bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with the growth of ground-glass opacity nodules on chest computed tomography.
Authors: Lee Jin Hwa , Bae Ji Yun , Han Ye ji , Ryu Yon Ju , Shim Sung Shine , Kim Yookyung , Chang Jung Hyun 
Published: September 2018

e20051 Background: Chest computed tomography (CT) has become increasingly popular for screening and various reasons, and many cases of ground-glass opacity pulmonary nodules (GGN) that cannot be detected by simple chest radiography have been found incidentally. However, the natural history of GGN is not well understood and guidelines for the evaluation and follow-up of GGN have not yet been established yet. The purpose of this study was to investigate the clinical and CT scan characteristics associated with the growth of GGNs. Methods: We retrospectively reviewed GGN on chest CT performed between March 2011 and February 2014 at a tertiary referral hospital. Data were collected for the patient's age, sex, underlying lung disease, history of malignancy or comorbidities, size, border, number of GGN and presence of solid portion in GGN. For each GGN, an increase in size over time was investigated. We applied a Cox regression analysis to identify factors associated with the growth of GGN. Results: In a total of 504 patients, 916 GGN were found on chest CT. The mean age of the subjects was 59.6 years and 37% of men. The mean follow-up was 17.1 months. Cox regression analysis was performed on age, sex, history of malignancy, maximum diameter of GGN, number of GGN, margins of GGN, and presence of solid portion in GGN. History of malignancy (adjusted hazard ratio [HR] 1.770, 95% confidence intervals [CI] 1.049-2.986, p = 0.032), solitary nodule (adjusted HR 2.335, 95% CI 1.401-3.867, p = 0.001), and nodules with the longest diameter of 10 mm or more (adjusted HR 1.833, 95% CI 1.032-3.253, p = 0.039) were associated with the growth of GGN. Conclusions: A history of malignancy, solitary nodule, and nodules with the longest diameter of 10 mm or more may increase in size in the future. Therefore, the history of malignancy and the size and number of nodules should be considered to determine the duration of follow-up and appropriate biopsy timing.
The role of race and economic characteristics in the presentation and survival of patients with surgically-resected non-small cell lung cancer.
Authors: McKie Kerri , Varlotto John M. , Voland Rick , Flickinger John Charles , DeCamp Malcolm M. , Maddox Debra , Rava Paul , Fitzgerald Thomas J. , Walsh William Vincent , Liebmann James Edward , Uy Karl , Oliveira Paulo , Rassaei Negar , Wakelee Heather A. , Patel Manali I. , Zhang Jianying , Ali Suhail M. , Belani Chandra Prakash , Baima Jennifer , Stock Cameron 
Published: September 2018

e20053 Background: To investigate the inter-relation between economic, marital, and known histopathologic/therapeutic prognostic factors in presentation and survival of surgically-resected lung cancer patients in nine different ethnic groups. Methods: A retrospective review of the SEER database was conducted through the years 2007-2012. Population differences were assessed via chi-square testing. Multivariable analyses(MVA) were used to detect overall survival(OS) differences in the total surgical population (TS, N = 35,689) and in an early-stage (T1-T2 < 4cm N0) surgically-resectable population(ESR, N = 17,931). Results: In the TS population, as compared to Whites, Blacks and Hispanics were more likely to present with younger age, adenocarcinomas, less married partnerships, no insurance, fewer stage I tumors, and fewer nodes examined, but their surgical procedure types and OS/LCSS were the same. MVA demonstrated that lower OS was associated with males, single/divorced/widowed partnership, lower income(TS only), and Medicaid insurance. MVA also found that all ethnic groups had a similar (Hispanics, Blacks) or better OS compared to Whites. 90-day mortality and positive nodes were correlated with not having insurance and not being married, but not ethnicity. Conclusions: In TS and ESR groups, OS was not different in the two largest ethnic groups (Black, Hispanic) as compared to Whites, but was related to single/widowed/divorced status, Medicaid insurance, and income (TS group only). Nodal positivity was associated with patients who did not have a married partner or insurance suggesting that psycho-social variables may impact disease biology in addition to the known histopathologic and treatment variables in patients undergoing surgical resection of early-stage lung cancer.
Preexistence of CT findings with usual interstitial pneumonia (UIP) pattern correlates to radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT).
Authors: Koyama Junji , Kitazono Satoru , Ariyasu Ryo , Saiki Masafumi , Sonoda Tomoaki , Kawashima Yosuke , Takano Natsuki , Oguri Tomoyo , Nishikawa Shingo , Yanagitani Noriko , Horiike Atsushi , Ohyanagi Fumiyoshi , Oikado Katsunori , Kozuka Takuyo , Nishio Makoto 
Published: September 2018

