[18F]FDG PET-CT radiomics signature to predict pathological complete response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer: a multicenter study.

OBJECTIVES: This study aims to develop and validate a radiomics model based on 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG PET-CT) images to predict pathological complete response (pCR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: One hundred eighty-five patients receiving neoadjuvant chemoimmunotherapy for NSCLC at 5 centers from January 2019 to December 2022 were included and divided into a training cohort and a validation cohort. Radiomics models were constructed via the least absolute shrinkage and selection operator (LASSO) method. The performances of models were evaluated by the area under the receiver operating characteristic curve (AUC). In addition, genetic analyses were conducted to reveal the underlying biological basis of the radiomics score. RESULTS: After the LASSO process, 9 PET-CT radiomics features were selected for pCR prediction. In the validation cohort, the ability of PET-CT radiomics model to predict pCR was shown to have an AUC of 0.818 (95% confidence interval [CI], 0.711, 0.925), which was better than the PET radiomics model (0.728 [95% CI, 0.610, 0.846]), CT radiomics model (0.732 [95% CI, 0.607, 0.857]), and maximum standard uptake value (0.603 [95% CI, 0.473, 0.733]) (p < 0.05). Moreover, a high radiomics score was related to the upregulation of pathways suppressing tumor proliferation and the infiltration of antitumor immune cell. CONCLUSION: The proposed PET-CT radiomics model was capable of predicting pCR to neoadjuvant chemoimmunotherapy in NSCLC patients. CLINICAL RELEVANCE STATEMENT: This study indicated that the generated 18F-fluorodeoxyglucose positron emission tomography-computed tomography radiomics model could predict pathological complete response to neoadjuvant chemoimmunotherapy, implying the potential of our radiomics model to personalize the neoadjuvant chemoimmunotherapy in lung cancer patients. KEY POINTS: • Recognizing patients potentially benefiting neoadjuvant chemoimmunotherapy is critical for individualized therapy of lung cancer. • [18F]FDG PET-CT radiomics could predict pathological complete response to neoadjuvant immunotherapy in non-small cell lung cancer. • [18F]FDG PET-CT radiomics model could personalize neoadjuvant chemoimmunotherapy in lung cancer patients.

Penetrating chest trauma caused by a falling metallic bar: a case report.

Background: Impaling injuries to the chest are relatively rare and often lethal. Initial evaluation, resuscitation, and surgical planning can be challenging for emergency physicians and surgeons. Chest trauma can be classified as either closed or penetrating, depending on whether or not the pleural cavity is open. Penetrating objects entering chest cavity frequently make an entrance and exit and are often accompanied by visceral/vascular damage. Open thoracotomy or video-assisted thoracic surgery (VATS) are considered the first-line approaches for severe penetrating chest trauma. Case Description: A 63-year-old male patient sustained a penetrating chest trauma caused by a T-shaped metallic bar falling from a height of 16 meters above the ground. After laboratory and imaging tests, as well as pre-operative preparation, the object was pulled out from the entry site after disinfection with surgical standby. Closed chest tube drainage was promptly performed, with chest tubes inserted through the entry and exit sites. The patient was discharged on postoperative day 14 in a good condition. Regular telephone follow-ups over 3 years showed that the patient recovered well after discharge. Conclusions: For penetrating non-cardiac chest trauma patients in stable condition, it is necessary to complete an exhaustive imaging evaluation to determine the specific position of the foreign body and identify any injuries to major vessels and organs. If the condition permits, direct removal of foreign bodies is allowed, ideally under VATS control. Surgeons should evaluate the best option for each case based on the available resources.

Multiple bronchiolar adenomas/ciliated muconodular papillary tumors of the bilateral lung with tumor budding and potential malignant transformation into squamous cell carcinoma: a case report and literature review.

Background: Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is a rare lung tumor characterized by ciliated, mucous and basal cells. Recently, some cases of driver mutations or malignant transformations have been reported. However, the nature of BA/CMPT remains controversial. Here, we report a case of bilateral pulmonary multiple BAs with tumor budding and squamous metaplasia. Case Description: A 55-year-old man presented with multiple small nodules in the lower lobes of the bilateral lungs on physical examination 7 years prior. During the past 3 years of regular follow-up, some nodules had slightly enlarged. Because the nodules were mostly solid, the patient underwent video-assisted thoracoscopic segmentectomy of the left lower lung. A postoperative pathological diagnosis of BA was made. In all lesions, the fusion and mutation of major driver genes were not detected by next-generation sequencing (NGS). No recurrence or metastasis was observed after 37 months of follow-up. Notably, all five resected lesions were BA/CMPT, and one lesion was accompanied by squamous metaplasia and tumor budding. Conclusions: Our report found that BA/CMPT with squamous metaplasia and tumor budding has the potential to transform into lung squamous cell carcinoma, expanding its connection with malignant transformation. Smoking may be one of the risk factors. We also found that BA/CMPT can be multiple lesions rather than a solitary lesion.

