bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of the Lung Immune Prognostic Index (LIPI) in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab.
Authors: Ruiz Bañobre Juan , Areses Manrique María C. , García Campelo Rosario , Lopez Rafael , Afonso Afonso Francisco J. , Casal Rubio Joaquín , Vázquez Estévez Sergio , Raposeiras Cristina Azpitarte , Amenedo Margarita , Santomé Lucía , Fírvida Pérez José Luis , Mosquera Martínez Joaquín , Cortegoso Alexandra , Vilchez Simó Rocío , Huidobro Vence Gerardo , Fernández Núñez Natalia , Quiroga Veiga Nazaret , García Mata Jesús , Alonso-Jáudenes Curbera Guillermo , Anido Herranz Urbano 
Published: May 2019

e20645 Background: The lung immune prognostic index (LIPI) has been proposed as a new biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 or programmed death ligand 1 therapy. In this study, we investigate the prognostic and predictive utility of the LIPI in a multicentric nivolumab monotherapy-based cohort. Methods: 153 patients with available baseline LIPI were included. Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The impact of the baseline LIPI on survival (PFS and OS), and DCR and ORR was assessed by Cox and logistic regression models respectively, adjusted for age, sex, ECOG-PS, smoking status, histology, TNM stage at diagnosis, presence of brain metastases and number of prior regimens. All p values were 2-sided, and those less than 0.05 were considered statistically significant. Results: 50.3% (n = 77) of the patients had a good (0 factors) LIPI, while 41.2% (n = 63) and 8.5% (n = 13) had intermediate (1 factor) and poor (2 factors) LIPI respectively. No significant differences were observed between the LIPI groups according to clinicopathologic characteristics. A high LIPI was significantly associated with poor OS in univariate (HR = 3.12, 95% CI 2.12 – 4.60; p < 0.0001) and multivariate (HR = 3.10, 95% CI 2.09 – 4.58; p < 0.0001) analyses. A high LIPI was associated with poor PFS (HR = 1.49, 95% CI 1.07 – 2.07; p = 0.02), but this correlation did not reach a statistical significance in multivariate analysis (HR = 1.37, 95% CI 0.98 – 1.92; p = 0.07). A higher LIPI was associated with a lower disease control rate in univariate (OR = 0.50, 95% CI 0.29 – 0.85; p = 0.01) and multivariate (OR = 0.55, 95% CI 0.31 – 0.98; p = 0.04) analyses. Conclusions: This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.
Landscape of lung cancer molecular biology in a NON-selected population.
Authors: Marcos Rosa Ana , Ceballos Jaime , Filipovich Elena , Mazarico Jose Maria , Tur Raquel , Martin Maria Rocio , Ales-Martinez Jose 
Published: May 2019

e20648 Background: The molecular study of non-small cell lung cancer (NSCLC) allows for targeted treatment. EGFR and ALK alterations have been observed in 14% and 5% of Caucasian patients (p) respectively. These alterations are mainly detected in women with adenocarcinoma (ADC) and non-smokers. In a non-selected (all comers) NSCLC population from Ávila (Spain) we found a different profile. Methods: We collected data from 185 consecutive p the Pathology Department database of Hospital Nuestra Señora de Sonsoles from 2012 to 2017. All p were tested for EGFR and ALK. Analyses were done with Cobas or Therascreen tests. Results: EGFR mutations were found in 11 p out of 185 (6.7%). Histology was ADC in 8 p (72.7%) and squamous cell carcinoma (SC) in 3 p (27.3%). Male (m) & smokers: 4/11 (36,4%). The type of mutation was: Exon 20: 3 p (27.3%). 2 m and 1 female (f). 2 smokers and 1 former smoker. 2 ADC and 1 SC; Del 19: 4 p (36.4%). 1 m and 3 f. 1 non-smoker, 2 former smokers and 1 smoker. 3 ADC and 1 SC; Exon 21: 4 p (36,4%). 2 m and 2 f. 3 non-smokers and 1 smoker. 3 ADC and 1 SC. All p. received treatment with 1st generation anti-EGFR drugs for a median 6.4 months (m). Progression Free Survival was 6.39 m (exon 20: 5.1 m; Del 19: 6.5 m; exon 21: 7.2 m). Overall survival was 18.0 m (exon 20: 26.1 m; Del 19: 18.2 m; exon 21: 11.8 m). ALK translocation was found in 5 p out of 158 (3.2%). Histology was ADC in 3 p (60%) (all f, 2 non-smokers and 1 former smoker) and SC in 2 p (40%) (2 smoker m.) Conclusions: Although the small sample size prevents definitive conclusions, EGFR mutations in exon 20 are more frequent in smokers and mutations in exon 21 in non-smoking patients with ADC. ALK translocation was observed independent of sex, tobacco or histologic type. For EGFR and ALK alterations, screening based on sex or pathology would have missed findings with therapeutic implications. We conclude it is important to extend the analysis of molecular alterations to all patients with NSCLC since more of them could benefit from targeted drugs.[Table: see text]
Galician lung cancer group: Afatinib´s data as first-line treatment for elderly patients.
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