e20063 Background: RP is a major toxicity commonly observed in NSCLC patients who receive CRT; RP prediction is a critical issue. Although preexisting interstitial pneumonia (IP) is considered as one of the risk factors of RP, the correlation between interstitial lung shadows (ILSs) in the pretreatment CT scan and RP is not well examined. Methods: We reviewed patients with stage III NSCLC who received CRT at our hospital from January 2011 until December 2014. The pretreatment CT scans were retrospectively evaluated, and preexisting ILSs were classified according to the ATS/ERS/JRS/ALAT statement for idiopathic pulmonary fibrosis (IPF) as follows: UIP pattern, possible UIP pattern, and others (not UIP pattern). The incidence, severity, and features of RP were compared between ILS patterns. Results: In total, 105 patients with stage III NSCLC had received CRT. ILSs in pretreatment CT scans were identified in 16 (15.2%) of 105 patients. Of all the identified patterns, one (0.9%) was UIP pattern, six (5.7%) were possible UIP pattern, and nine (8.6%) were not UIP pattern. Grade 3 or higher RP was observed in 2 of 7 (28.6%) patients with UIP pattern or possible UIP pattern and 1 of 9 (11.1%) patients with not UIP pattern ( P = 0.55). RP that extended outside the irradiation field like an acute exacerbation of IP was observed in 4 of 7 (57.1%) patients with UIP pattern or possible UIP pattern and 1 of 9 (11.1%) patients with not UIP pattern ( P = 0.106). Conclusions: Preexistence of ILSs classified as UIP pattern or possible UIP pattern should be considered as a risk factor for severe or extensive RP after CRT.
Downregulation of CPA4 to suppress NSCLC proliferation by inducing apoptosis and G1 arrest.
Authors: Fu Yangyang , Huang Xiaoying , Wang Liangxing 
Published: September 2018

e20074 Background: Carboxypepidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Previous study discovered that CPA4 may participate in cell growth and differentiation of prostate epithelial cells. Meanwhile, CPA4 is a printed gene and thought to be involved in prostate cancer aggressiveness. As is reported, CPA4 was increased in NSCLC tissues compared to normal lung tissues and high expression of CPA4 was correlated with poor prognosis of NSCLC patients. However, the role of CPA4 play in lung tumorigenesis is still unclear. Methods: We examined the mRNA and protein expression level of CPA4 via real-time PCR and immunohistochemistry in NSCLC tissues and adjacent tissues. Growth assays both in vitro and in vivo were performed to elucidate the role of CPA4 may play in lung cancer and Fluorescence Activated Cell Sorter was conducted to uncover the putative mechanism. Results: CPA4 expression was increased both in mRNA and protein levels in NSCLC tissues compared to adjacent tissues. MTT and colony formation assays showed that downregulation of CPA4 in H1299 and A549 cells inhibited lung cancer cells proliferation. We further confirmed this result by using cellomics and celligo. Depleting CPA4 also suppressed tumor growth in mice. Mechanically, we found that suppressing CPA4 expression in lung cancer cells could induce apoptosis and G1 arrest. We supposed that CPA4 expression may be associated with caspase family and it needs further studies. Conclusions: Collectively, we demonstrate that decreased CPA4 inhibits NSCLC proliferation via inducing apoptosis and G1 arrest.
Histological features and survival in NSCLC patients treated with surgery with curative intention.
Authors: Cárdenas Quesada Nuria , Ortega Granados Ana Laura , Márquez Lobo Bélgica , Vivo Molina María Carmen , Rosa Garrido Carmen , Piedra Fernández Inmaculada , Sevilla López Sebastián , Cerro Antonio Bravo , Lacárcel Bautista Celia , Pérez Chica Gerardo , Nieto Serrano José , García Verdejo Francisco José , Luque Caro Natalia , Fernández Garay David , Moreno Jimenez Miguel Angel , Plata Fernández Yessica , Núñez Torres María Isabel , Sánchez Rovira Pedro 
Published: September 2018

