bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent TP53 mutation adversely impact the efficacy of crizotinib in ROS1-rearranged lung cancer patients.
Authors: Gen Lin , Xu Huamin , Zhao Jun , Kong Jinliang , Ai Xinghao , Yu Fenglei , Du Kaiqi , Zhu Lingjun , Li Lin , Ma Hongxia , Wang Qiaoli , Xiong Huanhuan , Chen Rongrong , Xia Xuefeng 
Published: May 2019

e20535 Background: ROS1 tyrosine kinase inhibitors (TKIs) are now standard of care for patients with advanced ROS1-rearranged NSCLC. But factors that may affect the efficacy of ROS1 TKIs remain to be explored. Methods: We conducted a retrospective multicenter study of lung cancer patients with ROS1 rearrangements. Treatment and survival follow-up was done and clinical records were reviewed. PFS distribution was analyzed by Kaplan-Meier method with log-rank test. Results: In total, we included 94 lung cancer patients with ROS1 fusion genes profiled by next-generation sequencing from May 2016 to September 2018. Fifty of them were female. The median diagnosis age was 54 (25-83). The most common histologic type was adenocarcinoma, which was confirmed in 75 of 78 patients with available pathological results. The most common fusion partners were CD74, EZR, SDC4 and SLC34A2 identified in 42, 19, 12 and 8 patients respectively. Concurrent actionable mutations were uncommon for ROS1 fusion-positive patients. The most frequent concomitant mutated gene was TP53, which was detected in 33% of all the patients. After excluding 29 patients who were lost to follow-up at the very start, the median follow-up time was 8.5 (0-28) months from the moment when mutation profiling was performed. Thirty-nine patients received treatment with crizotinib, among whom 27 were treatment-naïve patients. The median PFS of the 39 patients with crizotinib was not reached yet. Patients with baseline CNS metastasis tend to have shorter PFS compared to patients without (median, 12 vs NR, p = 0.0073). Besides, concurrent TP53 mutations were correlated with worse PFS (median, both NR, p = 0.0417). Mutation profiles of 10 patients were derived from ctDNA testing. No difference was found in PFS between these 10 patients with others whose genomic profiles were based on fresh tissue or FFPE specimens, suggesting that plasma ctDNA serves as good specimen source for mutation profiling to monitor clinical treatment. Conclusions: Concurrent TP53 mutation and presence of CNS metastasis are associated with decreased PFS of ROS1-positive patients treated with crizotinib.
Interim report on CIV recombinant human endostatin in combination with docetaxel/cisplatin (DP)) in comparison to DP in the first-line treatment of phase IIIb/IV squamous-cell NSCLC (JSLCG-001): A multicenter, open-label, randomized phase III controlled study (NCT: 02513342).
Authors: Huang Jian'An , Song Yong , Shi Minhua , Feng Jian , Lv Xuedong 
Published: May 2019

e20541 Background: Endostar registration Phase III and post-marketing Phase IV clinical study had confirmed Endostar in combination with Platinum double drugs can improve the NSCLC patients’ outcomes of ORR, PFS and OS. However, It influenced on the patients’ compliance for Endostar day 1-14 intravenous infusion (I.V). Endostar day 1-7 continuous intravenous infusion (CIV) can have the compliance improved obviously. So, we carried out this phase III trial to confirm the efficacy and safety of CIV Endostar in combination with DP regimen for first line treatment of phase IIIB/IV squamous-cell NSCLC. Methods: The planed 188 patients with phase IIIB/IV squamous-cell NSCLC without the history of chemotherapy would be randomly assigned to receive Endostar and DP (Endostar, 15mg/m2/d, civ, d1-7; Docetaxel, 60mg/m2/d, iv, d4; Cisplatin, 75mg/m2/d, iv, d4), or DP (Docetaxel, 60mg/m2/d, iv, d1; Cisplatin, 75mg/m2/d, iv, d1). The cycle was every 3 weeks and 4-6 cycles would be needed in total in each groupl. After 4-6 cycles, CIV Endostar in Endostar+DP group would maintain till PD. The primary end point was PFS. Results: The interim data from 94 cases was included in the analysis. The median PFS in Endostar+DP group was 6.8 months ( 95% CI, 4.0-9.6) versus 3.1 months ( 95% CI, 2.9-3.4) in DP group ( P = 0.024 ). The response rate was 33% in Endostar+DP versus 31% in DP group ( P = 0.838 ). The AEs in each group was comparable. No unexpected AEs in Endostar+DP was found. Conclusions: This preliminary result showed Endostar in combination with DP improved PFS significantly (P = 0.024). Among patients with advanced, previously untreated squamous-cell NSCLC, the longer PFS was related to CIV Endostar on the duration of maintenance. Clinical trial information: NCT02513342.