LncRNA RP11­805J14.5 functions as a ceRNA to regulate CCND2 by sponging miR­34b­3p and miR­139­5p in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common lung cancer with high incidence. The prognosis of LUAD is poor due to its aggressive behavior. Long non­coding RNAs (lncRNAs) have been reported as a key modulator on LUAD progression. Therefore, the present study aimed to clarify the molecular mechanism of lncRNAs in LUAD development. The expression of lncRNA RP11­805J14.5 (RP11­805J14.5) in LUAD tissues and cells was quantified based on the data in The Cancer Genome Atlas (TCGA). Cell viability was determined using Cell Counting Kit­8 method. Apoptotic cells were sorted and determined by flow cytometry. Cell migration and invasion abilities were detected by the Transwell assay. Luciferase reporter experiment and RNA pull­down assay were utilized to determine the interactions between RP11­805J14.5, microRNA (miR)­34b­3p, miR­139­5p, and cyclin D2 (CCND2). A xenograft tumor was established to determine tumor growth in vivo. RP11­805J14.5 was highly expressed in LUAD and associated with poor survival of LUAD patients. Knockdown of RP11­805J14.5 suppressed LUAD cell growth, invasion, migration and tumor growth, indicating that RP11­805J14.5 is an important regulator of LUAD. Our study demonstrated that the regulation of RP11­805J14.5 on LUAD was mediated by CCND2 whose expression was regulated by sponging miR­34b­3p and miR­139­5p. The expression of RP11­805J14.5 was increased in LUAD, and the knockdown of RP11­805J14.5 expression suppressed LUAD cell growth, invasion and migration by downregulating CCND2 by sponging miR­34b­3p and miR­139­5p, indicating that RP11­805J14.5 could be a prospective target for LUAD therapy.

Circular RNA circFOXO3 facilitate non-small cell lung cancer progression through upregulating HMGB3 via sponging miR-545-3p/miR-506-3p.

PURPOSE: Circular RNAs (circRNAs) have emerged as a pivotal regulatory element in the progression of human cancers. Being an important member of circRNAs, circFOXO3 has been implicated in tumor invasion or metastasis of non-small cell lung cancer (NSCLC); however, the molecular mechanism underlying this promoting effect remains an enigma. The present study aims to study the function of circFOXO3 and dissect the relevant intracellular network in the progression and metastasis of NSCLC. METHODS: Quantitative real time PCR (RT-qPCR) assay and Western blotting were used to quantify the levels of RNAs and proteins respectively. starBase v2.0 and luciferase assay were used to validate the target of circRNAs or miRNAs. Cell Counting Kit-8 (CCK-8) assay was adopted to examine cell viability. Transwell was used to determine cell invasion and migration. Xenograft model was established to detect tumor growth. RESULTS: RT-qPCR showed that circFOXO3 was overexpressed in NSCLC cells and tissues. Knockdown of circFOXO3 not only inhibited NSCLC cell proliferation, migration and invasion in vitro but also suppressed tumor growth in vivo. starBase v2.0 and luciferase assay results collectively suggested that circFOXO3 sponged miR-545-3p and miR-506-3p. Dual-inhibition of circFOXO3 and its target miRNAs suppressed the reduction of cell proliferation, migration and invasion induced by siRNA of circFOXO3 (si-circFOXO3), demonstrating that the effect of circFOXO3 on NSCLC was dependent on sponging miR-545-3p and miR-506-3p. Further bioinformatic analysis and biochemistry experiments revealed that miR-545-3p and miR-506-3p regulated the expression of a family member of high-mobility group box, HMGB3. CONCLUSION: Here, we show thatcircFOXO3 in NSCLC promotes the proliferation, migration and invasion of NSCLC cells, thereby promoting tumor growth. We further find that circFOXO3 sponges miR-545-3p/miR-506-3p that bind to 3'-UTR of HMGB3 mRNA, which constitutes the major network fulfilling the circFOXO3's promoting effect. Therefore, we proposed that circFOXO3 could be a potential therapeutic target for NSCLC.

