Publications by authors named "Mengzhao Wang"

151 Publications

[Advances and Clinical Application of Malignant Probability Prediction Models for 
Solitary Pulmonary Nodule].

Zhongguo Fei Ai Za Zhi 2021 Aug 30. Epub 2021 Aug 30.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

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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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.29DOI Listing
August 2021

Study protocol: A single-arm, multicenter, phase II trial of camrelizumab plus apatinib for advanced nonsquamous NSCLC previously treated with first-line immunotherapy.

Thorac Cancer 2021 Aug 18. Epub 2021 Aug 18.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: For advanced nonsquamous non-small cell lung cancer (NSCLC), the mechanisms of resistance to first-line immunotherapy are not clear. Immune checkpoint inhibitors (ICIs) in combination with agents targeting other pathways may serve as second-line therapy options. Apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) could increase the efficacy of camrelizumab (an ICI agent). The efficacy and safety of this combination regimen as a second-line therapy for NSCLC patients after failure on first-line immunotherapy has not previously been evaluated.

Methods: In this single-arm, multicenter, phase II trial, metastatic nonsquamous NSCLC patients previously treated with single-agent ICI or ICI plus chemotherapy will be enrolled. Participants will receive intravenous camrelizumab 200 mg D1 and oral apatinib 250 mg D1-21 for a 21-day cycle. The study treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is progression-free survival by investigator. Secondary endpoints are overall survival, objective response rate, disease control rate, duration of response by investigator, quality of life, safety, and toxicity.

Conclusions: This trial will provide evidence of the benefit of treatment with camrelizumab combined with apatinib in advanced nonsquamous NSCLC patients who were previously treated with first-line immunotherapy.
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http://dx.doi.org/10.1111/1759-7714.14113DOI Listing
August 2021

Feasibility and reliability of evaluate PD-L1 expression determination using small biopsy specimens in non-small cell lung cancer.

Thorac Cancer 2021 Sep 21;12(17):2339-2344. Epub 2021 Jul 21.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Background: Programmed cell death ligand-1 (PD-L1) is a useful biomarker in non-small cell lung cancer (NSCLC) patients who would probably benefit from immunotherapy. In most patients with advanced stage NSCLC, only small biopsy specimens were available for the evaluation of PD-L1 expression. In this study, we evaluated the feasibility and reliability of PD-L1 testing on small biopsy samples.

Methods: Small specimens of advanced NSCLC patients obtained via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), endobronchial biopsy (EBB), or computed tomography (CT)-guided core-needle biopsy were collected. Tumor cell count and tissue sufficiency for PD-L1 immunohistochemistry (IHC) were evaluated and compared. The clinical course of patients who received immunotherapy in the study population was also examined.

Results: Tissue acquisitions for PD-L1 testing in three groups were all above 90%, with no statistically significant differences. The PD-L1 expressions levels were concordant in most patients with more than one sample (8/11). In the EBB group, PD-L1-positive patients had higher objective response rate (ORR) (53.2% vs. 26.9%, p = 0.048) and longer progression-free survival (PFS) (312 vs. 179 days, p = 0.035) than PD-L1 negative patients. In the core needle biopsy group, patients with positive PD-L1 expression also trended to have higher ORR and longer PFS. However, in the EBUS-TBNA group, both ORR and PFS were similar between patients with positive or negative PD-L1 expression.

Conclusions: This study showed that EBUS-TBNA, EBB, and core needle biopsy provides adequate samples for PD-L1 testing. The predictive value of PD-L1 expression on different small samples still warrants further studies.
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http://dx.doi.org/10.1111/1759-7714.14075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410567PMC
September 2021

Case Report: THSD7A-Positive Membranous Nephropathy Caused by Tislelizumab in a Lung Cancer Patient.

Front Immunol 2021 10;12:619147. Epub 2021 May 10.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Immune checkpoint inhibitors (ICIs) became the standard treatment for many different kinds of cancers and can result in a variety of immune-related adverse events (irAEs). IrAEs of kidney are uncommon and consists of different pathology types. Among the different types, membranous nephropathy (MN) is rare and have not been well-described. Since MN can also be associated with malignancies, differential diagnosis in patients receiving ICIs who develop MN can be very difficult. We present the case of a 74-year-old man with metastatic non-small cell lung cancer who developed MN after ICIs therapy. The patient tested positive for thrombospondin type-1 domain-containing 7A antibodies (THSD7A) when diagnosed with MN. Supplementary examinations revealed the predisposing antigen in the primary tumor and present of the antibody after immunotherapy, which corresponded to the patient's clinical course of nephropathy. Treatment consisting of systemic glucocorticoids and rituximab resulted in a good clinical response, and the THSD7A antibodies were no longer detected. In this case, we first discuss the potential mechanism of immunotherapy related MN, in which the activation of humoral immunity may play an important role.
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http://dx.doi.org/10.3389/fimmu.2021.619147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141750PMC
June 2021

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial.

