ABSTRACT
Lung cancer remains to have the highest morbidity and mortality rates in China among known malignant tumors. Novel drugs and regimens have been sought because of the limited efficiency of traditional chemotherapy and radiotherapy in lung cancer treatment. In the last 20 years, rapid developments in molecular targeted therapy and immunotherapy have increased clinical efficacy and benefitted patients with cancer. Treatments for lung cancer are the most rapidly developed among treatments for solid tumors, pioneering tumor precision medicine. This manuscript reviews the evolution and development of targeted therapy and immunotherapy and discusses existing problems and future directions in the precision therapy of lung cancer.
ABSTRACT
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. .
ABSTRACT
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.
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Early diagnosis and screening are of great significance for improving the prognosis of patients with lung cancer. Low-dose helical computed tomography (LDCT) reduces lung cancer mortality by about 20％, making it the most effective screening tool. However, high false-positive rates, costs, and potential harms highlight the need for complementary biomarkers. The diagnostic performance of biomarkers such as noninvasive autoantibody and plasma/serum microRNA (miRNA) were shown in several studies, making them approved for early diagnosis in our country, Europe and the United States, and their role in screening is being explored in ongoing studies.
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Objective To investigate the diagnostic value of EBUS imaging features for metastatic mediastinal/hilar lymph node enlargement in lung cancer.Methods The lung cancer patients with a pathological diagnosis and without preoperative anti-tumor treatment who got the EBUS-TBNA examination from October 2009 to September 2011 were retrospectively analysis.422 lung cancer patients with 683 mediastinal / hilar lymph nodes were enrolled in this study,including 335 males and 87 females; the median age is 61 years old (range 24-82),EBUS lymph node ultrasound image and the final pathological or follow-up results were compared by the statistical analysis.Homogeneity in the lymph node EBUS image feature was defined as:uniform echo in the ultrasound images,cortex existed in the peripheral areas,medulla existed in lymph central with a slightly stronger echo and represent as a small strip.Heterogeneity was defined as: the ultrasound image was defined as uneven echo involved with coagulation necrosis sign,which was the hypoechoic areas without blood flow in the lymph nodes and represent no blood flow in the CDPI mode.The coagulation necrosis was associated with necrosis within the lymph node.In addition,if the CNS region occupied more than 11％ of the entire lymph node in a complete lymph node or just a part of huge lymph nodes in the EBUS imaging window frame,we also regard it as heterogeneity.If a complete lymph node was seen in the EBUS imaging window frame,we measured the longest diameter to the long axis and its vertical maximum diameter to the short axis.If the lymph node was huge and extended the EBUS imaging window frame,we measured the longest diameter in the frame as the long axis of its vertical maximum diameter to be the short axis.As to the EBUS-TBNA negative lymph nodes,we regarded it was malignant lymph node if the diameter of the lymph node increased by 20％ in the patients who did not received any chemotherapy or radiotherapy or the diameter of the lymph node increased or decreased by 20％ in the patients who received any chemotherapy or radiotherapy six month later in the chest enhanced CT scan,otherwise,it was identified as benign lymph node.We used the RECIST 1.1 solid tumors criteria to evaluate the efficacy of the chemotherapy.Results 422 patients were enrolled this study including 93 squamous carcinomas,137 adenocarcinomas,97 small cell lung cancer,42 poorly differentiated non-small cell lung cancer,29 adenosquamous carcinoma and 24 other malignant tumors (including large cell carcinoma,sarcomatoid carcinoma,carcinoid tumors,etc).The sensitivity of the EBUS-TBNA was 93.8％ (396/422).The diagnostic methods and results in the 683 lymph nodes were as the following: 506/683 (74.1％) was confirmed as cancer by the EBUS-TBNA while 177/683 (25.9％) was diagnosed as benign disease.Among these,32/683 (4.7％) was confirmed as cancer and 57/683 (8.3％)was confirmed as benign disease by surgery,9/683 (1.3％) was confirmed as cancer and 79/683 (11.6％) was confirmed as benign disease by the method of follow-up.the sensitivity for the EBUS-TBNA to be malignant was 506/547 (92.5 ％),specificity was 136/136 (100％),positive predictive value was 506/506 (100％),negative predictive value was 136/177(76.8％) and accuracy was 642/683 (94.0％).The short axis diameter in the 683 lymph nodes ranged from 0.40cm to 4.60cm with an average diameter of (1.58 ± 0.68) cm.Among them,the short axis diameter in the malignant lymph node was (1.75 ± 0.63) cm,and in the benign lymph nodes was (0.92 ± 0.40) cm.527 lymph nodes presented heterogeneity under the ultrasound imaging,in which,519/527 (98.5 ％)were malignant lymph nodes.While,156 lymph nodes presented homogeneity and 28/156 (17.9％) were malignant lymph nodes (x2 =489.5,P ＜0.01).In the heterogeneous lymph node with a short axis diameter more than 1.0cm,the sensitivity to be malignant was 89.4％,specificity was 100％ and accuracy was 89.6％.In the homogeneous lymph node with a short axis diameter less than 0.8cm,the sensitivity to be benign was 43.8％,specificity was 67.8％ and accuracy was 48.1％.Conclusion EBUS-TBNA is new biopsy method for the mediastinal / hilar lymph node.The classification based on EBUS imaging-based lymph node ultrasound image features was helpful to identify the procedure for the diagnostic purposes and could help to distinguish the benign or malignant mediastinal / hilar lymph node in lung cancer patients.