e20662 Background: There are scarcy data or studies on safety and efficacy of afatinib in elderly patients. 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. Main objectives were to asses safety, dose reductions and as well as its effects on effectiveness of the treatment in patients 70 years old or older (elderly patients) comparing with data from patients under 70 years of age. Results: 45 patients were included in our analysis (33 women, 12 men). Median age was 71.2 years (39-91) with 24 patients (53.3%) being 70 years old or older. Common adverse events grade 3/4 were mucositis and skin toxicity (28.6% in patients under 70 years and 20.8% in elderly patients) and diarrhea (9.5% and 16.7% respectively). The dose was reduced in 47.6% patients under 70 vs 75% in elderly patients. Treatment was discontinued in 14.3% patients vs 20.8% patients respectively owing to adverse events. Overall response was 76% and 62.5% respectively. Disease control rates were 90.3% (95% CI: 96.7-83.8) and 83.3% (95% CI: 98.2-68.4) respectively. Median progression free survival (PFS) was 27 months (95% CI 14.8-39.1) and overall survival was not reached. By ages, median PFS was 20 months (95% CI: 7.4-32.5) vs not reached in elderly patients although being unable to demonstrate differences in progression-free survival between both groups. Conclusions: PFS was 20 months in people under 70 years vs not reached in elderly patients. Elderly patients need more treatment interruption or dose adjustments compared with younger patients, but this does not seem to impair safety and does not compromise effectiveness either.
Molecular profiling as predictor of outcomes in a Brazilian cohort of stage IV lung cancer.
Authors: Peruzzo Nicolas , Ce Coelho Juliano , Macedo Gabriel de Souza , Andreis Tiago Finger , Gössling Gustavo , Buiar Pedro Grachinski , Rocha Débora Leite , Ashton-Prolla Patricia 
Published: May 2019

e20668 Background: Lung cancer is the leading cause of cancer deaths globally. In stage IV non-small cell lung cancer (NSCLC), identification of a tumor driver mutation is critical, since it tailors treatment. We aimed to analyze clinical outcomes according to molecular profiling in patients (pts) with stage IV NSCLC. Methods: In this retrospective cohort study, we enrolled 57 pts with stage IV NSCLC treated at a public hospital in Southern Brazil between 2016 and 2018. Results: Median follow-up was 20.3 months, 53% were men, mean age was 65 years, 86% had smoked, 84% had de novo metastatic NSCLC and 96% had non-squamous carcinoma. Regarding molecular profiling, somatic mutations in KRAS, EGFR and BRAF were identified in 33%, 16% and 4% of pts, respectively. None of the pts had ALK mutations, and in 47% no identifiable driver mutation was found. In the EGFR-mutated subgroup, 67% had a deletion of exon 19, 22% had the exon 21 L858R mutation and 11% had exon 20 mutations. Palliative systemic therapy (PST) was delivered to 60% of the pts. Two or more lines of PST were delivered to 23%. The main reason for upfront best supportive care was ECOG PS 3-4 (poor). In the subgroup of pts with sensitizing EGFR mutations (8 pts), 75% received Gefitinib, the only anti-EGFR drug available in our public health system; the other pts died before recognition of the mutation. Median Progression Free-Survival was 6.3 months overall, 10.3 months for EGFR-mutated pts, 7.6 months for KRAS-mutated, 7.5 months for BRAF-mutated, and 5.2 months for pts with no mutation identified. Median Overall Survival (OS) was 7.7 months overall, 13.2 months for EGFR-mutated pts, 7.4 months for KRAS-mutated, 12.9 months for BRAF-mutated, and 5.3 months for pts with no mutation identified. In the Cox regression multivariate analysis, poor PS (HR 3.80, P < 0.0001) and second-line PST (HR 0.23, P = 0.002) were independent predictors of OS. No driver mutations were predictors of OS, although we did find a tendency towards better OS in pts with EGFR mutations and worse OS in pts with KRAS mutations or no identifiable mutation. Conclusions: In this cohort, genotyping results did not predict survival outcomes. This is probably due to the small number of pts studied, and data should be reanalyzed in larger cohorts.
Therapeutic efficacy comparison of six major EGFR-TKIs in non-small-cell lung cancer patients with an activating EGFR mutation: A network meta-analysis.
Authors: Wu Fang , He Jingyi , Wu Sixuan , Huang Yan , Li Yizheng , Zhao Lishu , Hu Chunhong 
Published: May 2019

