Exosomes in NSCLC: Analysis of its cargo as a source of biomarkers

Impact of burn-out syndrome in oncology personnel and its improvement through specific interventions

Abstract Background Burn-Out Syndrome (BOS) in oncology nurses, has few experiences reported about its incidence and impact in its three different areas: emotional and physical exhaustion, cynism and despersonalization and no personal nor profesional fulfillment. There is a lack of resources for its diagnosis and management, although it impacts negatively in the patient attention/ care quality and the quality of institutional processes, added the personal impact in personal workers lives. Our objective was to determine the incidence of the BOS in our workers, analyze its causes and reduce in 20% the percentage of workers suffering or at risk of suffering BOS. Methods 23 nurses / nurse assis…

First analysis of the National Lung Cancer Register in Spain (RTT).

e13608Background: The Spanish Lung Cancer Group (GECP) initiated a Tumor Thoracic Register (RTT) in September 2016 with the aim of evaluating accurate, basic data concerning this oncological pathol...

Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer.

// Sonia Molina-Pinelo 1, 2 , Ana Salinas 1 , Nicolas Moreno-Mata 2 , Irene Ferrer 1, 2 , Rocio Suarez 1, 2 , Eduardo Andres-Leon 1 , Manuel Rodriguez-Paredes 4, 5 , Julian Gutekunst 4 , Eloisa Jantus-Lewintre 6, 7 , Carlos Camps 8, 9 , Amancio Carnero 1 , Luis Paz-Ares 1, 2 1 Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain 2 Medical Oncology Department, Hospital Universitario Doce de Octubre & Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain 3 Thoracic Surgery Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain 4 Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany…

Prognostic value of CTCs in advanced NSCLC patients treated with platinum-based chemotherapy

Abstract Background Lung cancer is the leading cause of cancer-related mortality worldwide. At diagnosis, 70% of patients present advanced disease being chemotherapy the standard of care. Although, specific tumour biomarkers that allow a better treatment selection and monitoring is absent at the moment. Enumeration and characterization of circulating tumor cells (CTCs) have the potential to perform as a prognostic biomarker for a precision medicine approach to lung cancer care. The present study was conducted to validate the characterization CTCs from patients with advanced Non-small cell lung cancer (NSCLC) as a valuable tool for anticipating the disease evolution and the therapy response.…

Abstract 4010: Prognostic role of miRNAs in resectable non-small cell lung cancer

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA BACKGROUND MicroRNAs (miRNA) are a class of small RNAs that regulate gene expression, and are implicated in several diseases including cancer. The aim of this study was to analyze the prognostic implications of deregulated miRNAs identified by NGS in a previous study performed on resectable-NSCLC tumor samples. MATERIAL AND METHODS Fresh-frozen tumor and normal adjacent lung tissue samples (N = 195) were obtained by surgical resection from NSCLC patients and storage in RNAlater® at -80°C until analysis. RNA was isolated biological specimens by Trizol based-methods. 22 deregulated miRNA were analyzed in paired t…

ECO Experts’ consensus on establishing renal cancer healthcare quality measures in Spain.

220 Background: The ECO Foundation (Excellence and Quality in Oncology) proposes to establish a set of healthcare quality measures (including indicators and standards) for the diagnosis, treatment and follow-up of renal cancer in Spain which all healthcare professionals involved can assume, being suitable for implementation in the continuous improvement process of our healthcare system. Methods: a) International literature review on the quality of healthcare in renal cancer; b) multidisciplinary driving group (9 oncologists with expertise in renal cancer plus 2 methodologists) to identify and choose possible quality measures to be applied in Spain; c) global evaluation of the relevance of …

Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population

Abstract Background The objective of this study was to conduct a cost-effectiveness evaluation of pemetrexed compared to docetaxel in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) for patients with predominantly non-squamous histology in the Spanish healthcare setting. Methods A Markov model was designed consisting of stable, responsive, progressive disease and death states. Patients could also experience adverse events as long as they received chemotherapy. Clinical inputs were based on an analysis of a phase III clinical trial that identified a statistically significant improvement in overall survival for non-squamous patients treated with pemetrexed compared …

The Quality Oncology Practice Initiative program: Experience in Spain.

