bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the extent of brain metastasis affect outcome of non-small cell lung cancer patients treated with chemotherapy?
Authors: Choi Yong Won , Ahn Mi Sun , Lee Hyun Woo , Kang Seok Yun , Choi Jin-Hyuk 
Published: May 2019

e20616 Background: More than one third of advanced non-small cell lung cancer (NSCLC) patients (pts) experience brain metastases in the course of their disease. Although the outcome of NSCLC pts with brain metastasis is generally poor, identifying subgroups of pts that could benefit from appropriate therapeutic approach is clinically important, particularly in EGFR tyrosine kinase inhibitor (TKI) era. Methods: A retrospective review was conducted on 85 NSCLC pts with synchronous brain metastasis who underwent at least first-line chemotherapy, after treatment (Tx) for brain metastasis (gamma knife surgery or fractionated stereotactic radiotherapy : 42, whole brain radiation therapy : 38, surgical resection : 1, and no Tx : 4) from Jan 2002 to Dec 2013. Overall survival (OS) of all pts was analyzed according to the clinicopathological characteristics, Tx modality for brain metastasis, and chemotherapy. Results: The median OS for all pts after the initiation of first-line chemotherapy was 9 months. In univariate analysis, pts who received TKI (13 months versus 6 months, p= 0.001) and third- or further-line chemotherapy (15 months versus 6 months, p< 0.001) had significantly longer median OS. The presence of extracranial extrathoracic metastasis, number of brain metastasis, and Tx modality for brain metastasis showed no significant association with OS. In multivariate analysis, third- or further-line chemotherapy (24 pts) was the only independent prognostic factor for favorable OS ( p< 0.001). Pts who underwent third- or further-line chemotherapy were characterized by high proportion of non-squamous histology ( p= 0.016), extracranial extrathoracic metastasis ( p= 0.015), and TKI Tx ( p< 0.001). Conclusions: The present study suggests that judicious but active use of chemotherapy after appropriate Tx for brain metastasis may result in favorable outcome in NSCLC pts with synchronous brain metastasis, regardless of the number of brain metastatic lesions or local Tx modalities.
Analysis of a profile of lipid metabolism genes in advanced non-small cell lung cancer.
Authors: Merino Maria , Fernández Lara , Ramirez de Molina Ana , Moreno Juan , Colmenarejo Gonzalo , Falagan Sandra , Gómez César , Lopez-Gomez Miriam , Zambrana Francisco , Jimenez Gordo Ana M. , Aguayo Cristina , Casado Enrique , Sereno Moyano Maria 
Published: May 2019

e20619 Background: Non- small cell lung cancer (NSCLC) is one of the tumors with the highest mortality rate. The underlying metabolic alterations involved in its carcinogenesis are becoming more interesting. According to this, the analysis of the dysregulation of genes involved in lipid metabolism (LM) is subject to a growing research. To evaluate a profile of genes involved in lipid metabolism in NSCLC, we analyzed the correlation of this gene expression profile with different clinical-pathological variables. Methods: We performed a retrospective analysis of 22 genes related to LM in samples of NSCLC as well as clinical-pathological features. Advanced NSCLC patients enrolled from 2008 through 2015 were included. Clinical and pathological data were collected from medical reports. This study was approved in our ethical committee and all patients signed the consent inform. Samples were deparaffinated and RNA was extracted using RNeasy FFPE Kit (Qiagen Gmbh, Germany). A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software (Integromics Inc., Madison, USA) was used to detect and determine the quality control and differential expression analyses of data. Quantification of gene expression was calculated with the 2–ΔCt method. The Kaplan–Meier method was used for survival probabilities, and the log-rank test was to test differences between subgroups. Results: Ninety patients with advanced NSCLC were included. Median age was 64, 68/90 (75%) were male; 46/90 (51%) were ECOG 1; 68/90 (75%) adenocarcinoma vs 22/90 (24%) squamous; 47/90 (52%) smokers and 34% former smokers; metformine intake was presented in 9/90 (10%) and statins 24/90 (27%). In retrospective RT-PCR analysis including a lipid metabolism gene profile of 22 genes, we obtained an overexpression of 2 genes (an Acyl-CoA sintetase and a adipocine encoding gene). They were significantly correlated with overall poor survival in the multivariate analysis (table). These results were confirmed in an in silico validation using 994 NSCLC patients from TCGA study. Conclusions: This is the first study demonstrating a significant relation with a poor survival between a metabolic lipid gene profile expression and survival in advanced non- small cell lung cancer [Table: see text]
Clinical implication of inflammation-based serologic biomarkers and tissue biomarkers on hyperprogression in NSCLC patients receiving immune checkpoint blockers in real world.