e20080 Background: New classification of adenocarcinomas and better typing of histological characteristics of lung tumors leads us to wonder if these histological data could have a prognostic repercussion in the NSCLC who were into curative intent surgery Methods: We followed 95 patients with stage I-III NSCLC underwent surgery in a 4 year period (2010-2013), until August 2016. Most patients were male (82%), smokers (90%, 44% exsmokers and 56% active , median age at diagnosis was 64 years, 47% had a previous COPD, and 52% were diagnosed of NSCLC without any symptom of lung cancer. 79% patients had lobectomy or sleeve resection, and 21% pneumonectomy. 47% patients had adjuvant chemotherapy (CT) Results: We found no significant differences in age of diagnosis between men (64.95 y) and women (58.65 y) (p = 0.066) nor in survival time. Median disease-free survival (DFS) is 15 months and overall survival (OS) is 49 months. If we analyze DFS from surgery to the first relapse, most happen at first 2 years (80%). By stage, OS at 5 years is 73% in stage IA, 58% stage IB, 46% stage IIA, 36% stage IIB, 24% for stage IIIA and 9% in IIIB. We had 49% adenocarcinomas (most frequent, 53%, acinar subtype), and 51% squamous, and we found no significant difference between histologies, nor between subtypes. But there was a significant difference between DFS, favorable for mild lymphoid response (20 months) with respect to moderate or intense response (11 months) Conclusions: We found that we are underusing adjuvant CT. In our group there is no difference in survival for tumor size, linfovascular invasion, histological grade or histology, but we found a better DFS for mild lymphoid response vs moderate-intense pattern. This finding may be related to the antitumor activity of the immune system, and we want to validate it prospectively, and its relationship with subsequent immune therapy response.
Apatinib to enhance antitumor activity of gefitinib in non-small cell lung cancer.
Authors: Li Fang , Zhu Tengjiao , Zhu Xiang , Wang Jiadong , Liang Li 
Published: September 2018

e20086 Background: Gefitinib, an oral EGFR-TKI, is recommended as the first-line therapy for non-small cell lung cancer (NSCLC) patients with EGFR mutations. Apatinib is an oral TKI against VEGFR-2 and is effective as third- or later-line treatment in advanced NSCLC. EGFR and VEGF/VEGFR pathways are interrelated. We conducted this study to explore the effect of gefitinib plus apatinib therapy in NSCLC and the possible mechanism. Methods: Cell viability assay was performed on 4 NSCLC cell lines (A549, H1975, H1650 and HCC827) to determine IC50 of gefitinib, apatinib and their combination for growth inhibition. The nude mice were injected i.h. with H1975 cells to establish EGFR mutated NSCLC xenograft tumor. Tumor volume was recorded every three days. Immunohistochemistry for Ki67 and PCNA expression was performed to detect tumor cell proliferation in mice. In addition, the expression levels of key proteins were detected by immunohistochemistry and western blot, respectively. Results: The H1975 cells were the most susceptible to the combination of gefitinib and apatinib, with lowest IC50 value of 0.44 ± 0.09, compared with other cells. In H1975 xenograft model, gefitinib plus apatinib showed markedly higher inhibiting effect on tumor volume than both gefitinib and apatinib mono-therapy. Moreover, the expressions of both Ki67 and PCNA significantly decreased in mice after combined therapy than either gefitinib or apatinib alone, indicating that the combined therapy was superior to mono-therapy of gefitinib or apatinib in suppressing cell proliferation in mice. Additionally, there was an obviously higher expression of EGFR, pho-EGFR, VEGFR, pho-VEGFR, VEGFA, p-mTOR, t-mTOR, p-AKT, t-AKT, p-Erk, and t-Erk in mice treated with gefitinib plus apatinib than mono-therapy. Furthermore, the much stronger inhibitory effect on angiogenesis of gefitinib plus apatinib therapy was revealed, as more expression of CD31 than both gefitinib and apatinib mono-therapy. Conclusions: Apatinib significantly potentiated the antitumor effect of gefitinib in NSCLC both in vivo and vitro. These findings support a great therapeutic potential role for the combination of apatinib and EGFR-TKI in the treatment of NSCLC in clinic.
Priming PD-L1 expression by chemotherapeutic agents in non-small cell lung cancers.
Authors: Lin Emily Pei-Ying , Yang Ching-Yao , Lin Ching-Wen , Huang Bo-Tsang , Lai Wei-Yun , Tseng Yi-Ting , Yang Pan-Chyr 
Published: September 2018