214 Background: Patient care quality is a discipline that is being considered highly important in today’s healthcare. Quality Oncology Practice Initiative (QOPI) is a referral worldwide in terms of quality for oncology practices. The ECO Foundation is a platform of experts representing the major Spanish hospitals involved in the treatment of cancer patients. ECO reached an agreement with QOPI in order to involve Spanish hospitals in the participation of the QOPI program. Methods: Two rounds of data collection were carried out (Fall 2015 and Spring 2016). Practices had to registered on-line and submit data into the platform provided by QOPI. ECO Foundation offers all centres the support of …

QIM19-125: Nonclinical Needs of Cancer Patients in Spain Under Different Perspectives: A Comparative Study

Background: Patients with cancer and their caregivers express unmet needs beyond the clinical approach to cancer. The ECO Foundation (Quality and Excellence in Oncology) and the Spanish Association Against Cancer (AECC) have promoted a qualitative research study with the objective to identify and compare the perceptions of newly diagnosed and 2–3 years after diagnosis cancer patients, caregivers, oncologists, nurses, and social workers in relation to a set of nonclinical needs expressed by cancer patients and caregivers, and to obtain concrete and feasible proposals for improvement aimed at satisfying these needs. Methods: A multidisciplinary group of experts developed a questionnaire about…

Investigation of Complement Activation Product C4d as a Diagnostic and Prognostic Biomarker for Lung Cancer

[EN] Background There is a medical need for diagnostic biomarkers in lung cancer. We evaluated the diagnostic performance of complement activation fragments. Methods We assessed complement activation in four bronchial epithelial and seven lung cancer cell lines. C4d, a degradation product of complement activation, was determined in 90 primary lung tumors; bronchoalveolar lavage supernatants from patients with lung cancer (n = 50) and nonmalignant respiratory diseases (n = 22); and plasma samples from advanced (n = 50) and early lung cancer patients (n = 84) subjects with inflammatory lung diseases (n = 133), and asymptomatic individuals enrolled in a lung cancer computed tomography screenin…

Bladder cancer index : Cross-cultural adaptation into Spanish and psychometric evaluation

Background: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. Methods: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha.…

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

Abstract: Prostate cancer is the second most diagnosed cancer in males in the world. Plasma quantification of prostate-specific antigen substantially improved the early detection of prostate cancer, but still lacks the required specificity. Clinical management of prostate cancer needs advances in the development of new non-invasive biomarkers, ameliorating current diagnosis and prognosis and guiding therapeutic decisions. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. These miRNAs are expressed in the cells and are also present in cell-derived extracellular vesicles such as exosomes. Exosomes have been shown to act as…

Carcinoma of unknown origin: Deep genomic profile helps to achieve an accurate diagnosis

Clinical utility of plasma-based digital next-generation sequencing (NGS) in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping.

9101Background: Approximately 20 % of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. In this study, we have anal...

Ribonucleotide Reductase Messenger RNA Expression and Survival in Gemcitabine/Cisplatin-Treated Advanced Non-Small Cell Lung Cancer Patients

Abstract Purpose: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. Experimental Design: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcit…

CD5 and CD6 as immunoregulatory biomarkers in non-small cell lung cancer

Background: The study of immune surveillance in the tumour microenvironment is leading to the development of new biomarkers and therapies. The present research focuses on the expression of CD5 and CD6-two lymphocyte surface markers involved in the fine tuning of TCR signaling-as potential prognostic biomarkers in resectable stages of non-small cell lung cancer (NSCLC).; Methods: CD5 and CD6 gene expression was analysed by reverse transcription quantitative polymerase chain reaction (RTqPCR) in 186 paired fresh frozen tumour and normal tissue samples of resected NSCLC.; Results: Patients with higher CD5 expression had significantly increased overall survival (OS, 49.63 vs. 99.90 months, P=0.…

Tumor expression levels of CSC markers in resectable non-small cell lung cancer.

7562 Background: Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. T...

Evaluation of Spanish hospitals participating in the Quality Oncology Practice Initiative program.

222 Background: Measuring and tracking quality of care is highly relevant in today’s healthcare. The Quality Oncology Practice Initiative (QOPI) program is a referral for evaluating oncology practices worldwide. The ECO Foundation (Excellence and Quality in Oncology), a collaboration of oncology experts from the major Spanish hospitals involved in cancer treatment, reached an agreement with ASCO (American Society of Clinical Oncology) to include Spanish hospitals in its QOPI program. Methods: We analyzed the results of the QOPI core module measures from 19 Spanish hospitals submitting their data in nine rounds (from Fall 2015 to Fall 2019). Results: Of the 19 hospitals, 15 participated mor…