PD-1/PD-L1 immunotherapy for advanced lung cancer: An electronic medical database based real world study in China.
Authors: Zhao Xiao , Sun Qiong , Sun Sheng Jie , Shi Weiwei , Jiao Shun Chang 
Published: May 2019

e20543 Background: Immunotherapy has shown promising results for clinical management of various cancers. We reported our real world experience with PD-1 or PD-L1 immunotherapy in management of advanced lung cancer patients in China. Methods: This is a single-center retrospective study based on the de-identified electronic medical data collected in routine clinical practice. A total of 198 advanced lung cancer (stage IIIA-IV) patients who underwent anti-PD-1/PD-L1 therapy at Chinese People's Liberation Army General Hospital between 2015 and 2018 were included. Progression free survival and overall survival of patients were estimated by Kaplan-Meier methods. The treatment-related adverse events were also analyzed. Results: Median age of patients was 60.0 years (33.0-88.0 years). Most patients were male (150, 75.8%), smokers (116, 61.7%) and had a KPS score ≥70 (169, 97.7%). Of 198 patients, 106 (53.5%) had adenocarcinoma and 54 (17.3%) had squamous cell carcinoma. Thirty-one (15.7%) patients had CNS metastases. Seventy-one (38.8%) patients received two or more prior therapies. Estimated progression free survival was 5.6 months and overall survival was 24.5 months. One-hundred twenty-seven (64.1%) patients had documented to suffer adverse events, most commonly gastrointestinal adverse events and liver damage (Table). Conclusions: Our study showed survival benefits of PD-1/PD-L1 immunotherapy in advanced NSCLC patients in clinical practice. Safety profile was comparable to the previous studies. Our study supports the benefits of PD-1/PD-L1 immunotherapy in clinical management of advanced lung cancer patients. [Table: see text]
miR-200c in extracellular vesicles as a circulating biomarker of EGFR-TKI response and a mediator of EGFR-TKI sensitivity in heterogeneous NSCLC.
Authors: Lin Chienchung , Su Wu-Chou 
Published: May 2019

e20547 Background: Through intercellular transfer of EV(extracellular vesicles) miRNA, tumor cells can confer drug resistance to each other and contribute to tumor heterogeneity. However, the mechanisms why EGFR-TKI can be effective in heterogeneous NSCLC with low abundances of EGFR mutations remain unknown. The aim of the study is to investigate the significance of EV miRNA in mediating the efficacy of EGFR-TKI in heterogeneous NSCLC and serving as the biomarker of response to EGFR-TKI. Methods: We first evaluate if EVs from EGFR mutant cell (PC9) can affect EGFR-TKI sensitivity of EGFR wild type cell (CL1-5, H1299) in vitro co-culture system and i n vivo. We then identified the differential miRNA panel by comparing EVs from PC9 to those from CL1-5. Finally, we verified if the expressions level of these miRNA are different in blood EVs from patient with good response compared to those with poor response to EGFR-TKI. Results: We first verified that CL1-5 can take up labelled EVs from PC9 under time-lapse microscope and EGFR mutant DNA can be detected in recipient EGFR wild-type cell using digital PCR. We found EVs from PC9 enhanced gefitinib sensitivity of CL1-5. And co-culturing PC9 with CL1-5 enhanced CL1-5 gefitinib sensitivity which was reversed by adding GW4789, the inhibitor of exosome secretion. In subcutaneous CL1-5 animal model, in comparison to treating with gefitinib or PC9 EVs alone, only the combination treatment with gefitinib and PC9 EVs delayed cancer growth. Using