e20671 Background: EGFR-TKIs are the standard in the first line treatment for patients with advanced NSCLC with EGFR activating mutations.This network meta-analysis was undertaken to compared all the EGFR-TKIs in terms of PFS, overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Methods: The PubMed and Embase databases were screened for relevant studies. We extracted data of ORR, DCR, PFS, and OS from enrolled studies and performed multiple treatment comparisons based on bayesian network meta-analysis. Due to the differences in design of each clinical study, two rounds of analysies were performed. We first compared the therapeutic efficacy of the first-generation TKIs (erlotinib and gefitinib), second-generation TKIs (afatinib or dacomitinib) and third-generation TKIs based on A7471028, ARCHER 1009, LUX-Lung 7, ARCHER 1050 and FLAURA studies. The following comparison between first-generation TKIs (gefitinib, erlotinib and icotinib) and second-generation TKIs was performed based on ICOGEN, A7471028, ARCHER 1009, WJOG 5108L, CTONG 0901, LUX-Lung 7 and ARCHER 1050 studies. Results: Eight trials with 2154 patients and 6 TKIs (gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib) were included. The first round analysis indicated that Osimertinib ranked best among all the TKIs in terms of DCR, 1y-PFS and 1y-OS. Afatinib ranked first among these similar agents with ORR. The second round analysis showed that second-generation TKIs had potentially better efficacy compared with first-generation TKIs. Icotinib seemed to work best in first-generation TKIs and ranked first among first- and second-generation TKIs in terms of 1y-OS. Conclusions: The third-generation TKIs had better therapeutic efficacy compared with the first-generation TKIs and the second-generation TKIs. However, the second-generation TKIs had better efficacy compared with first-generation TKIs. [Table: see text]
Soluble biomarker signature to predict outcome of patients with non-small-cell lung cancer (NSCLC) treated with anti-PD1/PDL1 monoclonal antibodies.
Authors: Garde-Noguera Javier , Jantus-Lewintre Eloisa , Gallach Sandra , Vidal-Martinez Jose , Blasco Ana , Garcia Sanchez Jose , Zhang Feiyu , Aparisi Francisco , Honrubia Peris Beatriz , Condori Farfan Lauren , Torres Martinez Susana , Piera Molons Nuria , Murado-Pardo J. , Gisbert-Criado R. , Calabuig-Fariñas Silvia , Camps Carlos 
Published: May 2019