QIM19-135: The Quality Oncology Practice Initiative Program: Experience in Spain

Background: Patient quality care is a discipline that has acquired enormous relevance in today’s healthcare. The Quality Oncology Practice Initiative (QOPI) is a referral worldwide in terms of quality for oncology practices. The ECO Foundation is a foundation of experts representing the major Spanish hospitals involved in the treatment of cancer patients. ECO reached an agreement with ASCO to involve Spanish hospitals in the QOPI program. Methods: 6 rounds of data collection have taken place (Fall 2015 to Round 1 2018). Practices had to register online and submit data into the QOPI platform, and the ECO Foundation offered all centers the necessary support. 17 Spanish hospitals have particip…

Lung tumorspheres reveal cancer stem cell-like properties and a score with prognostic impact in resected non-small-cell lung cancer

AbstractThe high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were established, using sphere-forming assays for CSC enrichment and adherent conditions for the control counterparts. Patient-derived tumorspheres showed self-renewal and unlimited exponential growth potentials, resistance against chemotherapeutic agents, invasion and differentiation capacities in vitro, and superior tumorigenic potential in vivo. Using quantitative PCR, gene express…

Increased quality of life in patients with breakthrough cancer pain after individualized therapy: the CAVIDIOM study.

Cancer patients can experience flares of pain, called breakthrough pain (BTcP), despite treatment with painkillers. Although BTcP can be excruciating, its intensity and other characteristics depend on several factors, including its treatment. However, even if treated, BTcP can impair quality of life for cancer patients. We assessed quality of life in 118 patients with advanced cancer and BTcP treated in 13 medical oncology departments across Spain. We treated BTcP with individualized therapy, taking into account both pain-related and patient-related factors. We also measured quality of life using a specific, widely-used questionnaire at the study visits: at onset of individualized pain ther…

Clinical impact of using a deep genomic profile in carcinoma of unknown origin

MicroRNA profiling associated with non-small cell lung cancer: next generation sequencing detection, experimental validation, and prognostic value

[EN] Background: The average five-year survival for non-small cell lung cancer (NSCLC) patients is approximately 15%. Emerging evidence indicates that microRNAs (miRNAs) constitute a new class of gene regulators in humans that may play an important role in tumorigenesis. Hence, there is growing interest in studying their role as possible new biomarkers whose expression is aberrant in cancer. Therefore, in this study we identified dysregulated miRNAs by next generation sequencing (NGS) and analyzed their prognostic value. Methods: Sequencing by oligo ligation detection technology was used to identify dysregulated miRNAs in a training cohort comprising paired tumor/normal tissue samples (N = …

Immune Checkpoints Score and CD8+ T Cells Infiltration Are Independent Prognostic Biomarkers in Resected Nsclc

Oncology beyond the hospital: 7 years taking care of cancer patients from the very begining until the last consequences.

75 Background: Comprehensive and continuous care is esential for the correct management of cancer patients. To achieve this, specific programs for early diagnosis and long survivor care are needed. Since 2007, within the project “Oncology beyond the Hospital: Oncologic assistance at the Universitary General Hospital of Valencia”, the Oncologist Liaison was created. Methods: Two tracks were designed: High-resolution track for patients with suspicion of non-diagnosed cáncer; and Oncologist Liaison track, to organize the follow-up of cáncer long survivors. We present a descriptive and retrospective study by reviewing medical records of patients referred to the high-resolution diagnostic consu…

Differential expression of tumorspheres in CSC-markers and signaling pathways from non-small cell lung cancer.

e23276Background: Chemoresistance, tumor progression and metastasis have made of lung cancer the first cause of death cancer-related worldwide. Cancer stem cells (CSCs) are small subpopulations of ...

MA04.09 Study of Exosomes in NSCLC for Biomarkers Searching

Clinical utility of plasma-based digital next-generation sequencing in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping

[Background] Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping. [Patients and methods] We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a h…

MiRNA profiling by NGS in resectable non-small cell lung cancer: Prognostic implications.

7559 Background: MicroRNAs (miRNA) regulate gene expression, and are implicated in several processes like tumorogenesis. Here, we applied a multiplexed NGS approach to study differentially expressed miRNAs (tumor/ normal) in a cohort of resectable NSCLC patients and its correlation with clinical outcome. Methods: RNA was isolated from frozen lung specimens (tumor/ normal) from 33 patients. High-quality samples were analyzed and enriched in the miRNA fraction. Libraries were prepared according to manufactured instruction (SOLID), and miRNAs were sequenced. Data analysis was carried out using CLCbio software. First, raw data were annotated using miRBase and normalized by total reads followed …

Upregulated Mirna 21 in Kras Mutated Patients is Related to Prognosis in Resectable Non-Small Cell Lung Cancer

CD5 and CD6: Evaluation of their role as prognostic biomarkers in resectable non-small cell lung cancer

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation.