A patient with metastatic non-small cell lung cancer who received pembrolizumab monotherapy after stereotactic body radiotherapy had progression-free survival of nearly 5 years: a case report.

Lung cancer is a malignancy with the highest morbidity and mortality in the world. Radiotherapy, chemotherapy, targeted therapy, and immunotherapy have been widely used to treat metastatic non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT), also known as stereotactic ablation radiotherapy (SABR), can precisely deliver a high dose of radiation to a target in a limited area. SBRT has been established as the standard treatment for patients with early NSCLC who are unsuitable for operation or refuse surgery and patients with oligometastatic NSCLC who are not suitable for surgery. As an immunologic agent, pembrolizumab has been approved to treat metastatic NSCLC in certain countries, including China and the United States. Increased tumor proportion score (TPS) can reduce pembrolizumab's immunotherapeutic effect, while SBRT can reduce TPS and enhance immunotherapy efficacy. However, there have been no reports in China on metastatic NSCLC patients who have received pembrolizumab monotherapy after stereotactic body radiotherapy (SBRT). Here, we present a case of progression-free survival (PFS) of nearly 5 years with pembrolizumab monotherapy after SBRT for metastatic NSCLC. This case is the patient with the most prolonged medication duration and who experienced the most efficacious treatment among the patients with metastatic NSCLC reported in the Chinese literature.

Prognostic impact of lymphadenectomy on outcomes of sublobar resection for non-small cell lung cancer ≤1 or >1 to 2 cm.

BACKGROUND: Lymphadenectomy is an important part of surgical treatment for non-small cell lung cancer (NSCLC). However, the prognostic impact of lymph node (LN) dissection for patients with NSCLC ≤1 and >1 to 2 cm who underwent sublobar resection is still unclear. METHODS: A group of patients numbering 7,627 with NSCLC 2 cm or less who underwent sublobar resection were identified from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and November 2015. The overall survival (OS) and lung cancer-specific survival (LCSS) were evaluated among patients who had undergone dissection of ≥4 LNs, 1 to 3 LNs or who had no-LN dissection; log-rank and Cox proportional-hazards regression analyses were used for the evaluation. RESULTS: Patients with NSCLC ≤2 cm who underwent ≥4 LNs dissection had better OS and LCSS compared with those who underwent dissection of 1 to 3 LNs or who had no-LN dissection after sublobar resection. Subgroup analysis showed that dissection of ≥4 LNs had better OS and LCSS than those of 1 to 3 LNs dissection in NSCLC >1 to 2 cm, whereas had similar OS and LCSS in NSCLC ≤1 cm. Multivariate Cox analysis showed that dissection of 1 to 3 LNs was not an independent risk factor of OS and LCSS than dissection of ≥4 LNs in NSCLC ≤1 cm after sublobar resection. CONCLUSIONS: The extent of LN dissection is associated with the survival outcomes in patients with NSCLC ≤2 cm after sublobar resection. Dissection of ≥4 LNs should be recommended for NSCLC >1 to 2 cm, whereas surgeons can rely on surgical skills and patient profiles to decide ≥4 LNs or 1 to 3 LNs dissection for NSCLC ≤1 cm during sublobar resection.

Knockdown of TOR signaling pathway regulator suppresses cell migration and invasion in non-small cell lung cancer via the regulation of epithelial-to-mesenchymal transition.

Non-small cell lung cancer (NSCLC) is one of the most common cancer types worldwide. Previous studies have indicated that TOR signaling pathway regulator (TIPRL) is involved in the progression of NSCLC. However, the underlying mechanisms of the role of TIPRL in regulating NSCLC metastasis have remained largely elusive. In the present study, the expression pattern of TIPRL in NSCLC was analyzed using The Cancer Genome Atlas (TCGA) dataset. Furthermore, Kaplan-Meier curve analysis was performed to evaluate the prognostic value of TIPRL in NSCLC, using the Kaplan-Meier Plotter and TCGA datasets. Loss-of-function assays were performed to determine the effects of TIPRL on cell migration and invasion. The results suggested that TIPRL was upregulated in NSCLC and positively associated with an advanced Tumor-Node-Metastasis stage. A higher expression level of TIPRL was associated with shorter overall and disease-free survival times in patients with NSCLC. To the best of our knowledge, the present study was the first to report that TIPRL acts as a metastasis promoter in NSCLC. Silencing of TIPRL suppressed A549 cell migration and invasion. Mechanistically, the present study indicated that TIPRL knockdown significantly promoted epithelial-cadherin expression, whereas it suppressed twist and vimentin expression in A549 cells. In conclusion, the present analysis suggested that TIPRL may serve as a biomarker for the prognosis of NSCLC and as a future target for its treatment.

