Search

Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and lethal tumor with poor prognosis. Its survival period ranges from four months to one year, and the 5-year survival rate is only about 10%. MPM is highly resistant to chemotherapy, and conventional treatments such as cisplatin combined with pemetrexed or raltitrexed only have a certain effect in about 20% of patients. In recent years, with the continuous in-depth understanding of the genetic variation characteristics of MPM, some progress has been made in the molecular mechanism underlying the chemotherapy resistance of MPM. This article will summarize the research progress of the molecular mechanism underlying the chemotherapy resistance of MPM, including BAP1 gene mutation, microRNA, MTA1-mediated DNA damage repair pathway, GITR-GITRL pathway, TGFa pathway, tumor stem cell, EGFR, and PTEN. The aim of this work is to provide a reference for exploring new therapeutic targets and combined treatment options for MPM.

Background and objective Targeted therapies are ineffective in lung squamous cancer (LUSC), and the low response rate of immunotherapy hampers its application in LUSC, so it is urgent to explore new strategies for LUSC treatment. Ferroptosis plays an important role in tumour suppression. The aim of this study was to investigate the role and mechanism of targeting 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) in regulating ferroptosis in LUSC cells, in order to provide a new research direction for LUSC therapy. Methods The expression of HMGCS1 in LUSC was analysed by The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) online databases; the relationship between HMGCS1 and survival time of lung cancer was analysed by the Kaplan-Meier Plotter online survival database; the expression level of HMGCS1 in LUSC tissues was verified by immunohistochemistry. After interfering with HMGCS1 expression by small interfering RNA (siRNA), cell activity and cell migration ability were detected by CCK8 and Transwell assay; apoptosis was detected by flow cytometry after interfering with HMGCS1 or after treatment with the HMGCS1 inhibitor of hymeglusin; Fe2+, reactive oxygen species (ROS) and lipid peroxidation levels were detected by flow cytometry and high-content confocal fluorescence imaging systems, respectively in SKMES cells after inhibition of HMGCS1; and Western blot was performed to detect the expression of ACSL4, GPX4 and SLC7A11, which are markers of the ferroptosis pathway after inhibition of HMGCS1. Results HMGCS1 mRNA and protein levels were significantly high in LUSC; siRNA interference with HMGCS1 expression inhibited the proliferative activity and migration ability of LUSC cells, but had no significant effect on apoptosis. Interference with HMGCS1 or treatment with the HMGCS1 inhibitor of hymeglusin significantly promoted intracellular Fe2+, ROS and lipid peroxidation levels in SKMES cells, and induced ferroptosis in LUSC cells; Western blot assay showed that inhibition of HMGCS1 significantly promoted the expression of ACSL4. Conclusion Inhibition of HMGCS1, a target of LUSC, promotes ferroptosis in lung cancer cells and provides a research basis for screening new therapeutic targets for LUSC.

Background and objective The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. Methods The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. Results WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. Conclusion This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts’ discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.

Background and objective Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). Methods This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. Results This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. Conclusion Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

With the deeper understanding of the pathophysiology and pathogenesis of non-small cell lung cancer (NSCLC) which threatens human health, NSCLC treatment has entered a new era. Transition from traditional treatment based on surgery, radiotherapy and chemotherapy to individualized and precise targeted therapy and safer and more effective immunotherapy. Immune checkpoint inhibitor therapy has been approved as a first-line or second-line treatment for advanced NSCLC, and has achieved extraordinary clinical results. Meanwhile, other types of immunotherapy are rarely explored in NSCLC. Chimeric antigen receptor modified T cells (CAR-T cells) perform well in treating several hematological malignancies. However, it is not ideal for treating patients with solid tumors including NSCLC. This review aims to systematically explain the latest progress of CAR-T in the treatment of NSCLC, mainly including: CAR molecular target selection, CAR-T function enhancement and related toxicity management, as well as the difficulties and prospects of CAR-T treatment of NSCLC. It aims to open up new perspectives and unique ideas for the immunotherapy of NSCLC, and contribute to the building of tumor immunotherapy.

The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.

Immune checkpoint inhibitors (ICIs) have been used more and more Increasingly in clinical oncology treatment, which has significantly improved the prognosis of cancer patients. Over-activation of T cells and related signaling pathways may cause immune-related adverse effects. Renal immune side-effects are relatively rare, but some of them are serious and fatal. This review analyses of the Incidence, clinical and pathological manifestations of ICIs-induced renal injury, and focuses on the differential diagnosis and treatment. Because there are many secondary factors that need to be differentiated from immune mechanism, renal biopsy should be performed if necessary to determine the important decision.

Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system, with the incidence rate ranging from 0.1% to 12%, and 80% occurring within the first 4 months of ICI application. It can cause lesions in various parts of the nervous system, including aseptic meningitis, meningoencephalitis, necrotizing encephalitis, brainstem encephalitis, transverse myelitis and other central nervous system diseases. It can also cause cranial peripheral neuropathy, multifocal radicular neuropathy, Guillain-Barre syndrome, spinal radicular neuropathy and myasthenia gravis, myopathy, etc. For these complications of the nervous system, diagnosis could be made by sufficient collection of disease manifestations combined with imaging, cerebrospinal fluid examinations, electro-encephalogram or electro myography to exclude infection or tumor progression. In the treatment of severe cases, ICIs should be discontinued and treated with high doses of glucocorticoid or gamma globulin with systemic support. After neurological adverse reactions, the prognosis of severe cases is poor.

Immune checkpoint inhibitors (ICIs) have made remarkable breakthroughs in cancer treatment. However, the widely use of ICIs is associated with a spectrum of immune-related adverse events (irAEs). These adverse events can affect any organ system. In this article, we have made a systemic review about the clinical characteristics of rheumatic irAEs, and also summarized irAEs in patients with pre-exsiting rheumatic disease. We also focus on the management of rheumatic irAEs.

Immune checkpoint inhibitors (ICIs) have been widely used in management of malignant tumor. Programmed death ligand 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been introduced to treat non-small cell lung cancer (NSCLC) in recent years. Currently, PD-1/PD-L1 inhibitors are considered to have minor side effects and do not independently increase the risk of infection. However, they may cause immune-related adverse events (irAEs) that can require immunosuppressive therapy with corticosteroids and/or immunosuppressants, leading to opportunistic infections. Furthermore, there were reports about reactivation of chronic/latent infections without irAEs. Thus, immune checkpoint inhibitor related infections have drawn more and more attention in the world. In this paper, we described the potential mechanism, available clinical data and recommendation of diagnosis and management for PD-1/PD-L1 inhibitor related infections.

Immune checkpoint inhibitors (ICIs) represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Dermatologic toxicities appear to be one of the most prevalent irAEs. The most common symptoms are maculopapular rash and pruritus. Serious dermatologic AEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis, are rare. In this review, we summarized guidelines of management of immunotherapy-related toxicities and case reports, and proposed treatment recommendation.

As a new type of anti-cancer drugs, immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic effects in many malignant tumors. By virtue of their targets and mechanisms of action, ICIs can cause autoimmune and inflammatory effects, termed immune-related adverse events (irAEs). Unlike traditional therapies, irAEs are latent and unstable. Severe adverse reactions will force patients to discontinue treatment and even affect their survival. Therefore, with the wide application of ICIs in clinical practice, clinicians need to fully understand the possible adverse reactions of such drugs and appropriate treatment strategies, in order to improve the survival rate and treatment effect of patients receiving ICIs. In this article, we review the incidence, clinical features, diagnosis and treatment of immune-related endocrine events that may occur with administration of ICIs.

Immunocheckpoint inhibitors (ICIs) activated the patients’ tumor immunity to kill the tumor cell, and brought new hope to patients with tumor. However, a series of immunocheckpoint inhibitors related adverse effects (irAEs) may also occur based on immune injury. Glucocorticoids are the basis for the treatment of such irAEs. However, the usage, dosage and course of treatment of glucocorticoid in irAEs are different from those in classic autoimmune diseases. Meanwhile, long-term use of large doses of glucocorticoids may cause serious adverse effects too. In this paper, the mechanism, dosage forms, adverse effects and management of glucocorticoids are described in detail, providing references and suggestions for oncologists to apply glucocorticoids in clinical practice.

The increasing use of target therapy and immunocheckpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, more and more adverse side-effects and toxicities of these medications had been reported, affect almost all human organs including the eye. These adverse effects may affect the entire ocular tissues, like eyelid, eye lashes, conjunctiva, cornea, uvea, retina, optic nerve and so on, which are always been ignored by patients and doctors. In this paper we will summarize the characteristics of the related ocular diseases and give our advice on how to diagnose and manage these diseases.

The increasing use of immunocheckpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immunocheckpoint inhibitors, mainly activated T-cell immunity, may attack normal tissues and organs of the human body and lead to a variety of adverse effects. In the lung, they could induce checkpoint inhibitor associated pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and had a potentially fatal risk if it was not being properly treated. We will summarize the characteristics of CIP and give our advice on how to manage immunocheckpoint inhibitor associated pneumonitis.