J Thorac Oncol 2021 09 23;16(9):1512-1522. Epub 2021 May 23.

Peking Union Medical College Hospital, Department of Pulmonary Medicine, Beijing, People's Republic of China.

Introduction: Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC).

Methods: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points.

Results: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]).

Conclusions: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.
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http://dx.doi.org/10.1016/j.jtho.2021.05.005DOI Listing
September 2021

[COVID-19 Vaccination for Cancer Patients: Progress and Preliminary Recommendations].

Zhongguo Fei Ai Za Zhi 2021 Jun 24;24(6):377-383. Epub 2021 May 24.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College 
Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

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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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246390PMC
June 2021

Sputum cell-free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR-TKIs.

Cancer Med 2021 05 1;10(10):3323-3331. Epub 2021 May 1.

Department of Pathology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.

Background: Sputum cell-free DNA (cfDNA) is a valuable surrogate sample for assessing EGFR-sensitizing mutations in patients with advanced lung adenocarcinoma. Detecting EGFR exon 20 p.T790 M (p.T790 M) is much more challenging due to its limited availability in tumor tissues. Exploring sputum cfDNA as an alternative for liquid-based sample type in detecting p.T790 M requires potential improvement in clinical practice.

Methods: A total of 34 patients with EGFR-sensitive mutation-positive lung adenocarcinoma and acquired resistance to the first generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled. The sputum samples, and paired tumors and/or plasma samples were tested for p.T790 M mutation and concordance of p.T790 M status among the three sample types was analyzed.

Results: The overall concordance rate of p.T790 M mutation between sputum cfDNA and tumor tissue samples was 85.7%, with a sensitivity of 66.7% and a specificity of 100%. The sensitivity for detecting p.T790 M in sputum cfDNA was 100%, 66.7%, and 0% in the three sputum groups of malignant, satisfactory but no malignant cells, and unsatisfactory, respectively. The combined results of plasma cfDNA testing and sputum cfDNA testing further increased the sensitivity to 100% for p.T790 M detection in satisfactory but no malignant cells sputum group.

Conclusion: These findings revealed that cfDNA from malignant or satisfied but no malignant cells sputum is considered suitable for detecting p.T790 M mutation in patients with acquired resistance to first or second-generation EGFR-TKIs. The sputum cytological pathological evaluation-guided sputum cfDNA testing assists in significantly improving the sensitivity of p.T790 M detection, bringing significant value for the maximal application of third-generation EGFR-TKIs in second-line treatment.
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http://dx.doi.org/10.1002/cam4.3817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124129PMC
May 2021

Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study.

J Thorac Oncol 2021 08 26;16(8):1403-1414. Epub 2021 Apr 26.

Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.

Introduction: ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC).

Methods: Patients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety.

Results: ZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018-February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41-2.69, niraparib) and 1.36 months (1.31-1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46-0.95, p = 0.0242). Median overall survival was 9.92 months (9.33-13.54, niraparib) and 11.43 months (9.53-not estimable, placebo); HR = 1.03 (95% CI: 0.62-1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41-2.56, niraparib) and 1.41 months (1.31-2.00, placebo); HR = 0.88 (95% CI: 0.61-1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients.

Conclusions: ZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.
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http://dx.doi.org/10.1016/j.jtho.2021.04.001DOI Listing
August 2021

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Mar;24(3):141-160

Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing 100142, China.

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.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143963PMC
March 2021

Lighting Direction Affects Leaf Morphology, Stomatal Characteristics, and Physiology of Head Lettuce ( L.).

Int J Mol Sci 2021 Mar 19;22(6). Epub 2021 Mar 19.

Department of Horticulture, Division of Applied Life Science (BK21 Program), Graduate School of Gyeongsang National University, Jinju 52828, Korea.

