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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.

G724S is a rare mutation induced by different generations of tyrosine kinase inhibitors (TKIs). No clinical effective drugs toward G724S mutation have been reported till now. We analyzed the interaction of three drugs (afatinib, gefitinib, osimertinib) with epidermal growth factor receptor (EGFR) from three aspects: the spatial structure of the binding region, the scoring function value, and the interaction force between drug molecules and active center of EGFR. Our results indicate that afatinib remains effective to patients with EGFR Exon19Deletion(Ex19Del) and G724S mutations whereas osimertinib and gefitinib are not, which is consistent with other reports. Afatinib is reported to be effective against G724S mutation, but no long‐term clinical survival has been reported till now. A patient with stage IV adenocarcinoma was found to have Ex19Del/G724S mutation. Treated with afatinib, he received a progression‐free survival of more than 1 year. With the guidance of this case report, we provide the clinical evidence of using afatinib for patients with G724S mutations and obtaining long‐term clinical survival. Key Points Guided by protein‐drug docking, afatinib is more effective to EGFR G724S mutation compared with osimertinib and gefitinib.A patient with Ex19Del/G724S mutation obtained long‐term survival with afatinib treatment., This brief communication presents the case of a patient with acquired Ex19Del/G724S mutation who was treated with afatinib and obtained long‐term clinical benefit.

By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.

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.

Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.

Alterations in brain function in Parkinson’s disease (PD) patients with diphasic dyskinesia have not been investigated. We aimed to explore the alterations in regional brain function. Each of 53 levodopa (LD)-treated PD patients had two resting-state functional magnetic resonance imaging (rs-fMRI) scans in the same morning, before and after taking LD. The regional homogeneity (ReHo) approach was used to reveal local synchronization changes. Two-way factorial repeated measures analysis of covariance, with group as a between-subject factor and LD effect as a within-subject factor, was performed to explore the two main effects and interaction. Interactive analysis was used to show outcomes that combined disease status and LD effect. Spearman’s correlations were used to detect associations between interactive brain regions and severity of dyskinetic symptoms, assessed by the Unified Dyskinesia Rating Scale (UDyRS) scores, along with moderation analyses. There was no significant difference in the main group effect analysis. Significantly different clusters obtained from main LD effect analysis were in left caudate nucleus and putamen. ReHo values decreased in the caudate nucleus and increased in the putamen during the ON state after taking LD. Interaction between group and LD effect was found in left medial superior frontal gyrus (mSFG), where there were the lowest ReHo values, and was negatively correlated with UDyRS scores in the diphasic dyskinetic group during the ON state. The relationship was independent of LD dose. Abnormal local synchronization in the mSFG is closely associated with the development of diphasic dyskinesia in PD patients.

Background: Convalescent plasma (CP) has been used successfully to treat many types of infectious disease, and has shown initial effects in the treatment of the emerging 2019 coronavirus disease (COVID-19). However, its curative effects and feasibility have yet to be confirmed by formal evaluation and well-designed clinical trials. To explore the effectiveness of treatment and predict the potential effects of CP with COVID-19, studies of different types of infectious disease treated with CP were included in this systematic review and meta-analysis. Methods: Related studies were obtained from databases and screened according to the inclusion criteria. The data quality was assessed, and the data were extracted and pooled for analysis. Results: 40 studies on CP treatment for infectious diseases were included. Our study found that CP treatment could reduce the risk of mortality, with a low incidence of adverse events, promote the production of antibodies, lead to a decline in viral load, and shorten the disease course. A meta-analysis of 15 controlled studies showed that there was a significantly lower mortality rate in the group treated with CP (pooled OR = 0.32; 95% CI = 0.19–0.52; p

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.

Lung cancer is the most fatal and frequently diagnosed malignant tumor. Neoadjuvant therapy is a promising approach for prolonging survival and increasing the chance of cure rates for patients with potentially resectable disease. Currently, many therapeutic alternatives, including chemotherapy, targeted therapy, and immunotherapy, are continually being explored to enrich the content of neoadjuvant therapy. However, neoadjuvant therapy remains to have no unified evaluation standards. Overall survival (OS) is the “gold standard” for evaluating the clinical benefit of cancer treatment, but it needs years for a reliable evaluation. Hence, researchers need to identify surrogate endpoints that can predict OS accurately and reliably without long follow-up periods. In this review, we describe the research progress of different neoadjuvant therapies and explore their response evaluation, aiming to identify stronger predictors of OS.