e20087 Background: Immunotherapy targeting PD-1/PD-L1 axis has yielded fruitful results in non-small cell lung cancers (NSCLCs). Evidences showed that treatment responses are likely correlated with tumor PD-L1 expression levels, which is especially true in the first line setting. Results from Keynote-021 suggested that pembrolizumab plus platinum-pemetrexed doublet came out with better overall response rate and progression free survival as compared to chemotherapy alone even in the PD-L1 low-expression group. Nevertheless, grade III and IV toxicities were much frequently observed in the combinational arm. The aim of the current study is to investigate the effect of chemotherapeutics on PD-L1 priming in NSCLCs so as to provide a better option in the chemo-immunotherapy combinational setting. Methods: NSCLC cell lines CL1-5, CL141, and H1299 were treated with a platinum-based drug (cisplatin), microtubule-targeted agents (paclitaxel or vinorelbine), or antimetabolites (pemetrexed or gemcitabine) for 24 to 72 hrs. The concentration of each drug selected for experiments was stepping-down titrated from the IC50s, with the maximum concentration allowed being 10 μM. The priming effects of chemotherapeutics on PD-L1 expression were evaluated with RT-qPCR, Immunoblotting and FACSCalibur flow cytometer. The functionality of the induced PD-L1 was examined by the T cell cytotoxic assay and the IL-2 production ability, done with co-cultured systems containing chemo-primed tumor cells and activated T cells. Results: The results showed that pemetrexed or gemcitabine, but not cisplatin, paclitaxel or vinorelbine, effectively induced PD-L1 expression at concentrations below the IC50s. Membranous distribution of the induced PD-L1 was observed. Addition of anti-PD-L1 blocking antibody in the co-cultured system increased T cell cytotoxic ability and promoted IL-2 production, implicating the biological functionality of the induced PD-L1. Conclusions: The data suggested that pemetrexed or gemcitabine effectively primed the expression of biologically functional PD-L1 in NSCLC cells. The results implicate that pemetrexed or gemcitabine alone may be a good combinational candidate for PD-L1-targeted therapy in NSCLCs.
Distant outcomes of chemoimmunotherapy with recombinant interferon-gamma for acinar-type adenocarcinoma of the lung.
Authors: Pyltsin Sergey P. , Lazutin Yuriy N. , Ayrapetova Tamara G. , Chubaryan Anna V. , Anistratov Pavel A. , Leyman Igor A. , Shogenov A. S. , Gappoeva M. A. , Afaunov M. Kh. 
Published: September 2018

e20090 Background: We performed a comparative analysis of disease-free survival (DFS) after adjuvant chemoimmunotherapy (ACIT) with recombinant interferon-gamma in combination therapy and standard adjuvant chemotherapy (ACT) of patients with acinar-type adenocarcinoma of the lung. Methods: The study included 63 patients who received radical surgery for stage I-IIIA adenocarcinoma in 2009-2012. Group 1: 33 patients with ACIT after radical pneumonectomy, carboplatin AUC = 5 on day 1 and etoposide 100 mg/m2 on days 1, 3 and 5; i.v. ingaron 500 000 IU/m2 but no more than 1 million IU for one injection on days 2, 4 and 6. Carboplatin was replaced by cisplatin 100 mg/m2 in ACIT after lobectomy. Group 2: 30 patients with similar ACT without ingaron. The interval between courses was 21 days. Survival was estimated by Kaplan-Meier method, and differences were compared using log-rank test. Results: Group 1: 28 (84.8%) patients received 3 ACIT courses, 5 (15.2%) – 2 courses. Group 2: 27 (90%) patients received 3 ACT courses and 3 (10%) – 2 courses. Analysis of the Kaplan-Meier curves showed a tendency to a 8% increase in 5-year DFS that was 58% in Group 1 and 50% in Group 2 (p = 0.064). Conclusions: 5-year DFS increase by 8% demonstrates the expediency of further studies involving more patients which will allow revealing statistically significant differences in long-term results of treatment.
Veristrat based stratification of responses to immune checkpoint blockade (ICB).
Authors: Walker Paul R. , Sharma Nitika , Stroud Chipman Robert Geoffrey , Muzaffar Mahvish , Cherry Cynthia R. , Cherukuri Sulochana Devi , Parent Teresa , Hardin Jessica 
Published: September 2018