Background: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. Methods: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach’s alpha.…

Oral vinorelbine versus etoposide with cisplatin and chemo-radiation as treatment in patients with stage III non-small cell lung cancer: A randomized phase II (RENO study)

Objectives: Concomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC), The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting. Material and methods: An open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomizedl:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on d…

EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale.

EpCAM, known as an epithelial cell adhesion molecule, plays an essential role in cell adhesion, migration, metastasis and cell signalling. Rather than acting as an apoptosis antagonist, it induces cellular proliferation that impacts the cell cycle, and as a signalling transducer it uses and enhances the Wnt pathway, which is significantly relevant in cell renewal and cancer. EpCAM has become a marker of circulating tumour cells (CTCs) in lung cancer due to its specificity, and its high and stable expression level. Recent findings have allowed us to relearn and discover EpCAM again as a CSCs marker by demonstrating its role in human epithelial cancer progression. In line with this, the focus…

P1.05-013 Lung Tumorspheres as a Platform for Testing New Therapeutic Strategies in Non-Small Cell Lung Cancer

Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients.

Abstract Background: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor γ, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. Patients and methods: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patien…

Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer

Abstract: Introduction: The discovery of driver mutations in non-small cell lung cancer (NSCLC) has led to the development of genome-based personalized medicine. Fifteen to 20% of adenocarcinomas harbor an epidermal growth factor receptor (EGFR) activating mutation associated with responses to EGFR tyrosine kinase inhibitors (TKIs). Individual laboratories' expertise and the availability of appropriate equipment are valuable assets in predictive molecular pathology, although the choice of methods should be determined by the nature of the samples to be tested and whether the detection of only well-characterized EGFR mutations or rather, of all detectable mutations, is required.Areas covered:…

ANGIOMET: Analysis of the correlations between angiogenic markers and outcome in patients (p) with advanced nonsquamous NSCLC (NS-NSCLC) treated with carboplatin, paclitaxel, and bevacizumab (CPB).

e19014 Background: In NS-NSCLC CPB achieved median OS > 1 y and supported use of B. A broad range of predictive/prognostic markers explored for B use. In VEGF pathway ligands and receptors play an ...

How sustainable are new treatment strategies for NSCLC?

Abstract 4424: Cancer stem cells-related microRNAs have prognostic implications in non-small cell lung cancer

Abstract Background: Lung cancer stem cells (CSCs) are a small population of stem-like cells that remains largely unknown. MicroRNAs (miRNAs) regulation of CSCs gene expression has been reported, constituting a promising therapeutic target. The aim of this study was to isolate and analyze differential expression of a set of miRNAs in tumorspheres from lung cancer cell lines and tumor tissue from resectable non-small cell lung cancer (NSCLC) patients and to determine the prognostic implications of these miRNAs in a cohort of resected-NSCLC patients. Methods: Lung CSC-related miRNAs (miR-145-5p, miR-188-5p, miR-218-5p, miR-34a-5p, miR-21-5p and miR-125a-5p) were analyzed in cells from seven N…

62P Novel therapeutic strategies in NSCLC: Lung-tumorspheres as an effective in vitro screening platform

NGS‐based liquid biopsy profiling identifies mechanisms of resistance to ALK inhibitors: a step toward personalized NSCLC treatment

Despite impressive and durable responses, nonsmall cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase (ALK) inhibitors (ALK‐Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next‐generation sequencing (NGS) upon disease progression. We collected 26 plasma and two cerebrospinal fluid samples from 24 advanced ALK‐positive NSCLC patients at disease progression to an ALK‐I. These samples were analyzed by NGS and digital PCR. A tool to retrieve variants at the ALK locus was developed (VALK tool). We identified at least one resistance mutation in the ALK locus in ten (38.5%) p…

Final results of RENO study: Randomized phase II of oral vinorelbine or etoposide with cisplatin and chemo-radiation in stage III NSCLC. SLCG 10/02.

e20521Background: This study aims to compare efficacy and safety of two widely used combinations of cisplatin (P) in this setting: as etoposide (E) and vinorelbine. This last, in its oral formulati...

