Objective: This study aimed to determine the optimal surgical procedure for early-stage pulmonary carcinoids (PCs). Background: PCs, comprising typical carcinoids (TCs) and atypical carcinoids (ACs), are rare low-grade malignant tumors. We determine the optimal surgical management for early-stage PCs using data from the Surveillance, Epidemiology, and End Results registry. Methods: Clinical and survival data of patients with early-stage PC tumors with a diameter ≤3 cm were retrieved. The Kaplan-Meier method and logrank tests were used to assess the differences in overall survival (OS). Subgroup analyses were also performed. To reduce the inherent bias of retrospective studies, two propensity score matching (PSM) analysis with (PSM2) or without (PSM1) consideration of lymph node assessment were performed. Results: In total, 2934 patients with PCs, including 2741 (93.42%) with TCs and 193 (6.58%) with ACs, were recruited. After PSM1 analysis, TC patients in the lobectomy group had a significantly better OS than those in the sublobar resection group (P = 0.0067), which is more remarkable for patients with a tumor diameter of 2 cm < T ≤ 3 cm (P = 0.0345) and those aged < 70 years (P = 0.0032). However, survival benefits were not found after PSM2 analysis which balanced lymph node assessment. In multivariate cox analysis, age < 70 years, female, TC histology and adequate lymph node assessment were associated with better OS. Conclusions: Sublobar resection may not significantly compromise the longterm oncological outcomes in early-stage PCs ≤3 cm in size if lymph node assessment is performed adequately. Further validation in large randomized clinical trials is warranted.

A ciliated muconodular papillary tumor (CMPT) or bronchiolar adenoma (BA) is a rather rare and unique type of lung tumor characterized by tripartite cellular components with a papillary‐predominant structure including ciliated columnar cells, mucinous cells, and basal cells. Here, we present the case of a 64‐year‐old woman who was diagnosed with CMPT in our center. In addition to reporting the clinicopathological characteristics of this case, we also conducted whole exome sequencing (WES) to explore the underlying mechanism. According to current evidence, CMPTs tends to be benign or of low grade malignancy. However, this requires further validation.

Crizotinib showed significant antitumor effect in patients with advanced ROS1‐rearranged non‐small cell lung cancers (NSCLC). Most recently, many studies have explored the feasibility and efficacy of target therapy for perioperative application in NSCLC. Here, we describe a female patient who was diagnosed with stage IIIB lung adenocarcinoma exhibiting a CCDC6‐ROS1 rearrangement by high‐throughput sequencing. The tumor and lymph nodes showed durable response after the treatment of crizotinib. Given that a radiological downstaging was indicated, a right lower lobectomy and systemic lymphadenectomy were successfully performed. The pathological response was 60% and the tumor, nodes, and metastases (TNM) stage was ypT2bN0M0. The PD‐L1 expression and activity of immunological cells were also investigated.

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a structure of covalently closed continuous loops, which can regulate gene expression by acting as a microRNA sponge or through other mechanisms. Recent studies have identified that the expression of candidate circRNAs are dysregulated in various tumors and hence are considered as promising diagnostic or therapeutic targets across cancer types. However, the expression and function of circRNAs in lung adenocarcinoma (LUAD) remains unclear. In this article, we investigated the expression of circRNAs in LUAD via MiOncoCirc, which is the first and comprehensive database characterizing circRNAs across >2,000 cancer samples using an exome capture RNA sequencing. We identified seven abnormally expressed circRNAs in LUAD, including circCDR1-AS, circHIPK3, circFNDC3B, circPCMTD1, circRHOBTB3, circFAM13B, and circMAN1A2, as well as conducted a literature review about the function and features of these circRNAs. Previous studies have demonstrated that circCDR1-AS, circMAN1A2, and circHIPK3 were upregulated and significantly correlated with a poor survival, or promoted the tumor progression in lung cancer, whereas other circRNAs have not been fully explored. Besides, we reviewed all the publications regarding circRNAs and LUAD, and noticed that the dysregulation of these circRNAs impacts the development of LUAD through a variety of regulatory mechanisms. In conclusion, the underlying mechanisms of aberrant expression and functions of circRNAs in LUAD are worthy of being further investigated.