Immunotherapy for malignant tumors is a hot spot in current research and treatment of cancer. The activation of programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA)-4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune-checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune-related adverse events (irAEs). The digestive system, including gastrointestinal tract and liver are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune related organs, which are the commonly affected system of irAEs. This review separately explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.

Immunotherapy of malignant tumors has become a hot spot in the field of cancer research and treatment, bringing new hope to patients with advanced cancer. Activation of molecular programmer death protein-1 and T lymphocyte-associated antigen 4-related signaling pathways at the immunological checkpoint can inhibit T lymphocyte activation and thereby block the inflammatory response. Tumor cells achieve immune escape by activating the molecular pathways associated with immune checkpoints. The immune checkpoint inhibitor can wake up T lymphocytes and enhance the body's clearance of tumor cells. However, the role of immune checkpoint inhibitors is not specific to tumor cells, and it can cause side effects of multiple systems including the cardiovascular system while killing tumor cells. We will summarize the relevant cardiac side effects and give advice on how to manage it.

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.

Small cell lung cancer (SCLC) is a refractory cancer with high degree of malignancy, rapid disease progression, poor prognosis and easy recurrence. In the past 30 years, the traditional treatment of SCLC, mainly chemotherapy and radiotherapy, has not changed significantly, and the effective treatment method for clinical needs is extremely urgent. The rapid development of precision medicine has revealed the molecular biological characteristics of SCLC, so its diagnosis and treatment will into a new era. At present, some studies have shown that anti-angiogenic drugs, immunotherapy and so on have improved the efficacy of SCLC treatment to some extent, and there are more studies on the diagnosis and treatment of SCLC, so a new field of SCLC treatment are coming and bringing more survival benefits to patients. New studies on targeted therapy, anti-angiogenesis drugs and immunotherapy of molecular pathology of SCLC are emerging. This paper reviews the new diagnosis and treatment methods of SCLC to provide new guidance for its clinical treatment.

Background and objective The aim of this study was to investigate the clinical features of paraneoplastic limbic encephalitis (PLE) with small cell lung cancer (SCLC) and improve clinical diagnosis and treatment. Methods The clinical data of 15 patients with SCLC combined with PLE from January 1980 to May 2017 were collected from Beijing Union Hospital. Their symptoms and laboratory data were analyzed and the prognosis of the patients was followed. Results PLE is a rare disease, the incidence rate in SCLC is about 0.842%. The data may be underestimated because of misdiagnose or missed diagnosis; High incidence crowd of the disease is the middle-aged male smoker, the tumor-node-metastasis (TNM) stages of them are later than others; Typical neurological symptoms include varying degrees of short-term memory loss, seizures and varying degrees of mental disorders; neurological symptoms usually occur before the onset of cancer or respiratory symptoms appear, an average of about 2 months be taken from onset to diagnosis; Serum antibody (anti-Hu, GABA-R-Ab), cerebrospinal fluid, head magnetic resonance imaging (MRI) and electroencephalogram (EEG) of the patients has abnormalities; Videography, especially computed tomography (CT) is a good means of screening the primary tumor, pathology diagnosis mainly rely on bronchoscopy; The treatment of primary tumors can be more effective in alleviating the nervous system symptoms than immunotherapy. Conclusion Paraneoplastic limbic encephalitis is a rare paraneoplastic syndrome in nervous system caused by malignant neoplasms often characterized by facial neurological symptoms. The disease are usually associated with lung cancer (especially SCLC). Its nervous system symptoms occur earlier than the tumor diagnosis. Early diagnosis and treatment for primary tumors will increase the benefit.

Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is one of the downstream pathways of cytokine signaling transduction. It regulates cell development, differentiation, proliferation, apoptosis and so on. The pathway is not only involved in the regulation of normal physiological processes, but also significant in the development of tumors, especially in hematologic malignancies. In recent years, with the further research of JAK/STAT signaling pathway, it has been found that the pathway also plays a key role in the development of solid tumors. Here we reviewed the research advances of JAK/STAT signaling pathway in lung cancer, especially the mechanisms of development, metastasis and drug resistance, and the application of inhibitors which targeting JAK/STAT signaling pathway in the treatment of lung cancer.

The incidence of ALK gene rearrangement in non-small cell lung cancer (NSCLC) was about 3% to 5%. ALK gene inhibitors have made great breakthrough in recent years, significantly extending the survival period of patients with ALK(+) advanced NSCLC. But the majority of patients will be acquired drug resistance after treatment. This article has been explained separately from the ALK genetic background, the detection method, the treatment of the three generations of ALK inhibitors and the strategy after drug resistance. It is desire to have reference value and reference meaning for clinical work.

