Ceritinib as First-line Treatment for Advanced Lung Adenocarcinoma with COX7A2L-ALK Fusion: A Case Report and Literature Review / 中国肺癌杂志

Lung cancer is the most common in incidence and mortality worldwide. With the development of next generation sequencing (NGS) detection technology, more and more patients with rare anaplastic lymphoma kinase (ALK) fusion mutations were detected. A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors. The best response of the patient was assessed as partial response (PR) with Ceritinib treatment. By literature review, 22 cases of rare ALK fusion were reported in 19 articles. Combined with this case, 23 cases were analyzed. The objective response rate (ORR) was 82.6% (19/23) and disease control rate (DCR) was 95.7% (22/23) for rare ALK fusions patients treated with ALK inhibitors. Lung adenocarcinoma patients with rare ALK fusion could benefit from ALK inhibitors.
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Advances in Molecular Subtyping, Characteristics and Therapeutic Strategies of Small Cell Lung Cancer / 中国肺癌杂志

Small cell lung cancer (SCLC) is a malignant tumor with remarkable proliferative and invasive ability, which has very poor clinical prognosis due to lack of effective treatments. In recent years, researches on cells, animal models and tumor samples have promoted the identification of molecular subtypes of SCLC, discovered unique biological and clinical characteristics, and proposed potential specific therapeutic targets for different subtypes. This will encourage the development of more accurate therapeutic strategies towards SCLC, with a view to improving the prognosis of the patients. This article will review the current SCLC molecular subtypes, focus on the clinical characteristics and therapeutic strategies of different SCLC subtypes, and propose reasonable suggestions for the future treatment of SCLC.
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Immune checkpoint inhibitors for the treatment of non-small cell lung cancer brain metastases / 中华医学杂志(英文版)

Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ . Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.

Blocking Adenosine/A2AR Pathway for Cancer Therapy / 中国肺癌杂志

Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies.
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Advances and Clinical Application of Malignant Probability Prediction Models for Solitary Pulmonary Nodule / 中国肺癌杂志

With the popularization of computed tomography (CT) examinations, the incidence of solitary pulmonary nodules (SPNs) has increased significantly. The assessment of benign and malignant pulmonary nodules is crucial to the diagnosis and treatment of lung nodules. Many models for predicting the malignant probability of lung nodules have been developed. These models assess the malignant probability of lung nodules based on the clinical and imaging characteristics of patients. In recent years, malignant probability prediction models have gradually attracted attention in China. Based on the researches on the malignant probability prediction model of pulmonary nodule, focusing on the establishment or verification of the model in the Chinese patient population, this paper reviews the research progress and clinical application of the malignant probability prediction model of pulmonary nodule, and proposes ideas for the future development.
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COVID-19 Vaccination for Cancer Patients: Progress and Preliminary Recommendations / 中国肺癌杂志

The pandemic of coronavirus disease 2019 (COVID-19) has had a serious impact on global health. COVID-19 vaccines may be one of the most effective measure to end the pandemic. High infection risk and higher serious incident and mortality rates have been shown in cancer patients with COVID-19. Therefore, cancer patients should be the priority group for COVID-19 prevention. Until now, data of COVID-19 vaccination for cancer patients is lacking. We review the interim data of safety and immune-efficacy of COVID-19 vaccination in cancer patients based on the latest studies. Due to the complicated immune systems of cancer patients caused by the malignancy and anticancer treatments, we proposed preliminary specific COVID-19 vaccination recommendations for cancer patients with different anticancer treatments and at different stages of the disease. Preventing COVID-19 with vaccinations for cancer patients is crucial, and we call for more large-scale clinical trials and real-world studies, for further COVID-19 vaccination recommendations development.
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Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#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.@*CONCLUSIONS@#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.

Clinical-radiological-pathological Characteristics of 297 Cases of Surgical Pathology Confirmed Benign Pulmonary Lesions in Which Malignancy Could Not Be Excluded in Preoperative Assessment: A Retrospective Cohort Analysis in a Single Chinese Hospital / 中国肺癌杂志

BACKGROUND@#Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease.@*METHODS@#From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted.@*RESULTS@#297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%).@*CONCLUSIONS@#Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.