small RNA sequencing, we identified a unique miRNA profile allowing discriminating EV from PC9 cells to those from CL1-5; MiRNA 200 family including 200a, 200b, 200c and mir429 were up-regulated significantly in PC9 EV. From Aug 2015 to Sep 2017, sixteen patients with good response (PFS > 12M) or poor response (PFS < 6M) to EGFR-TKI were enrolled and blood were collected for EV miRNA isolation. Ten of these blood samples were qualified for miRNA analysis and mir200a and 200c were found up-regulated in good responder to EGFR-TKI. The transfection of mir200c in CL1-5 cells not only inhibited the oncogenic pathway contributing to EGFR-TKI resistance including Stat3, Akt, EMT and BIM pathway but also enhanced gefitinib sensitivity of CL1-5 cells. Conclusions: Our data suggested mir200c from blood EV serve as a biomarker of response to EGFR-TKI and mir200c may mediate EGFR-TKI sensitivity in heterogenous EGFR mutant NSCLC.
Peripheral neuropathy among patients with NSCLC undergoing chemotherapy.
Authors: Tyczynski Jerzy Edward , Zhang Dongmu , Bach Bruce Allen 
Published: May 2019

e20552 Background: Peripheral neuropathy (PN) occurs in NSCLC patients and may be due to various factors. One of the major factors is chemotherapy treatment. This study assessed the frequency and risk of PN among chemotherapy exposed NSCLC patients. Methods: This retrospective cohort study used the Optum claims in 2015-2017. The main inclusion criteria included: at least 2 diagnosis (Dx) claims for lung cancer; no other systemic cancer Dx within 6 months prior to the NSCLC Dx; at least one line of systemic anti-cancer treatment after the NSCLC Dx; presence of secondary metastatic disease. NSCLC was identified using a published algorithm. PN was identified by at least one claim with ICD-9/ICD-10 PN diagnosis code. Patients were followed from the earliest chemotherapy treatment date until a censoring event (PN Dx, end of enrollment, death, or end of study interval). Descriptive statistics were used to describe demographics; the Cox model and logistic regression were used to analyze risk associated with PN. Results: A total of 5082 patients were identified with an average age of 70.9 years (SD = 8.7) and 52% of male. Most common first line of treatment (LoT) was carboplatin + paclitaxel (31.9%); 32.7% of patients received a 2nd line, 7.6% received a 3rd line, and 1.7% received a 4th or higher line. 857 patients had PN during the follow-up period (16.9%). Median Charlson comorbidity index (CCI) was 1, and mean 1.7 (SD = 1.8). Patients with CCI of 4+ (716 patients) had nearly 60% elevated risk of PN as compared with CCI = 0. Patients with diabetes presented the OR (odds ratio) of 1.58; patients with a history of PN had a higher risk of PN after the initiation of chemotherapy (OR = 3.90). Compared with the PN risk during 1st LoT (reference), the OR of developing PN during 2nd and 3rd+ LoTs was elevated to 1.78 (95%CI 1.49-2.11; p < 0.0001) and 2.61 (95%CI 2.03-3.34; p < 0.0001), respectively. The most common type of PN was sensory neuropathy (33%), then polyneuritis (21%) and diabetic polyneuropathy (18%). Conclusions: PN is common in NSCLC patients. This analysis shows that the risk of PN in NSCLC patients increases significantly along increasing number of LoT. A history of PN and presence of diabetes play an important role as risk factors of PN during anti-cancer systemic treatment.
Understanding biological driver mutations and mechanism of resistance to EGFR-tyrosine kinase inhibitors in lung cancer patients using a novel translational platform.
