). Clinical and genomic features, and immune landscape were investigated among eight groups. The external data sets of 990 lung cancers from The Cancer Genome Atlas and 76 melanomas treated with immune checkpoint inhibitors (ICI) were utilized to evaluate TIME scoring and explore prognostic and predictive accuracy. RESULTS: The representative histological type including adenocarcinoma and squamous cell carcinoma, and driver mutations such as epidermal growth factor receptor and TP53 mutations were different according to the T-score. The numbers of somatic mutations and predicted neoantigens were higher in Thi (G5-8) than Tlo (G1-4) tumors. Immune selection pressure against neoantigen expression occurred only in Thi and was dampened in Thi/Ilo (G5-6), possibly due to a reduced number of T cells with a high proportion of tumor specific but exhausted cells. Thi/Ilo/Shi (G5) displayed the lowest immune responses by additional immune suppressive mechanisms. The T-score, I-score and S-scores were independent prognostic factors, with survival curves well separated into eight groups with G5 displaying the worst overall survival, while the opposite group Tlo/Ihi/Slo (G4) had the best prognosis. Several oncogenic signaling pathways influenced on T-score and I-scores but not S-score, and PI3K pathway alteration correlated with poor prognosis in accordance with higher T-score and lower I-score. Moreover, the TIME score predicted the efficacy of ICI in patients with melanoma. CONCLUSION: The TIME score capturing complex interactions among tumor proliferation, antitumor immunity and immunosuppression could be useful for prognostic predictions or selection of treatment strategies in patients with lung cancer.

[Identification of neoantigens and development of antigen-specific immunotherapy].

Cancer cells harboring somatic mutations give rise to neoantigens, which are immunologically foreign in nature to be distinguished from itself, showing high immunogenicity and, thus, induce specific T-cell responses against cancer. Therefore, neoantigens are expected to be promising targets for anti-cancer immunotherapy. The general methods used to identify candidate neoantigens are as follows: (1) non-synonymous mutations are identified by whole exome and RNA sequencing; (2) neoantigens from the mutations are predicted based on in silico MHC ligand prediction algorithm; (3) specific T-cell responses toward the candidate neoantigens are verified using tumor infiltrating T cells or peripheral blood mononuclear cells. In hematological malignancy, several neoantigens have been identified as an important treatment target. In contrast with solid malignancies, the occurrence of frameshift mutations and fusion genes producing neoantigens are high. A shared neoantigen derived from frameshift mutation of nucleophosmin I, which is often observed in acute myeloid leukemia, was reported to induce specific immune responses in vitro and in vivo. We should examine neoantigens as possible target of novel immunotherapy despite several issues to be addressed for clinical application.

Impact of Sarcopenia on Surgical Outcomes in Non-small Cell Lung Cancer.

BACKGROUND: Sarcopenia influences overall survival (OS) and tumor progression in non-small cell lung cancer (NSCLC) patients. However, the impact of postoperative complications and the outcome of limited surgery have not been highlighted. Therefore, the aim of this study is to elucidate the prognostic impact of sarcopenia on surgical outcomes. PATIENTS AND METHODS: This study included NSCLC patients who had undergone lung cancer resection between 2007 and 2017. Sarcopenia was confirmed based on computed tomography of the cross-sectional area of the psoas muscle at the third lumbar vertebra level. We used propensity score-matched analysis to elucidate the impact of sarcopenia on postoperative complications and limited surgery. RESULTS: A total of 391 patients were enrolled, including 198 sarcopenic patients. Multivariate analysis showed that sarcopenia was an independent unfavorable prognostic factor associated with OS and recurrence-free survival [hazard ratio (HR), 3.33, P < 0.001; HR, 2.76, P < 0.001, respectively]. Regarding the incidence of postoperative complications, there was no difference between sarcopenic and nonsarcopenic patients (69/198 versus 55/193, P = 0.19). After propensity score matching, among patients without sarcopenia, the 5-year OS was lower in those with limited surgery than in those with standard surgery (70.7% vs. 96.4%, P = 0.011). In contrast, among sarcopenic patients, there was no difference in the 5-year OS between patients with limited surgery and those with standard surgery (53.2% vs. 60.7%, P = 0.66). CONCLUSIONS: Sarcopenia is a prognostic predictor for poor OS and may contribute to the selection of limited surgery for sarcopenic patients. Preoperative assessment of sarcopenia may provide clinically important information.