YRDC is upregulated in non-small cell lung cancer and promotes cell proliferation by decreasing cell apoptosis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality worldwide. yrdC N6-threonylcarbamoltransferase domain containing protein (YRDC) has been demonstrated to be involved in the formation of threonylcarbamoyladenosine in transfer ribonucleic acid. However, the molecular mechanisms underlying NSCLC progression remain largely unclear. The present study revealed that YRDC was upregulated in NSCLC samples compared with adjacent non-cancerous tissues by analyzing datasets obtained from the Gene Expression Omnibus and The Cancer Genome Atlas. Higher expression of YRDC was associated with overall survival time and disease-free survival time in patients with NSCLC, particularly in lung adenocarcinoma. Furthermore, knockdown of YRDC in NSCLS cell lines significantly suppressed cell growth and cell colony formation in vitro. Additionally, the results demonstrated that silencing of YRDC induced apoptosis of A549 cells. Then, the protein-protein interaction networks associated with yrdC N6-threonylcarbamoltransferase domain containing protein (YRDC) in NSCLC were subsequently constructed to investigate the potential molecular mechanism underlying the role of YRDC in NSCLC. The results revealed that YRDC was involved in the regulation of spliceosomes, ribosomes, the p53 signaling pathway, proteasomes, the cell cycle and DNA replication. The present study demonstrated that YRDC may serve as a novel biomarker for the prognosis prediction and treatment of NSCLC.

Lobectomy with high-position single-intercostal two-port video-assisted thoracoscope for non-small cell lung cancer is a safe and effective surgical procedure.

BACKGROUND: High-position single-intercostal two-port video-assisted thoracic surgery (VATS) technique has been used for thoracic diseases. It can effectively avoid postoperative chronic pain compared with the traditional three-port VATS. This study aimed to evaluate the safety and efficacy of high-position single-intercostal two-port video-assisted thoracoscopic lobectomy. METHODS: From June 2014 to December 2018, a total of 474 patients in our hospital with non-small cell lung cancer (NSCLC) underwent lobectomy with a high-position single-intercostal two-port video-assisted thoracoscope. A retrospective study of these patients was conducted, and follow-up was performed to analyze the patients' 3- and 5-year survival rates. RESULTS: Of the total number of patients, 27.6%, 41.4%, and 31% underwent surgery between the third, fourth, and fifth intercostals, respectively. During the operation, 31 patients were converted to open surgery or three-port thoracoscopic surgery. The average surgical time was 160.9±44.9 min, the average postoperative hospital stay was 5.6±3.4 days, the incidence of postoperative complications was 7.2%, and the average number of lymph nodes resected was 13.6±5.3. The 3-year overall survival (OS) rate of IA1, IA2, IA3, IB, IIA, IIB and IIIA was 99.0%, 98.6%, 96.3%, 91.2%, 85.7%, 66.7%, and 60.8%, respectively. Meanwhile, the 5-year OS rate of IA1, IA2, IA3, IB, and IIIA was 99.0%, 94.5%, 87.5%, 85.5%, and 43.3%, respectively. CONCLUSIONS: Lobectomy with a high-position single-intercostal two-port video-assisted thoracoscope for NSCLC is a safe and effective surgical procedure.

Case Report: Osimertinib achieved remarkable and sustained disease control in an advanced non-small-cell lung cancer harboring EGFR H773L/V774M mutation complex.

Missense mutations in EGFR exon 20 are rare in non-small-cell lung cancer (NSCLC), and mostly insensitive to the first generation tyrosine kinase inhibitors (TKIs) of EGFR. However, their responses to the third generation TKI are unclear. Here, we reported a patient with advanced NSCLC harboring a rare EGFR H773L/V774M mutation complex. Although he was irresponsive to the first generation TKI gefitinib, he demonstrated sustained disease control to osimertinib, suggesting that this complex is an activating mutation of EGFR and can be suppressed by osimertinib. The follow-up genetic profiling revealed multiple acquired new mutations that might be related to his resistance to osimertinib. This finding would provide valuable experience for future treatment of the same mutations.