Plants are exposed to numerous biotic and abiotic stresses, and light is one of the most important factors that influences the plant morphology. This study was carried out to examine how the lighting direction affected the plant morphology by investigating the growth parameters, epidermal cell elongation, stomatal properties, and physiological changes. Seedlings of two head lettuce ( L.) cultivars, Caesar Green and Polla, were subjected to a 12 h photoperiod with a 300 μmol·m·s photosynthetic photon flux density (PPFD) provided by light emitting diodes (LEDs) from three directions: the top, side, and bottom, relative to the plants. Compared with the top and side lighting, the bottom lighting increased the leaf angle and canopy by stimulating the epidermal cell elongation in leaf midrib, reduced the leaf number and root biomass, and induced large stomata with a low density, which is associated with reduced stomatal conductance and carbohydrate contents. However, the proline content and quantum yield exhibited no significant differences with the different lighting directions in both cultivars, which implies that the plants were under normal physiological conditions. In a conclusion, the lighting direction had a profound effect on the morphological characteristics of lettuce, where the plants adapted to the changing lighting environments.
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http://dx.doi.org/10.3390/ijms22063157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003708PMC
March 2021

Prognostic impact of maximum standardized uptake value on F-FDG PET/CT imaging of the primary lung lesion on survival in advanced non-small cell lung cancer: A retrospective study.

Thorac Cancer 2021 03 29;12(6):845-853. Epub 2021 Jan 29.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Positron emission tomography/computed tomography (PET/CT) has been recognized for diagnosing and staging lung cancer, but the prognostic value of standardized uptake value (SUV) on F-FDG PET/CT imaging in patients with advanced non-small cell lung cancer (NSCLC) remains controversial.

Methods: We performed a retrospective analysis of patients with advanced NSCLC who had undergone F-FDG PET/CT before systemic treatment between June 2012 and June 2016. The relationship between the maximum SUV (SUVmax) of the pulmonary lesion and lesion size was evaluated via Spearman's correlation analysis. We collected patients' clinical and pathological data. Univariate and multivariate analyses were performed to analyze the factors influencing survival.

Results: We included 157 patients with advanced NSCLC. Among these, 135 died, 13 survived, and nine were lost to follow-up (median follow-up period, 69 months). SUVmax was correlated with lesion size and was significantly greater for tumors ≥3 cm than for tumors <3 cm (10.2 ± 5.4 vs. 5.6 ± 3.3, t = -6.709, p = 0.000). Univariate analysis showed that survival was associated with gender, tumor size, epidermal growth factor receptor gene mutation or anaplastic lymphoma kinase rearrangement, SUVmax of the primary lung lesion, and treatment lines. Multivariate analysis showed a significant correlation between SUVmax of the primary lung lesion and survival. The mortality risk of patients with SUVmax ≤6 was 35% lower than that of patients with SUVmax >6 (HR = 0.651, 95% confidence interval, 0.436-0.972; Wald value, 4.400; p = 0.036).

Conclusions: The SUVmax of the primary lung lesion on PET/CT is significantly correlated with survival in treatment-naive patients with advanced NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952805PMC
March 2021

[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].

Zhongguo Fei Ai Za Zhi 2020 Dec;23(12):1059-1065

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

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.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.104.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786230PMC
December 2020

Genomic characteristics of driver genes in Chinese patients with non-small cell lung cancer.

Thorac Cancer 2021 02 9;12(3):357-363. Epub 2020 Dec 9.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Background: The aim of this study was to determine the demographic profile of driver gene alterations, especially low-frequency gene alterations in Chinese patients with non-small cell lung cancer (NSCLC).

Methods: A total of 7395 Chinese patients with NSCLC were enrolled in the study. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded specimens collected via either surgical resection or biopsy.

Results: The frequent genomic alterations found in the study were EGFR mutations (51.7%), KRAS mutations (13.1%), MET alterations (5.6%; 3.2% copy number gains and 0.5% exon 14 skipping mutation), HER2 alterations (7.0%; 2.0% copy number gains and 5.4% mutations), ALK alterations (7.2%; 3.9% rearrangements), RET rearrangements (1.4%), ROS1 rearrangements (0.9%), and NTRK rearrangements (0.6%). The EGFR mutation rate was found to be significantly higher in women than in men (69.1% vs. 38.5%, P < 0.001), while the KRAS mutation (17.5% vs. 7.3%, P < 0.001) and MET alteration rates (6.5% vs. 4.5%, P < 0.001) were significantly higher in men than in women. The EGFR mutation rate tended to decrease with age in the group aged >40 years, while the KRAS mutation rate tended to increase with age. The HER2 mutation (13.9% vs. 6.7%, P < 0.001) and ALK alteration rates (14.3% vs. 6.9%, P < 0.001) were significantly higher in the group aged <40 years than in groups aged 40 years or older.