e20512 Background: Veristrat (Biodesix, Boulder, CO) is a blood based proteomic assay that is dominated by inflammatory proteins and is prognostic and predictive in metastatic NSCLC after treatment with platinum based chemotherapy (Gregorc et al, Lancet 2014). Smoldering inflammation in the tumor microenvironment regulates and escalates cancer invasion, angiogenesis and immune surveillance escape (Balkwill and Mantovani, Lancet 2001). There is preclinical evidence to suggest that the tumor microenvironment can be altered with immunomodulatory interventions (Martino et al, 2016). While immune checkpoint blockade has shown durable benefit in metastatic NSCLC, the response rates still hover around 20%. As a result, identification of predictive biomarkers are of critical importance. The predictive value of the Veristrat assay with respect to ICB is poorly defined. Methods: At our institution, 83 pts with metastatic lung cancer pts were treated with nivolumab between 6/2015 to 12/2016. The following clinicopathologic characteristics were abstracted from medical records: tumor histology, Veristrat status, no. of doses of nivolumab, irAEs and overall survival. Results: Of the 83 pts, 65 pts were found to have NSCLC. Veristrat status was available for 17/65 of these pts. Nine pts were identified to have “Veristrat good” and seven pts were “Veristrat poor”. Median number of nivolumab doses was 4. Median survival for all patients was 30 weeks. Median survival was 20 weeks for “Veristrat poor” and 26 weeks for “Veristrat good”(p = 0.68). Grade 3-4 irAEs were noted in 5/9 patients with “Veristrat good” and 5/7 patients with “Veristrat poor”. Conclusions: “Veristrat poor” pts treated with ICB have a lower median survival as compared to “Veristrat good” pts. Our study did not meet statistically significant end point due to limited sample size. Further studies are needed to identify poorly immunogenic tumors and develop novel treatment approaches to optimize outcomes. [Table: see text]
EGFR status evaluation by liquid biopsy during first-line therapy in patients with advanced NSCLC.
Authors: Zanelli Francesca , Pagano Maria , Bonelli Candida , Casali Bruno , Cavazza Alberto , Farnetti Enrico , Gnoni Roberta , Larocca Mario , Nicoli Davide , Pinto Carmine 
Published: September 2018

e20524 Background: over the past decade, personalized management based on the molecular features of tumours in patients with advanced non small-cell lung cancer (NSCLC) has entered routine clinical practice. The poor performance of many advanced NSCLC patients may limit invasive biopsies. The liquid biopsy is a diagnostic procedure performed on cancer-derived material obtained in blood samples. In this abstract, we will describe our experience with liquid biopsies. Methods: In the Reggio Emilia Clinical Cancer Centrefrom March 2016 to December 2016, 42 patients with advanced NSCLC were analyzed that had had or had already started first line therapy. The liquid biopsy was repeated at each imaging response evaluation by thoracic-abdominal compound tomography (CT) scan performed every 3 months. In the liquid biopsy, the mutational status of EGFR was analyzed with real time PCR (KIT cobas EGFR mutation test v2 CE-IVD Roche); in tissue, it was evaluated by pyrosequencing. Results: 21/42 liquid biopsies were EGFR-mutated (12/21 eson 19 and 9/21 eson 21). In 3/21 (14.3%) cases, the tissue biopsies showed wild type (WT) EGFR. 6 liquid biopsies were also performed at time 0 (diagnosis). All liquid biopsies of EGFR WT remained WT during treatment and imaging evaluation. The median number of liquid biopsy tests for patients was 2 (range 1-3). In 4/21 cases, T790M was performed: 3 cases in both liquid biopsies and tissue, and 1 case in tissue but not in liquid biopsy. TKi therapy was ineffective in this patient with T790M mutation detected in tissue, but not in liquid biopsy. In all patients, the disappearance of the T790M mutation during TKi therapy was related to disease progression. In 11 cases, modification of EGFR mutation status during treatment anticipated CT scan evidence of disease progression (median = three months). Conclusions: the liquid biopsy is an excellent resource. In our experience the liquid biopsy is the sensitive method of choice during treatment of advanced NSCLC patients. EGFR modification status during TKi therapy showed advanced disease progression.