Aim: To clarify the regulatory roles of GLDCV1, the first identified truncated glycine decarboxylase (GLDC), on cancer stem cells and tumorigenesis. Materials & methods: RT-PCR or RT-qPCR, immunoblotting and immunohistochemical staining were applied to assess gene expression. MTT, BrdU incorporation and colony formation assays were used to examine cell proliferation capacity. Soft agar colony formation and in vivo transplantation were applied to evaluate cellular transformation and tumorigenesis. Results & conclusion: Expression of GLDCV1 or GLDC was enhanced in non-small-cell lung cancer cell line and clinical samples. GLDCV1 overexpression induced MRC5 cell proliferation, transformation and tumorigenesis. Additionally, GLDCV1 increased lactate production and cancer stem cell marker expression and activated ERK and P38 pathways. Our study gained deeper insight into GLDC oncogene.

Abnormal dopaminergic modulation of the cortico-basal ganglia motor loops results in the emergence of levodopa-induced dyskinesia (LID). We focused on alterations in the gray matter (GM) volume and the cortical thickness of the brain, especially in cortico-basal ganglia motor loops, in Parkinson's disease (PD) with diphasic dyskinesia. 48 PD patients with diphasic dyskinesia, 60 PD patients without dyskinesia and 48 healthy controls (HC) were included. Voxel-based morphometry (VBM) was applied to get GM images from MRI brain images. FreeSurfer was used to get cortical thickness. Distinct analyses of covariance (ANCOVA) and linear contrasts were performed for early- and late-onset PD groups. The severity of diphasic dyskinesia was evaluated by the Unified Dyskinesia Rating Scale (UDysRS). Finally, the correlations between mean volumes of clusters showing differences and the UDysRS scores were performed by Pearson's correlation. The GM volumes of precentral gyri were increased in PD patients with diphasic dyskinesia when compared with those without dyskinesia, which were positively correlated with UDysRS scores in PD patients with diphasic dyskinesia. However, there was no significant difference in cortical thickness among groups. The increased precentral gyri GM volumes might be associated with the pathogenesis and the severity of diphasic dyskinesia.

Targeted therapy and immunotherapy have changed the treatment modes for advanced non-small cell lung cancer (NSCLC), moving from second-line to first-line treatment and significantly extending patients' survival. Surgery and chemoradiotherapy remain the main treatment options for patients with locally advanced lung cancer, but recurrence and metastasis still occur in some patients. The survival rates of conventional perioperative chemotherapy among NSCLC patients have increased by only 5%. Therefore, more studies have begun to explore targeted and immune neoadjuvant/adjuvant therapies in early-stage and locally advanced NSCLC, and the relevant clinical research data have shown good efficacy and safety profiles. This article summarizes several clinical studies of critical importance.

Impulse control disorders (ICD) in Parkinson’s disease (PD) might be attributed to misestimate of rewards or the failure to curb inappropriate choices. The mechanisms underlying ICD were reported to involve the lateralization of monoamine network. Our objective was to probe the significant role of lateralization in the pathogenesis of ICD. Twenty-one PD patients with ICD (PD-ICD), thirty-three without ICD (PD-no ICD), and thirty-seven healthy controls (HCs) were recruited and performed T1-weighted, diffusion tensor imaging (DTI) scans and resting state functional magnetic resonance imaging (rs-fMRI). By applying the Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer, we evaluated participants’ synchronicity of functional connectivity and structural changes between hemispheres. Also, tract-based spatial statistics (TBSS) was applied to compare fiber tracts differences. Relative to PD-no ICD group, PD-ICD group demonstrated reduced VMHC values in middle frontal gyrus (MFG). Compared to HCs, PD-ICD group mainly showed decreased VMHC values in MFG, middle and superior orbital frontal gyrus (OFG), inferior frontal gyrus (IFG) and caudate, which were related to reward processing and inhibitory control. The severity of impulsivity was negatively correlated with the mean VMHC values of MFG in PD-ICD group. Receiver operating characteristic (ROC) curves analyses uncovered that the mean VMHC values of MFG might be a potential marker identifying PD-ICD patients. However, we found no corresponding asymmetrical alteration in cortical thickness and no significant differences in fractional anisotropy (FA) and mean diffusivity (MD). Our results provided further evidence for asymmetry of functional connectivity in mesolimbic reward and response inhibition network in ICD.

Lung cancer is one of the most important and lethal cancers in the world. Human epidermal growth factor 2 (HER2) is a member of the erbB receptor tyrosine kinase family. The incidence of HER2 kinase domain mutations in adenocarcinoma of lung ranges from 1% to 3%. HER2 V659D mutation is located in the trans-membrane domain (TMD) with only a few cases reported before, and importantly, there were no more standard and effective ways for this kind of diseases until now. Afatinib irreversibly blocks all kinase-competent HER family members. Apatinib is one of the small-molecule oral anti-angiogenesis-targeted agents developed firstly in China, and it's a highly selective inhibition of the activity of VEGFR-2. This report presents an advanced lung adenocarcinoma patient with HER2 V659D mutation who was treated with combination of Afatinib and Apatinib. He achieved good efficacy and tolerable adverse reactions.