Results of EGFR Mutations Detected in Pleural Effusion and Its Clinical Significance in 132 Patients with Advanced Non-small Cell Lung Cancer: A Retrospective Study in A Single Center / 中国肺癌杂志

BACKGROUND@#The lack of pathological quality control standard in detecting epidermal growth factor receptor (EGFR) gene mutation in malignant pleural effusion leads to confusion in the interpretation of detection results and the clinical use of EGFR-tyrosine kinase inhibitor (TKI). Therefore, it is very important to propose quality control standards and guide the detection of EGFR mutation in pleural effusion. The aim of this study is to retrospectively analyze the results of EGFR gene mutation in pleural effusion sediment section according to strict pathological quality control standards, and the therapeutic effect of EGFR-TKIs guided by this detection results.@*METHODS@#From January 2012 to June 2018, the clinical data of patients with pleural effusion collected from Department of Pathology of Peking Union Medical College Hospital were analyzed retrospectively. Among them, 132 patients with relatively complete clinical data and with EGFR gene mutation detection of paraffin-embedded pleural effusion sediment section according to the established quality control standard were included. According to the results of EGFR gene mutation, it was divided into positive group and negative group, and the efficacy of EGFR-TKIs in different groups was compared.@*RESULTS@#After the centrifugation of pleural effusion, the sediment was embedded in paraffin, sectioned, and observed under the microscope after HE staining. If the number of tumor cells ≥100, it met the pathological quality control standard, and it could be used for subsequent EGFR gene mutation detection. EGFR gene mutations were detected in 72 (54.5%) of 132 patients. EGFR-TKIs were used in 69 of 72 mutation positive patients. Of 60 EGFR mutation negative patients, only 15 used EGFR-TKIs. In EGFR mutation positive group, the disease control rate (DCR) was 95.8%, and the median progression-free survival (PFS) was 11 months. In EGFR mutation negative group, the DCR was 0%, and the median PFS was 1 month. The DCR and PFS were significantly different between the two groups (P<0.05).@*CONCLUSIONS@#According to the pathological quality control standards, the embedded section of pleural fluid sediment can be used to detect EGFR gene mutation, and the results can be used to guide the clinical use of EGFR-TKIs.

Clinical-radiological-pathological Characteristics of 297 Cases of Surgical Pathology Confirmed Benign Pulmonary Lesions in Which Malignancy Could Not Be Excluded in Preoperative Assessment: A Retrospective Cohort Analysis in a Single Chinese Hospital / 中国肺癌杂志

BACKGROUND@#Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease.@*METHODS@#From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted.@*RESULTS@#297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%).@*CONCLUSIONS@#Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.

Clinical Predictive Factors associated with First Line EGFR-TKI Efficacy in Advanced NSCLC Patients with EGFR Mutations / 中国肺癌杂志

BACKGROUND@#Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated some dramatic efficacy in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, progression-free survivals (PFS) among those patients who were treated with first line EGFR TKIs were inconsistent. The aim of this study is to explore the association of clinical prognostic factors with EGFR-TKI efficacy in advanced NSCLC patients.@*METHODS@#The demographic and clinical characteristics of 203 patients with activating EGFR mutation treated with first generation TKI as a first-line therapy were retrospectively reviewed.@*RESULTS@#Of the 203 patients enrolled in this study, 139 patients had progression of disease and 63 patients died. The subjects had a median follow up duration of 21.1months and a median PFS of 14.3 months. Partial response (PR) was achieved in 127 (66.1%) patients and stable disease (SD) rate was achieved in 55 (28.6%) patients. In univariate analysis, patients with 2 or higher ECOG score (5.1 vs 16 months, P=0.033), SD as best overall response (9.5 vs 17.9 months, P=0.030), extrathoracic metastasis (11.7 vs 27.5 months, P=0.004), liver metastasis (4.1 vs 16.0 months, P=0.000), bone metastasis (13.3 vs 21.5months, P=0.027) and pulmonary embolism (5.5 vs 16.6 months, P=0.005) had shorter PFS than those without the listed factors. Multivariable Cox regression analysis showed best overall response (HR=1.825, 95%CI: 1.107-3.008, P=0.018) and liver metastasis (HR=1.694, 95%CI: 1.146-5.756, P=0.022) were independent predictive factors of shorter PFS.@*CONCLUSIONS@#Despite the high efficacy of EGFR-TKI, SD as best overall response and liver metastasis predicts poorer PFS in advanced NSCLC patients with EGFR gene mutations receiving first-line therapy treatment.