The Prognostic Impact of Pericardial Fat Volumes in Resected Non-small Cell Lung Cancer.

BACKGROUND: Pericardial fat (PF) has not been considered a prognostic biomarker for overall survival (OS) in lung cancer. This study was designed to elucidate the impact of PF on prognosis of resected non-small cell lung cancer patients. METHODS: We retrospectively reviewed a total of 349 patients who underwent lung resection and received high-resolution computed tomography in our institute. PF volume was calculated. PF extended vertically from the diaphragm to the bifurcation of the right main pulmonary artery. Propensity score matched analysis was used to compare OS between the high- and low-PF groups. RESULTS: PF volume increased according to body mass index (p < 0.001). Receiver operating characteristics (ROC) curve analysis for 3-year OS showed the possibility of better predictivity of PF than body-mass index (area under the curve, 0.66 vs. 0.61, p = 0.010). Cutoff level of PF volume was determined based on the ROC with 122 cm3. Five-year OS was poorer in the low-PF group (63.5% vs. 73.4%; p = 0.002). After propensity score matching, each group consisted of 89 cases. Five-year OS was poorer in the low-PF group (66.5% vs. 82.7%; p = 0.008). A Cox proportional hazards model showed low-PF volume was associated with poorer OS (hazard ratio, 2.14; p = 0.009). The number of respiratory-related deaths was higher in the low-PF group (10/89 vs. 2/89, p = 0.032). CONCLUSIONS: Low-PF volume may be associated with poor OS with an increase in the number of respiratory-related deaths. Patients with low-PF volume require careful follow-up after surgery.

Long-term impact of complications after lung resections in non-small cell lung cancer.

BACKGROUND: Postoperative complications after lung resection are common and fatal. The immediate effects of postoperative complications are related to poor prognosis; however, the long-term effects have not been assessed. Thus, this investigation aimed to clarify the long-term effects of postoperative complications among patients with resected non-small cell lung cancer (NSCLC). METHODS: This retrospective cohort study included 345 patients with resected NSCLC from a single institution. We used the Clavien-Dindo classification to classify postoperative complications. Postoperative complications were defined as complications with a Clavien-Dindo grade of ≥2. The Kaplan-Meier method was used to evaluate survival. Prognostic factors were analyzed using a Cox proportional hazard model. RESULTS: There were 110 patients with postoperative complications (31.9%). The 5-year overall survival (OS), recurrence-free survival (RFS), and cause-specific survival (CSS) rates were significantly lower in patients with complications than in those without complications [OS: 66.1%, 95% confidence interval (CI): 55.4-74.8% vs. 78.0%, 95% CI: 71.8-83.1%, P=0.001; RFS: 48.8%, 95% CI: 38.1-58.7% vs. 70.8%, 95% CI: 64.2-76.4%, P<0.001; CSS: 82.7%, 95% CI: 72.8-89.3% vs. 88.2%, 95% CI: 82.8-92.0%, P=0.005]. The 5-year OS was lower in the pulmonary complication group than in the other complication group (58.1%, 95% CI: 40.0-72.4% vs. 70.5%, 95% CI: 56.6-80.6%, P=0.033). Postoperative complications were indicated as a poor prognostic factor for OS (hazard ratio, 1.67; 95% CI: 1.11-2.53; P=0.002). CONCLUSIONS: Postoperative complications were associated with unfavorable OS because of the worse prognosis of postoperative pulmonary complications.

Postoperative C-reactive Protein Is a Predictive Biomarker for Survival After Non-small Cell Lung Cancer Resection.

BACKGROUND/AIM: Preoperative C-reactive protein (CRP) is well recognized as a prognostic factor of non-small cell lung cancer (NSCLC). The present study aimed to elucidate the prognostic impact of postoperative CRP in patients with NSCLC following lung resection. PATIENTS AND METHODS: We retrospectively reviewed 336 patients with NSCLC treated with lung resection. CRP levels were measured at postoperative week 6 (CRP6w; range: 4-8 weeks). Patients were divided into two groups based on CRP6w median value (5.0 mg/l); the 5-year overall survival (OS) as well as the recurrence-free survival (RFS) was evaluated in both groups. RESULTS: Five-year OS and RFS were worse in the high-CRP6w group than in the low-CRP6w group (62.9% vs. 82.9%; p<0.001, 48.4% vs. 76.1%; p<0.001, respectively). Subgroup analysis for pathological stage I and ≥II also revealed worse OS in the high-CRP6w group. Multivariate analysis revealed an association between high CRP6w and worse OS (hazard ratio, 2.23; p<0.001). CONCLUSION: CRP6w may serve as a prognostic biomarker in patients with resected NSCLC.

