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Currently, only a few options are available for the treatment of patients with small-cell lung cancer (SCLC) after the failure of first-line platinum-based chemotherapy. The present study aimed to evaluate the efficacy and safety of apatinib plus chemotherapy for second-line treatment of advanced SCLC.This prospective clinical trial recruited patients treated with apatinib plus second-line chemotherapy until disease progression or intolerable toxicity. Logrank test power analysis was used for calculating samples. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.A total of 29/31 enrolled patients were available for response evaluation until October 2019. The ORR and DCR were 27.59% (8/29) and 96.55% (28/29), respectively. The median PFS and OS were 7.36 months and 14.16 months, respectively, indicating better efficacy compared with the standard second-line chemotherapies. The most common adverse events (AEs) were neutropenia (41.94%, 13/31), followed by leucopenia (35.48%, 11/31) and thrombocytopenia (25.81%, 8/31). The grade 3-4 AEs occurred in 12 (38.71%) patients, of which neutropenia (19.35%, 6/31), leucopenia (9.68%, 3/31), and proteinuria (6.45%, 2/31) were most common. Patients receiving an initial dose of apatinib 250 mg had a better tolerance.Antiangiogenic therapy plus chemotherapy had encouraging efficacy in advanced SCLC patients, which provides an insight into the current status of second-line therapy in SCLC.

Background There is limited data on the clinical outcome, long‐term survival and tolerability of sequential therapy of first‐line crizotinib followed by alectinib in a real‐world setting for Chinese patients with advanced ALK+ NSCLC. Methods The medical records of patients who received sequential therapy with first‐line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK‐TKIs) were collected from six centers in China. Combined time treatment to failure (C‐TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause. Results A total of 61 patients were included in our study. Fifty‐two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK‐TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow‐up of 34.3 months, C‐TTF was 39.2 months and estimated 5‐year OS was 68.6% in the overall population. Conclusion Sequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely., Sequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits in a Chinese population. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.

Multiple primary lung cancer (MPLC) refers to the simultaneous occurrence of two or more lung primary malignant tumors in one individual. The detection rate of MPLC has increased significantly in recent years, and the distinction between MPLC and lung metastasis has strong clinical significance. Whole exome sequencing (WES) can clearly identify the heterogeneity between MPLC nodules. Here, we report a case of a 50‐year‐old Asian female without a history of smoking. She underwent a lung computed tomography (CT) scan and three ground‐glass nodules (GGNs) were found which were pathologically confirmed as atypical adenomatous hyperplasia (AAH), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA), respectively. We performed WES on the three pulmonary nodules and analyzed the sequencing results. We believe that this is the first published report of a case of “three phases” of lung adenocarcinoma analyzed by WES. Under the same genetic background and internal environment, these three nodules showed significant genetic differences and developed into “three phases” of lung adenocarcinoma. Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets. Key points Significant findings of the study We used WES to analyze the gene mutation status of three tumors in one individual. We found that even if under the same genetic background, AAH, MIA and IA showed significant genetic differences and developed into “three phases” of lung adenocarcinoma. What this study adds Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets., We analyzed the origin and evolution of lung adenocarcinoma based on the WES results of MPLC in one individual. Analysis of the WES results reflects a progressive genomic evolution at the single nucleotide level, which we believe supports the lung adenocarcinoma model from AAH to MIA and ADC. Meanwhile, we explored possible potential driver genes and therapeutic targets.

Multiple primary lung cancers (MPLCs) refers to two or more primary malignant tumors that occur simultaneously or successively in the lung of the same patient. Distinguishing MPLCs from intrapulmonary metastases is important for treatment strategy and prognosis. MPLCs have been considered as having different origins and clonal evolutionary processes. Whole genome sequencing (WGS) and whole exome sequencing (WES) are regarded as an effective way to identify the relationship and differentiation among MPLC nodules. Here, we report the case of a 63‐year‐old MPLC male patient who smoked for 40 years. Two nodules were found on chest computed tomography (CT) scan, which were further confirmed by pathology to be lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC), respectively. WES of the two different nodules was performed, and the results showed that there was a significant genetic difference between the two nodules. Further analysis of the tumor mutation burden (TMB) of the two tumor lesions showed that the TMB of the squamous cell carcinoma was higher than that of the adenocarcinoma, indicating that the squamous cell carcinoma had a higher mutation frequency. According to the pathology and WES sequencing results, MPLCs for this case were regarded as independent of each other, with different origins and clonal evolutionary processes. In this case report, we emphasize that WES should play an important role in determining the origin of MPLC clones, and also make some explorations for the further discovery of new potential driver genes and therapeutic targets., In this case report, we emphasize that WES should play an important role in determining the origin of MPLC clones, and also make some explorations for the further discovery of new potential driver genes and therapeutic targets.