Immunological checkpoint inhibitors have been approved for a short period of time in China, and real-world clinical data are still in the collection stage. Reports of domestic programmed death-1 (PD-1) treatment-related adverse reactions are rare. The author reported a case of hypotension in the process of Pembrolizumab infusion and successful infusion after blood pressure recovery, hoping to provide reference for the application of immunological checkpoint inhibitors, to provide patients with the greatest clinical benefit.

Background and objective Epidermal growth factor receptor (EGFR) and KRAS gene are important driver genes of non-small cell lung cancer (NSCLC). The studies are mainly focused on detection of EGFR gene for advanced NSCLC, and the mutation feature of EGFR and KRAS gene in early NSCLC tissue is unknown. This study aims to investigate the mutations of EGFR and KRAS gene in NSCLC, and the relationship between the genotype and clinicopathologic features. Methods The hotspot mutations in EGFR and KRAS gene in 754 tissue samples of stage I-IIIa NSCLC from Department of Pathology, Peking Union Medical College Hospital were detected by modified amplification refractory mutation system (ARMS) real-time PCR kit, and analyzed their correlation with clinical variables. Results The hotspot mutation rates in EGFR and KRAS were 34.5% and 13.1% respectively, and there were EGFR-KRAS double mutations in 3 samples. The mutation rate of EGFR was higher in females than that in males (39.5% vs 29.4%, P=0.076), significantly increased in adenocarcinomas (38.7%) compared to that in the other forms of NSCLC (P

Background and objective Lung cancer is the most common malignancy and is the leading cause of cancer-related death worldwide. Thus, this disease severely threatens human health. This study aims to identify the relationships between serum albumin and urea level and the clinical pathological characteristics and survival time in patients with lung cancer. Methods A total of 1,098 patients with lung cancer were diagnosed by pathology and tested the serum albumin and urea level in West China Hospital of Sichuan University during January 2008 to December 2013. According to the levels of albumin and urea, patients were divided into the normal level group (negative group) and abnormal level group (positive group). The differences of patients' clinical pathological characteristics and survival time in the two groups were analyzed. Results Differences in age, sex, histological classification, liver metastasis and pleural metastasis were statistically significant between the two groups of serum albumin (P

Background and objective Standard care for patients with inoperable advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. The ideal concurrent chemotherapy regimen has not been determined. The aim of this study is to retrospectively analyze the efficacy and safety of concurrent radiotherapy with carboplatin/paclitaxel administrated every three weeks (PC three-week regimen) in inoperable advanced NSCLC and compare them with the results of cisplatin/etoposide. Methods The 43 patients with inoperable advanced NSCLC receiving concurrent chemotherapy in Peking Union Medical College Hospital from January 2012 to June 2014 were enrolled and analyzed. Of them, 15 patients received carboplatin/paclitaxel with concurrent thoracic radiotherapy; the other 28 patients received cisplatin/etoposide. Clinical characteristic, efficacy and toxicity data were compared in these two groups. Results For the overall population, the objective response rate (ORR) and disease control rate (DCR) were 41.9% and 90.7% respectively. The median progression free survival (PFS) was 10.6 months (95%CI: 7.4-13.8). And the median overall survival (OS) was 19.2 months (95%CI: 15.3-23.1). There were no significant differences in response rates (ORR: 33.3% vs 46.4%; DCR: 86.7% vs 92.9%, P=0.638), PFS (6.6 months vs 12.2 months, P=0.389), or OS (16.1 months vs 22.1 months, P=0.555) in either group. The adverse events were generally manageable and no treatment-related deaths occurred. Conclusion Compared with PE, PC three-week regimen concurrent thoracic radiotherapy for inoperable advanced NSCLC has the similar efficacy and acceptable toxicity profile, which can be used in clinical setting.

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor but highly sensitive to chemotherapy and radiotherapy. At present, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. In this study, we analyzed the survival among all extensive-stage SCLC and patients who received first-line chemotherapy and determined prognostic factors. Methods Total of 394 patients who were diagnosed as extensive-stage small cell lung cancer from February 2001 to December 2011 hospitalized in Peking Union Medical College Hospital were collected. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the influence factors of survival. Results The median OS of all extensive-stage small cell lung cancer was 14.8 months; 1-year, 2-year and 5-year survival rates were 58.9%, 27.2% and 7.8%, respectively. According to the results of univariate and Cox multivariate analysis, OS of extensive-stage SCLC was closely associated with age (P=0.006), ECOG PS (P=0.021), liver metastasis (P

