Publications by authors named "Hanping Wang"

66 Publications

[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
March 2021

The complete chloroplast genome of (Benth.) Briq., a traditional Chinese herb.

Mitochondrial DNA B Resour 2021 Mar 16;6(3):907-908. Epub 2021 Mar 16.

College of Medicine, Xi'an International University, Xi'an, China.

(Benth.) Briq. is a traditional Chinese medicinal herb. The complete chloroplast genome sequence of was obtained by high-throughput sequencing platform. The chloroplast genome of is a circular form of 151,254 bp in length, with an average GC content of 37.85%. The genome contains a set of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on complete chloroplast genome sequences indicates that has a close relationship with . This study provides a molecular basis for the classification of .
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http://dx.doi.org/10.1080/23802359.2021.1886884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971225PMC
March 2021

The complete chloroplast genome of , a traditional Chinese herb.

Mitochondrial DNA B Resour 2021 Feb 8;6(2):337-338. Epub 2021 Feb 8.

College of Medicine, Xi'an International University, Xi'an, Shaanxi, China.

(Hemsley) H. Hara is a kind of traditional medical herb which can be used for cancer treatment. In this study, the complete chloroplast genome sequence of was assembled. Its complete circular chloroplast DNA length was 152,761 bp. The genome was made up of a large single-copy region of 83,655 bp, a small single-copy region of 17,660 bp, and a pair of inverted repeat regions of 25,723 bp. The genome totally encoded 129 genes, containing 85 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicated that had a close relationship with basil ().
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http://dx.doi.org/10.1080/23802359.2020.1860704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872541PMC
February 2021

The complete chloroplast genomes of and , two herbal species in tribe Mentheae of Lamiaceae family.

Mitochondrial DNA B Resour 2021 Jan 13;6(1):89-90. Epub 2021 Jan 13.

College of Medicine, Xi'an International University, Xi'an, Shaanxi, China.

Lamiaceae is one of the largest families in the kingdom Plantae, including lots of traditional Chinese herbs. and are two Lamiaceae species, which are most frequently used in Chinese traditional medicine. In the current study, the complete chloroplast genome sequences of two species were assembled. Their circular DNA lengths were 152,096 and 151,922 bp respectively. Both genomes were made up of a large single-copy region, a small single-copy region, and a pair of inverted repeat regions. Each genome totally encoded 133 genes, containing 88 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicated that both species belong to the Mentheae tribe of the Lamiaceae family.
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http://dx.doi.org/10.1080/23802359.2020.1847617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819123PMC
January 2021

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

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

Clinical characteristics and management of immune checkpoint inhibitor-related pneumonitis: A single-institution retrospective study.

Cancer Med 2021 Jan 19;10(1):188-198. Epub 2020 Nov 19.

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

Introduction: The increasing application of immune checkpoint inhibitors (ICIs) will cause more checkpoint inhibitor-related pneumonitis (CIP), which is a common cause of ICI-related death. The clinical management of CIP needs further optimization.

Methods: Patients who were managed at Peking Union Medical College Hospital (PUMCH) between February 2017 and December 2019 with a diagnosis of CIP were retrospectively analyzed. Clinical data including clinical manifestations, radiologic data, laboratory and bronchoscopy results, treatments, and outcomes were collected and analyzed. The Mann-Whitney test was used to compare patients with and without co-infections.

Results: In total, 48 CIP cases in 42 patients were analyzed. The median time from the first dose of ICI to the onset of CIP was 1.9 months (range: 0.1-13.7). Grade 3-4 (G3-4) accounted for 30 cases (71.4%). The most common symptoms were cough (88.1%) and dyspnea (78.6%). The median starting dose of equivalent prednisone (EP) was 55 mg (range: 30-200) for all patients. The median total duration of glucocorticosteroids (GCS) treatment was 42.5 days (range: 15-89). Three patients (7.14%) died because of infection. A higher starting dose and longer duration of GCS (≥30 mg/day; p = 0.001) were associated with opportunistic infection. Chest computed tomography (CT) showed diverse and asymmetrical lesions. Twelve patients were re-challenged, and six patients developed recurrent CIP.