Background Rapid eye movement (REM) sleep behavior disorder (RBD) is one of the common nonmotor symptoms of Parkinson’s disease (PD), characterized by frequently occurring REM sleep without muscle atonia. Our aim was to explore dynamic network connection changes in PD patients with RBD. Method On the basis of RBD screening questionnaire (RBDSQ), 126 PD patients were classified into those with probable RBD symptoms (PD-pRBD) and without probable RBD (PD-npRBD). We applied independent component analysis, sliding window approach and k-means clustering methods to clarify dynamic functional connectivity alterations. Results In contrast to PD-npRBD, PD-pRBD patients were liable to engage in a brain pattern mainly marked by weaker positive couplings between visual network (VIS) and default mode network (DMN), DMN and basal ganglia network (BG), and within DMN (State IV). In addition, we discovered that both PD patients with or without pRBD had shorter dwell time and fewer occurrences in State III, characterized by positive correlations between VIS and DMN, BG and DMN, and positive within-network coupling of sensorimotor network (SMN), relative to healthy controls. Conclusions Our study suggested that the weaker positive couplings between VIS and DMN, DMN and BG, and within DMN in State IV could be involved in the pathogenesis of PD patients with probable RBD on an overall level.

The ErbB family is composed of four cell membrane receptors: ErbB-1 (epidermal growth factor receptor or human epidermal growth factor receptor [HER]1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4). All members of the ErbB family play a critical role in regulating cell growth, proliferation and migration of tumours. Afatinib is an irreversible ErbB family inhibitor that is approved for second-line treatment of advanced squamous cell carcinoma (SqCC) that has progressed following platinum-based chemotherapy. Here we describe the case of a 56-year-old male Chinese patient with SqCC who had previously failed chemotherapy and radiotherapy and was subsequently enrolled in the LUX-Lung 8 study. The patient responded well to treatment with afatinib (40 mg/day). His disease stabilised after 8 weeks and a complete response was achieved after 12 weeks of treatment. Follow-up of this patient is ongoing; he is still alive and has not experienced disease progression in the 7 years since initiation of afatinib. The long-term response and prolonged survival in this patient provide additional evidence for second-line treatment with afatinib in patients with SqCC.

The association between lung cancer and trace element levels, such as serum copper (Cu) and zinc (Zn) levels and the Cu:Zn ratio, vary among different demographic groups; however, it is unknown whether variations in serum Cu and Zn levels and Cu:Zn ratios are related to the prediction and prognosis of lung cancer. We aimed to clarify this relationship in the Han Chinese population of Northeast China.We recruited 146 patients with lung cancer and 146 age- and resident area-matched cancer-free controls.Increased serum Cu and Zn levels and the Cu:Zn ratio were positively associated with lung cancer (OR: 72.243, 95% CI 24.159-216.030; OR: 3.513, 95% CI, 1.476-8.358, and; OR: 58.582, 95% CI, 20.023-171.395, respectively). The critical serum Cu level for the prediction of lung cancer was 1.37 mg/L (sensitivity, 77.4%; specificity, 84.9%), while the critical Cu:Zn ratio was 1.45 (sensitivity, 69.9; specificity, 88.4%). Patients with stage IV non-small-cell lung cancer (NSCLC) had higher serum Cu levels and a higher Cu:Zn ratio than patients with stage I, II, or III NSCLC.The serum Cu level and the Cu:Zn ratio are effective predictive indicators of lung cancer and may help evaluate the prognosis of patients with NSCLC.

Background Traditional measures of static functional connectivity may not completely reflect the dynamic neural activity of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). This study was aimed to investigate the dynamic changes of large-scale functional network connectivity in the temporal domain in PD patients with and without LID. Methods Using dynamic functional network connectivity (dFNC) analysis, we evaluated 41 PD patients with LID (LID group) and 34 PD patients without LID (No-LID group), on and off their levodopa medications. Group spatial independent component analysis, sliding-window approach and k-means clusters were employed. Results In OFF phase, we found no differences between PD subgroups in temporal properties. In ON phase, compared than No-LID group, LID group occurred more frequently and dwelled longer in strongly connected State 1, characterized by strong connections between visual network (VIS) and other networks. When switching from OFF to ON phase, LID group occurred more frequently and dwelled longer in State 2 and occurred less frequently and dwelled shorter in State 3 (both states were strongly connected), while No-LID group occurred more frequently and dwelled longer in State 5 (weakly connected). Additionally, correlation analysis further demonstrated that the severity of dyskinesia was only associated with frequency of occurrence and dwell time in State 2, dominated by inferior frontal cortex in cognitive executive network (CEN), strongly connecting with sensorimotor network (SMN) and VIS. Conclusions Using dFNC analysis, we found that compared to those without LID, PD patients with LID may be involved in the superexcitation of VIS, as well as interconnections between CEN and SMN, VIS, having impact on inhibition of motor circuits. The dFNC analysis might provide new insights into the neural mechanisms of LID in PD.