Authors: KIM Seoree , Kang Jin-Hyoung , Chun Sang Hoon , Kim Joori 
Published: May 2019

e20633 Background: Although immune checkpoint blockades (ICBs) therapy can lead to favorable and durable results by reinvigorating the anti-tumor immune response in some patients, many other patients experience poor prognosis and even tumor overgrowth can be seen in real practice. We aimed to assess these hyperprogressive disease (HPD) in patients who underwent ICB therapy. Methods: We retrospectively reviewed medical records of non-small cell lung cancer patients (n = 243) treated with anti-PD-1 or anti-PD-L1 monotherapy. HPD was defined as a tumor growth kinetics ratio > 2 during anti-PD-1/PD-L1 therapy and a time-to-failure of less than 2 months. We analyzed the association of Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and CRP-albumin ratio (CAR) with HPD and the difference of immune composition in TME by multiplex IHC. Results: Overall, 231 patients were included. The median age was 64.2 years; most patients were male (74.9%) and smokers (70.1%, n = 162). 25 patients (10.8%) met the criteria for HPD. Oncogenic drive mutant status was significantly associated with HPD (18.6% vs 9.04%; P = 0.001). Kaplan Meier overall survival estimates showed a clear trend toward worse outcomes for patients with HPD (median, 5.6 months; P < 0.001) than for those without (median, 7.4 months). We also analyzed the association of NLR, PLR and CAR with HPD. Serologic markers at the time of first response evaluation (post 6 weeks, i.e.,) showed a prognostic value for HPD after ICB use ( P < 0.001, 0.008, 0.017). In multiplex IHC, there was no difference in T cell related immune marker of CD 3/4/8/45RO and FOXP3, dendritic cell, NK cell and other co-inhibitory signal markers between two groups. However, the key point was the M2 polarized tendency in the HPD group when the macrophage M1 / 2 markers of CD68, CD163, CD206 and CCR7 were observed. This suggests that changes in the AXL pathway and EMT features associated with reinvigorating anti-tumor immunity in M2 polarized cells may lead to changes in poor prognosis to HPD. Conclusions: Despite improved recognition of HPD, its etiology and predisposing factors remain unclear, but it is clear that the prognosis becomes poor when it occurs. We observed that some serologic biomarkers (NLR, PLR and CAR. i.e.,) can be used to predict HPD. Multiplex IHC can be used not only to predict HPD, but also to validate its mechanism. Furthermore, we undergo whole exon sequencing and multiplex IHC to understand mechanism of Hyperprogression.
RET fusion in first/third-generation EGFR-TKIs resistance in advanced non-small cell lung cancer.