Conclusions: The clinical and imaging manifestations of CIP are various, and differential diagnosis of exclusion is essential. GCS at 1-2 mg/kg is feasible to treat CIP, but the duration of GCS ≥30 mg/day should be used with caution, given the high risk of acquired infections. Re-challenges of ICI are feasible, but the recurrence of CIP needs to be closely monitored.
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http://dx.doi.org/10.1002/cam4.3600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826478PMC
January 2021

Use of glucocorticoids in the management of immunotherapy-related adverse effects.

Thorac Cancer 2020 10 6;11(10):3047-3052. Epub 2020 Sep 6.

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

Immune checkpoint inhibitors (ICIs) activate host antitumor immunity to kill tumor cells. However, ICI therapy may be accompanied by a series of immunotherapy-related adverse effects (irAEs) caused by activated autoreactive T cells. Glucocorticoids are the mainstream therapy for irAEs. However, the usage, dosage and course of treatment of irAEs with glucocorticoids differs from those used in classic autoimmune diseases. Furthermore, the long-term use of large doses of glucocorticoids may cause serious adverse effects. In this article, the mechanism, dosage forms, adverse effects and management of glucocorticoids are described in detail, providing references and suggestions for oncologists to use glucocorticoids in the treatment of irAEs.
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http://dx.doi.org/10.1111/1759-7714.13589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529549PMC
October 2020

NLCIPS: Non-Small Cell Lung Cancer Immunotherapy Prognosis Score.

Cancer Manag Res 2020 17;12:5975-5985. Epub 2020 Jul 17.

Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People's Republic of China.

Introduction: Currently in China, many immune checkpoint inhibitors (ICIs) have been approved for the treatment of non-small cell lung cancer (NSCLC). Some patients can not benefit from ICIs, and approximately 50% of patients have immunotherapy-related toxicity. Therefore, it is necessary to monitor carefully the selection of immunotherapy population using biomarkers to maximize the benefit of patients with NSCLC.

Methods: A prospective analysis was performed on patients with advanced NSCLC who were treated with ICIS at our hospital from March 2018 to June 2019, up to the follow-up deadline of December 31, 2019. The primary end points were overall survival (OS) and progression-free survival (PFS), and the secondary end points were objective response rate and disease control rate. A lasso regression was used for the univariate analysis, and Cox regression analysis was used for the multivariate analysis. An efficacy prediction line chart was developed.

Results: A total of 63 patients were included in the study. The median PFS was 7.0 months (95% CI, 5.0-11.0) and did not reach the median OS. According to the lasso regression, significant univariate factors were smoking index, PD-ligand 1 expression, and neutrophil to lymphocyte ratio (NLR). According to the multivariate analysis, the Cox proportional hazards model showed that smoking index and NLR are independent predictors of PFS in immunotherapy. A model comprised of independent predictors was developed based on a multivariate logical analysis of the main cohort-non-small cell lung cancer immunotherapy prognosis score. This model is shown as a nomogram with a C-index of 0.801 (95% CI, 0.744, 0.858), which has high prediction accuracy.

Conclusion: This predictive model, including NLR and smoking index, can achieve a 1-year PFS in immunotherapy of patients. PD-1 inhibitors have been demonstrated to be effective and safe in the clinical treatment of patients with NSCLC.
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http://dx.doi.org/10.2147/CMAR.S257967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381788PMC
July 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

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

Relationship between the efficacy of immunotherapy and characteristics of specific tumor mutation genes in non-small cell lung cancer patients.

Thorac Cancer 2020 06 27;11(6):1647-1654. Epub 2020 Apr 27.

Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Background: Immune checkpoint inhibitors (ICIs) have greatly improved the prognosis and overall management of non-small cell lung cancer (NSCLC) patients, but in the long term less than 20% of patients benefit from treatment with ICIs. Therefore, it is necessary to guide the choice of immunotherapy population through biomarkers in order to maximize the benefit for NSCLC patients. This article mainly explores the relationship between the efficacy of immunotherapy and specific tumor mutation gene characteristics in an NSCLC population.