The outbreak of pneumonia caused by novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of 2019 quickly escalated into a global health emergency. Since its outbreak until the 29th of April 2020, the pandemic has affected more than 3 million of people and caused 207,973 deaths globally. SARS-CoV-2 belongs to the β-coronavirus genus of the Coronavirus family, and it shares the same subfamily with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV), all of which lead to severe pneumonia. For cancer patients, especially those with lung cancers, their immune systems are compromised due to the disease itself as well as the treatment for cancer. The weakened immunity of these patients puts them at a higher risk of not only developing diseases but severe diseases. In this study, through a literature review and data collection, we focus on the selection and consideration of antitumor treatment strategies for advanced lung cancer during the coronavirus disease 2019 (COVID-19) epidemic.

Levodopa-induced dyskinesias are common motor complication of Parkinson’s disease after 4–6 years of treatment. The hallmarks of dyskinesias include unilateral onset and the tendency to appear on the more affected body sides. There is a growing literature documenting the lateralization abnormalities are associated with the emergence of dyskinesias. Our investigation aimed to explore interhemispheric functional and its corresponding morphological asymmetry. A total of 22 dyskinetic patients, 23 nondyskinetic patients, and 26 controls were enrolled. Resting-state functional magnetic resonance imaging scans were performed twice before and after dopaminergic medication. Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer were employed to assess the synchronicity of functional connectivity and structural alternations between hemispheres. During OFF state, dyskinetic patients showed desynchronization of inferior frontal cortex (IFC) when compared to nondyskinetic patients. And during ON state, dyskinetic patients showed desynchronization of IFC and pre-supplementary motor area (pre-SMA) when compared to nondyskinetic patients. However, there was no corresponding significant asymmetries in cortical thickness. Moreover, the degree of desynchronization of IFC and pre-SMA in dyskinetic pateients during ON state were negatively correlated with the Abnormal Involuntary Movement Scale (AIMS) scores. Notably, among patients who showed asymmetrical dyskinesias, there was a significant negative correlation between VMHC values of IFC and dyskinesias symptom asymmetry. Our findings suggested that uncoordinated inhibitory control over motor circuits may underlie the neural mechanisms of dyskinesias in Parkinson’s disease and be related to its severity and lateralization.

The discovery of epidermal growth factor receptor ( EGFR) somatic mutations and the availability of tyrosine kinase inhibitors (TKIs) as targeted therapies have altered the therapeutic prospects of advanced non-small-cell lung cancer (NSCLC). G719X and S768I are uncommon mutations, and they often exist as compound mutations. A few reports have described the efficacy of first- and second-generation EGFR-TKIs. However, the efficacy of osimertinib in patients with these uncommon compound mutations is unknown. In this study, we reported the postoperative outcome of a patient with NSCLC and uncommon compound EGFR G719X and S768I mutations. After postoperative recurrence, the patient was treated with osimertinib, and an excellent and long-lasting clinical response was achieved. The patient has taken osimertinib for 31.0 months and exhibited a partial response, and her follow-up is ongoing.

Mn2+ doping has been developed to modulate the photoluminescence (PL) of CsPbCl3 perovskite quantum dots (PQDs). However, the doped Mn2+ may be expelled from the PQDs host with the long-term storing, resulting in inferior stability. Herein, CsPbCl3 PQDs doped with different concentrations of Mn2+ (Mn:CsPbCl3) are prepared by a hot injection method. Our photostability tests reveal that when the doping concentration is

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.

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. Methods: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. Results: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p

This study aimed to examine the prognostic role of the plasma 25-hydroxyvitamin D (25(OH)D) level in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based doublet first-line chemotherapy.A total of 195 advanced NSCLC patients were consecutively and prospectively hospitalized to receive platinum-based first-line chemotherapy. The baseline 25(OH)D level was measured at the time of diagnosis. Main outcome measures included overall survival (OS) and progression-free survival (PFS).With 10 ng/mL as the cutoff value for the baseline plasma 25(OH)D level, patients with 25(OH)D10 ng/mL (n = 54) and those with 25(OH)D ≥ 10 ng/mL (n = 141) were found to have similar characteristics in terms of age, sex, smoking status, pathological type, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical staging (all P-values0.05). The median OS values of patients with 25(OH)D10 ng/mL and ≥ 10 ng/mL were 17.9 months (95% confidence interval [CI], 14.4-21.4 months) and 20.8 months (95%CI, 17.9-23.8 months), respectively; the median PFS values were 9.4 months (95%CI, 8.2-10.5 months) and 9.4 months (95%CI, 8.3-10.5 months), respectively. Both univariate and multivariate analyses showed that having a plasma 25(OH)D level10 ng/mL was associated with a significantly shorter OS (P = 0.003; P = 0.009), while the baseline plasma 25(OH)D level was not significantly associated with PFS.Deficiency of 25(OH)D is an independent prognostic factor for a poor OS in advanced NSCLC patients treated with platinum-based first-line chemotherapy.