Authors: Yao Yu , Zhang Min , Liu Xiuju , Zhao Jun , Cheng Xiangyang , Zeng Aiping , Kong Jinliang , Zhang Hongliang , Chen Rongrong , Xia Xuefeng 
Published: May 2019

e20634 Background: EGFR-TKIs is the standard first/second-line treatment for EGFR-mutant advanced non-small-cell lung cancer (NSCLC). The mechanisms of EGFR-TKIs resistance are still under exploration. Acquired fusion have been reported contribute to EGFR-TKIs resistance. Here we focus on RET fusion in first/third-generation EGFR-TKIs resistant NSCLC. Methods: We retrospectively reviewed 3600 cases of EGFR-TKIs resistant NSCLC samples from 2016 to 2018 in our institute. Tumor biopsy, ctDNA or pleural effusion samples were analyzed using hybridization capture-based NGS ER-seq method, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number(CNV) variation at least 59 genes (range 59-1021 genes). Results: Seven cases with RET fusion were identified (7/3600, 0.2%), with co-occurring EGFR mutations. All were adenocarcinoma, median diagnosis age was 55 years old (range 38-84), four male and three female. Most common RET fusion subtype was CCDC6-RET (5/7, 71%), the other was NCOA4-RET (2/7, 29%). The primary EGFR mutation include four EX19del and three L858R. Six patients received prior first and third-generation EGFR-TKIs treatment. The seventh patient had received only gefitinib treatment, EGFR L858R + T790M + NCOA4-RET were discovered in his plasma when disease progression. Interestingly, one patient had EGFR EX19del + T790M + C797S (cis) + CCDC6-RET in plasma after osimertinib resistance. One patient who had EGFR L858R and NCOA4-RET chose lenvatinib, a RET inhibitor, and had a progression free survival of seven months. Conclusions: Broad NGS panel test suggests that RET fusion could be a rare mechanism of EGFR-TKIs resistance, include first and third-generation. There is no currently target treatment strategy available for these patients, and further investigations, like change target therapy drug or combined target therapy are needed.
Apparent diffusion coefficient and genetic mutations as effective indexes for radiotherapy time of brain metastases from lung cancer retrospective analysis.
Authors: Ren Ruimei 
Published: May 2019

e20641 Background: The potential value of apparent diffusion coefficient (ADC) before chemoradiotherapy and genetic mutation as monitors for radiotherapy time of lung adenocarcinoma patients with brain metastases were retrospective analysed. Methods: Fifty-seven patients of lung adenocarcinoma with brain metastases were enrolled into the clinical trial. Conventional magnetic resonance imaging (MRI) examination and diffusion weighted imaging (DWI) were performed one week before therapy and after two cycles of chemotherapy or after one month targeted therapy. Symptoms such as headache, nausea, vomiting would be alleviated with mannitol and dexamethasone. Chemotherapy,once every 3 weeks, using in these patients with wild gene included pemetrexed, DDP, bevacizumab (pemetrexed 500mg per square meter ; DDP 75mg per square meter and bevacizumab 15mg per kilogram). 27 Patients with genetic mutations includ ed 1 patient with ALK genetic mutations, 2 patients with T790 genetic mutations, the presence of EGFR mutations was determined by the presence of deletions with exons 19 in 9 patients and 20 in 10 patients and L858R point mutations in exon 21 in 5 patients. Patients with genetic mutations were given targeted drug therapy. After these above treatment, if brain metastasis symptoms persist, brain radiotherapy was performed ahead of schedule. Patients with no obvious symptoms or relieved symptoms after targeted therapy or chemotherapy, two-month review was performed with enhanced MRI, radiotherapy was not added until the lesion no longer continues to shrink. Results: In the cohort of patients with wild gene , when ADC values less than 1.01 in 15 patients, the maximum diameter of tumors were significantly decreased after two treatment cycles, While 14 patients with ADC values greater than 1.01, the maximum diameter of the tumors are no difference after two treatment cycles. After targeted therapy for one month, In patients with ALK and T790 genetic mutations, the maximum diameter of tumors were significantly decreased, while no difference in 18 patients and decreased in 6 patients with presence of EGFR. Conclusions: ADC values and genetic mutation may as effective indexes of radiotherapy time for lung adenocarcinoma patients with brain metastases.