Methods: This was a prospective analysis of patients with advanced NSCLC who visited the Department of Respiratory Medicine of Peking Union Medical College Hospital from March 2018 to June 2019 and were instructed to use PD-1 inhibitors. The follow-up deadline was 31 December 2019. The tumor pathological tissues were tested for tumor mutation genes, and the patients were evaluated for efficacy according to RECIST 1.1. The patients were divided into the durable benefit group (DCB) and the nonsustainable benefit group (NDB). DCB/NDB was used as the outcome variable. Various statistics methods were used to explore the independent predictors of long-term benefits associated with immunotherapy and to draw a progression-free survival curve for the relevant predictors.

Results: A total of 44 patients were examined for tumor mutation genes in pathological tissues; 20 in the DCB group and 24 in the NDB group. Specific gene mutations occurred in TP53 38.64%, KRAS 31.82%, EGFR 20.45%, BRCA 20.45%, ERBB (excluding EGFR) 18.18%, PTEN 15.91%, CDK4/6 13.64%, POLE 11.36%, MET 11.36%, PIK3CA 9.10%, FGFR 9.10%, BRAF 9.10%, JAK 9.10%, ALK 6.82%, POLD1 4.55%, BLM 4.55%. Chi-square test results showed that there were statistically significant differences between DCB and NDB groups with eight mutations such as KRAS. Logistic regression showed that the KRAS mutation was statistically significant (P < 0.001). Two accuracy indicators, Random Forest Classification of Mean Decrease Gini and Mean Decrease Accuracy, evaluated the importance of the impact of different gene mutations on the outcome. Under two different measures, the variables were all KRAS mutations. It is suggested that the mutation of the KRAS gene is an independent predictor of the long-term benefit of immunotherapy.

Conclusions: The mutation of KRAS gene in tumor tissues is an independent predictor of the long-term benefit of immunotherapy, and the predictive ability is better.
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http://dx.doi.org/10.1111/1759-7714.13447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262886PMC
June 2020

Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients.

Thorac Cancer 2020 06 23;11(6):1621-1632. Epub 2020 Apr 23.

Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Background: Many immune checkpoint inhibitors (ICIs) have been approved in China to treat non-small cell lung cancer (NSCLC). However, in the long term, less than 20% of patients benefit from ICIs. To maximize the benefit for NSCLC patients, it is necessary to guide the choice of immunotherapy through biomarkers. Recent studies have shown that gut microbiota can affect tumor response to immunotherapy and might be a potential predictive biomarker. This study analyzed the relationship between intestinal flora structure and metabolomic characteristics in NSCLC and the efficacy of ICIs.

Methods: Prospective analysis of samples from 63 patients with advanced NSCLC who attended the Department of Respiratory Medicine of the Peking Union Medical College Hospital from March 2018 to June 2019, and were prescribed programmed cell death 1 (PD-1) inhibitors, was carried out. The follow-up deadline was 31 December 2019. Stool samples were collected from all patients before the start of immunotherapy. DNA was extracted from all samples and libraries were constructed. This was followed by sequencing using the Illumina sequencing platform, and results were studied using a biological information data analysis process. We divided the data into two groups based on progression-free survival (PFS) ≥ six months and PFS < six months.

Results: The median PFS was 7.0 months, not reaching the median overall survival (OS). We obtained 373.5 G of original sequencing data. The phyla Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria accounted for most of the bacterial communities in the stool samples studied. Compared with the PFS < six-month group, the patients in the PFS ≥ six-month group had significantly higher β-diversity in the intestinal microbiome at the baseline level. There were also differences in composition between the two groups. Samples in the PFS ≥ six-month group were rich in Parabacteroides and Methanobrevibacter, while those in the PFS < six-month group were rich in Veillonella, Selenomonadales, and Negativicutes. The KO, COG, and CAZy databases were used to study functional group protein families, yielding 390 (KO), 264 (COG), and 859 (CAZy) functional group abundances, with significant differences between the two groups. Bacterial metabolites analysis suggested significant differences in the metabolic potential of methanol and methane between the two groups.