Objectives In this study, the alterations of structural topological properties in Parkinson's disease (PD) patients with levodopa-induced dyskinesias (LIDs) were explored using white matter structural network connectome derived from diffusion tensor imaging (DTI). Methods 21 dyskinetic PD patients, 21 non-dyskinetic PD patients and 25 healthy controls were studied in global and nodal topological properties of structural networks after controlling age, gender and education. Afterwards, post hoc analyses were performed to explore further differences. Finally, multiple linear regression analysis was employed to test the associations between significant different properties and the severity of dyskinesias in PD. Results Dyskinetic PD patients exhibited significant increased global efficiency, local efficiency, clustering coefficient, but decreased shortest path length compared with the non-dyskinetic. Additionally, increased nodal efficiency in bilateral inferior frontal gyrus (IFG), right putamen, right thalamus, and decreased nodal shortest path length in bilateral IFG and right thalamus, were discovered in dyskinetic PD in comparison with non-dyskinetic PD. Notably, a negative correlation between the Abnormal Involuntary Movement Scale (AIMS) scores and shortest path length of whole-brain network was found in PD with LIDs. Conclusions Our results indicated excessively optimized topological organization of whole-brain structural connectome in PD patients with LIDs. These findings also illustrated that excessively strengthened basal ganglia-thalamocortical nodal structural connections played an important role in the presence of LIDs.

Measurement of circulating tumor cells (CTC) offers promise as a clinical biomarker to monitor disease status, therapeutic response, and progression in cancer patients. However, its clinical value in lung cancer patients has not been fully explored. We systematically evaluate the association of CTCs with clinical variables and tumor markers in a cohort of lung cancer patients. Using the CELLSEARCH System, CTCs were detected in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients prior to therapy. Univariate analysis revealed that detection of CTC was related to histology, stage, tumor size, invasiveness, and lymphatic metastasis. CTCs were associated with distant metastases in NSCLC, but not in SCLC. Using multivariate analysis, we found that CTCs were independently correlated with disease stage, SCLC, and elevated serum neuron-specific enolase (NSE). These data suggest that CTCs are more likely to be detected in patients with stage IV disease and with SCLC, and that elevated serum NSE predicts the presence of CTCs.

Introduction: Weight-based dosing of NIVO over 60 minutes is approved in China for 2L NSCLC tx; however, more convenient flat dosing over a shorter infusion time has yet to be fully assessed in Asian pts. In addition, the benefit of NIVO in Asian pts with NSCLC and EGFR or ALK mutations, or hepatitis B virus (HBV) infection, has yet to be evaluated. CheckMate 870 (NCT03195491) is a phase 3b trial assessing a flat dose of NIVO infused over 30 minutes for previously treated NSCLC in Asian pts. Methods: Eligible pts had stage IIIB/IV NSCLC with 1-2 prior systemic tx and ECOG PS 0-1. Pts with HBV had to have a viral titer < 500 IU/mL. Pts received NIVO 240 mg over a 30-minute infusion, Q2W, until progression, unacceptable toxicity, or for ≤ 2 years. The primary endpoint was high-grade (G; G3-5) tx-related select adverse events (AEs) in non-HBV infected pts. Results: Of 400 treated pts, 394 were from China; 34 pts had EGFR mutations, and 383 were non-HBV infected. Median (range) age was 61 (27-80) y and 78% were male. Clinical data cutoff was May 30, 2019, median duration of tx was 3 mo. The most common categories for G3-4 tx-related select AEs in non-HBV infected pts were hepatic (2%), skin (2%), pulmonary and endocrine (1% each). There were no G5 tx-related select AEs reported in non-HBV infected pts. No G3-5 tx-related select AEs were reported in HBV-infected pts (n = 17). There were 2 tx-related deaths, due to myocarditis (non-HBV infected pt) and lung infection (HBV-infected pt). G3-4 treatment-related AEs (TRAEs) were reported in 13% of all treated pts, and 2% had G3-4 TRAEs leading to discontinuation. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) are shown in the Table. Conclusions: Flat-dosing of NIVO 240 mg over 30 minutes was well tolerated and active in a predominantly Chinese pt population with previously treated NSCLC, including pts with EGFR mutations or HBV infection. These results are similar to pivotal trials of NIVO for previously treated NSCLC. No new safety signals were reported. Table.OS, PFS, and ORR among subgroups in CheckMate 870OSMedian PFSa,mo (95% CI)ORRaMedian,mo (95% CI)6-mo rates (%)n (%)All treated (N = 400)NR (11.7–NR)753.7 (3.1–3.9)62 (16)HBV statusbNo HBV (n = 383)NR (11.6–NR)753.7 (3.1–3.9)59 (15)With HBV (n = 17)NR (10.0–NR)822.0 (1.6–NR)3 (18)EGFR mutation statuscPositive (n = 34)NR (9.6–NR)851.9 (1.7–3.6)5 (15)Not detected (n = 261)NR (11.4–NR)743.6 (2.7–3.9)37 (14)Tumor histologyNon-squamous (n = 264)NR (11.5–NR)763.4 (2.1–3.8)37 (14)Squamous (n = 136)NR (10.5–NR)724.7 (3.1–5.6)25 (18)Tumor PD-L1 expressiond≥ 1% (n = 169)NR (11.7–NR)745.4 (3.7–5.6)42 (25)< 1% (n = 174)13.2 (10.9–NR)773.1 (2.0–3.8)15 (9)Minimum follow up was 10 mo.aPer investigator;bHBV status is a protocol pre-specified enrollment cohort; the number of pts with HBV entering the study was capped at 60 (15% of the total population);cThe number of pts entering the study with EGFR mutations was capped at 40;dOf all treated patients, 343 (86%) were evaluable for tumor PD-L1 expression level. NR, not reached. Citation Format: Shun Lu, Ying Cheng, Jianying Zhou, Mengzhao Wang, Jun Zhao, Gongyan Chen, Baocheng Wang, Jifeng Feng, Zhiyong Ma, Lin Wu, Changli Wang, Shucai Zhang, Kewei Ma, Jun Liang, Yong Song, Jie Wang, Yi-Long Wu, Ang Li, Ting Ma, Jianhua Chang. Flat-dose nivolumab (NIVO) as second-line (2L) treatment (tx) for Asian patients (pts) with advanced non-small cell lung cancer (NSCLC): CheckMate 870 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT218.