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Objective To evaluate the diagnostic role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the smear and culture negative tuberculosis.Methods The tuberculosis suspected patients with spu-tum-negative for three times and with hilar or mediastinal lymphadenopathy were randomly divided into 2 groups,study group received EBUS-TBNA and bronchoalveolar lavage group(BAL) examination,control group received BAL examination only.Chi-square test was used to compare their diagnostic sensitivity and negative predictive value.Results Totally 82 patients were included this study,40 patients were in control group and 42 in the study group.In the control group,tuberculosis was confumed in only 8 cases by means of bacteriological examination in the BAL fluid,27 were confirmed by the following surgery ordiagnostic treatment of anti-Tuberculosis,and the other 5 cases were diagnosis as other diseases; In the study group,tuberculosis was confirmed in 28 patients through bacteriological and pathological examination,8 were false negative and the other 6 were diagnosis as non-tuberculosis diseases.The diagnostic sensitivity in the study group was significantly higher than that in control group (77.8％ verus 22.9％,x2 =21.4,P ＜ 0.01 ) ; and the negative predictive value in the EBUS-TBNA group was also significantly higher than that in the BAL group (42.9％ VS 15.6％,x2 =3.97,P =0.046).Complications were similar inthese 2 groups,only 1 case of intervention required puncture site bleeding happened in the study group.Conclusion EBUSTBNA has a higher sensitivity and negative predictive value in the diagnosis of smear and culture negative pulmorary tuberculosis patients with hilar or mediastinal lymph nodes.This technique is a safe method with few complications than the traditional BAL examination.It may play an important role in the diagnosis of smear and culture negative tuberculosis patients.
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OBJECTIVE To investigate antimicrobial resistance and molecular epidemiology profiles of meticillin-resistant Staphylococcus aureus(MRSA)sampled from lower respiratory tract.METHODS Totally 107 MRSA strains were isolated from lower respiratory tract specimens at Shanghai Pulmonary Hospital between Dec 2005 and Dec 2006.PVL genes were detected by PCR.The genotypes of SCCmec were identified by multiplex PCR.The antimicrobial resistance of MRSA were tested by Kirby-Bauer agar dilution.We also performed the homology of 32 MRSA strains using pulsed-field gel electrophoresis(PFGE).RESULTS All of the 107 MRSA strains were negative in the PVL locus detection and the most frequent SCCmec types were type Ⅲ(81.3%),the others including type Ⅱ(15.9%),type Ⅳ(2.8%),type Ⅰ and type Ⅴ were not found in this group.Those 3 different types of SCCmec were all resistant to ?-lactam antibiotics,less resistant to rifampin,and susceptible to vancomycin,teicoplanin and daptomycin.The resistant rate of those 3 types were different to the non-?-lactam antimicrobial drugs such as trimethoprim/sulfamethoxazole,clindamycin,erythromycin,gentamicin,levofloxacin,and tetracycline,the resistant rate in the types Ⅱ and Ⅲ was significantly higher than the type Ⅳ.PFGE analyses assorted the 32 MRSA strains into 4 PFGE patterns:pulsotype A(25 strains),including subtypes A1(17strains),A2(1 strain)and A3(7 strains);pulsotype B(5 strains),pulsotype C(1 strain),and pulsotype D(1 strain).CONCLUSIONS This study does not found positive PVL locus in the MRSA strains in our hospital,the most frequent SCCmec types are type Ⅲ and some are type Ⅱ.PFGE presented that there are outbreaks of MRSA in ICU ward and TB ward No 5 at that time and the pandemic strains are subtypes A1 and A3,most of these MRSA strains are multiple resistant,which deserves attention from both the clinical staff and infection-control department of the hospital.