Conclusions: We found a close correlation between intestinal microbiome β-diversity and anti-PD-1 immunotherapy response in Chinese patients with advanced NSCLC. The intestinal flora composition, functional group protein family, and KEGG metabolism also differed between the two groups. Differences in pathways and flora metabolites were also noted.
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http://dx.doi.org/10.1111/1759-7714.13442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262920PMC
June 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

Clinical recommendations on diagnosis and treatment of immune checkpoint inhibitor-induced renal immune-related adverse events.

Thorac Cancer 2020 06 30;11(6):1746-1751. Epub 2020 Mar 30.

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

Immune checkpoint inhibitors (ICIs) are nowadays widely used in clinical oncology treatment, and significantly improve the prognosis of cancer patients. However, overactivation of T cells and related signaling pathways caused by ICIs can also induce immune-related adverse effects (irAEs). Renal immune side-effects are relatively rare, but some are serious and fatal. Acute kidney injury (AKI), diagnosed mainly by percentage increases in serum creatinine (sCr), is the most common clinical manifestation, while acute tubulointerstitial nephritis (ATIN) is the main cause of ICI-related AKI. Urinalysis analysis and sediment evaluation, 24 hour urine protein and sCr are helpful in screening and monitoring renal irAEs. Multiple potential causes for AKI are involved during cancer therapy, and should be differentiated from the immune mechanisms of ICIs. Under these circumstances, a renal biopsy should be considered which is essential for clinical decision-making. Steroids are an effective treatment option for renal irAEs. Most patients who experience ICI-related ATIN achieve a partial or complete renal recovery with prompt diagnosis and treatment. Multidisciplinary collaborations of different specialists will improve the effectiveness and outcome in the management of ICI irAEs.
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http://dx.doi.org/10.1111/1759-7714.13405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262914PMC
June 2020

Single-center study to determine the safety and efficacy of CT-707 in Chinese patients with advanced anaplastic lymphoma kinase-rearranged non-small-cell lung cancer.

Thorac Cancer 2020 05 17;11(5):1216-1223. Epub 2020 Mar 17.

Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Introduction: It has been proven that ALK-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitors while the chemotherapy resistance is unavoidable. In this study, safety and antitumor activity of the novel ALK inhibitor (ALKi) CT-707 were evaluated in Chinese patients with advanced ALK-rearranged NSCLC.

Methods: This single-center, open-label phase I study recruited adult patients with ALK-rearrangement (confirmed by fluorescence in situ hybridization and/or immunohistochemistry) of locally advanced/metastatic malignancies including NSCLC. This study consisted of two parts: dose escalation and dose expansion. CT-707 was administered orally once a day for 21 days.

Results: A total of 13 patients who were treated with CT-707 from 450 to 600 mg (in the dose increasing phase) were enrolled in this trial (two patients were previously treated with crizotinib). There were 12 patients diagnosed with lung adenocarcinoma and one patient with malignant pleural mesothelioma. After treatment, grade 3 diarrhea (600 mg once a day) was found as dose-limiting toxicity (DLT).The most common adverse events included diarrhea (92%), elevated aspartate aminotransferase (61%), elevated alanine aminotransferase (54%), hair loss (38%), and vomiting (31%). The overall response rate was 77% (10/13). Among all patients, four of the five patients who did not receive any treatment, one of the two patients who had received treatments with crizotinib, and five of the six patients who received standard chemotherapy achieved partial response (PR). One patient reached a complete remission (CR).

Conclusions: This study indicated that CT-707 is clinically effective as a new antitumor drug for Chinese lung adenocarcinoma patients with ALK rearrangement. It is safe and reliable and the dose-expansion phase recruitment has started.
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http://dx.doi.org/10.1111/1759-7714.13376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180692PMC
May 2020

Risk of COVID-19 for patients with cancer.

Lancet Oncol 2020 04 3;21(4):e181. Epub 2020 Mar 3.

Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 100730 Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(20)30149-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129735PMC
April 2020

Clinical diagnosis and treatment of immune checkpoint inhibitor-associated adverse events in the digestive system.

Thorac Cancer 2020 04 28;11(4):829-834. Epub 2020 Feb 28.