Introduction: In the previous phase II clinical trial (NCT03215693), ensartinib, a next generation (NG) ALK TKI, showed comparable efficacy to other NG ALK TKIs in the post-crizotinib setting. In the preplanned biomarker analysis, we investigated the efficacy and the resistance mechanisms of ensartinib via longitudinal ctDNA analysis. Methods: Pts with stage IIIB/IV ALK+ NSCLC, and had progressive disease (PD) after crizotinib were eligible. Plasma samples from this trial were prospectively collected for ctDNA analysis at baseline (BL), cycle 3 day 1 (C3D1) and the end of treatment (EOT). Plasma DNA was analyzed using a 212-gene sequencing panel. ctDNA amount was defined as the sum of variant allele fraction (VAF) of ALK fusions and mutations. Cox model was applied for multivariate analysis. Results: Between 9/2017 and 7/2019, 182 pts were enrolled in the trial. In total, 178 were included in the full analysis set (FAS), with a median PFS (mPFS) of 9.8 months (95% CI, 7.5 to 11.7 months). 169 pts were evaluable by independent review committee (IRC), with an ORR of 57.7% (95% CI, 50.2% to 65.3%). A total of 431 ctDNA samples were analyzed, including 168 at BL, 165 at C3D1, and 106 at EOT (8 overlappings between C3D1 and EOT). 168 (99.4%) pts had evaluable ctDNA at BL. The median ctDNA amount was 0.00704. The higher ctDNA amount was associated with liver metastases, bone metastases, and TP53 mutations. Tumor burden, as measured by the sum of the target lesions' longest diameters, also positively correlated with ctDNA amount (Pearson correlation 0.261; p < 0.001). Multivariable Cox regression revealed that high level of ctDNA amount and TP53 mutations at BL was significantly associated with poor PFS independently (p =0.020 and p < 0.001) (Table). 106 (62.7%) pts had evaluable ctDNA at both BL and EOT. Compared to baseline, the frequency of certain ALK mutations significantly increased at EOT, such as G1269A (7.5% vs 21.7%), G1202R (3.8% vs 17.0%) and E1210K (0% vs 10.4%). TP53 statusctDNA amountTP53 Wildtype TP53 Mutations Low amountHigh amount(n = 34)(n = 134)(n = 46)(n = 47)mPFS, months (95% CI) 11.7 (9.8, 14.0) 4.2 (3.0, 5.6)9.3 (5.6, 11.7) 4.2 (2.8, 5.5)HR (95% CI); p value2.50 (1.65, 3.79) ; p < 0.0012.34 (1.52, 3.61) ; p < 0.001 Consistent with the change in frequency, the abundance of G1269A, G1202R, and E1210K also trended to increase at EOT, while the abundance of C1156Y and I1171X had a downward trend in most pts. Conclusions: Consistent with previous reports, ensartinib showed high clinical efficacy. Longitudinal ctDNA analysis could be a powerful tool in predicting treatment outcomes and revealing resistant mechanisms of ensartinib. We observed G1269A, G1202R and E1210K as the major resistant mutations to ensartinib. Additional analyses are ongoing and results will be updated and reported in the meeting. Citation Format: Yunpeng Yang, Jie Huang, Tao Wang, Jianya Zhou, Jing Zheng, Jifeng Feng, Wu Zhuang, Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Gang Wu, Yubiao Guo, Chengzhi Zhou, Kewei Ma, Jian Fang, Weineng Feng, Yunpeng Liu, Zhendong Zheng, Gaofeng Li, Ning Wu, Wei Song, Xiaoqing Liu, Shijun Zhao, Lieming Ding, Li Mao, Giovanni Selvaggi, Larry Zhu, Shanshan Xiao, Li Zhang. Longitudinal circulating tumor DNA (ctDNA) analysis predicts response and reveals the resistance mechanisms of ensartinib in ALK+ NSCLC patients (pts) progressed on crizotinib: Updated analysis of a phase II clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2997.

