bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of MET exon 14 skipping in Chinese non-small cell lung cancer (NSCLC) patients.
Authors: Zhang Baihua , Xia Yu , Zhang Jiujin , Yu Jin , Chen Min , Yao Wei , Zhao Juan , He Jiqiang , Mok Tony S. K. , Wang Kai 
Published: May 2020

e21525 Background: MET exon 14 skipping ( METex14) has been identified as a precise biomarker for MET-targeted therapy. Most METex14 alterations occur in patients (pts) with non-small cell lung cancer (NSCLC). Here, we present the clinical, pathological, and genomic characteristics of Chinese NSCLC pts harboring METex14. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor and matched blood samples from 3433 pts were collected from December 2017 to January 2019 for a 450 cancer gene targeted next-generation sequencing (NGS) panel. Genomic alterations (GAs) including single nucleotide variations, short and long insertions/deletions (Indels), copy number variations, and gene rearrangements were assessed. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: A total of 35 (1.0%) pts harbored the GAs predicted to cause METex14, which was lower than that of the Western population (3%), and comparable to data in previously reported Chinese NSCLC pts. METex14 mutation rates were 10.5% in sarcomatoid carcinoma, 1.5% in adenosquamous carcinoma and 1.0% in adenocarcinoma. The median age of pts with METex14 was 65 years (range 46-85) and 46% were female. Compared with wild-type (WT) pts, those harboring METex14 were significantly associated with older age (median age: 65 vs. 60 years, respectively, p = 0.005) and earlier stage (stage I & II ratio: 67.7% vs 42.0%, respectively, p < 0.0001). METex14 alterations included 17 samples (48.6%) that were base substitutions located on the non-coding adjacent splice acceptor (1), donors (7), and other splice acceptors (9), and 18 (48.6%) Indels located on the non-coding adjacent splice acceptors (8), donor (1), other splice acceptor (1), and exon/intron junctions (7). MDM2, FRS2, and CDK4 amplification was observed in 22.9%, 20.0%, and 17.1%, respectively, of pts with METex14, which was significantly higher than in WT pts (P < 0.001). Concurrent EGFR mutations were rarely observed with METex14 compared with WT pts (8.6% vs. 51.7%, respectively, p < 0.0001). Concurrent MET amplification was identified in 3 samples with METex14, and no other driver genes were found. Conclusions: METex14 occurred in 1.0% of Chinese NSCLC pts and showed a significantly higher prevalence in sarcomatoid carcinoma. METex14 observed in pts with NSCLC were associated with increased concurrent MDM2, FRS2, and CDK4 amplification and decreased EGFR mutation, suggesting that METex14 acts as a driving oncogenic factor in NSCLC.
Evaluation of blood-based proteomic biomarkers associated with response to anti-PD-1 treatment in NSCLC.
Authors: Dupuis Nicholas , Lopez-Lastra Silvia , Dumont Clement , Dozio Vito , Beeler Kristina , Sklodowski Kamil , Romano Emanuela 
Published: May 2020

e21531 Background: Immune checkpoint inhibitors have remarkably improved the natural history of patients with non-small cell lung cancer (NSCLC), with improved clinical responses and overall survival compared to standard therapy. However, most unselected NSCLC patients do not respond, highlighting the need of theranostic biomarker discovery. In a cohort of NCSLC patients treated with anti-PD-1-blockade, we investigate baseline blood-based parameters with a high-throughput quantitative proteomics workflow, based on data independent acquisition mass spectrometry (DIA-MS). Quantified proteins are evaluated as potential circulating biomarkers for predicting the response to therapy. Methods: Plasma samples from 49 NSCLC subjects treated with anti-PD-1-blockade were prepared for mass spectrometry. All samples were analyzed on a Thermo Scientific Q Exactive HF-X operated in a DIA mode using capillary flow liquid chromatography with separation over a 40 min gradient. DIA data was extracted with Spectronaut to quantify expressed proteins. Results: Across all samples, 605 proteins were quantified and 17 were significantly associated (log2 fold change > 0.58 and q-value < 0.05) with Responders (SD + PR) vs Non-Responder (PD) groups. Functional mapping and unsupervised clustering of regulated proteins identifies three major subject groups based on protein expression profiles: Group A is characterized by high expression of acute phase proteins (e.g. SAA1/2, CRP), Group B has low overall protein expression, and Group C has high expression glycolysis related enzymes (ALDOA, GAPDH) and focal adhesion proteins (VCL). Consistent with previous studies the Group A, with high levels of acute phase proteins, had poor overall survival relative to the other two families (HR = 2.2 [1.2-4.2], p = 0.003). Notably, Group C is comprised largely of Non-Responders (8/12) yet had improved overall survival relative to Group A (HR = 2.5 [1.2-5.0], p = 0.004). Conclusions: Plasma proteomic profiling with capillary flow DIA-MS enables quantification protein profiles in a hypothesis free manner. Poor outcomes on anti-PD-1 therapy was confirmed for subjects with elevated acute phase proteins. However, a subgroup with high focal adhesion and glycolysis proteins had improved survival despite containing non-responder subjects, requiring further investigation.
The association between STK11/LKB1 and/or KEAP1 mutations and response to PD-1/PD-L1 inhibitors in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Miller Meagan Elizabeth , Patel Meera , Althouse Sandra K. , Hanna Nasser H. , Mamdani Hirva 
Published: May 2020