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

Immunotherapy for malignant tumors is a hot spot in current research and the treatment of cancer. The activation of programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA)-4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune-checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune-related adverse events (irAEs). The digestive system, including the gastrointestinal tract and liver which are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune-related organs, is the most commonly affected system of irAEs. This review explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.
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http://dx.doi.org/10.1111/1759-7714.13338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113043PMC
April 2020

Tocilizumab for Fulminant Programmed Death 1 Inhibitor-Associated Myocarditis.

J Thorac Oncol 2020 03;15(3):e31-e32

Department of Respiratory Medicine, Peking Union Medical College Hospital, Beijing, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2019.09.080DOI Listing
March 2020

Niche differentiation in the rhizosphere and endosphere fungal microbiome of wild Sm.

PeerJ 2020 5;8:e8510. Epub 2020 Feb 5.

College of Life Sciences, Shaanxi Normal University, Xi'an, China.

Background: The plant microbiome is one of the key determinants of plant health and metabolite production. The plant microbiome affects the plant's absorption of nutrient elements, improves plant tolerance to negative environmental factors, increases the accumulation of active components, and alters tissue texture. The microbial community is also important for the accumulation of secondary metabolites by plants. However, there are few studies on the niche differentiation of endophytic microorganisms of plants, especially at different elevations.

Methods: We investigated the effects of altitude on the community composition of endophytic fungal communities and the differentiation of endophytic microorganisms among different niches in Sm. The rhizosphere soil, roots, rhizomes and leaves of wild-type Sm. at different altitudes were sampled, and the fungal communities of all samples were analyzed by internal transcribed spacer one amplification sequencing.

Results: The results showed that in rhizosphere soil, the number of operational taxonomic units (OTUs) that could be classified or identified decreased significantly with increasing altitude, whereas in the endosphere of plants, the total number of OTUs was higher at intermediate altitudes than other altitudes. Furthermore, the structural variability in the rhizosphere fungal community was significantly lower than that in the endophytic communities. In addition, our results confirmed the presence of niche differentiation among members of the endophytic microbial community. Finally, we also determined that the predominant genus of mycobiota in the rhizome was . This study provides insight into the relationships between the endosphere microbiome and plants and can guide the artificial cultivation of this plant.
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http://dx.doi.org/10.7717/peerj.8510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007733PMC
February 2020

Clinical diagnosis and treatment of immune checkpoint inhibitors-related endocrine dysfunction.

Thorac Cancer 2020 04 11;11(4):1099-1104. Epub 2020 Feb 11.

Department of Respiratory, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

As a new class of antitumor drugs, immune checkpoint inhibitors (ICIs) have shown remarkable efficacy toward the treatment of various malignant tumors. By virtue of their targets and mechanisms of action, ICIs can cause autoimmune and inflammatory effects, termed as immune-related adverse events (irAEs) and unlike the adverse reactions of traditional therapies, irAEs are occult and not fixed, with some serious adverse reactions forcing patients to stop treatment which might even affect their survival. Therefore, with the wide clinical application of ICIs, clinicians need to fully understand the possible adverse reactions of these drugs and devise reasonable treatment strategies to improve the survival rate and therapeutic effects of patients receiving ICIs. In this article, we review the incidence, clinical manifestations, diagnosis and treatment of immune-related endocrine events that may occur with the administration of ICIs.
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http://dx.doi.org/10.1111/1759-7714.13347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113039PMC
April 2020

Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor-related hematological adverse events.

Thorac Cancer 2020 03 3;11(3):799-804. Epub 2020 Feb 3.

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

Immune checkpoint inhibitors (ICIs) are able to reactivate the immune system, thereby enhancing the anti-tumor effects. However, over-activated T cells may induce immune-related adverse events (irAEs). Hematological irAEs are rarely reported which mainly represent monolineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even life-threatening diseases such as hemophagocytic lymphohistiocytosis. Here, the clinical manifestations of hematological irAEs are summarized and recommendations for diagnosis and treatment proposed. KEY POINTS: Significant findings of the study • Hematological immune-related adverse events (irAEs) caused by checkpoint inhibitors are rare and may sometimes be life-threatening. This study summarizes the manifestations of hematological irAEs and proposes preliminary recommendations for diagnosis and treatment. What this study adds • Much still remains unknown regarding hematological irAEs caused by checkpoint inhibitors. This study delineates the overview of hematological irAEs, and provides practical treatment suggestions, in particular addressing the issue of rechallenge.
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http://dx.doi.org/10.1111/1759-7714.13281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049514PMC
March 2020

Clinical diagnosis and treatment recommendations for ocular toxicities of targeted therapy and immune checkpoint inhibitor therapy.