Next Steps after Negative Results Obtained by EBUS-TBNA from Patients Suspected Clinically Lung Cancer with Mediastinal Lymphnode Metastasis / 中国肺癌杂志

BACKGROUND@#Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is well known as an important technique for diagnosis and staging of lung cancer. But a standard protocol to deal with patients who have a negative pathology result still needs to be defined. Herein, we describe the subsequent procedures of these patients in a single center.@*METHODS@#A total of 1,412 patients with clinical suspected lung cancer and mediastinal metastasis who underwent EBUS-TBNA were collected between September 2010 and December 2016. Among them, 51 patients with nonspecific pathology result were included and retrospectively analyzed.@*RESULTS@#The 51 patients were stratified into five groups by clinical characterize and follow-up procedures: (1) Diagnosed by other bronchoscopy procedures group (9 cases). Abnormalities of tracheobronchial tree were found during visual examination in the majority of patients (8 cases). Biopsy, endobronchial brushing, bronchoalveolar lavage, and transbronchial lung biopsy (TBLB) were used to get a specific diagnosis. (2) EBUS-TBNA re-biopsy group (11 cases). Patients in this group had normal mucosal appearance and airway lumen. Re-biopsy were performed on patients in this group. (3) Surgery group (6 cases). Patients underwent surgery after negative result of EBUS-TBNA. Five of them were confirmed with non-nodal metastasis after surgery. (4) Underwent other pathology diagnosis group (15 cases). patients in this group had other metastasis sites besides midiastinal lymph node. Computed tomography (CT)-guided fine-needle aspiration and lymph node biopsy were performed. (5) Follow-up group (10 cases). None invasive procedure was used in this group. The median follow up time was 38 months. One patient was diagnosed lymphoma during the follow up.@*CONCLUSIONS@#Diagnostic procedures should be chosen based on the clinical character in EBUS-TBNA negative patients with suspected lung cancer. Long time follow-up is very important in patients whose diagnosis is apparently unknown.

A Retrospective Study of 42 Lung Cancer Patients with Pancreatic Metastases / 中国肺癌杂志

BACKGROUND@#A number of patients with lung cancer have distant metastases at the time of diagnosis. The most common sites for metastases are liver, brain, etc. However pancreatic metastasis is relatively rare, with an insidious onset and poor prognosis. There are no sufficient recognition and attention of lung cancer with pancreatic metastasis. The aim of this study was to summarize the pathological characteristics, clinical manifestations, therapies and prognosis of pancreatic metastases of lung cancer, thus further exploring better managements for the best prolonged survival or quality of life.@*METHODS@#42 patients of lung carcinoma with confirmed pancreatic metastases hospitalized at the Peking Union Medical College Hospital from January 1998 to December 2018 were identified. We reviewed all medical documentations for complete information including diagnosis, treatment, prognosis features.@*RESULTS@#24 (57%) patients were asymptomatic or presented with non-specific symptoms. 18 (43%) patients had symptoms related to pancreatic metastases, such as acute pancreatitis, obstructive jaundice or pain of lumber back. The median overall survival (OS) was 8.8 months. Multivariate analysis suggested patients with symptoms had a poor prognosis compared with patients without pancreatic symptoms [(hazard ratio, HR)=2.645, 95%CI: 1.013-6.910, P=0.047]. Patients received chemotherapy had better prognosis versus those who did not [HR=0.158, 95%CI: 0.049-0.512, P=0.002].@*CONCLUSIONS@#Pancreatic metastasis of lung cancer is rare and the prognosis is poor. Chemotherapy can prolong survival significantly. Local radiotherapy of the pancreas may alleviate local symptoms, improve quality of life, facilitate further systemic chemotherapy for patients to prolong survival. Patients with symptoms related to pancreatic metastases can benefit from the comprehensive treatment of chemotherapy combined with local pancreatic radiotherapy.