e21538 Background: Advanced non-small cell lung cancer (NSCLC) patients with tumors harboring STK11/LKB1 or KEAP1 mutations have inferior treatment outcomes when treated with PD-1/PD-L1 blockade, regardless of KRAS status, PD-L1 score, or TMB score (Skoulidis et al, Cancer Discovery 2018, ASCO abstract 102, 2019). Methods: Retrospective clinical databases from Indiana University and Karmanos Cancer Institute were queried to identify patients from 2008-2019 with advanced NSCLC treated with PD-1/PD-L1 monotherapy (group A) or concurrent chemotherapy + PD-1/PD-L1 inhibitors (group B) whose tumors harbored STK11/LKB1 and/or KEAP1 mutations. Patients were characterized by best response, progression of disease (PD) or non-PD (complete response (CR) + partial response (PR) + stable disease (SD)). Patient and disease characteristics, response, and duration of response (> vs. < 6 months) were recorded. Results: A total of 77 patients met the above criteria (55 in group A, 22 in group B). 52 of 55 patients in group A received prior chemo. Patient and disease characteristics and outcomes are summarized in the table. Conclusions: STK11/LKB1 and/or KEAP1 mutations are independent of PD-L1/TMB status, although most patients had PD-L1 of <1%. Nearly ½ of patients with STK11/LKB1 and/or KEAP1 mutations achieve at least SD with PD-1/PD-L1 inhibitor monotherapy and more than 50% of those with non-PD maintain that response status for > 6 mos. The frequency and duration of non-PD in this population is higher in patients receiving chemotherapy + PD-1/PD-L1 concomitantly. [Table: see text]
KEAP1/NFE2L2 as a prognostic biomarker on immunotherapy and correlation with immune infiltrates in non-small cell lung cancer (NSCLC).
Authors: Zhu Hongyuan , Yu Yunfang , Zheng Yating , Xu Bin , Zheng Shaopeng , Zeng Fanjun , Xie Wenzhuan , Huang Luyu , Li Fasheng , Lin Weihuan , Liao Guoqing , Wu Shaowei , Liu Xinyi , Huang Mengli , Zhou Haiyu 
Published: May 2020