Authors: Babu Govind K. , Chaudhuri Padmaparna , Koppak Deepak , Biswas Manjusha 
Published: May 2019

e20555 Background: Lung cancer causes ~1.69 million deaths globally and 5-year survival rate is < 20%. Surgery is preferred for patients with early stage NSCLC, however, in > 50% cases lung cancers are diagnosed at an advanced stage. EGFR-TKIs, erlotinib and gefitinib have shown benefit in patients harboring sensitizing EGFR mutations, although 20-30% of NSCLC patients do not show good clinical response to EGFR-TKIs despite having the mutations. Several factors have been identified for de novo and acquired resistance to first generation EGFR-TKIs, including secondary mutations such as T790M, aberrant activation of bypass pathways such as amplification of c-MET, or other abnormalities in downstream pathways including KRAS mutations or loss of PTEN among others. There exist significant inter-patient variations in response profiles and mechanisms of resistance, which often confounds treatment selection on a personalized level, especially if first-line therapy fails. Methods: We have developed a patient tumor derived ex vivo platform technology using multi-disciplinary systems biology-based approach that recreates a patient’s tumor microenvironment by preserving the tumor-stromal architecture and immune contexture. Fresh tumor biopsies and 10-ml blood were collected from patients with IRB approval and patient consent. Tumors obtained from 21 lung cancer patients were grown ex vivo on our platform in presence of PBMC and autologous sera. The tumors were treated with standard of care chemotherapies and EGFR inhibitors, and drug efficacy on tumors were measured. Results: Of 18 tumor samples treated with EGFR-TKIs, 4 were predicted responders to gefitinib and 14 were predicted non-responders to EGFR-TKIs (erlotinib or gefitinib). Of the 14 non-responders, 7 were predicted responders to carboplatin/pemetrexed and/or carboplatin/docetaxel. Patients were followed, and clinical data was captured. Whole genome sequencing and mutational analysis was done on the tumors. Hits were validated by immunohistochemical assays. Data from molecular signatures of the tumors with functional, phenotypic assays, were used to delineate mechanism of resistance in individual lung cancer patients to EGFR-TKIs. Conclusions: We have developed an ex vivo, personalized platform, which enables prediction of treatment response on an individual level, and also aids in capturing resistance mechanisms for identifying actionable targets.
Multicenter observational prospective study of nivolumab (Nivo) as 2+ line treatment in advanced refractory NSCLC pts: Clinical and quality of life outcomes.
Authors: Orlova Rashida , Laktionov Konstantin , Bolotina Larisa , Breder Valeriy Vladimirovich , Danilova Anastasia , Filippova Elena , Kornietskaya Anna , Kramchaninov Mikhail , Kushniruk Eugenia , Latipova Dilorom , Ledin Evgeny , Mochalova Anastasia , Moiseenko Fedor Vladimirovich , Nikitina Tatiana , Orlov Sergey , Protsenko Svetlana , Sarantseva Ksenia , Stroyakovskiy Daniil , Zinkovskaya Anna , Ionova Tatyana 
Published: May 2019

e20567 Background: We aimed to evaluate clinical and quality of life (QoL) outcomes of Nivo as 2+ line treatment in NSCLC pts within expanded access program and real world practice. Methods: Adult pts with advanced refractory NSCLC were enrolled in 11 centers in RF. All the pts received Nivo 3 mg/kg q2w. Tumor response was assessed using RECIST v. 1.1, adverse events (AEs) – NCI CTCAE v3.0. Patients filled out RAND SF-36 and ESAS-R at baseline, 1, 3, 6 and 12 mos after treatment start. Overall survival (OS) and progression-free survival (PFS) curves were evaluated by the Kaplan-Meyer method and compared by the log-rank test. GEE method was used for QoL analysis; χ2 test – for disease control rate (DCR) comparison. Results: The preliminary analysis was performed in the group of 200 pts with median follow-up 7.4 mos (65% – males; median age – 62 y.o.; ECOG 0-1 – 81%; former/current smokers – 70.5%; non squamous NSCLC – 64%; ≥2 