An expression signature characterizes cancer stem cells from lung adenocarcinoma patients

Molecular subtyping of colon cancer (CC) based on mutational status of RAS, BRAF, and DNA mismatch repair (MMR) proteins. Prognostic value.

e15094Background: CC is a heterogeneuous disease with clinical, pathological and biological variability. Molecular classification could indentify prognostic subtypes. Methods: 105 patients with sta...

Identification of quality care indicators in prostate cancer.

213 Background: Despite the attempts made to improve prostate cancer management with the development and implementation of clinical practice guidelines, the inefficiencies and differences that usually occur in ordinary clinical care of patients with prostate cancer significantly contribute to increase the variations in the patterns of care and patients outcomes, and costs to the health system. The goal of this project was to establish parameters for improving the care of patients with prostate cancer through the development and validation of quality indicators for the management of this disease. Methods: The ECO Foundation is a platform of experts representing the major Spanish hospitals i…

EGFR mutant cfDNA and CTC detection as biomarkers in patients diagnosed with advanced non-small cell lung cancer.

e23039Background: One of the most promising developments in translational cancer has been the emergence of liquid biopsy as a non-invasive biomarker. CTCs and cfDNA offer valuable prognostic and pr...

Clinical utility of plasma-based digital next-generation sequencing in oncogene-driven non-small-cell lung cancer patients with tyrosine kinase inhibitor resistance

[Objectives] Resistance to tyrosine-kinase inhibitors (TKIs) is a clinical challenge in patients with oncogene-driven non-small-cell lung cancers (NSCLC). We have analyzed the utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) to impact the clinical care of patients with TKI resistance.

Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma

OBJECTIVE: Complement C4d-containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas. SUBJECTS AND METHODS: C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied. RESULTS: C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.0…

Analysis of immunosuppressive factors produced by tumorspheres in NSCLC: Prognostic value of galectin-3 in adenocarcinoma

Abstract Background Cancer stem cells (CSCs) are targets poorly recognized by the immune surveillance system given that they induce an immunosuppressive microenvironment. The aim of this work is to study the interactions between CSCs and the immune microenvironment in NSCLC. Methods Tumor cells from 8 resected NSCLC patients and 12 cell lines were established as tumorspheres enriched in CSCs and as monolayers. The gene expression of IL-4, IL-10, IL6, IL8 and LGALS-3 was analyzed by RTqPCR. Results were validated at a protein level by a sensitivity bead-based multiplex immunoassay using the Millipore kit for Luminex 100/200. The prognostic value of these factors in silico was determined in a…

Applicability of ctDNA at diagnosis and during the monitoring of EGFR-mutated patients

Interleukin‐6 concentration changes in plasma and saliva in bisphosphonate‐related osteonecrosis of the jaws

To determine the plasma and saliva levels of IL-6 in patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to investigate whether there is a correlation between more advanced stages of BRONJ and levels of IL-6.We studied three groups: group 1 consisted of 30 patients with BRONJ due to intravenous bisphosphonates (ivBP), group 2 consisted of 25 patients treated with ivBP but without BRONJ, and group 3 consisted of 15 healthy controls. In each case, we assayed plasma and saliva IL-6 samples using an ELISA test.Significantly, higher IL-6 values were found in both saliva and plasma in group 1 vs groups 2 and 3 (P  0.01). Group 1 showed no differences in plasma or saliva IL-…

Analysis of the immune microenvironment in resected non-small cell lung cancer: the prognostic value of different T lymphocyte markers

[EN] The prognosis of non-small cell lung cancer (NSCLC) remains poor and heterogeneous and new biomarkers are needed. As the immune system plays a pivotal role in cancer, the study of immune-related markers may provide valuable prognostic information of NSCLC. In 122 formalin-fixed, paraffin-embedded tumor tissue samples from early-stage NSCLC, tumor and tumor-near stromal areas were microdissected and gene expression levels of conventional and regulatory T cell markers were assessed by quantitative polymerase chain reaction. Also, the presence of infiltrating CD4+, CD8+, and FOXP3+ cells in tumor samples was assessed by immunohistochemistry. The relative proportion of conventional and reg…

Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics

Abstract Background The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. Patients and methods The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates…

Abstract 3354: Characterization of lung tumorspheres by gene expression and flow cytometry: differential expression in CSC-related markers and signaling pathways

