Background: Diagnosing and treating synchronous multiple primary lung cancers (sMPLC) are complex and challenging. This study aimed to report real‐world data on the comprehensive diagnosis and treatment of patients with early‐stage sMPLC.Materials and Methods: A single‐center cohort study was carried out and a large number of patients with early‐stage sMPLC were included. A single‐ or two‐stage surgery was performed to remove the primary and co‐existing lesions. The “X” strategies, including ablation, SBRT, and EGFR‐TKIs treatment, were applied to treat the high‐risk residual lesions. Wide panel‐genomic sequencing was performed to assess the genetic heterogeneity of the co‐existing lesions.Results: A total of 465 early‐stage sMPLC patients with 1198 resected lesions were included. Despite most patients being histologically different or harboring different genetic alternations, about 7.5% of the patients had the same histological type and driver gene mutation changes, comprehensive re‐evaluation is thus needed. The “Surgery + X” strategy showed remarkable efficacy and safety in treating multiple lesions. Follow‐up data revealed that the T2 stage (p = 0.014) and the solid presence of a primary lesion (p < 0.001) were significantly related to tumor recurrence. And a T2‐stage primary tumor had a significantly higher rate of developing new lesions after the initial surgery (p < 0.001).Conclusions: In real‐world practice, histopathological and radiological evaluation combined with genetic analyses could be a robust diagnostic approach for sMPLC. The “Surgery + X” treatment strategy showed remarkable efficacy, superiority, and safety in the clinical treatment of early‐stage sMPLC.

Lung adenocarcinoma featured as mixed ground-glass opacity (mGGO) doubled its volume half of the time in comparison with that featured as pure ground-glass opacity (pGGO). The mechanisms underlying the heterogeneous appearance of mGGO remain elusive. In this study, we macro-dissected the solid (S) components and ground-glass (GG) components of mGGO and performed single-cell sequencing analyses of six paired components from three mGGO patients. A total of 19,391 single-cell profiles were taken into analysis, and the data of each patient were analyzed independently to obtain a common alteration. Cancer cells and macrophages were the dominant cell types in the S and GG components, respectively. Cancer cells in the S components, which showed relatively malignant phenotypes, were likely to originate from both the GG and S components and monitor the surrounding tumor microenvironment (TME) through an intricate cell interaction network. SPP1^hi macrophages were enriched in the S components and showed increased activity of chemoattraction, while macrophages in the GG components displayed an active antimicrobial process with a higher stress-induced state. In addition, the CD47–SIRPA axis was demonstrated to be critical in the maintenance of the GG components. Taken together, our study unraveled the alterations of cell components and transcriptomic features between different components in mGGOs.

The role of the epidermal growth factor receptor (EGFR) mutation status testing in lung squamous cell carcinoma (SqCC) remains controversial. Evidence of the effectiveness of osimertinib in SqCC with EGFR T790M mutation is limited. Here, we describe a hitherto unreported case of a stage III SqCC patient with compound mutation of EGFR exon 19 deletion (19Del) and T790M mutation. Pathological complete tumor response was achieved after treatment with osimertinib. We suggest that EGFR mutation testing should be performed in Asian patients who have not been definitively diagnosed with SqCC due to small lung biopsy samples. Osimertinib has shown good efficacy in SqCC harboring a “primary” resistance mechanism (EGFR T790M).Key points: An unreported case of stage III squamous cell carcinoma with synchronous occurrence of EGFR exon 19 deletion (19Del) and T790M mutation. Complete tumor response was achieved after treatment with osimertinib.EGFR mutation testing should be performed in Asian patients who are not definitively diagnosed with SqCC due to small lung biopsy samples. Osimertinib has shown good efficacy in SqCC harboring a “primary” resistance mechanism (EGFR T790M).

Background The increase in the incidence of pulmonary nodules has made computed tomography (CT) screening a requirement for diagnosis and treatment. Small pulmonary nodule detection during video‐assisted thoracoscopic surgery (VATS) or thoracotomy is frequently challenging; however, accurate and efficient localization of nodules is critical for precise resection. Herein, we introduce and evaluate the feasibility and safety of a novel technique for preoperative pulmonary nodule localization. Methods From March 2018 to December 2019, 140 patients with 153 pulmonary nodules measuring <2 cm in diameter were enrolled in this study. Preoperative, CT‐guided localization was performed on each nodule with an injected mixture of tissue adhesive and iohexol. Patient and nodule characteristics, localization data, complications, surgical data, and pathological results were analyzed. Results All 153 nodules in 140 patients were successfully marked preoperatively and detected during surgery (n = 153/153). Mean nodule size was 8.7 ± 2.6 mm, and mean distance from nodule to pleura was 7.9 ± 8.2 mm. The mean procedural time was 8.7 ± 1.0 min. Nine patients (6.4%) underwent two simultaneous nodule localizations and two patients (1.4%) underwent three simultaneous nodule localizations. Pneumothorax (17/140, 12.1%), pain (6/140, 4.3%), and pungent odor (5/140, 3.6%) were the major complications. No patient required further treatment, and no allergic reactions or embolisms were observed. Conclusions Preoperative CT‐guided nodule localization using a mixture of tissue adhesive and iohexol is an efficient technique for localizing small and impalpable pulmonary lesions, including multiple pulmonary nodules. Our study demonstrates that this novel method is safe and straightforward to implement.