e21551 Background: Molecular characterization studies revealed recurrent KEAP1/ NFE2L2 alterations in non-small cell lung cancer (NSCLC). Previous studies have confirmed that KEAP1/NFE2L2 mutations are a poor prognostic factor for chemotherapy in patients with NSCLC. Nevertheless, it is unclear whether KEAP1/NFE2L2 mutations (MUT) of liquid biopsy can predict the efficacy of immunotherapy in NSCLC. Methods: Two independent cohorts (the OAK and POPLAR study cohort) with data from approximately 853 patients with advanced NSCLC were used to analyze the prognostic effect of KEAP1/NFE2L2 on immunotherapy. In addition, based on a deconvolution algorithm (known as CIBERSORT), we comprehensively analyzed the tumor-infiltrating immune cells present in NSCLC. The fraction of 22 immune cells subpopulations was evaluated to determine the associations between each cell type and KEAP1/NFE2L2 mutation status utilizing data from 1268 patients by lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) in TCGA pan-cancer cohort. Results: The OAK and POPLAR study cohort of NSCLC patients showed that KEAP1/NFE2L2 MUT was associated with poorer overall survival (OS), and progression-free survival (PFS) (OS: HR = 1.7, P < 0.001; PFS:HR = 1.4, P < 0.001) on immunotherapy, even after EGFR and ALK mutations were excluded, significant difference can also be gained (OS:HR = 1.8, P < 0.001; PFS:HR = 1.5, P < 0.001). Then, the NSCLC patients were subdivided into LUAD and LUSC, the OS and PFS of patients with KEAP1/NFE2L2 MUT is lower than wild-type (WT) (OS:HR = 1.8, P < 0.001; PFS:HR = 1.4, P = 0.0014) in LUAD, significant differences were obtained even when EGFR and ALK mutations were excluded (OS:HR = 1.9, P < 0.001;PFS:HR = 1.6, P < 0.001). In LUSC, patients with KEAP1/NFE2L2 MUT have lower OS (HR = 1.4, P = 0.0473),and there was no difference on PFS (HR = 1.2, P = 0.1588) between KEAP1/NFE2L2 MUT and WT, when EGFR and ALK mutations were excluded, the survival results did not change significantly. In addition, KEAP1/NFE2L2 MUT was positively correlated with infiltrating levels of plasma cells, T cells CD4 memory activated, T cells follicular helper, and Macrophages M1, but negatively correlated with infiltrating levels of T cells CD4 memory resting, monocytes, Dendritic cells activated, Mast cells resting, and Neutrophils in NSCLC. The immunoinfiltration of LUAD was significantly different from that of LUSC. Conclusions: These findings suggest that KEAP1/NFE2L2 can be used as a poorer biomarker for determining prognosis on immunotherapy and immune infiltration in NSCLC.
Gender disparities in hormone positive lung cancer.
Authors: Xia Bing , Feldman Rebecca , Cozen Wendy , Kang Irene , Raez Luis E. , Borghaei Hossein , Kim Chul , Nagasaka Misako , Mamdani Hirva , Vanderwalde Ari M. , Pai Sachin Gopalkrishna , Lopes Gilberto , Socinski Mark A. , Wozniak Antoinette J. , Kim Edward S. , Spira Alexander I. , Liu Stephen V. , Nieva Jorge J. 
Published: May 2020

e21552 Background: Lung cancer has not declined in U.S. women as much as it has in men over the past 20 years despite similar rates of smoking cessation among the genders. We explored whether differences in hormone receptor status could contribute to the reason for the observation. Methods: A total of 3,256 non-small lung cancer (NSCLC) tumor samples submitted for molecular profiling between 2013-2018 were retrospectively identified for having hormone receptor (HR) expression results. HR-positive (HR+) status was defined as ≥ 1+ and 1% nuclear staining of Estrogen Receptor alpha (SP1, Ventana) and/or Progesterone Receptor (IE2, Ventana) by immunohistochemistry. DNA sequencing by NGS included cases sequenced by the Illumina MiSeq hot spot 47 gene panel (n = 2753) and Illumina NextSeq 592 gene panel (n = 503). Tumor mutation burden (TMB) was measured by counting somatic non- synonymous missense mutations on the 592 gene panel and ≥ 10 mutations/Megabase (mut/Mb) was considered high. Fisher’s Exact, Chi- square and likelihood ratio (LR) tests were utilized for statistical analyses. Results: Hormone receptor positivity (HR+) was identified in 318 women and 186 men, 504/3256 or 15% of NSCLC. EGFR mutation subtypes observed were Exon19del (46%), L858R (28%), uncommon non-classical (17%), G719X|S768I|L861Q (5%). HR+ occurred more commonly in women compared to men (20% vs 11%, p < 0.001). HR+ NSCLC had the same age distribution as HR-negative (HR-) cancers (range: 16-94 and 18-93, respectively). Compared to patients (pts) who were HR-, pts with HR+ NSCLC were more likely to harbor activating EGFR mutations in men and women (LR 1.39, p = 0.0017), and less likely to have mutations in TP53 (LR 0.83, p = 0.0076), K-RAS (LR 0.66, p < 0.0001), or translocations in ALK (LR 0.46 p = 0.0190). No differences in the incidence of ERBB2 or BRAF mutations were identified. The median tumor mutational burden was equivalent in HR+ vs. HR- pts, both 9 mut/MB. Conclusions: The disparity in the prevalence of hormone receptors in lung cancers affecting men and women deserves further exploration. The presence of hormone receptors in NSCLC is increased in women and in tumors bearing EGFR mutations. Further elucidation of the mechanism and dual targeting of EGFR and ER in patients with HR+ NSCLC deserves exploration.
Histopathological prognostic markers in metastatic lung adenocarcinoma, validation of stromal fibrosis and immunoscore as easy to interpret findings and their correlation with survival.
Authors: Rojas Puentes Luis Leonardo , Ruiz-Patiño Alejandro , Mayorga Diana Carolina , Rodríguez July Katherine , Ávila Coy Jenny Mireya , Bravo Espinosa Melissa Andrea , Arrieta Oscar , Zatarain-Barron Zyanya Lucía , Barron Feliciano Barron , Carranza Hernan , Otero Jorge M. , Vargas Carlos Alberto , Archila Pilar , Sotelo Rodríguez Diana Carolina , Martin Claudio , Recondo Gonzalo , Pino Luis , Rolfo Christian Diego , Rosell Rafael , Cardona Zorrilla Andres Felipe 
Published: May 2020