Abstract Chemoresistance, progression and metastasis have made of lung cancer the first cause of cancer mortality. These features were linked to a subpopulation of cells, named cancer stem cells (CSCs), which remain largely unknown. The aim of this study was to isolate and characterize CSCs from lung cancer cell-lines and tumor-tissue from resectable non-small cell lung cancer (NSCLC). Methods: Tumor cells from resected NSCLC and cell lines (H1650, H1993, A549, and PC9) were grown in monolayer and as spheroids. RTqPCR was performed to analyze the mRNA expression of CSCs-related genes: CSC-markers (EPCAM1, ALDH1A1, CD166, ABCG2, CD44, CD133); pluripotency genes (KLF4, OCT4, NANOG, SOX2, MYC,…

Lung tumorspheres as a drug screening platform against cancer stem cells.

Treatment resistance and metastasis are linked to cancer stem cells (CSCs). This population represents a promising target, but remains unexplored in lung cancer. The main objective of this study was to characterize lung CSCs and discover new therapeutic strategies.

LungBEAM: A prospective multicenter study to monitor stage IV NSCLC patients with EGFR mutations using BEAMing technology

Abstract Objectives The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non‐small cell lung cancer (NSCLC) patients treated with first‐ or second‐generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods Stage IV NSCLC patients with locally confirmed EGFR‐TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to…

MicroRNAs: Promising New Antiangiogenic Targets in Cancer

[EN] MicroRNAs are one class of small, endogenous, non-coding RNAs that are approximately 22 nucleotides in length; they are very numerous, have been phylogenetically conserved, and involved in biological processes such as development, differentiation, cell proliferation, and apoptosis. MicroRNAs contribute to modulating the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules and so they play a key role in both health and disease. Angiogenesis is the process of new blood vessel formation from preexisting ones, which is particularly relevant to cancer and its progression. Over the last few years, microRNAs have emerged as critical regulat…

Prognostic role of immune checkpoint-related genes in resectable lung adenocarcinomas.

11085 Background: Immune checkpoints blockade has demonstrated promising clinical results in NSCLC patients. In this study we have investigated the prognostic role of immune checkpoint markers (CTLA4, PD1 and PDL1) in resectable lung adenocarcinoma (ADC). Methods: RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) from resectable ADC patients (n=92). RT-PCR was performed to analyze the expression of CTLA4, PD1 and PDL1 by the use of hydrolysis probes. Relative gene expression was assessed by Pfaffl formula and normalized by CDKN1B and ACTB as endogenous genes (selected by geNorm algorithm). Statistical analyses were considered significant at p<0.05. Results: Patient’s…

Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC

[EN] Background Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods Clinically annotated, resected stage I¿III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is¿>1% for most of the ~150 (13 genes) mutations covered in the multiplex test.…

Soluble biomarker signature to predict outcome of patients with non-small-cell lung cancer (NSCLC) treated with anti-PD1/PDL1 monoclonal antibodies.

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 c…

Implementation of the quality training program in Spain.

e18296 Background: The ECO Foundation is a collaboration of experts representing the major Spanish hospitals in the pursuit of excellence in cancer treatment. Since 2015, ECO has been collaborating with ASCO (American Society of Clinical Oncology) in quality initiatives in cancer care, like the QOPI (Quality Oncology Practice Initiative) program and the QOPI Certification Program (QCP). The Quality Training Program (QTP) is a 6-month program with 3 in-person learning sessions that prepares oncology teams to design implement and lead successful quality improvement activities in their practices. In 2018, ECO reached a new agreement with ASCO to implement this program in Spain. Methods: The Q…

Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro

Background/Objective Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on prolifer…

Interactions of cancer stem cell and immune microenvironment in non-small cell lung cancer (NSCLC)

Comprehensive cross-platform comparison of methodologies for noninvasive EGFR mutation testing: Results of the RING observational trial.

e21518 Background: Several platforms for non-invasive EGFR testing are currently used in the clinical setting, with sensitivities ranging from 30 to 100%. Comparison studies in prospective cohorts remain limited and reports evaluating mutant allelic fractions (MAFs) are particularly scarce. The RING observational trial (ClinicalTrials.gov identifier NCT03363139) was designed to comprehensively analyze the concordance between methodologies for EGFR mutation detection in blood. Methods: Seventy-two EGFR mutant NSCLC patients were enrolled in the trial. Plasma samples were prospectively collected at progression to first line Tyrosine Kinase Inhibitor and tested for EGFR mutations by 7 methodo…