Analysis of real-world data (RWD) on treatment (tx) sequencing in patients with advanced non-small cell lung cancer (aNSCLC).
Authors: Ma Meng , Zhou Xiang , Goldsweig Howard , Hahner Nicholas , Han Dianwei , Dietz Matthew , Jones Scott , Mullaney Tommy , Redfern Arielle , Jappe Whitney , Liu Zongzhi , Yadav Kamlesh , Zimmerman Michelle , Prentice Tony , Pan Qi , Hirsch Fred R. , Oh William K. , Schadt Eric E. , Li Dan , Chen Rong 
Published: May 2019

e20642 Background: While optimal sequencing of systemic therapy in aNSCLC is critical to achieve maximal clinical benefit, it is practically challenging to study tx sequencing through clinical trials. RWD allow retrospective, observational studies to examine tx patterns and associated clinical outcomes. Methods: 1,609 aNSCLC patients who received systemic therapies at Mount Sinai hospitals were analyzed for the number of line of therapy (LOT), therapeutic modalities (chemotherapy, targeted therapy and immunotherapy), and the sequence in which treatments were given when LOT > 1. Time to tx discontinuation (TTD) was used as a surrogate clinical endpoint for outcomes. Results: 578 of the 1,609 (36%) patients received more than one LOT. 356 (22%) received tyrosine kinase inhibitors (TKIs), and 297 (16%) received immune checkpoint inhibitors (CPIs). Kaplan-Meier analysis revealed that among 297 patients who received CPIs, median TTD was longer in the 1st line setting (295 days, 95% CI 169 to 523; n=132) than when LOT > 1 (169 days, 95% CI 113 to 269; n=165), although the difference was not statistically significant (P=0.092, log-rank test). No difference of TTD on TKIs was observed between LOT = 1 and LOT > 1 (P=0.51). With respect to tx sequencing, when patients (n=94) received TKIs as the 1st LOT, 60%, 35%, and 5% of them received another TKI, chemotherapy, or a CPI-containing regimen, respectively, as the 2nd LOT. Among patients (n=370) who progressed on 1st line platinum-based chemotherapy, 52%, 32%, and 16% received another chemo regimen, a CPI-containing regimen, or a targeted therapy, respectively, as the 2nd LOT; these percentages shifted significantly toward more CPIs (24%, 66%, 10% for chemo, CPI, targeted, respectively) when only 2016-2018 data were examined. In the 2nd line setting after platinum therapy, TTD was significantly longer in the CPI group (332 days, 95% CI 169-484) compared to the chemo group (88 days, 95% CI 65-100; P<0.0001), consistent with results from pivotal clinical trials. Conclusions: As the tx algorithm of aNSCLC has been evolving rapidly, we observed diverse tx patterns in RWD. Various tx sequences may impact patient outcomes, and therefore warrant further investigation.
Phase (Ph) I/II study of pembrolizumab (P) with gemcitabine (G) in patients (pts) with previously-treated advanced (Adv) non-small cell lung cancer (NSCLC).
Authors: Sanborn Rachel E. , Duffy Regan M. , Fisher Brenda K , Perlewitz Kelly Shea , Wallen Herschel D. , Li Rui , Redmond William L , Koguchi Yoshinobu , Fox Bernard A. 