e21566 Background: Several histopathological markers have been associated with immune system activity and its relationship with clinical outcomes in lung cancer. Determination of tumor infiltrating lymphocytes as well as specific subpopulations could reveal cytotoxic potential. Additionally, changes in stromal composition and fibrosis could also reflect potential cellular interactions with the tumor lesions. In this study we validate these two findings as potential prognostic factors. Methods: A retrospective cohort analysis of patients with advanced lung adenocarcinoma treated in a reference center in Bogota, Colombia was conducted. Demographic as well as treatment variables were collected between January 2018 and December 2019. In addition to clinical outcomes, the percentage of stromal fibrosis and immunoscore were estimated for all biopsy samples by a trained oncological pathologist. Results: A total of 133 patients were included. Male predominance (51.1%) with Karnofsky performance scores (KPS) greater than 80 and 19% of prior cigarette exposure (26 patients) was identified in the cohort. Median overall survival of the cohort was 27.1 months (95%CI 22.1-NA) and progression free survival of 19.4 months (95%CI 18-24.5 months). Percentage of fibrous stroma and immunoscore were associated with a benefit in both OS and PFS. For patients who presented with a low stromal fibrosis, defined as harboring less than 10%, OS reached a median of 25.1 months (95%CI 21.5- 40.5 months) compared to 38.7 months for patients with high fibrosis (95%CI 27.7 months – NA), (p = 0.02). In terms of immunoscore, values under 40% were associated with a longer median OS (38.7 months, [95%CI 31.3- 58.6 months] vs 22.1 months [95%CI19.8- 42.3 months], p < 0.001). Immunoscore and stromal fibrosis were not codependent variables (p < 0.001), suggesting that these markers offer independent prognostic value with regards to OS. Conclusions: Stromal fibrosis and immunoscore serve as prognostic factors that could be easily interpreted and evaluated in order to offer prognostic classification of patients with metastatic adenocarcinoma of the lung.
Age and gender specific lung cancer incidence and mortality in Hungary: Trends from 2011 through 2016.
Authors: Galffy Gabriella , Kiss Zoltan , Bogos Krisztina , Moldvay Judit , Bittner Nora , Vastag Aladar , NAGY-ERDEI ZSOFIA MARIA , Rokszin Gyorgy , Ostoros Gyula , Dr Szabone Dr Muller Veronika Judit , Sarosi Veronika , Polanyi Zoltan , Nagy Balazs , Horvath Krisztian , Abonyi-Toth Zsolt , Voko Zoltan , Tamási Lilla 
Published: May 2020

e21572 Background: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database. Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between 1st January 2011 and 31th December 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any anti-cancer treatment different from lung cancer protocols were excluded. Results: In 2011, 4,522 new male lung cancer cases were registered in the NHIF database, while we found 4,176 incident patients in 2016. The number of female patients increased from 2,636 to 2,828 during the same period. The mean age at diagnosis was 64.51 years for men (SD±9.85) and 64.93 years for women (SD±11.19) in 2011, increasing steadily to 65.80 years (SD±9.41) and 65.99 years (SD±10.45), respectively. Lung cancer incidence and mortality increases with age, peaking in the 70–79 age group (375.0/100,000 person-years) among males, while at 60–69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46 to 3.01 (p < 0.0001) among the 70–79 age group. We found 2-11% decrease in male incidence rate at most age groups, while a significant 1-3% increase was observed in older females ( > 60) annually during the study period. Conclusions: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary is decreasing in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population.
Management of lung cancer in elderly population: A mono-centric retrospective study at University Hospital of Caen, Normandy, France.
Authors: Oulkhouir Youssef , Bergot Emmanuel , Madelaine Jeannick , Stchepinsky Boris 
Published: May 2020