Conclusions: The frequency of different driver genes was diverse in different age-gender groups, and the results of this study may assist clinicians in clinical decision-making and the development of public healthcare strategies in the future.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: This study demonstrated that the frequency of different driver genes was diverse in different age-gender groups. What this study adds It may enable clinicians to make clinical decisions, and assist government, pharmaceutical researchers and insurance companies develop public healthcare strategies.
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http://dx.doi.org/10.1111/1759-7714.13757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862783PMC
February 2021

Current management of chemotherapy-induced neutropenia in adults: key points and new challenges: Committee of Neoplastic Supportive-Care (CONS), China Anti-Cancer Association Committee of Clinical Chemotherapy, China Anti-Cancer Association.

Cancer Biol Med 2020 11 15;17(4):896-909. Epub 2020 Dec 15.

Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China.

Chemotherapy-induced neutropenia (CIN) is a potentially fatal and common complication in myelosuppressive chemotherapy. The timing and grade of CIN may play prognostic and predictive roles in cancer therapy. CIN is associated with older age, poor functional and nutritional status, the presence of significant comorbidities, the type of cancer, previous chemotherapy cycles, the stage of the disease, specific chemotherapy regimens, and combined therapies. There are many key points and new challenges in the management of CIN in adults including: (1) Genetic risk factors to evaluate the patient's risk for CIN remain unclear. However, these risk factors urgently need to be identified. (2) Febrile neutropenia (FN) remains one of the most common reasons for oncological emergency. No consensus nomogram for FN risk assessment has been established. (3) Different assessment tools [e.g., Multinational Association for Supportive Care in Cancer (MASCC), the Clinical Index of Stable Febrile Neutropenia (CISNE) score model, and other tools] have been suggested to help stratify the risk of complications in patients with FN. However, current tools have limitations. The CISNE score model is useful to support decision-making, especially for patients with stable FN. (4) There are still some challenges, including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN. In view of the current reports, our group discusses the key points, new challenges, and management of CIN.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721096PMC
November 2020

A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer.

Ther Adv Med Oncol 2020 24;12:1758835920965849. Epub 2020 Nov 24.

Division of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China.

Background: Carboxyamidotriazole (CAI), a calcium channel blocker, inhibits tumor cell proliferation, metastasis, and angiogenesis. This trial aimed to determine whether CAI combined with conventional chemotherapy could prolong progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients.

Methods: Patients were assigned into groups (3:1 ratio) to receive either chemotherapy + CAI or chemotherapy alone. Cisplatin (25 mg/m) was administered by intravenous infusion on days 1, 2, and 3, and vinorelbine (25 mg/m) on days 1 and 8 of each 3-week cycle for four cycles. CAI was administered at 100 mg daily with concomitant chemotherapy; this treatment was continued after chemotherapy was ceased until serious toxicity or disease progression had occurred. PFS was the primary endpoint, and the secondary endpoints were objective response rate (ORR), disease control rate, overall survival (OS), and quality of life.

Results: In total, 495 patients were enrolled in the trial: 378 in the chemotherapy + CAI group and 117 in the chemotherapy + placebo group. PFS was significantly greater in the chemotherapy + CAI [median, 134 days; 95% confidence interval (CI) 127-139] than in the chemotherapy + placebo (median, 98 days; 95% CI: 88-125) group, with a hazard ratio of 0.690 (95% CI: 0.539-0.883;  = 0.003). There was no difference in the OS rates of both groups. The ORR was greater in the chemotherapy + CAI group than in the chemotherapy + placebo group (34.6% 25.0%,  = 0.042). Adverse events of ⩾grade 3 occurred more frequently in the CAI group [256 (68.1%) 64 (55.2%);  = 0.014].

Conclusion: CAI + platinum-based chemotherapy prolonged PFS and could be a useful therapeutic option to treat NSCLC.

Clinical Trial Registration: chinadrugtrials.org.cn identifier: CTR20160395.
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http://dx.doi.org/10.1177/1758835920965849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692340PMC
November 2020

Risk and prognosis factors for systemic sclerosis with lung cancer: A single-centre case-control study in China.

Int J Clin Pract 2021 Apr 20;75(4):e13819. Epub 2020 Nov 20.

Department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objective: To analyse clinical characteristics, risk and prognosis factors for systemic sclerosis (SSc) patients with lung cancer.