Advanced Pneumonic-type Lung Carcinoma: A Retrospective Study of Clinical-radiological-pathological Characteristics with Survival Analysis in A Single Chinese Hospital / 中国肺癌杂志

BACKGROUND@#Pneumonic-type lung carcinoma is a special type of lung cancer both clinically and radiologically. Here we present our experience on pneumonic-type lung carcinoma in an attempt to investigate the clinical, radiological and pathological features, diagnostic procedures, treatment, and prognosis of this type of tumor.@*METHODS@#Pathologically confirmed lung cancer with a chest CT characterized by ground glass opacity or consolidation was defined as pneumonic-type lung carcinoma. Cases with advanced pneumonic-type lung carcinoma admitted to Peking Union Medical College Hospital (PUMCH) from January 1, 2013 to August 30, 2018 were enrolled. Retrospective analysis of clinical data and survival follow-up of these patients was conducted.@*RESULTS@#A total of 46 cases were enrolled, all of which were adenocarcinoma. Cough (41/46, 89.1%) and expectoration (35/46, 76.1%) were the most prominent symptoms. The most frequent chest CT findings were ground glass attenuation (87.0%), patchy consolidation (84.8%), and multiple ground-glass nodules (84.8%). Multiple cystic changes (40%) and cavitation (13%) were also quite frequent. Ipsilateral and contralateral intrapulmonary metastasis were noted in 95.3% and 84.8% of cases respectively. The median duration from symptom onset to diagnosis was 214 days (95%CI: 129-298). Both surgical lung biopsy and CT-guided percutaneous lung biopsy had a diagnostic yield of 100%. Transbronchial lung biopsy (TBLB) combined with bronchoalveolar lavage (BAL) had a diagnostic yield of 80.9% (17/21). Sputum cytology had a diagnostic yield of 45% (9/20). Twenty-six cases were invasive mucinous adenocarcinoma (26/46, 56.5%) and the remainder were unable to identify pathological subtypes due to lack of adequate biopsy sample size. EGFR mutation was detected in 15.8% (6/38) of patients and ALK rearrangement was detected in 3.0% (1/33) of patients. The median overall survival for these patients was 522 d (95%CI: 424-619). In patients without EGFR mutation or ALK rearrangement, chemotherapy significantly improved survival (HR=0.155, P=0.002,2). The median overall survival was 547 d (95%CI: 492-602 d) with chemotherapy and 331 d (95%CI: 22-919) without chemotherapy.@*CONCLUSIONS@#Diagnosis of pneumonic-type carcinoma is usually delayed due to clinical and radiological features mimicking pulmonary infection. TBLB combined with BAL has a quite high diagnostic yield. The most frequent histological type is invasive mucinous adenocarcinoma. The incidence of EGFR mutation or ALK rearrangement is low in pneumonic-type carcinoma. For patients without cancer driver genes, chemotherapy is recommended to improve overall survival.

Diagnosis and Treatment Recommendation and Exploration for Critical and Refractory Adverse Effects Related to Immunocheckpoint Inhibitors / 中国肺癌杂志

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.

Clinical Diagnosis and Treatment Recommendations for the Pneumonitis Associated with Immune Checkpoint Inhibitor / 中国肺癌杂志

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.

Clinical Diagnosis and Treatment Recommendations for Ocular Toxicities of Target Therapy and Immune Checkpoint Inhibitor Therapy / 中国肺癌杂志

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.

Efficacy and safety of anlotinib in 16 patients with advanced non-small cell lung cancer / 中华内科杂志