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor and sensitive to chemotherapy and radiotherapy. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. The aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. Methods 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected. χ2 test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. Results The patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. The median OS in second-line chemotherapy as 7.0 months and was relevant with smoking history (P=0.004), ECOG PS (P

Background and objective At present, surgery is advocated for stage IIIa non-small cell lung cancer (NSCLC), and the survival of them is determined by many factors. The aim of this study is to analyze the influencing factors of prognosis for stage IIIa surgical patients. Methods Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological finding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically significant. Results 151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. The median OS and PFS of the whole group were 38.9 and 12.9 months respectively. The median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. The median PFS of them were 14.9 and 19.8 months respectively. There were no significant differences of OS and PFS between two groups. Univariate and multivariate analysis indicated that postoperative chemotherapy had a significant influence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a significant influence on PFS (P

Background and objective Epidermal growth factor receptor (EGFR) gene mutation is the most important predictor of the efficiency of EGFR-tyrosine kinase inhibitors in the treatment of non-small cell lung cancer (NSCLC). The detection of EGFR gene mutations can guide individual therapies for NSCLC. Numerous methods are used to detect EGFR gene mutation and each method has different features. This study aims to establish a real-time polymerase chain reaction (PCR) method for the detection of EGFR gene mutations using amplification refractory mutation system (ARMS) specific primers and Taqman fluorescence probes. Methods ARMS specific primers for the two EGFR gene mutations (E746_A750 and L858R) and Taqman fluorescence probes for the detection of the target sequence were carefully designed by the Primer Premier 5.0 software. Then, using the recombinants containing E746_A750 and L858R mutations as the study objects, we further analyzed the sensitivity and lower limit of this method, and then determined the cutoff ΔCt value to evaluate specific or non-specific amplification. A total of 100 clinical samples were collected and used to detect the EGFR gene mutations using this method. Results The lower limit of this method for the detection of EGFR gene mutation was 10 copies if no interference of wild-type EGFR gene or background DNA existed. Regarding the method sensitivity, the detection resolution was as high as 1% and 0.1%-0.5% in the background of 500 and 5,000 copies/μL wild-type EGFR gene, respectively. Regarding the method specificity, non-specific amplifications were found when it was used to detect 21 L858R mutations in leukocyte DNA samples from healthy volunteers. However, the minimal ΔCt value was 14.48. Non-specific amplifications were not found when detecting 19 Del mutations. Among the 100 clinical samples, 39 mutations were detected (19 Del and 21 L858R were 21 and 18, respectively) using this method. The total mutation rate was 39.0%. Conclusion The proposed ARMS-TaqMan real-time PCR method for the detection of 19 Del and 21 L858R mutations in EGFR gene was rapid, simple, sensitive, specific, and applicable in the clinical setting.

Background and objective Platinum-based doublet chemotherapy is still the standard first-line treatment for non-small cell lung cancer (NSCLC). Previous studies have demonstrated that pemetrexed combined with platinum had promising efficacy and safety profile in NSCLC, especially in patients with nonsquamous NSCLC. This trial was conducted to evaluate the efficacy and safety of pemetrexed made in China as first-line treatment. Methods The present study was a randomized, controlled, multicenter clinical trial. Patients were randomly assigned (1:1) to receive cisplatin plus pemetrexed chemotherapy (PC group) or gemcitabine plus cisplatin (GC group) every 3 weeks. The primary end point was progression free survival (PFS) and the secondary end points included 1 year survival rate, objective response rate (ORR), survival without grade 3/4 toxicity (SWT3/4) and safety profile. Results A total of 288 patients from 20 institutions across China were enrolled into the study. Based on the Full Analyses Set (FAS), the PFS was 168 days (5.6 months) vs 140 days (4.7 months) (P=0.16), one year survival rate was 50.0% vs 54.9% (P=0.47), ORR was 24.4% vs 14.2% (P=0.06) in the PC group and the GC group, respectively; Survival without grade 3/4 toxicity was 11.3 months in GC group vs 8.1 months in PC group (P=0.23). In terms of the safety, side effects were less observed on the PC group (81.95% vs 93.75%, P=0.003). The main side effects included leukopenia, neutropenia, emesis, anemia, thrombopenia. Conclusion The both regimens have similar efficacy as the treatment for advanced nonsquamous NSCLC, but pemetrexed plus cisplatin regimen has better safety profile and seems to have longer PFS, which makes it a new option as the first line setting.