Thorac Cancer 2020 03 4;11(3):810-818. Epub 2020 Feb 4.

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

The increased use of targeted therapy and immune checkpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, increasing numbers of immune-related adverse events (irAEs) of these medications have been reported, affecting almost all human organs including the eye. These adverse effects may affect the entire ocular region, including the eyelid, eye lashes, conjunctiva, cornea, uvea, retina and optic nerve, and have thus far been largely ignored by patients and doctors. In this review, we summarize the characteristics of ocular diseases related to irAEs and advise on how to diagnose and manage these diseases. KEY POINTS: This review will enable clinical oncologists to recognize, diagnose, and manage targeted therapy and immune checkpoint inhibitor-related ocular adverse events.
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http://dx.doi.org/10.1111/1759-7714.13327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049480PMC
March 2020

Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections.

Thorac Cancer 2020 03 22;11(3):805-809. Epub 2020 Jan 22.

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

Immune checkpoint inhibitors (ICIs) have been widely used in the management of malignant tumors. Programmed death 1 (PD-1)/PD-1 ligand (PD-L1) inhibitors have been introduced to treat non-small cell lung cancer (NSCLC) in recent years. Currently, PD-1/PD-L1 inhibitors are considered to have minor side effects and do not independently increase the risk of infection. However, they may cause immune-related adverse events (irAEs) that require immunosuppressive therapy with corticosteroids and/or immunosuppressants, leading to opportunistic infections. Furthermore, there have been reports describing reactivation of chronic/latent infections without irAEs or having received immunosuppressants. Thus, immune checkpoint inhibitor related infections have received more attention worldwide. In this paper, we review available clinical data, describe the potential mechanism, and propose recommendations for the diagnosis and clinical management of PD-1/PD-L1 inhibitor-related infections.
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http://dx.doi.org/10.1111/1759-7714.13313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049502PMC
March 2020

Management of immune checkpoint inhibitor-related adverse events: A review of case reports.

Thorac Cancer 2020 03 22;11(3):498-504. Epub 2020 Jan 22.

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

Immune checkpoint inhibitors represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Management of irAEs is based on clinical experience because it is not easy to conduct prospective trials to evaluate the best treatment strategy. Using a combination of search terms in the PubMed and Embase databases, we reviewed all cases in the English language citing toxicities associated with either pembrolizumab, nivolumab, ipilimumab, atezolizumab, tremelimumab, durvalumab, avelumab or any combination of these agents published before 20 May 2019. A total of 128 reports with 239 cases were included in the study. Here, we summarize the spectrum of toxicities, safety in special patients, rechallenging after irAEs and agents used for treatment of irAEs in those reports.
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http://dx.doi.org/10.1111/1759-7714.13315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049490PMC
March 2020

Histologic transformation of lung cancer during pembrolizumab therapy: A case report.

Thorac Cancer 2020 03 16;11(3):793-796. Epub 2020 Jan 16.

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

Immune checkpoint inhibitors that block the programmed death 1/programmed death ligand 1 pathways are widely used to treat advanced lung cancers. There are seldom cases of histologic transformation reported after treatment with immunotherapy. Here, we report the case of a 69-year-old man with stage IV lung squamous cell carcinoma. He received pembrolizumab monotherapy and had a partial response. After 22 cycles of pembrolizumab, chest computed tomography (CT) showed a left hilar tumor, bilateral pleural effusion and lymphadenopathy. The cytology of pleural effusion and bronchoscopic biopsy of an intraluminal lesion revealed small cell lung cancer. After two cycles of chemotherapy (etoposide/carboplatin), CT scan revealed shrinkage of lesions. This is the first case of lung squamous cell carcinoma with histologic transformation after treatment with pembrolizumab alone.
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http://dx.doi.org/10.1111/1759-7714.13312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049493PMC
March 2020

Abivertinib in patients with T790M-positive advanced NSCLC and its subsequent treatment with osimertinib.