Methods: SSc patients with lung cancer admitted to Peking Union Medical College Hospital from February 1992 to December 2018 were included. Age and sex-matched controls were selected from a pool of SSc patients without lung cancer during the same period. Conditional logistic regression and Cox proportional-hazard regression were used to identify risk factors and prognosis factors. The Kaplan-Meier method was used to draw the survival curve and calculate median survival.

Results: Nineteen SSc patients with lung cancer and 76 controls were included. The mean age at lung cancer diagnosis was 54.4 ± 10.2 years. In all 19 cases the lung cancer had been diagnosed after SSc and the median interval between SSc onset and lung cancer onset was 10.5 years (range 2.0-36.2 years). Among SSc patients with lung cancer, the median follow-up time and median survival were 2.6 years and 1.4 years, respectively. In the sex and age-matched conditional logistic multivariable regression analysis, family history of malignancy (OR 4.930, 95%CI 1.926-12.619, P = .001), ILD (OR 7.701, 95%CI 1.009-58.767, P = .049) were independent risk factors for lung cancer among SSc patients, and considering sex and age of SSc onset, SSc patients with more advanced staging of lung cancer (HR 3.190, 95%CI 1.127-6.126, P = .06) had poorer prognosis.

Conclusion: Lung cancer is not uncommon in SSc patients, especially those with family histories of malignancy or ILD. Early detection of lung cancer is of vital importance for better prognosis.
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http://dx.doi.org/10.1111/ijcp.13819DOI Listing
April 2021

Rational design of a far-red fluorescent probe for endogenous biothiol imbalance induced by hydrogen peroxide in living cells and mice.

Bioorg Chem 2020 10 26;103:104173. Epub 2020 Aug 26.

School of Chemistry and Chemical Engineering, Institute of Fluorescent Probes for Biological Imaging, University of Jinan, Jinan 250022, Shandong, China. Electronic address:

Intracellular biothiols are correlated with many diseases such as nerve disorder and Parkinson's disease likely due to a redox imbalance. In this work, we designed an ultrafast fluorescent probe (Cou-DNBS) for biothiols with a large Stokes shift (131 nm). The probe was constructed through linking the 2,4-dinitrobenzenesulfonyl moiety as the specially recognizing biothiols site to an iminocoumarin fluorophore Cou-NH obtained by fusing an additional benzene ring. The presence of biothiols could ultrafast perform a significant fluorescence emission at 617 nm upon the excitation of 480 with the low limits of detection (2.5 nM for Cys, 1.7 nM for Hcy and 0.84 nM for GSH). HRMS spectra as well as theoretical calculations further evidenced the rationale of recognition mechanism. Furthermore, the probe can successfully visualize endogenous biothiol recovery in living cells damaged by HO.
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http://dx.doi.org/10.1016/j.bioorg.2020.104173DOI Listing
October 2020

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer.

ESMO Open 2020 08;5(4)

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Background: Immunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy.

Patients And Methods: CD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated via dual-immunofluorescence staining. Targeted DNA sequencing was performed on NSCLC specimens. Survival analysis was performed using the Cox model.

Results: Using 2+/3+ as a CD47 positive (CD47) expression cut-off, the prevalence of CD47 expression in NSCLC was 33.0% (63/191), significantly higher than in pulmonary infectious diseases. CD47 expression was significantly higher in female, non-smoking and adenocarcinoma patients (p=0.020, p<0.001 and p<0.001, respectively). Furthermore, CD47 expression was significantly correlated with epidermal growth factor receptor mutation (p<0.001). The expression of CD47 (H-score) in NSCLC was negatively correlated with tumour PD-L1 expression (p=0.0346) and tumour mutation burden (p=0.0107). CD47 expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035).

Conclusion: This study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47 expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.
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http://dx.doi.org/10.1136/esmoopen-2020-000823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445354PMC
August 2020

[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].

Zhongguo Fei Ai Za Zhi 2020 Sep 10;23(9):792-799. Epub 2020 Aug 10.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

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.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.104.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519955PMC
September 2020

Clinicopathological characteristics of lung cancer in patients with systemic sclerosis.

Clin Respir J 2020 Dec 7;14(12):1131-1136. Epub 2020 Sep 7.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China.

Background And Objectives: Systemic sclerosis (SSc) is a connective tissue disorder (CTD) associated with an increased risk of malignancy including lung cancer (LC). Our objective was to provide a description of demographics and clinicopathological characteristics of LC patients with SSc.