Clinical and molecular characteristics of the patients in the liquid biopsy study in mEGFR-NSCLC in a Spanish population (OPH-1).

e21515 Background: The liquid biopsy (LB) is an important tool in the diagnostic and follow up of the patients with non-small cell lung cancer (NSCLC) and can provide big information about the mutational variability of the disease during of the treatment. Methods: We conducted a multicenter study with 200 patients with EGFR-mutated NSCLC, treated with first-line TKI therapy. We analyse the ctDNA by dPCR pre-treatment, at 8 weeks, at 7 months and at the progression of the disease (PD). Results: A total of 200 patients (60% women / 40% men) were included. The median of age was 68-year. The never smokers were 56% and 34% ex-smokers. 92% of the cases were adenocarcinomas. According to the stag…

Analysis of gut microbiota in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoints blockers

Abstract Background The microbiota community is considered as an organ of the human body. Recent studies have found that dysbiosis may have an impact on the interaction between immune regulation and tumor treatment. The main objective of this study is to characterize the gut microbiota in patients with non-small cell lung cancer (NSCLC) in advanced stages, and its relationship with obesity, smoking habits, clinical pathological features and response to treatment with immune-checkpoints blockers (ICB). Methods 16S rRNA gene sequencing was performed on 48 stool samples from advanced NSCLC patients prior to treatment with ICB (PD-1 inhibitor and PD-L1 inhibitor). The database used for the taxo…

Prognostic Impact of Vegfa in Resectable Non-Small-Cell Lung Cancer

ABSTRACT Aim: Angiogenesis is a main process which happens in tumors and that promotes its growth, invasive capacity and metastasis. Host genetic variability within VEGF pathway may affect angiogenic signaling and alter patient's sensitivity to anti-angiogenic therapies and therefore the prognostic. The goal in the present study is to analyze the prognostic value of several SNPs in angiogenic genes and the relative expression of those genes, using a cohort of patients diagnosed with resectable non-small cell lung cancer. Methods: This study included 127 resectable (I-IIIA) NSCLC patients. RNA and DNA extractions from tissues were performed using Trizol®. 20 ng of DNA were used for studies o…

Lung tumorspheres as a platform for testing new therapeutic strategies in lung cancer.

e23177Background: Resistance to treatment is one of the causes influencing the high mortality of lung cancer. This feature seems to be dependent of a small subset of special characteristics of self...

Snps in Angiogenic Factors As Predictive Markers for Outcome in Patients (P) with Advanced Non-Squamous Nsclc (NS-NSCLC) Treated with Carboplatin, Paclitaxel (CP) and Bevacizumab (BEV). Final Results of Angiomet Spanish Lung Cancer Group Trial

Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer

Simple Summary Non-small cell lung cancer (NSCLC) is the second most commonly diagnosed cancer and the leading cause of cancer-related death worldwide. Clinical decision-making depends on the histological classification; however, tissue biopsy is frequently not technically feasible due to tumor location or limited tissue samples. Therefore, we propose to find clinical, molecular and histological biomarkers using a minimally invasive approach based on the analysis of the cargo of the blood extracellular vesicles. Exosomes are membranous vesicles present in several biological fluids, which carry biological information to distant tissues, regulating several tumor processes. This study aims to …

Prospective multicenter real-world RAS mutation comparison between OncoBEAM-based liquid biopsy and tissue analysis in metastatic colorectal cancer

[EN] BACKGROUND: Liquid biopsy offers a minimally invasive alternative to tissue-based evaluation of mutational status in cancer. The goal of the present study was to evaluate the aggregate performance of OncoBEAM RAS mutation analysis in plasma of colorectal cancer (CRC) patients at 10 hospital laboratories in Spain where this technology is routinely implemented. METHODS: Circulating cell-free DNA from plasma was examined for RAS mutations using the OncoBEAM platform at each hospital laboratory. Results were then compared to those obtained from DNA extracted from tumour tissue from the same patient. RESULTS: The overall percentage agreement between plasma-based and tissue-based RAS mutatio…

Treatment patterns for metastatic colorectal cancer in Spain

Abstract Purpose The primary aim of this retrospective study was to describe the treatment patterns according to the type of treatment received by patients with metastatic colorectal cancer (mCRC) in Spain. Methods This was a retrospective, observational, multicenter study performed by 33 sites throughout Spain that included consecutive patients aged 18 years or older who had received or were receiving treatment for mCRC. Results At the time of inclusion, of the 873 evaluable patients, 507 (58%) had received two lines, 235 (27%) had received three lines, 106 (12%) had received four lines, and the remaining patients had received up to ten lines. The most frequent chemotherapy schemes were th…

The future of precision medicine, strengths and weaknesses: An expert position paper.

e18879Background: Precision medicine (PM) is an emerging field. Guidelines are needed to develop this approach in an efficient and sustainable way. Methods: Twenty-one Spanish top oncologists met t...