e20685 Background: Immunotherapy with anti-PD1/PDL1 monoclonal antibodies has become the second line standard treatment for most patients diagnosed of advanced Non-Small-Cell lung cancer (NSCLC). The aim of this study is to assess the utility of circulating biomarkers such as sPDL1, sPDL2, sCD137, sIDO, sTIM3, sCD28, sCD27, sCTLA4, sHVEM, sLAG3, sCD80 and sGITR for predicting efficacy of immunotherapy with anti-PD1/PDL1 therapies. Methods: Blood samples were collected before treatment from 50 NSCLC patients who received anti PD1/PDL1 therapies (second line). Plasma biomarkers´ levels were measured by Multiplex bead-based assays. Continuous variables were categorized using the median as a cut-off. Non parametric test were used for correlations between analytical variables and clinical-pathological parameters and response rate analysis. For survival analysis (progression free survival-PFS and overall survival-OS) Kaplan Meier curves and long-rank test were performed. Results: 50 patients met inclusion criteria. Biomarkers associated with better outcome in terms of Response Rate or PFS were sPDL1, sIDO, sCD137 and sGITR. Median plasma levels of sPDL1, sCD137, sIDO and sGITR were 80.5, 168.7, 64.92s and 114.43 ng/ml respectively. ORR was higher in patients with high levels of CD137 (75 vs 25%, p = 0.28), GITR (83.3 vs 16.7%, p = 0.009) and sPDL1 (66.7 vs 33.3%, p = 0.07). Median PFS was significantly higher for patients with high sPDL1 levels (NR vs 3 months, p = 0.017), and there was a favourable trend for patients with higher serum levels of CD137 (NR vs 5.07, p = 0.11), sIDO (NR vs 5.57 months, p = 0.08); and sGITR (14.33 vs 5.57 months, p = 0.16). Combination of these biomarkers allowed the identification of three groups: group1 (0-1 positive biomarker), group2 (2 positive biomarkers) and group 3 (3 or 4 positive biomarkers), with significant differences in ORR (8.3 vs 25 vs 66.7%, p = 0.01), PFS (median 3.2, 1.1 and NR months, p = 0.01) and OS (median 2.3, 5.0 and NR months, p = 0.02). Conclusions: Circulating immune markers can be reliable detected in plasma of advanced NSCLC patients. In patients treated with anti-PD1 antibodies. sCD137, sIDO, sGITR and sPDL1 seem to be related to the degree of response or PFS. Combination of these biomarkers might be helpful to predict efficacy of immunotherapy treatment.
Initiation of targeted therapy based on ctDNA only in metastatic NSCLC.
Authors: Bustamante Alvarez Jean Gabriel , Dittmar Kristin , Janse Sarah A , Kiourtsis Stephanie , Owen Dwight Hall , Bertino Erin Marie , He Kai , Carbone David Paul , Otterson Gregory Alan 
Published: May 2019

e20687 Background: Next generation sequencing (NGS) of circulating tumor DNA (ctDNA) can identify sensitizing and resistance mutations in Non-Small Cell Lung Cancer (NSCLC). ctDNA is helpful when tissue is insufficient for genomic testing, or repeat biopsy is undesirable. Here we report a single institution experience of ctDNA testing on diagnosis (DX) and progression (PD), and how this intervention can help avoid further invasive interventions and warrant change in management. Methods: This is a single institution retrospective study of advanced NSCLC patients (pts) who had ctDNA from plasma tested using Guardant360, which identifies somatic genomic alterations by massively parallel sequencing of target genes. An institutional CLIA tissue panel using FISH (for MET, RET, ROS1 and ALK) and NGS for selected genes was used for tissue analysis. Actionable mutations are those with FDA approved (EGFR, ALK, ROS, BRAF) or NCCN recommended targeted therapies (RET fusions and MET amplifications or MET Exon 14 skipping mutation). All the included patients had cancer confirmed by pathology analysis. IRB approval was obtained prior to data collection. Results: A total of 163 ctDNA samples from 143 pts were evaluated (82 at DX and 81 on PD) . 17 out of 82 (20.7%) ctDNA samples sent at DX had actionable mutations identified (4 EGFR exon 19 deletion, 2 EGFR Exon 21 L858R, 1 EGFR L861R, 4 EML4-ALK Fusion, 2 CD74-ROS1 Fusion, 2 MET exon 14 skipping mutation, 2 KIF5B-RET fusion). 7 out of 82 (8.5%) pts initiated targeted therapy based on ctDNA results only (5 with no or insufficient tissue available, 2 with negative tissue analysis). Among them, 1 CR, 5 PR, and 1 SD were achieved. For the 2 pts with negative tissue analysis , one had initial PR for 4 months with crizotinib and on progression tissue rebiopsy was positive for ALK rearrangement on FISH, for L1152R on NGS and on ctDNA for EML4-ALK Fusion, ALK G1202R and L1152P. On second line this patient achieved a near CR with Carboplatin/Pemetrexed/Pembrolizumab. The second patient with negative tissue had CD74-ROS1 fusion on ctDNA and achieved a CR with crizotinib for 8 months. The Response Rate for patients started on targeted therapies based on ctDNA only was 85%. Conclusions: A substantial number of NSCLC pts benefited from targeted ctDNA NGS by identifying actionable mutations that led to appropriate targeted treatments. Initiation of targeted therapy for advanced NSCLC was possible based on ctDNA testing only .
Immune gene expression and bayesian network analysis in advanced non small cell lung cancer (NSCLC) patients treated with immunotherapy.
Authors: Baglivo Sara , Bianconi Fortunato , Tofanetti Francesca Romana , Ricciuti Biagio , Pistola Lorenza , Siggillino Annamaria , Reda Maria Sole , Mencaroni Clelia , Currà Maria Francesca , Teti Valeria , Metro Giulio , Bellezza Guido , Minotti Vincenzo , Roila Fausto , Ludovini Vienna 
Published: May 2019