Methods: Lung cancer patients with SSc admitted to Peking Union Medical College Hospital from January 2000 to August 2017 were reviewed. Demographic and clinicopathologic data were collected.

Results: Of the 12 cases included in our study, all were female. No patients had a history of smoking. The most common histological type was adenocarcinoma, followed by squamous cell carcinoma and small-cell carcinoma. No driver mutation was identified in the five patients undergoing genetic testing. Eight patients had interstitial lung disease (ILD). Six were manifested as nonspecific interstitial pneumonia (NSIP) and two as usual interstitial pneumonia (UIP). Four (33.3%) patients underwent surgical resection. Among them, two had ILD with a normal preoperative pulmonary function tests (PFT). Eight (66.7%) patients received chemotherapy. Radiotherapy was administered in only one (8.3%) patient. No grade 3/4 adverse events were documented.

Conclusion: The predominance of female patients in our study is different from that reported in general lung cancer patients. A high proportion of patients has SSc-ILD, including NSIP and UIP. Surgery or radiotherapy could still be considered in carefully selected patients with ILD.
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http://dx.doi.org/10.1111/crj.13249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754367PMC
December 2020

Programmed cell death 1 (PD-1)/PD-ligand 1(PD-L1) inhibitors-related pneumonitis in patients with advanced non-small cell lung cancer.

Asia Pac J Clin Oncol 2020 Dec 5;16(6):299-304. Epub 2020 Aug 5.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Immune-related pneumonitis is an uncommon but potentially fatal immune-related adverse event in advanced non-small cell lung cancer (NSCLC) patients during treatment with anti-programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1). Underlying emphysema, interstitial lung disease (ILD), and previous radiation therapy for lung cancer might be factors precipitating immune-related pneumonitis. The incidence of immune-related pneumonitis is reported to be higher in those treated with PD-1 inhibitors than in those treated with anti-PD-L1 inhibitors. Early detection and diagnosis and appropriate management according to the severity are critical to improving the prognosis. The first-line physicians, including the primary responsible oncologists, family doctors, emergency physicians and NSCLC patients should be trained to identify and report symptoms of immune-related pneumonitis as early as possible. Multidisciplinary treatment teams involving clinicians (including ILD specialists and lung cancer specialists), radiologists and pathologists are recommended for the treatment of immune-related pneumonitis.
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http://dx.doi.org/10.1111/ajco.13380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754394PMC
December 2020

Renal immune-related adverse events of immune checkpoint inhibitor.

Asia Pac J Clin Oncol 2020 Dec 23;16(6):305-311. Epub 2020 Jun 23.

Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

The status of immune checkpoint inhibitors (ICPIs) is raising in the treatment of malignancy for their effectiveness. The ICPIs therapy takes the risk of off-target toxicity because of immune system overactivation, including renal toxicity. It was declared that the renal toxicity was rare. However, with the increasing experience of ICPIs therapy, the renal immune-relate adverse events of ICPIs were reported more and their management was launching an enthusiastic discussion nowadays. In this review, we focused on the mechanism of ICPIs related renal irAEs (immune-related adverse events), the clinical and pathological manifestation of different forms of renal injury, and management strategies when the renal irAEs happened. Good management of irAEs might need help from Multi-Disciplinary Treatment and could promote a better clinical practice on ICPIs.
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http://dx.doi.org/10.1111/ajco.13387DOI Listing
December 2020

Successful treatment of pulmonary inflammatory myofibroblastic tumor with platinum-pemetrexed: The first report of two cases.

Thorac Cancer 2020 08 3;11(8):2339-2342. Epub 2020 Jun 3.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Pulmonary inflammatory myofibroblastic tumor (IMT) is a rare tumor. Here, we report two cases of pulmonary IMT successfully treated with platinum and pemetrexed. The results from this study suggest that platinum-pemetrexed might be an effective therapy in patients with IMT, but requires further investigation.
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http://dx.doi.org/10.1111/1759-7714.13520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396391PMC
August 2020

Clinical recommendations on lung cancer management during the COVID-19 pandemic.