lines of previous treatment – 53%, bone mts – 22%). DCR was revealed in 60.3% pts (108/179 pts, median first evaluation – 2.1 mos); 13 pts died before first response evaluation; 8 pts were not evaluated for response at cut-off. DCR was higher in squamous NSCLC (66%, squamous vs 51%, non squamous; χ2 = 4.0, p = .045). Median OS – 11.5 mos (95%CI 8.3–14.7), median PFS – 4.2 mos (95%CI 3.5–4.9). Patients with poor ECOG (ECOG 2-3 vs 0-1: median OS – 5.6 mos vs 12.4 mos, median PFS – 2.7 vs 4.2 mos) and those with bone mts (with mts vs without mts: median OS – 5.0 vs 12.5 mos, median PFS – 2.8 vs 4.1 mos) had worse survival; log-rank p < 0.05. QoL improved during 6 mos of treatment in more than 50% pts; average increase by 60% of mean Integral QoL Index (IQoLI) at different time-points was observed. Upon GEE, IQoLI improvement during 12 mos was revealed (p < .0001). The severity of fatigue and dyspnea, which had the highest burden at base-line, decreased during 6 mos of treatment in more than 50% and 30% pts, consequently. AEs were registered in 32.7% pts (median of Nivo treatment – 2 mos); among them 17 pts had grades 3-4 AEs; 5 pts – SAEs. Conclusions: Preliminary results of this study support the acceptable efficacy and safety of Nivo in NSCLC pts. Nivo treatment leads to meaningful QoL improvement and decrease of symptom burden in this patient population.
Clinical significance of Ki-67 index expression in advanced non-small cell lung cancer.
Authors: Wang Di ming , Shi Qingming 
Published: May 2019

e20576 Background: It is unclear how the Ki-67 index expression affects the objective response to chemotherapy in non-small cell lung cancer(NSCLC). The study analyzed the relationship among the Ki-67 index, the objective response rate and progression-free survival(PFS) of chemotherapy in ad-NSCLC. Methods: 112 patients of advanced NSCLC in our hospital from 2014 to 2017 were studied. Both EGFR and ALK were wild type in adenocarcinoma patients, and no gene test was performed in squamous carcinoma. The relationship among Ki-67 index ,tumor stage, response of chemotherapy and progression-free survival was analyzed by univariate and multivariate analysis.Ki-67 index was used to predict the objective response of chemotherapy by receiver operating characteristic curve(ROC curve). Results: The objective response rate of chemotherapy was 61.6%(69/112);squamous carcinoma was 69.1%(38/55);adenocarcinoma was 54.4%(31/57). Ki-67 index(P = 0.000) and tumor stage(P = 0.025) were the factors influencing the objective efficacy of chemotherapy.Ki-67 index was linearly correlated with tumor stage (r = 0.341,P = 0.001).In the univariate and multivariate analyses, the Ki-67 index was significantly associated with the objective response to chemotherapy (B = -0.069,P = 0.000).Ki-67 index expression can accurately predict the objective response rate of ad-NSCLC chemotherapy by ROC curve(P < 0.0001,AUC = 0.7467,95%CI = 0.6578-0.8356):squamous carcinoma group (P = 0.0003,AUC = 0.8065,95%CI = 0.6922- 0.9208), adenocarcinoma group (P = 0.0193, AUC = 0.681,95%CI = 0.536-0.8262).In the test cohort, the sensitivity of the Ki-67 index to the objective response rate of chemotherapy was 93.02%.In the squamous carcinoma group the sensitivity was 94.12%.In the adenocarcinoma group the sensitivity was 65.54%.The best Cut-off was 55% for the adenocarcinoma group with good chemotherapeutic efficacy and the adenocarcinoma group with poor efficacy. The best Cut-off value was 65% in squamous carcinoma group with good curative effect and squamous carcinoma group with poor curative effect.The overexpression of Ki-67 index was a negative prognostic factor for PFS in ad-NSCLC (P < 0.0001):squamous carcinoma (P = 0.0055), adenocarcinoma (P < 0.0001). In multivariate Cox analysis, Ki-67 index (P = 0.000) and stage (P = 0.001) were negative factors of PFS. Conclusions: Ki-67 index is a clinically significant biomarker in ad-NSCLC, which can predict the objective efficacy of chemotherapy. The high expression of Ki-67 might be an indicator of the shortened PFS time.