e20693 Background: Immune checkpoint inhibitors (ICIs) have revoluzionized the therapeutic paradigm for different types of cancer including NSCLC. Clinical benefit, however, is limited to a minority of patients. The only adopted predictive biomarker, PD-L1 IHC testing, suffers from some limitations. A better understanding of biomarkers associated with response to ICIs is needed. Here, we studied immune gene expression profile and association with clinical response to immunotherapy in advanced NSCLC patients (pts) treated with ICI. Methods: A total of 37 Formalin-fixed, paraffin-embedded (FFPE) samples from advanced NSCLCs were analyzed by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) (ThermoFisher Scientific) to measure the expression level of 395 genes associated with 36 functional groups including checkpoint pathways, lymphocyte regulation and cytokine interactions, using the Ion Chef and Ion Torrent PGM. Gene level differential expression analysis were performed with the Torrent Suite and Transcriptome Analysis Console (TAC) 4.0 Software. Gene network analysis based on Bayesian algorithm was performed by GeneMANIA database querying with the genes selected through mRNA expression analysis. Results: Among 37 FFPE samples only 18 showed more than 300 OIRRA detectable target genes. In this subgroup, gene expression analysis revealed 7 genes (CCR2, CRTAM, FASLG, SELL, TIGIT, TNFRSF4, and TP63) up-regulated and one gene (CXCL8) down-regulated (p-value < 0.05) in ICI-responders compare to ICI-no responders. Bayesian enrichment computational analysis of the eight gene expression signature showed a more complex network which involves other 10 genes (SIRPG, GZMK, XCL2, CD8A, CD2, IFNG, SIT1, TAGAP, PTPRC and GZMH), correlated with different functional groups. Three main immune-pathways were identified (p < 0.01) (T cell activation, leucocyte activation and migration) involving TIGIT, TNFRSF4, CCR2 and CXCL8 genes among the gene expression signature identified. Conclusions: Our results revealed an immune response gene expression signature of 8 genes differentially expressed between ICI and ICI-no responders. Cancer systems biology analysis approach strengthen our findings identifying an immune molecular network and confirm the correlation of the gene expression signature with relevant immune regulatory functions. If validated, our results may have an important role for the development of a robust test to select patients properly and predict immune response to enable precision immunotherapy.
Demoralization and associated features in an Italian sample of end-of-life cancer patients.
Authors: Airoldi Mario , Bovero Andrea , Botto Rossana , Adriano Beatrice , Opezzo Marta , Tesio Valentina , Torta Riccardo 
Published: May 2019

e23004 Background: Demoralization is an expression of cancer-related existential distress that emerges from feelings of loss and changes linked to a life-threatening clinical condition. It is characterized by subjective incompetence, sense of failure, hopelessness, loss of purpose/meaning and low self-esteem. The study aimed to explore prevalence, latent dimensions and associated features of demoralization in a sample of end-of-life cancer patients. Methods: Participants were recruited for a cross-sectional assessment. For each patient, demoralization, anxiety, depression, physical symptoms, pain, spiritual well-being, and dignity were evaluated through validated rating scales and personal and medical data were gathered by a clinician. Final sample consisted of 235 end-of-life cancer patients with a Karnofsky Performance Status (KPS) lower than 50 and a life expectancy of few weeks. Results: High levels of demoralization occurred in 22.6% (n = 53) of patients. Sixty-four participants (27.2%) had low demoralization and 50.2% (n = 118) had moderate demoralization. Emotional Distress and Inability to Cope, Loss of Purpose and Meaning, Worthlessness, Sense of Failure and Dysphoria were the five latent dimensions of demoralization emerged from the factor analysis. Demoralization was significantly associated with depression, anxiety, dignity, spiritual well-being and the physical symptoms except for nausea and breathing problems. Conclusions: Demoralization levels seem to be higher in this distinctive population than in advanced cancer patients. This could be due to the fact that end-of-life cancer patients are in a severe clinical condition and nearing death. The emerged demoralization dimensions could be five forms of expression of the existential distress typical of this illness phase. The considerable number of patients suffering from demoralization strengthen the need for psychological interventions in order to reduce the existential distress at the end of life, focusing on finding meaning and detecting spiritual concerns.