Published: May 2019

e20652 Background: P has demonstrated improved survival alone or with chemotherapy in untreated adv NSCLC. G may increase antigen cross-presentation and prime CD8 T cell response via tumor apoptosis. This study evaluated P + G in pts with previously-treated adv NSCLC naïve to anti-PD1. Methods: The study included ph 1 (previously reported), then single arm ph II, 1-3 prior therapies, regardless of PD-L1 status. Treatment: G, 1250 mg/m2, Days (D) 1 & 8 + P 200 mg D 1; 21-day cycles. G given max 6 cycles, P max 2 years. Tumor tissue was collected for PD-L1 (22C3). Immune response via whole blood immunophenotyping and ProtoArray was conducted. Results: 16 pts enrolled. Male/Female: 8/8; Age 53-75 (Median 64.5); ECOG 0/1: 2/14 pts, respectively. Median prior therapies: 1 (Range (R) 1-3). Median cycles: 4 (R 1-24). Primary reason for discontinuation: progression. Toxicity was primarily attributed to G, including Gr 3: neutropenia (5), leukopenia (3), anemia (2); lymphopenia, URI, hyponatremia (1 each). Gr 4: 1 hypoxia attributed to intrapulmonary hemorrhage from G. Other toxicities attributed to both G and P included dyspnea (2), pneumonitis (2) (Gr 3). Progression free survival (PFS): 3.2 months (m) (R 0.6-18.5 m). Overall survival (OS) is not yet mature (4 pts in follow up). 14/16 pts were evaluable for response. Stable disease (SD): 9 (56%); partial response (PR): 2 (13%); progression (PD): 3 (19%). 2 pts discontinued prior to first evaluation (1 pulmonary hemorrhage; 1 clinical progression). 1 pt had SD as best response for 18.5 m before PD. Disease control rate (DCR; CR + PR + SD): 56%. 12 pts were PD-L1 evaluable (central). 2 pts had PD-L1 testing through alternate source (22C3). Of the 14 pts with PD-L1 result: PD-L1 0%: 8 (50%); PD-L1 10-40%: 3; ≥50%: 3 (19% each) PFS of 0% PD-L1: 3.75 m (1 PR, 6 SD; DCR 88%). PFS ≥50% PD-L1: 3 m (1 SD, 0 PR). Exploratory immune profiling showed late peripheral immune activation in 3 of 6 pts with Cycle 6 samples (all SD; PFS 5.8 m). ProtoArray analysis is pending. Conclusions: P+G was a feasible combination, without unexpected toxicity. The majority of pts had 0% PD-L1 expression. PFS was not associated with PD-L1 level. PFS did not differ from G or P alone. OS pending. Clinical trial information: NCT02422381.
Real-world clinical experience of the Galician Lung Cancer Group: Afatinib in patients with EGFR positive mutation.
Authors: Agraso Busto Sara , Varela Vanesa , Fernández Núñez Natalia , Firvida Jose-luis , Santomé Lucía , Afonso Francisco Javier , Azpitarte Cristina , De Dios Alvarez Noemi , Garcia Jorge , Campos Balea Begoña , Areses Manrique Maria Carmen , Pereiro Corbacho Diego , Huidobro Gerardo , Lazaro Quintela Martin , Casal Rubio Joaquín 
Published: May 2019

e20654 Background: Treatment with tyrosine kinasa inhibitors has been a revolution for the patients with non-small cell lung cancer and EGFR positive mutation, especially in patients with exon 19 deletions. Afatinib seems one of the best options of treatment. Methods: Retrospective study on patients from differents hospitals in Galicia (Spain) diagnosed of metastasic lung adenocarcinoma with EGFR positive mutation who have received first line treatment with afatinib between July 2015 and September 2018 were included. The main objective was to compare our clinical experience concerning response rate, progression free survival and toxicity with published data. Results: 45 caucasians patients were included in our analysis (33 women, 12 men). Median age was 71.2 years (range 39-91 years) and 29 patients had never smoked. Exon 19 deletion was the most common mutation (41 patients, 91.1%). The objective overall response was 68.9% (95% CI: 82.4-55.3), complete responses were observed in 6 patients (13.3%) and partial responses were found in 25 patients (55.6%). Stable disease was observed in 8 patients (17.8%) and disease progression in 1 patient (2.2%), 5 patients have not been re-evaluated (11.1%). Median progression free survival (PFS) was 27 months (95% CI: 14.8-39.1) and overall survival was not reached. Common adverse events grade 3/4 were mucositis and skin toxicity in 11 patients (24.4%) and diarrhea in 6 patients (13.3%), respectively. The dose was reduced in 28 patients (62.2%) and treatment was discontinued in 8 patients (17.8%) owing to adverse events. Conclusions: Median PFS in our patients is 15 months longer than the information retrieved from differents studies with similar response rates and toxicity. This might be due to a majority of population with exon 19 deletion which, according to published data, seems to benefit more from afatinib than from other EGFR mutations.