Thorac Cancer 2020 03 14;11(3):594-602. Epub 2020 Jan 14.

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

Background: Abivertinib is a novel oral, third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that overcomes T790M-induced resistance in non-small cell lung cancer (NSCLC) patients. Here, we report the results of a complete and detailed clinical data of patients treated with abivertinib at our hospital in a phase I dose escalation/expansion study of abivertinib.

Methods: NSCLC patients with the EGFR T790M mutation were orally administered abivertinib (150-300 mg) twice daily for cycles of 28 continuous days and tumor response was assessed. Further data regarding subsequent treatment protocols and survival were collected.

Results: A total of 28 NSCLC patients were included. Of the 24 assessable patients, 12 (50%) achieved a partial response (PR), and six (25%) achieved stable disease (SD). Median progression-free survival (PFS) was 5.9 months (95% confidence interval (CI): 3.259-8.541) and median overall survival (OS) was 17.9 months (95% CI: 11.36-24.5). For salvage therapy in 15 (53.6%) patients after abivertinib, the median PFS following osimertinib treatment was 12 months. The median total treatment duration for the two third-generation EGFR TKIs was 15.9 months (95% CI: 12.5-19.3). The most frequent abivertinib-associated adverse effects were elevated hepatic transaminases (10/28, 35.7%) and diarrhea (10/28, 35.7%).

Conclusions: Abivertinib is a unique novel third-generation EGFR TKI with good tolerance and efficacy in EGFR T790M(+) NSCLC patients. For patients with progressive disease after treatment with abivertinib, osimertinib could be an option for subsequent therapy but further studies are required.

Key Points: Abivertinib is a novel third-generation EGFR TKI targeting the EGFR T790M mutation Abivertinib is well tolerated and efficacious in T790M-positive patients Abivertinib has a unique structure, efficacy, and resistance mechanism compared with osimertinib Osimertinib treatment after AC0010 showed a good response.
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http://dx.doi.org/10.1111/1759-7714.13302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049520PMC
March 2020

Clinical manifestation and management of immune checkpoint inhibitor-associated cardiotoxicity.

Thorac Cancer 2020 02 17;11(2):475-480. Epub 2019 Dec 17.

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

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1), its ligand (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) have revolutionized cancer treatment by recovering the attack of T lymphocytes on the malignant cells. They have improved clinical outcomes dramatically in multiple types of advanced-stage malignancies. Even though the tolerance and safety profiles are generally good, it has been widely reported that ICIs can cause severe or fatal immune-related adverse events (irAEs), since the activated T lymphocytes are not specific for tumor cells. Cardiac irAEs appear to occur less frequently than irAEs in other organ systems but are notorious for high mortality. Here, we aim to identify and characterize the ICI-associated cardiotoxicity and summarize the optional diagnosis and treatment strategies.
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http://dx.doi.org/10.1111/1759-7714.13250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996973PMC
February 2020

Management of immune checkpoint inhibitor-related dermatologic adverse events.

Thorac Cancer 2020 02 9;11(2):488-492. Epub 2019 Dec 9.

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

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. The unique spectrum of immune-related adverse events (IrAEs) may occur during treatment. Dermatologic toxicities appear to be one of the most prevalent immunotherapy-related adverse events. The most common symptoms are maculopapular rash and pruritus. Serious dermatologic toxicities including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms are rare. In this review, we summarize guidelines of management of immunotherapy-related toxicities, case reports, and proposed treatment recommendation.
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http://dx.doi.org/10.1111/1759-7714.13275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997012PMC
February 2020

Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.

Thorac Cancer 2020 01 24;11(1):191-197. Epub 2019 Nov 24.

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

The increasing use of immune checkpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immune checkpoint inhibitors, mainly activated T-cells, can attack normal tissues and organs in the body and lead to a variety of adverse effects. In the lung, these attacks can induce checkpoint inhibitor pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and has the potential to be fatal if not treated correctly. In this review, we summarize the characteristics of CIP and provide advice on how to manage this disease.
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http://dx.doi.org/10.1111/1759-7714.13240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938759PMC
January 2020