[ST Segment Elevation on Electrocardiogram (ECG) during Pleural Lavage with Distilled Water;Report of a Case].

Pleural lavage with distilled water is often employed in lung resection to eliminate malignant cells. Here we report a case of transient ST segment elevation on electrocardiogram (ECG) during pleural lavage with distilled water. A 73-year-old female was referred to our hospital because of an abnormal shadow on a chest roentogenogram. Chest computed tomography scan revealed a mass in left S4+5 segment of left upper lobe. It was proved to be adenocarcinoma of the lung by transbronchial lung biopsy and she underwent left upper lobectomy. During pleural lavage with distilled water, ST segment was elevated on ECG. In this case, it was because that the pericardium was excised and the myocardium was exposed to distilled water during pleural lavage.

Impact of the favorable prognosis of patients with lung cancer adjoining bullae.

BACKGROUND: Lung cancer adjoining bullae (LC-AB) is an uncommon manifestation. The clinical characteristics and prognosis of LC-AB remain unclear. The aim of this study is to investigate the clinical features and overall survival (OS) of patients with LC-AB following lung resection compared to non-LC-AB group. METHODS: We retrospectively investigated 291 consecutive patients with lung cancer who underwent curative resection in a single institution between April 2007 and March 2015. A total of LC-AB was 52 patients. LC-AB was determined using thin slice computed tomography (CT) imaging and pathological findings. Survival analysis was calculated using the Kaplan-Meier method. We used a Cox proportional hazards model for the univariate and multivariate analysis to identify prognostic factors. RESULTS: The LC-AB group showed a higher frequency of younger patients (P=0.017), former or current smokers (P=0.011), men (P=0.021), tumor location in the upper lobe (P=0.031), moderately or poorly differentiated tumor histology (P<0.001), pleural indentation (P=0.007), and non-adenocarcinoma histology (P=0.016) than the non-LC-AB group. The 5-year survival and recurrence-free survival (RFS) rates were significantly higher in the LC-AB group than the non-LC-AB group (88.5% vs. 74.9%, P=0.010, 75.4% vs. 61.3%, P=0.030, respectively). Multivariate analysis using a Cox proportional hazard model of OS showed that LC-AB was an independent prognostic factor [hazard ratio (HR): 0.30, 95% confidence interval (CI): 0.12-0.77, P=0.012]. CONCLUSIONS: Patients with LC-AB had better OS than those with non-LC-AB. Thus, LC-AB may be an independent favorable prognostic factor following curative resection.

Impact of Postoperative Pneumonia Developing After Discharge on Long-Term Follow-up for Resected Lung Cancer.

BACKGROUND: Postoperative nosocomial pneumonia is a common immediate complication following lung resection. However, the incidence and mortality of pneumonia developing after discharge (PDAD) for lung-resected patients during long-term observation remain unclear. The aim of this study was to investigate the clinical features of PDAD in patients with resected lung cancer. METHODS: We conducted a retrospective cohort study of 357 consecutive patients with lung cancer who had undergone lung resection at a single institution, between April 2007 and December 2016. The clinical characteristics, pathological features, and overall survival were analyzed. Propensity score matched analysis was used for the evaluation of overall survival between PDAD and non-PDAD groups with adjusted relevant confounding factors. RESULTS: PDAD was observed in 66 patients (18.5%). The cumulative incidence of PDAD was 14.9% at 3 years and 21.6% at 5 years. Mortality of PDAD was 30.3%. Multivariate analysis demonstrated that the risk factors for PDAD were age (OR 1.07; P = 0.005), oral steroid use (OR 5.62; P = 0.046), and lower-lobe resection (OR 1.87; P = 0.034). After propensity score matching, 52 patients with PDAD and 52 patients without it were compared. The incidence of PDAD resulted in a worse 5-year overall survival (56.1 vs. 69.3%; P = 0.024). The Cox proportional hazards model indicated that PDAD was associated with poor overall survival (HR 1.99, P = 0.027). CONCLUSIONS: Our findings revealed a high incidence and mortality of PDAD among patients who had undergone lung resection with long-term follow-up. Therefore, PDAD could be associated with poorer overall survival.