This study was aimed to characterize clinicopathological features and prognosis of patients with adenosquamous lung carcinoma (ASC). Among the 2531 patients with lung cancer who underwent surgery between January 2000 and June 2012 in our hospital, 59 were histologically diagnosed as having ASC. The clinicopathological features and follow-up data of ASC patients were collected and analyzed statistically. Superior lobectomy was accomplished in 40 patients, middle and inferior lobectomy in 3, lobectomy plus partial resection of contralateral lung in 5, partial lung resection in 4, and pneumonectomy in 7. Moreover, 22 cases were found to be adenocarcinoma-predominant, and 18 to be squamous cell carcinoma-predominant. The median survival time was 13.6 months, and the 1-, 3-, and 5-year survival rates were 59.9%, 36.4% and 31.2%, respectively. Of the 52 cases with tissue specimens available, 11 had an EGFR mutation (21.2%) and 2 had a KRAS mutation (3.8%). Multivariate analysis showed that histology subtype, pleural invasion, TNM stage, and postoperative treatment were all independent prognostic factors. The data from the current study demonstrated that SCC-predominant histology represents a better prognosis of ASC. Histology subtype, pleural invasion, TNM stage, and postoperative treatment are independent prognostic factors for ASC and adjuvant therapy may help control the disease.

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.

Aims and Background Early detection and diagnosis remains an effective yet challenging approach to improve the clinical outcome of patients with cancer. Low-dose computed tomography screening has been suggested to improve the diagnosis of lung cancer in high-risk individuals. To make screening more efficient, it is necessary to identify individuals who are at high risk. Methods and Study design We conducted a case-control study to develop a predictive model for identification of such high-risk individuals. Clinical data from 705 lung cancer patients and 988 population-based controls were used for the development and evaluation of the model. Associations between environmental variants and lung cancer risk were analyzed with a logistic regression model. The predictive accuracy of the model was determined by calculating the area under the receiver operating characteristic curve and the optimal operating point. Results Our results indicate that lung cancer risk factors included older age, male gender, lower education level, family history of cancer, history of chronic obstructive pulmonary disease, lower body mass index, smoking cigarettes, a diet with less seafood, vegetables, fruits, dairy products, soybean products and nuts, a diet rich in meat, and exposure to pesticides and cooking emissions. The area under the curve was 0.8851 and the optimal operating point was obtained. With a cutoff of 0.35, the false positive rate, true positive rate, and Youden index were 0.21, 0.87, and 0.66, respectively. Conclusions The risk prediction model for lung cancer developed in this study could discriminate high-risk from low-risk individuals.

Background and Aims Circulating tumor cells (CTCs) have prognostic significance in patients with metastatic cancer, but their utility in predicting the response to tumor therapy is unknown. This study examined the correlation of CTCs with the therapeutic response in small cell lung cancer (SCLC). Methods Clinical and pathological data from 96 SCLC patients were evaluated in this study. CellSearch kits were used to detect CTCs in peripheral blood samples. Statistical analysis was performed using Fisher exact test and Mann-Whitney U test. Results At baseline, 47 (50.0%) SCLC patients had detectable CTC counts. Serum neuron-specific enolase (NSE) was found to be associated with CTC thresholds. However, no significant differences were observed for an association of any threshold CTC count with the treatment response, with gender, age (≤60 or >60 years), smoking status, syndrome of inappropriate antidiuretic hormone (SIADH), or Ki67 expression. Conclusion Detection of CTCs in SCLC patients was associated with serum NSE but not with response to cancer therapy.