Thorac Cancer 2020 07 29;11(7):2067-2074. Epub 2020 May 29.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Coronavirus disease 2019 (COVID-19) is spreading worldwide, and has been declared as an international public health concern. Patients with lung cancer are highly susceptible to infection compared to healthy individuals because of systemic immunosuppression induced by malignancy and anticancer therapy. Furthermore, patients with cancer demonstrate poorer outcomes following infection. Hence, patients with lung cancer should be considered a priority group for COVID-19 prevention. Furthermore, the routine treatment of patients with cancer has been affected during the COVID-19 pandemic, and patients may not have been able to undergo timely and effective antitumor treatment, thereby indicating a poor prognosis. Here, we provide some suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer who have fever and respiratory symptoms. Our medical team also provide clinical recommendations on lung cancer management during the COVID-19 pandemic, for carrying out meticulous and individualized clinical management of lung cancer patients and maximum protection to effectively prevent COVID-19. KEY POINTS: Significant findings of the study This article provides suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer with fever and respiratory symptoms. What this study adds This article makes clinical recommendations on lung cancer management during the COVID-19 pandemic.
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http://dx.doi.org/10.1111/1759-7714.13498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283707PMC
July 2020

Immunotherapy as second-line treatment and beyond for non-small cell lung cancer in a single center of China: Outcomes, toxicities, and clinical predictive factors from a real-world retrospective analysis.

Thorac Cancer 2020 07 29;11(7):1955-1962. Epub 2020 May 29.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Background: Real-world evidence of second-line treatment and beyond with immune checkpoint inhibitors (ICIs) in Chinese patients is lacking. Here, we aimed to assess the efficacy, responses, and immune-related side effects of anti-PD-1 agents in real-life practice.

Methods: We retrospectively analyzed consecutive patients who received nivolumab or pembrolizumab monotherapy at Peking Medical College Hospital. We collected baseline characteristics, evaluated treatment efficacy, and categorized immune-related adverse effects (irAEs). Predictive factors of treatment response were also determined.

Results: The study included 97 patients with a median age of 64 years. The majority of patients were male, with nonsquamous histological type and advanced stage tumor, and had a history of smoking. Most patients received ICIs as second-line therapy. Expression of PD-L1 was detected in 34.11% patients. Overall response rate (ORR) and disease control rate (DCR) were 16.49% and 60.82%, respectively. None of the patients achieved complete response (CR). The median PFS and OS were150 days and 537 days, respectively. The incidence of immune-related toxicities was similar to the one previously reported. Patients with driver gene mutations had shorter PFS than patients without, while patients who encountered irAE had relatively longer PFS.

Conclusions: The real-world clinical outcome of ICIs in second- and further-line NSCLC therapy is promising. Several characteristics may have predictive value for efficacy. Occurrence of irAEs during treatment was acceptable and could be an independent positive predictive for PFS.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Efficacy and safety profile of ICIs as second-line treatment or above for patients with NSCLC are promising in real world circumstances Incidence and median time to the occurrence of irAEs vary between organs WHAT THIS STUDY ADDS: Driver gene mutations are associated with lower progression-free survival Occurrence of irAEs is associated with higher progression-free survival.
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http://dx.doi.org/10.1111/1759-7714.13488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327684PMC
July 2020

Sputum Cell-Free DNA: Valued Surrogate Sample for Detection of EGFR Mutation in Patients with Advanced Lung Adenocarcinoma.

J Mol Diagn 2020 07 11;22(7):934-942. Epub 2020 May 11.

Department of Pathology, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China. Electronic address:

Sputum is a common cytologic sample type, but its potential use in EGFR mutation detection in patients with lung cancer is not fully evaluated. This study established an improved sputum cell-free DNA (cfDNA) extraction method study and applied a super-amplification refractory mutation system to detect the EGFR mutation status in sputum cfDNA. The sputum sediments were used for cytology evaluation. The study included 102 lung adenocarcinoma patients; 65 patients (63.7%) were positive for EGFR mutations in tumor samples. EGFR mutation status was positive in 30 patients (29.4%) by sputum cfDNA testing, achieving an overall sensitivity and specificity of 46.2% and 100%, respectively. Comparison of EGFR mutation status in tumor samples revealed that the sensitivity of testing sputum cfDNA in 40 patients with stage I to IIIA versus 62 patients with stage IIIB to IV was 24% (6/25) versus 65.0% (26/40). Through cytology evaluation, the sputum specimens from 62 advanced patients were classified into three categories: 10 were unsatisfactory; 34 were satisfactory but had no malignant cells; and 18 had malignant cells. The sensitivities of these three categories were 0% (0/8), 71.4% (15/21), and 100% (11/11), respectively. These findings revealed that with the improved cfDNA extraction method and sputum cytology evaluation, sputum cfDNA is a valuable surrogate sample type for detecting clinical EGFR mutations in advanced lung adenocarcinoma patients.
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http://dx.doi.org/10.1016/j.jmoldx.2020.04.208DOI Listing
July 2020

Treatment with or without bevacizumab as a first-line and maintenance therapy for advanced non-squamous non-small cell lung cancer: A retrospective study.