A 61‐year‐old Chinese man with a history of tuberculosis was found to have a large mass in the left lower lobe and multiple ground‐glass nodules (GGNs) on lung computed tomography (CT). Post‐operative pathology showed lung squamous carcinoma in the left lower lobe and mediastinal lymph node metastases, which were confirmed as lung adenocarcinoma. Multiple gene sequencing was performed, and no relationship was observed between the two primary sites. Chemotherapy consisting of four cycles of gemcitabine plus cisplatin were prescribed for this patient after the operation. After a period of two‐year follow‐up, the lung adenocarcinoma was found to have progressed with new metastases in the right cervical lymph nodes which had the same pathology and gene mutation as the metastatic mediastinal lymph nodes removed two years previously. Meanwhile, a primary lesion was found following PET‐CT scan, and the tuberculosis scar was determined as its point of origin. In conclusion, we have found that a tuberculosis scar is a risk factor of lung cancer, especially adenocarcinoma, and more attention should be paid to close monitoring and follow‐up by clinicians.

BACKGROUND Before tyrosine kinase inhibitor (TKI) therapy can be administered in patients with advanced non-small cell lung cancer (NSCLC), EGFR mutation testing is required. However, few studies have evaluated the extent of EGFR testing in real-world practice in China. METHODS A multicenter, observational study of EGFR testing in NSCLC patients in North China was conducted. Treatment-naive patients or those with postoperative recurrent stage IIIB/IV NSCLC were enrolled. The primary objective was EGFR testing rate. Secondary objectives included EGFR mutation status, EGFR testing methods and specimens, factors associated with EGFR testing, and overall survival with or without EGFR testing. RESULTS Overall, 2809 patients with stage IIIB/IV NSCLC were enrolled; 90.78% had adenocarcinoma. The EGFR screening rate was 42.54%. EGFR testing rates were higher in tumor samples obtained by lymph node puncture, and in patients with urban medical insurance, adenocarcinoma, non-smokers, or those located in developed cities (all P < 0.001). The EGFR mutation rate was 46.44%. The most commonly used specimens for EGFR testing were biopsy tumor samples (67.53%). PCR-based methods (72.05%), Sanger sequencing (5.36%), and Luminex liquid chip (5.10%) were the most frequently used testing platforms. Similar positive EGFR mutation rates were achieved with different platforms. TKI therapy was the first-line treatment administered to most EGFR-positive patients (56.22%), and chemotherapy in EGFR-negative patients (84.88%). Overall survival was higher in EGFR-tested than in untested patients (27.50 vs. 19.73 months; P = 0.007). CONCLUSION Real-world EGFR testing rates for NSCLC in North China were relatively low because of clinical and social factors, including medical insurance coverage.

Background Altered expression or function of mouse double minute-2 (MDM2) protein could contribute to lung carcinogenesis; thus, this study investigated MDM2-rs2279744 polymorphism together with other epidemiologic factors for their association with lung cancer risk. Methods A total of 500 lung cancer patients and 500 age and gender-matched healthy controls living in Northeastern China were recruited for genotyping of MDM2-rs2279744. Clinicopathological data was collected and subjected to univariate and multivariate analyses. Results In univariate analysis, the MDM2-rs2279744 G/G genotype versus T/T + T/G genotypes showed a tendency toward a higher incidence of lung cancer in the recessive model (P = 0.043). However, there were no significant differences when it was analyzed by the dominant, additive, or multiplicative models. A significantly increased lung cancer risk was observed associated with lower education level, lower body mass index, cancer family history, prior diagnosis of chronic obstructive pulmonary disease and pneumonia, exposure to pesticide or gasoline/diesel, tobacco smoking, and heavy cooking emissions when assessed by multivariate analyses. Moreover, MDM2-rs2279744 was still a significant risk factor even after incorporating environmental and lifestyle factors. However, there was no association between MDM2-rs2279744 and other factors. Conclusions The MDM2-rs2279744 G/G genotype was associated with a higher lung cancer risk, even after incorporating other epidemiologic factors.

Background and Aim: Bmi-1 is a transcriptional repressor belonging to the Polycomb group and is associated with the cell proliferation and carcinogenesis of a variety of human cancers. The level of Bmi-1 expression correlates with the aggressiveness of many cancers, and is considered an important marker for cancer diagnosis. However, its role in gastric carcinoma is unknown. Methods: We used lentiviral mediated interfering short hairpin RNA to knockdown Bmi-1 expression in gastric carcinoma human gastric cancer cell line (AGS cells), then tested the cell proliferation by MTT assay, rate of colony formation by colony formation assay, cell cycle distribution by fluorescence-activated cell sorting and cell invasiveness by cell invasion assay. To analyze the expression and localization of Bmi-1 in gastric tumor tissues, we further performed the immunohistochemistry analysis on a gastric cancer tissue array. Results: We found that knocking down Bmi-1 led to slower cell growth, lesser cell invasiveness, decelerated colony formation, and altered cell cycle progression. In addition, a positive relationship between nuclear expression of Bmi-1 and gastric cancer was observed, suggesting that nucleus localization of Bmi-1 in the cells may be a novel marker of gastric cancer. Conclusions: Our study highlights critical roles for Bmi-1 in gastric cancer, and suggests that Bmi-1 nuclear localization could be an important marker for the diagnosis of gastric cancer.