Background and objective The aim of this study is to detect the efficacy and toxicity of gemcitabine and vinorelbine (GN as second-line or further-line treatment) in refractory advanced non-small cell lung cancer (NSCLC) patients in China. Methods We retrospectively reviewed 53 NSCLC patients treated with this agent at four hospital in China from Jan 01, 2004 to Jun 30, 2010. Survival analysis was evaluated by Kaplan-Meier method. Results A total of 53 patients were analyzed in this study (28 patients in second-line and 25 in third- or further-line treatment). The objective response rate (ORR) was 9.4%. The disease control rate (DCR) was 56.6%. The progression-free survival (PFS) and median overall survival (OS) was 3.0 and 17.6 months, respectively. Univariate analysis, revealed performance status (PS) score was an independent prognostic factor for overall survival. Conclusion The GN agent is effective for the second-line or further- line treatment in advanced non-small cell lung cancer. The toxicity is well tolerated .

Background and objective It has been proven that the status of epidermal growth factor receptor (EGFR) gene mutation was related to effects of gefitinib in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study is to reports distribution of EGFR gene mutations in advanced NSCLC and their influence on effect of gefitinib. Methods From Jan 2007 to Dec 2009, 160 patients with advanced non-squamous NSCLC received EGFR mutation tests, and EGFR exon 19 and 21 were amplified by mutant-enriched PCR and analyzed by sequencing. Among those patients, 111 received gefitinib therapy. Overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan-Meier method and a Cox regression analysis was used to detect differences between strata. Results The percentage of EGFR mutation in advanced non-squamous NSCLC was 55%, and it was only significantly related with pathological type. OS of the patients with or without EGFR gene mutations were 29.0 months (95%CI: 24.2-33.8) and 21.0 months (95%CI: 14.7-27.3) respectively, and the difference was not significant. PFS of patients with or without EGFR gene mutations were 17.0 months (95%CI: 5.6-17.6) and 11.6 months (95% CI 8.6~25.4), and the difference was significant (P=0.022). Multivariate analysis shows that OS was significantly related with ECOG status, pathological type and EGFR mutation statuses, and PFS was significantly related to ECOG status, former regimens number and EGFR mutation statuses. There were no significant differences in OS and PFS between patients with EGFR exon 19 deletions and those with exon 21 point mutation. Conclusion PFS of patients with EGFR mutations was better than those without EGFR mutations, but OS was similar. There were no significant differences in OS and PFS between patients with EGFR exon 19 deletions and those with exon 21 point mutation.

Background and objective Chemotherapy has become the mainstay of first-line therapy. Non-platinum containing drugs are characterized by favorable toxicity profiles and is better tolerated than platinum-based regimens. The aim of this study is to detect the efficacy and toxicity of gemcitabine and vinorelbine (GN) in advanced non-small cell lung cancer (NSCLC) first-line treatment in China. Methods We retrospectively reviewed 67 NSCLC patients treated with this agent at five Hospital in China from Jan 2004 to Jun 2010. Survival analysis was evaluated by Kaplan-Meier method, multivariate analyses were performed to find prognostic markers using Cox proportional hazards model. Results A total of 67 patients were analyzed in this study. There were 52 patients with RRM1 negative and ERCC1 positive. The objective response rate was 34.3%. The disease control rate was 76.1%. The progression-free survival and median overall survival was 5.5 and 22.1 months, respectively. On multivariate analysis, performance status score and whether further treatment were independent prognostic factor for overall survival. Conclusion The GN agent is effective for the first line treatment in advanced non-small cell lung cacer. The toxicity is well tolerated.

Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC) who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390) trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg) combined with chemotherapy (carboplatin plus paclitaxel) treatment from August 2007 to February 2008. Adverse effects (AEs), objective response rate (ORR), median time to progression (TTP), and overall survival (OS) were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

Background and objective Quality of life (QoL) is an important end point in cancer patients, and depressive symptoms are significantly more frequent in lung cancer patients. The aim of this study is to observe the impact of chemotherapy on quality of life and emotion among lung cancer patients. Methods Fourty lung cancer patients were assessed with clinical outcomes, the EORTC QLQ-C30, SDS questionnaires before chemotherapy, one week after 2 cycles of chemotherapy, one week after 4 cycles of chemotherapy. Results Before chemotherapy, the scores of functioning scales were high, the rate of depression was 65%. After 2 cycles of chemotherapy, effective rate was 42.5%, the scores of cognitive function increase, the scores of role, emotional, social function decrease, the scores of dyspnoea decrease, the scores of pain, appetite loss, insomnia, constipation, diarrhea increase, the scores of Global quality of life decrease; the rate of depression was 70%. After 4 cycles of chemotherapy, effective rate was 23%, the scores of physical, role, emotional, social function decrease, the scores of symptom scales increase, the scores of dyspnoea, nausea and vomiting, appetite loss, financial impact increase, the scores of global quality of life decrease, the rate of depression was 87.5%. Conclusion Some patients have symptoms relieved, but during the chemotherapy, the patients have significant depression, the quality of life decrease. We should evaluate the quality of life and emotions of lung cancer patients, and give positive psychological intervention to improve the quality of life.