A retrospective study evaluating clinical predictors of duration of response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.
Authors: Ibrahim Yahya , Sankar Keerthana , Mouzaihem Hassan , Kim Seongho , Haddad Amy , Mamdani Hirva 
Published: May 2019

e20665 Background: Immune Checkpoint Inhibitors (ICI) with/without chemotherapy has become the standard of care for the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). Similar to the response rate, durability of response to ICI is quite variable. While programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) have been described to predict response to ICI, little is known about the clinical predictors of duration of response (DoR). Methods: A retrospective chart review of patients (pts) with advanced NSCLC treated with ICI based therapy at Karmanos Cancer Institute was conducted. Data were collected on demographics, clinical characteristics, and tumor characteristics. Univariable and multivariable cox regression analyses were performed for six pre-chosen covariates (histology, prior radiation therapy, brain metastasis, occurrence of immune-related adverse events (irAEs), statin use and smoking status) to see the associations with the DoR to ICI. Results: One hundred thirty-one pts were included in the analysis (68% adenocarcinoma, 60% received prior radiation, 20% had brain metastasis, 26% developed irAEs, 33% were on a statin, 69% former smokers, 12% current smokers and 19% never smokers). Overall median DoR was 149 days (range, 14-1934 days). On multivariable analysis, longer DoR to ICI was observed in pts with non-adenocarcinoma histology (HR: 0.65; p = 0.050; CI: 0.42-1.00, median DoR 242.5 days) and current smokers (HR: 0.53; p = 0.031; CI: 0.30-0.95, median DoR 206.5 days). Other variables, including the presence of brain metastasis, prior radiation therapy, occurrence of irAEs and statin use had no significant relationship with the DoR. Conclusions: Tumor histology and smoking status were statistically and clinically significant predictors of durability of response to ICI in advanced NSCLC, presumably secondary to higher tumor mutational burden. Presence of brain metastasis did not adversely impact DoR to ICI.
A novel biophysical based marker with multilevel, multiparameter expression for early stage cancer detection.
Authors: Wu Junjie , Jiang Gengxi , Ji Jiansong , Du Xuedong , Lin Yue , Tao Hongmei , Tang Xing , Yu Chris Chang 
Published: May 2019

e20673 Background: Early stage cancer detection remains to be elusive despite of many years of efforts. In this work, a bio-physical based marker (named Cancer Differentiation Analysis (CDA)) with multi-level and multi-parameter expression features has been developed which has shown a number of clear advantages over the traditional approaches such as bio-chemistry based marker, circulating tumor cell (CTC) and circuiting DNA (ct-DNA). In stage I non-small cell lung cancer (NSCLC), sensitivity and specificity reached a record high of 85.2% and 93.0%, respectively. Methods: In this study, 832 NSCLC cancer samples with pathological information and 642 samples from healthy individuals were measured in a single blind test. Peripheral blood of each individual was drawn in EDTA tubes. One class of bio-physical property in blood samples was utilized for CDA tests. The CDA data were first processed using an algorithm built from data base and subsequently analyzed using SPSS. The results were shown in the table. Results: The results indicated that CDA technology has a very good sensitivity and specificity even at stage I (85% and 93%, respectively), which is much better than those previously reported results by other methods. Conclusions: Initial results showed that CDA technology could effectively screen NSCLC patients from healthy individuals. As a novel bio-physical based cancer detection approach with multi-level and multi-parameter expressions, CDA technology could be a potential candidate for early stage cancer screening. [Table: see text]