Thorac Cancer 2020 07 14;11(7):1869-1875. Epub 2020 May 14.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Background: Pemetrexed and bevacizumab as monotherapies, or in combination, have been approved for maintenance therapy following platinum-based induction in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). The differences in the benefits of bevacizumab for treatment during early or late NSCLC have not yet been characterized.

Methods: We retrospectively analyzed data from 35 patients with advanced naïve NSCLC who had received pemetrexed/platinum with or without bevacizumab followed by maintenance therapy with pemetrexed alone or pemetrexed plus bevacizumab. The data were analyzed using the Kaplan-Meier method and Cox regression adjusted for risk factors. Patients were grouped according to treatment conditions. Group A received pemetrexed plus platinum followed by pemetrexed alone (Pem-Pt/Pem). Group B received pemetrexed plus platinum followed by pemetrexed and bevacizumab (Group B; Pem-Pt/Pem + Bev). Group C received pemetrexed, platinum, and bevacizumab during induction therapy, and pemetrexed as maintenance therapy (Group C; Pem-Pt + Bev/Pem + Bev). We assessed the significance of introduction of bevacizumab at different stages of treatment.

Results: A total of 13 (37.1%) patients were included in Group A, nine patients (25.7%) were included in Group B, and 13 patients (37.1%) were included in Group C. Among the 35 patients, 69.2% were male, and the median age was 59 years (range 40-75). The median progression-free survival (PFS) was 7.7 months (231 days, range 134-410 days) in Group A, 9.3 months (280 days, range 84-565 days) in Group B, and 8.0 months (241 days, range 108-665 days) in Group C. The median PFS was not significantly different among the three groups (P = 0.233). Similarly, bevacizumab did not significantly affect PFS (P = 0.630).

Conclusions: The addition of bevacizumab into induction chemotherapy or maintenance therapy provided limited benefits to PFS in our study, but previous studies suggested that bevacizumab may improve disease control. In that way, we presume that early use of bevacizumab may provide a greater benefit.
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http://dx.doi.org/10.1111/1759-7714.13469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327679PMC
July 2020

Opportunistic infections complicating immunotherapy for non-small cell lung cancer.

Thorac Cancer 2020 06 20;11(6):1689-1694. Epub 2020 Apr 20.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

Immunotherapy has produced durable responses in numerous advanced and metastatic cancers, especially advanced non-small cell lung carcinoma (NSCLC). However, opportunistic infection has become a major risk for patients who have received immune checkpoint inhibitors (ICIs). Early diagnosis of infection is difficult due to an acute disease course and heterogeneity in clinical manifestation. We retrospectively analyzed four cases with NSCLC who received ICIs and developed opportunistic infections. Two of our cases received antecedent glucocorticoids to treat immune-related adverse events (irAEs), whereas immunosuppressive agents were not used beforehand in the other cases. We highlight that opportunistic infections complicating immunotherapy can be severe and even fatal. When patients deteriorate after initial remission from irAEs by glucocorticoids, infections should be thoroughly investigated and carefully distinguished from an irAE flare. Bronchoscopy and bronchoalveolar lavage (BAL) are essential. In patients where limited results from traditional microbiological tests have been obtained, next-generation sequencing (NGS) of BAL fluid is beneficial in guiding a precise antimicrobial treatment. An antipneumocystis prophylaxis may also be considered in selected patients.
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http://dx.doi.org/10.1111/1759-7714.13422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262884PMC
June 2020

Significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections: implication from a family cluster.

Emerg Microbes Infect 2020 Dec;9(1):924-927

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Confirmative diagnosis of SARS-CoV-2 infections has been challenged due to unsatisfactory positive rate of molecular assays. Here we identified a family cluster of SARS-CoV-2 infections, with five of six family members were SARS-CoV-2-specific immunoglobin serology testing positive, while molecular assays only detected two of this five patients even repeated twice. We comprehensively analyzed this familial cluster of cases based on the clinical characteristics, chest CT images, SARS-CoV-2 molecular detection results, and serology testing results. At last, two patients were diagnosed with COVID-19, two were suspected of COVID-19, and two were considered close contacts. Our results emphasized the significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections, especially for COVID-19 close contacts screening.
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http://dx.doi.org/10.1080/22221751.2020.1752610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269047PMC
December 2020
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