Background and objective Non-small cell lung cancer (NSCLC) with mutations in the epidermal growth factor receptor (EGFR) is a distinct subgroup of NSCLC, which is particularly responsive to EGFR tyrosine kinase inhibitors (TKIs). The aim of this study is to detect EGFR mutations in paired serum of pre- and post-chemotherapy from advanced pulmonary adenocarcinoma patients to evaluate impact of chemotherapy on EGFR mutation status. Methods Magnetic beads were used for DNA extraction from paired serum of pre- and post-chemotherapy of 33 advanced pulmonary adenocarcinoma patients. The EGFR exon 19 and 21 were amplified by mutant-enriched nested PCR and analyzed by direct sequencing. Results EGFR mutations were detected in 39.4% (13/33) and 54.5% (18/33) serum samples of pre- and postchemotherapy, respectively. The EGFR mutation status was consistent in 54.5% (18/33) patients. Among 15 discordant cases, 10 changed from pre-chemo wild-type to post-chemo mutant-type status, while 5 from pre-chemo mutant-type to post-chemo wild-type status. Conclusion Chemotherapy may have influence on serum EGFR mutation status in advanced adenocacinoma patients.

Background and objective Controversies exists with regard to target volumes as far as thoracic radiotherapy (TRT) is concerned in the multimodality treatment for limited-stage small cell lung cancer (LSCLC). The aim of this study is to prospectively compare the local control rate, toxicity profiles, and overall survival (OS) between patients received different target volumes irradiation after induction chemotherapy. Methods LSCLC patients received 2 cycles of etoposide and cisplatin (EP) induction chemotherapy and were randomly assigned to receive TRT to either the post- or pre-chemotherapy tumor extent (GTV-T) as study arm and control arm, CTV-N included the positive nodal drainage area for both arms. One to 2 weeks after induction chemotherapy, 45 Gy/30 Fx/19 d TRT was administered concurrently with the third cycle of EP regimen. After that, additional 3 cycles of EP consolidation were administered. Prophylactic cranial irradiation (PCI) was administered to patients with a complete response. Results Thirty-seven and 40 patients were randomly assigned to study arm and control arm. The local recurrence rates were 32.4% and 28.2% respectively (P=0.80); the isolated nodal failure (INF) rate were 3.0% and 2.6% respectively (P=0.91); all INF sites were in the ipsilateral supraclavicular fossa. Medastinal N3 disease was the risk factor for INF (P=0.02, OR=14.13, 95%CI: 1.47-136.13). During radiotherapy, grade I, II weight loss was observed in 29.4%, 5.9% and 56.4%, 7.7% patients respectively (P=0.04). Grade 0-I and II-III late pulmonary injury was developed in 97.1%, 2.9% and 86.4%, 15.4% patients respectively (P=0.07). Median survival time was 22.1 months and 26.9 months respectively. The 1 to 3-year OS were 77.9%, 44.4%, 37.3% and 75.8%, 56.3%, 41.7% respectively (P=0.79). Conclusion The preliminary results of this study indicate that irradiant the post-chemotherapy tumor extent (GTV-T) and positive nodal drainage area did not decrease local control and overall survival while radiation toxicity was reduced. But the current sample size has not met designed requirements, and further investigation is warranted before final conclusions could be drawn.

Background and objective Recent studies indicated that Non-small cell lung cancer (NSCLC) patients with mutant K-RAS failed to benefit from adjuvant chemotherapy, and the cancer did not respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). These findings indicated that K-RAS gene status can be a biomarker to predict the sensitivity of EGFR TKIs. The aim of this study is to analyze K-RAS gene mutations with NSCLC patients in Cancer Center of Sun Yet-sen University. Methods 52 fresh frozen tumor tissues were collected and K-RAS genes were amplified by PCR. Then PCR amplification fragments were sequenced and analyzed. Results Somatic mutations in the codon 12 of K-RAS gene in tumors were identified from 2 of 52 (3.8%) patients. There were no relationships among K-RAS gene mutations and gender, pathology, smoking, differentiation and stage. Conclusion The frequency of K-RAS gene mutations with NSCLC in our center is very low and is similar to that in Asia patients, and is lower than that in Caucasian population.