Rationale:Lung cancer is a series of gene-driven disease. EGFR, ALK, and ROS1 are 3 major driver genes that play an important role in lung cancer development and precision management. Additionally, rare genetic alterations continue to be discovered and may become novel targets for therapy. T

Rationale: Comprehensive genomic profiling for non-small cell lung cancer (NSCLC) is likely to identify more patients with rare genetic alterations, including uncommon epidermal growth factor receptor (EGFR) gene mutation. Patient concerns: A 63-year-old Chinese woman who had never smoked visited our lung cancer clinic due to a chronic cough. Diagnosis: The patient was diagnosed with lung adenocarcinoma by transbronchial lung biopsy. An EGFR mutation (exon 20 insertion H773_V774insH, D770_N771insG, V769_D770insASV, D770_N771insSVD) was detected in the biopsy specimen by quantitative real-time PCR. Interventions: The patient was treated with osimertinib first, and the progression-free survival (PFS) was 4.4 months. After the disease progressed, the second genetic test of pleural effusion suggesting the EGFR exon 20-ins mutation site changed to A767delinsASVD only. Then the patient was treated with afatinib with informed consent. Outcomes: The treatment of afatinib in this patient was successful, PFS was 7.4 months. Lessons: To our knowledge, EGFR exon 20-ins mutation A767delinsASVD has never been reported, and the successful treatment of afatinib may provide a new therapeutic option for this type of exon 20 insertion mutations.

Small cell lung cancer (SCLC) is frequently associated with syndrome of inappropriate antidiuretic hormone (SIADH) secretion. In this study we investigated the prognostic value of SIADH in Chinese patients with SCLC.We prospectively studied a total of 385 patients with SCLC diagnosed in our institution. The relationship between the SIADH and treatment outcomes including progression-free survival (PFS) and overall survival (OS) were analyzed. Univariate analysis and Cox multivariate analyses were used for statistical analyses. PFS and OS curves were drawn using Kaplan-Meier method.The median PFS and OS in patients with SIADH was 6.7 months (95% confidence interval [CI]: 4.3-9.1) and 11.6 months (95% CI: 7.4-15.7), respectively. The corresponding PFS and OS in SCLC without SIADH was 9.2 months (95% CI: 8.6-9.8) and 19.2 months (95% CI: 16.5-21.9), respectively; the difference between groups was statistically significant (p = 0.007 and p = 0.000, respectively). The association of SIADH with poor PFS (p = 0.000) and OS (p = 0.002) retained its statistical significance after adjusting for potential confounding variables. In addition, PFS (p = 0.000) and OS (p = 0.000) of SIAHD patients with plasma sodium125 mmol/L or without plasma sodium recovery to normal level are both shorter than in patients without SIADH. OS in SIAHD patients with plasma sodium recovery time to normal level is also shorter than patients without SIADH (p = 0.03).SIADH is a common occurrence in patients with SCLC and is associated with poor prognosis for SCLC in Chinese patients.

Objective To determine the involvement of Toll-like receptor (TLR) 2, TLR9, and TLR2+9 in renal ischemia/reperfusion (I/R) injury. Methods Mice with gene knock-out of TLR2, TLR9, and TLR2+9 underwent renal I/R injury. Tubular damage, expression of proinflammatory cytokines and chemokines, and kidney dysfunction were evaluated on different days after reperfusion. Results Mice deficient in TLR2, but not TLR9, were protected from renal I/R injury with less tubular damage, decreased cytokine production, and lower serum creatinine and urea levels than wild-type mice. TLR2+9 double-deficiency did not have an additional effect on tissue injury compared with TLR2 deficiency alone. Conclusion These results suggest that activation of TLR2 signaling contributes to the pathogenesis of renal I/R injury, whereas TLR9 may be redundant for the development of this injury.

Distance-based indexing is a widely used technique for general purpose search. Pivot selection is the most crucial step of bulkloading a metric-space indexing tree. Current pivot selection methods are mainly based on linear methods. A non-linear method based on Locally Linear Embedding is proposed. Empirical results demonstrate that the performance of new method is superior to existing methods. Keywords-similarity search; metric-space indexing; pivot selection; locally linear embedding; dimensional reduction

BackgroundSmall cell lung cancer (SCLC) is the most devastating type of human lung cancer. Patients usually present with disseminated disease to many organs (extensive stage). This study was to investigate the efficacy and safety of cellular immunotherapy (CIT) with autologous natural killer (NK), γδT, and cytokine-induced killer (CIK) cells as maintenance therapy for extensive-stage SCLC (ES-SCLC) patients.MethodsA pilot prospective cohort study was conducted with ES-SCLC patients who had responded to initial chemotherapy. Patients received either CIT as maintenance therapy (CIT group), or no treatment (control group). Progression-free survival (PFS), overall survival (OS), and adverse effects were compared.ResultsForty-nine patients were recruited in this study, with 19 patients in the CIT group and 30 patients in the control group. The patient characteristics of the 2 groups were comparable except for age, as patients in the CIT group were older than those in the control group (P