IntroductionPrevious studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as biomarker for poor prognosis and survival in advanced-stage non-small cell lung cancer (NSCLC) patients. However, the merit of PD-L1 expression to predict the prognosis of early stage NSCLC patients who underwent complete resection remains controversial. In the present study, we performed a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in patients with early stage resected NSCLC.MethodsElectronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched until July 23 2020 for studies evaluating the expression of PD-L1 and the prognosis of resected NSCLCs. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also assessed.ResultsA total of 15 studies involving 3,790 patients were considered in the present meta-analysis. The pooled HR indicated that PD-L1 expression related to a much shorter DFS (HR = 1.56, 95% CI: 1.18–2.05, p &lt; 0.01), as well a significantly worse OS (HR = 1.68, 95% CI: 1.29–2.18, p &lt; 0.01). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male vs. female: OR = 1.27, 95% CI:1.01–1.59, p = 0.038), histology (ADC vs. SCC: OR = 0.54, 95% CI:0.38–0.77, p = 0.001), TNM stage (I vs. II–III: OR = 0.45, 95% CI:0.34–0.60, p = 0.000), smoking status (Yes vs No: OR = 1.43, 95% CI:1.14–1.80, p = 0.002) and lymph node metastasis (N+ vs N−: OR = 1.97, 95% CI:1.26–3.08, p = 0.003).ConclusionsThe results of this meta-analysis suggest that PD-L1 expression predicts an unfavorable prognosis in early stage resected NSCLCs. The role of personalized anti-PD-L1/PD-1 immunotherapy in the adjuvant settings of resected NSCLC warrants further investigation.

A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

A comprehensive search regarding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy or combination therapy in neoadjuvant settings of 11 types of solid cancer was performed using the PubMed, Cochrane and Embase databases, and the abstracts of various conferences were screened. Data presented in 99 clinical trials indicated that preoperative treatment with PD-1/PD-L1 combined therapy, particularly immunotherapy plus chemotherapy, could achieve a higher objective response rate, a higher major pathologic response rate and a higher pathologic complete response rate, as well as a lower number of immune-related adverse events compared with PD-1/PD-L1 monotherapy or dual immunotherapy. Although PD-1/PD-L1 inhibitor combination caused more treatment-related adverse events (TRAEs) in patients, most of the TRAEs were acceptable and did not cause marked delays in operation. The data suggest that patients with pathological remission after neoadjuvant immunotherapy exhibit improved postoperative disease-free survival compared with those without pathological remission. Further studies are still required to evaluate the long-term survival benefit of neoadjuvant immunotherapy.

Lung cancer is the most common primary malignancy and tends to metastasize to the brain.A multimodal approach, including systematic therapy (targeted therapy, chemotherapy, immunotherapy) and local consolidative therapy (surgical intervention, radiation therapy, ablation therapy), is essential for treatment of oligometastatic lung cancer. The systemic immunotherapy has been shown to increase response rate and survival, which then has the potential benefit of making localized treatment more feasible for some cases of oligometastatic cancer. We present a 62-year-old male with stage IVB lung adenocarcinoma with five metastases in the brain. Molecular testing exhibited KRAS and TP53 co-mutation, with negative PD-L1 expression. The patient received six cycles of platinum-based chemotherapy plus pembrolizumab and minimally invasive lobectomy, followed by maintenance therapy with pemetrexed and pembrolizumab.The patient achieved complete disease remission, with no sign of recurrence for 22 months post-treatment.Moreover, we investigated PD-L1 expression and infiltration of immunological cells in biopsy tissue and surgical specimen prior to and after immuno-chemotherapy using multiple immunohistochemistry stains.The different infiltration levels of immune cells for TP53 and KRAS co-mutation were also explored using The Cancer Genome Atlas (TCGA) database and Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). To our knowledge, this is the first reported case in which a brain oligometastatic non-small cell lung carcinoma (NSCLC) patient has achieved a complete response after immuno-chemotherapy plus local surgical resection.