Background and objective How to prolong progression free survival (PFS) and overall survival (OS) of patients with small cell lung cancer (SCLC) has been one of the hottest issues. We retrospectively reviewed our data to compare the survival of immediate with delayed topotecan after first-line therapy in SCLC. Methods In our retrospective study, 53 patients with SCLC were divided into two groups as follow: patients receiving topotecan-containing regimen as maintenance/consolidation (maintenance/consolidation chemotherapy group) and salvage chemotherapy (salvage chemotherapy group). The Log-rank test was used to assess the difference in OS between two groups. Cox regression model was used for the multivariable analysis of independent prognostic factors. Results Twenty-nine patients received topotecan as maintenance/consolidation treatment, whereas 24 patients salvage chemotherapy. The response rates were 51.7% and 41.7%, respectively. The median survival time were 20 months and 27 months respectively (P=0.89). Multivariate Cox regression analyses identified sex and stage as independent prognostic factors. Conclusion Efficacy of first-line therapy was improved by topotecan maintenance/consolidation treatment, which did not result in any significant survival benefits in SCLC.

Background and objective The relationship between the virus and carcinomas has attracted attention and China may be highly infected-District with HPV. It was unclear that whether there has been HPV infection in squamous cell carcinomas and the occurrence and development of lung cancer has the relation with HPV. This experiment applied situ hybridization and immunohistochemical techniques. This study is to investigate the relationship between the status of HPV16/18 infection between the expression of Bcl-2 and Bax in squamous cell carcinomas of the lung. Methods In 44 patients with squamous cell carcinomas of the lung, HPV 16/18 DNA was examined by in situ hybridization, expression of Bcl-2 and Bax was revealed by immunohistochemistry and koilocytes was detected in carcinomas tissues by morphologic examination. Results Of 44 patients with squamous cell carcinomas of the lung, 12 (27.27%) were found to be HPV negative. Twenty-three (52.27%) were found to be integrated form HPV, 9 (20.45%) were found to be large number of episomal form and a few integrated form HPV. And no simplex episomal form HPV was found. HPV 16/18 DNA could not be detected in 15 non-carcinomas tissues. A significantly higher 16/18 DNA positive rates in carcinomas tissues compared to non-carcinomas tissues (P

Background and objective Most patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy consisted of the third generation new drug got the disease in control (CR+PR+SD).In this study, we retrospectively reviewed our data to investigate the difference of survival between patients of disease control and progression (PD), and disease response (CR+PR) and stable (SD), to identify the prognosis factor correlated with survival. Methods In our retrospective study, 118 patients with stage IIIB (with malignancy pleural fluid) and IV NSCLC were identified who received the third generation new drug-based platinum or non-platinum regimens, the response of first-line chemotherapy were complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) according to RECIST criteria based on the records on the imaging reports papers. Results After first-line chemotherapy, 86 (72.9%) patients [CR2 (1.7%), PR47 (39.8%), SD37 (31.4%)) had disease control and 33 (27.1%) patients had progression disease. The median survival time of CR+PR+SD arm was significantly longer than PD arm (17.8 months vs 8.4 months, P=0.001), but there was no significant difference between CR+PR arm and SD arm (18.1 months vs 15.5 months, P=0.917), the PFS between two arms were no significantly different too (7.1 months vs 6.9 months, P=0.622). The Cox regression analysis shows that stage (IIIB or IV), chemotherapy lines (less than three lines or more than four lines) and disease control or not after first-line chemotherapy were independently prognosis factor of overall survival. Conclusion Our data shows that the survival of response and stable disease patients are better than that of patient with progression disease, the survival benefit of patients with stable disease and responses are no significantly difference.

There is a temporal disease-free period after 1st line chemotherapy in advanced non-small cell lung cancer (NSCLC), most of patients need 2nd line chemotherapy. The recommended drugs in the 2nd line were docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Single docetaxel is the established therapy for second-line treatment of NSCLC.Pemetexem was validated its indication in the 2nd line in advanced NSCLC through a phase III randomised clinical trial which was compared with docetaxel. Althoughthere were little toxicity, the further research can't find the survival benefit in high dose pemetrexed. EGFR-TKIs target therapy is a hot spot now. Gefitinib and erlotinib monotherapy have a good efficacy in the 2nd line. The research of gefitinib versus traditional chemotherapy manifested that its efficacy was no less than docetaxel, and was less toxicitity . The comparison of erlotinib with chemotherapy is going on. There are more and more other drugs proved their effect in the 2nd line, such as the efficacy of oral toptecan and vinflunine were similar to docetaxel.