Objective To evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC).Methods Patients with stageⅢB/ⅣNSCLC who progressed after two lines or more regimens were randomized into anlotinib group (12 mg daily from day 1 to 14 of a 21-day cycle) or placebo group with ratio of 2:1. Study drugs or placebo were given until disease progression or intolerable toxicity. The primary endpoint was overall survival (OS), and the second endpoints were progression free survival (PFS), objective response rate, and disease control rate. Results Between April 2015 and December 2015, twenty-four patients were assigned at Peking Union Medical College Hospital. The baseline characteristics of the anlotinib group (n=16) and placebo group (n=8) were fairly comparable. The median OS was 12.7 months in anlotinib group and 11.1 months in placebo group (P=0.460). The median PFS was 4.0 months in anlotinib group and 1.4 months in placebo group (P=0.065). The common adverse events were manageable such as hypertension, hand-foot syndrome, thyroiddy sfunction. No drug-related mortality occurred. Conclusions Anlotinib had a trend of improvement in OS and PFS as third-line treatment or beyond in advanced NSCLC compared with placebo with manageable toxicity.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration for The Diagnosis and Genotyping of Lung Cancer / 中国肺癌杂志

BACKGROUND@#Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has emerged as an innovative technique for diagnosis and staging of lung cancer. But whether the procedure can provide enough tissue for the detection of gene mutations is still to be defined. Here we evaluated the efficacy of lung cancer diagnosis and gene analysis using samples obtain via EBUS-TBNA.@*METHODS@#Patients with suspected lung cancer and mediastinal lesions were referred for EBUS-TBNA. Diagnosis and sub-classifications were made by pathologists. Samples with non-squamous non small cell lung cancer sub type were tested for the EGFR and/or ALK mutations.@*RESULTS@#A total of 377 patients were included in this study. The median needle passes were 2.07. Lung cancer was diagnosed in 213 patients. The diagnosis accuracy for malignancy was 92%. Epidermal growth factor receptor (EGFR) mutations, anaplasticlymphoma kinase (ALK) fusion genes and double genes analysis were successfully preformed in 84 (90%), 105 (95%) and 79 (90%) patients. The number of needle passes and the diameters of lymph node were not associated with the efficacy of gene testing in univariate analysis. However, samples of adenocarcinoma sub type showed a tendency associated with higher genotyping efficacy.@*CONCLUSIONS@#Tissue samples obtained through EBUS-TBNA are sufficient for pathological diagnosis and genetic analysis of lung cancer. The pathology type of sample affected genotyping efficacy.

Evaluation of efficacy and safety of crizotinib and its prognostic factors in patients with ALK-positive advanced non-small cell lung cancer / 国际肿瘤学杂志

Objective To investigate the efficacy and safety of crizotinib in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC),and focuse on analysis of its prognostic factors.Methods Fifty patients with advanced (stage m B-Ⅳ) ALK-positive NSCLC confirmed by cytology or histology in Peking Union Medical Collage Hospital from January 2013 to September 2016 were collected.The relevant clinical imformation and treatment protocols were recorded.The efficacy and safety of crizotinib were followed up,and its prognostic factors were analyzed.Results At the end of follow-up,the median progression free survival (PFS) of progressed patients (n =24) was 9.6 months (95％ CI:8.3-10.9 months),of which five patients died.The median follow-up time of non-progressed patients (n =26) was 10.7 months.The most common adverse event was abnormal liver function (48.0％,24/50).In the single factor analysis of Kaplan-Meier,younger or equal to 40 years old patients had a longer PFS (P =0.017),and the COX regression analysis (Enter method) also had statistical significance differences (HR =6.1,95％ CI:1.4-27.5,P =0.018).However,gender (HR =0.8,95％ CI:0.2-2.6,P =0.697),smoking history (HR =1.5,95％ CI:0.4-5.6,P =0.524),pathology (HR =1.1,95％ CI:0.3-4.2,P =0.922),tumor stage (HR =1.7,95％ CI:0.4-8.4,P =0.502),epidermal growth factor receptor (EGFR) mutant type (HR =0.4,95％ CI:0.4-4.3,P =0.461),EGFR unknown (HR =1.3,95％ CI:0.3-6.1,P =0.727),Eastern Cooperative Oncology Group Performance Status (ECOG) PS score (HR =2.0,95％ CI:0.6-6.8,P =0.290),the status of previous treatment (HR =0.6,95％ CI:0.2-1.8,P =0.385) and brain metastasis (HR=0.7,95％CI:0.1-3.2,P=0.628) were not associated with disease progression Conclusion Crizotinib has good efficacy and is safe and well-tolerated to advanced ALK-positive NSCLC patients,and age is the independent prognostic factor.