PD-1 antibody pembrolizumab administered at non-standard frequency in non-small cell lung cancer (NSCLC).
Authors: Sehgal Kartik , Shea Meghan , McDonald Danielle M. , Huberman Mark , Weiss Glen J. , VanderLaan Paul A , Costa Daniel Botelho , Rangachari Deepa 
Published: May 2019

e20617 Background: Pembrolizumab (P) administered every 3 weeks ± chemotherapy is a standard treatment option for advanced NSCLC. However, there have been no post-approval studies to determine the optimal frequency of administration or if longer intervals between administrations are effective. Methods: We conducted a retrospective review of patients with advanced NSCLC treated with P for at least 4 cycles at a single academic center (02/2016-12/2018). Patients received P-based regimens administered at a standard frequency (3 weeks ± 3 days, group A), ≥ 25% of total treatment cycles outside the standard frequency (group B), and < 25% of total treatment cycles outside the standard frequency (group C). We extracted demographic, tumor characteristic, treatment detail and outcomes data. Results: Of 84 P-treated patients, 43 (51%) were identified as receiving at least 4 cycles (groups A: 17, B: 10, C: 16). There were no significant differences in sex, stage at diagnosis, smoking status, tumor histology, driver oncogene mutations, PD-L1 expression, tumor mutation burden, line of therapy, performance status, or immune-related adverse events (irAEs). Patients in group A were more likely to receive P+chemotherapy (groups A: 41.2%, B: 10%, C: 6.3%; p = 0.03). The reasons for non-standard cycles were: patient-physician preference (65.4% patients), irAEs (15.4%), and non-irAE medical issues (42.3%). Time to treatment discontinuation was significantly longer in groups B & C receiving P-based therapy at longer non-standard intervals and with no statistically significant differences in overall survival. Conclusions: Our data, though limited by sample size and single institution design, shows that a significant proportion of patients receive P at extended intervals in routine clinical practice and with comparable outcomes as would be expected for those with advanced NSCLC receiving P at label-specified 3-week intervals. Given the durability of benefit seen in such patients, this requires confirmation in larger datasets and prospective trials so as to maximize patient experience and clinical outcomes while minimizing financial toxicity.
Survival analysis of anticoagulant treatment of non-small cell lung cancer.
Authors: Wang Junyan , Zhang Fan , Hong Lei , Jiang Da , Ma Minting , Wei Suju 
Published: May 2019

e20623 Background: More and more evidence shows that coagulation cascade reaction and some vascular factors can promote the deterioration of tumor. Preventive interventions for high-risk patients with venous thromboembolism can reduce cancer mortality and improve quality of life. Anticoagulants have anti-tumor activity and can participate in the process of adhesion, metastasis, invasion, thrombogenesis and immune escape of cancer cells. So we want to explore the effects of anticoagulants on the survival of patients with non-small cell lung cancer. Methods: This study retrospectively analyzed the clinical data of876 cases with non-small cell lung cancer. According to whether or not to apply anticoagulant drugs, it was divided into 2 groups including application group (270 cases) and non-application group (606 cases), and the survival status of the two groups were followed up. Results: The median survival ofthe non-application group was 14.2 months, the 1, 2, 3, and 5 years survival rates of patients were 56.6%, 31.8%, 21.0% and 6% respectively. The application group median survival of the application group was 17.7 months, the 1, 2, 3, and 5 years survival rates of patients were 66.6%, 36.6%, 28.8% and 16.8% respectively. The median OS and survival rate were extended in anticoagulation group compared with another. The overall comparison of the survival curves of the two groups by Log Rank was P = 0.016. Conclusions: Anticoagulant therapy can significantly improve the overall survival of patients with non-small cell lung cancer.