e21573 Background: Lung cancer is one of the leading causes of death worldwide and its incidence is increasing in the elderly patient population. Management of these population is not as well codified as that of younger patients due to their under-representation in clinical trials. The objective of this study is to assess the clinical characteristics, diagnostics and treatments in our population at the University Hospital of Caen (CHU). Methods: It was a retrospective monocentric study including all patients over 75 years old who were diagnosed with a lung cancer between January 1, 2014 and December 31, 2017 in our center of Caen. We analyzed epidemiological, clinical and therapeutic criteria. We evaluated the overall survival and according to the type of treatment used, the identification of factors of poor prognosis. Adverse events in that specific population of patients were analyzed. We also looked at the correlation between length of hospitalization and survival data. Results: 132 patients aged 75 to 95 years were included, with a large predominance of men. Almost 90% of our patients had comorbidities. The median survival of the entire population was 7 months. Factors identified as significantly influencing survival are the initiation of a specific cancer treatment, performans status, undernutrition, presence of comorbidities, age, stage of disease, and hospitalization at diagnosis. 58.9% of our patients received treatment including 60% chemotherapy and 17.7% surgery. 52% of patients treated with chemotherapy had Grade 3-4 toxicities. None of the patients treated with targeted therapy had any major side effects. 67.4% of our patients were hospitalized for diagnosis. The percentage of survival time spent in hospital is also significantly higher in the best supportive care group with a rate of 69% versus 25%. 14 patients had a diagnosis of early stage lung cancer. Surgery and radiotherapy were performed and were well tolerated. Conclusions: The elderly population with lung cancer managed in our center is highly diagnosed at an advanced stage and has many associated comorbidities affecting survival. Performans status, nutritional condition and inaugural hospitalization are factors of poor prognosis leading to exclusive palliative care. However, in early stages disease radical treatment good be performed and be well tolerated.
PD-1 inhibitor plus chemotherapy as 2nd/subsequent line therapy had similar clinical outcome with PD-1/PD-L1 inhibitor monotherapy in advanced NSCLC.
Authors: Zhai Xiaoyang , Tian Yaru , Yan Weiwei , An Ning , Zhu Hui 
Published: May 2020

e21600 Background: PD-1/PD-L1 inhibitor monotherapy has been approved as second line therapy in advanced non-small-cell lung cancer (NSCLC). The study aims to compare clinical outcome of PD-1 inhibitor plus chemotherapy with PD-1/PD-L1 inhibitor monotherapy as 2nd/subsequent line therapy in advanced NSCLC. Methods: The clinical data of NSCLC patients who received PD-1/PD-L1 inhibitor as 2nd/subsequent line therapy were retrospectively collected in our study. According to the therapy modality, patients were assigned to PD-1/PD-L1 inhibitor monotherapy group and PD-1 inhibitor plus chemotherapy group. Disease control rates (DCRs), progression free survival (PFS) and overall survival (OS) were evaluated between the 2 groups. The prognostic role of derived neutrophils-to-lymphocyte ratio (dNLR) on the outcomes was also evaluated at the same time. Results: From April 2017 to October 2019, a total of 84 patients were enrolled in the current study. Twenty-six patients were allocated to the PD-1/PD-L1 inhibitor monotherapy group and fifty-eight patients were allocated to PD-1 inhibitor plus chemotherapy group. Chemotherapy regimens were detailed as follow: liposome paclitaxel (n = 15), nab-paclitaxel(n = 12), docetaxel(n = 9), pemetrexed(n = 6), and others(n = 16). Disease control rates (DCRs) and overall survival (OS) were not significantly different between the two groups. Progression free survival (PFS) in the PD-1/PD-L1 inhibitor monotherapy was longer(median PFS: NR vs 4.4 months, p = 0.02). Univariate and multivariate analyses suggested that derived neutrophils-to-lymphocyte ratio (dNLR) was independent prognostic factor of OS and gender was independent prognostic factor of PFS. In the second-line therapy subgroup of 38 patients, OS and PFS were not significantly different in the two groups. In the subgroup of 46 patients of over 2nd line, PD-1/PD-L1 inhibitor monotherapy group had longer PFS (median PFS: NR vs 4.0 months, p = 0.01).The incidence of any grade adverse events (AEs) was no significant difference in the two groups. One patient in the PD-1 inhibitor plus chemotherapy group died of immune-related pneumonitis. Conclusions: The addition of chemotherapy to PD-1 inhibitor as 2nd/subsequent line therapy had similar clinical outcomes compared with PD-1/PD-L1 inhibitor monotherapy of advanced NSCLC patients.