Abstract 4330: Immune checkpoint expression score is an independent prognostic biomarker in resectable non-small cell lung cancer

Abstract BACKGROUND Immune checkpoints blockade, which activate antitumor immunity, has demonstrated promising clinical results in NSCLC. In this study we have investigated the prognostic role of immune checkpoint expression markers and its correlation with immune-cells infiltration and clinico-pathological characteristics in a cohort of resectable NSCLC patients. MATERIAL AND METHODS RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the expression of CTLA-4, PD-1 and PD-L1 by the use of hydrolysis probes. Relative gene expression was assessed by Pfaffl formula and normalized by the use of CDKN1B, GUS and ACTB as endogenous …

miRNA detection methods and clinical implications in lung cancer

[EN] Lung cancer is the leading cause of cancer death worldwide. Therefore, advances in the diagnosis and treatment of the disease are urgently needed. miRNAs are a family of small, noncoding RNAs that regulate gene expression at the transcriptional level. miRNAs have been reported to be deregulated and to play a critical role in different types of cancer, including lung cancer. Thus, miRNA profiling in lung cancer patients has become the core of several investigations. To this end, the development of a multitude of platforms for miRNA profiling analysis has been essential. This article focuses on the different technologies available for assessing miRNAs and the most important results obtai…

Prognostic Impact of Immune Microenvironment Markers in Tumor and Stroma in Resectable Nsclc

ABSTRACT Aim: Tumor-infiltrating immune cells have been proved to play an important role in tumor progression. In this study we have analyzed the expression of 11 immune related genes in both tumor and stroma samples of resectable NSCLC patients. Methods: In this retrospective study FFPE samples from 117 early-stage NSCLC patients of primary tumor tissue were used. The most representative areas of tumor and tumor stroma of each sample were carefully micro-dissected. RT-PCR using hydrolysis probes (TaqMan, Applied Biosystems) was performed to assess the expression of Treg markers such as: CD127, CD25, FOXP3, CTLA-4, IL-10, TGFB-1, LAG-3, GITR and TNFA as well as CD4 and CD8. Relative gene ex…

Analysis of the Gut Microbiota: An Emerging Source of Biomarkers for Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer

Simple Summary The immune checkpoint blockade (ICB), and concretely the blockade of the PD1/PDL1 axis, has opened up a new standard of treatment for non-small cell lung cancer (NSCLC). However, despite substantial advances in clinical care, many patients still remain refractory to these therapies. Biomarkers such as PD-L1 expression and tumor mutational burden have been associated with ICB efficacy, but the mechanisms underlying variable responses are not yet fully understood. Recently, the differential composition of the gut microbiota was studied as one of the variables accounting for interpatient heterogeneity in ICB responses. To better understand the potential role of the gut microbiot…

EP912 Characterization of the tumour microenvironment in high-grade serous ovarian cancer (HGSOC): prognostic value of the lymphocytic infiltration patterns and immune-related genes

Introduction/Background Lymphocytic infiltration areas (immunoreactive), frequently found in high-grade serous ovarian cancer (HGSOC), are associated with a better prognosis and increased survival. The cross-talk between tumour cells and lymphocytes conditions the capacity of the immune system (IS) to cope with the tumour in the so-called immune-checkpoints. Therefore, assessing IS-related genes and infiltration patters might provide valuable prognostic biomarkers. Methodology This retrospective study includes 57 samples from patients with HGSOC who underwent cytoreductive surgery at Hospital General (Valencia). Clinical variables, the features of the lymphocytic infiltration (pattern, loca…

New insights in non-small-cell lung cancer: circulating tumor cells and cell-free DNA

Lung cancer is the second most frequent tumor and the leading cause of death by cancer in both men and women. Increasing knowledge about the cancer genome and tumor environment has led to a new setting in which morphological and molecular characterization is needed to treat patients in the most personalized way in order to achieve better outcomes. Since tumor products can be detected in body fluids, the liquid biopsy, particularly, peripheral blood, has emerged as a new source for lung cancer biomarker's analysis. A variety of tumor components can be used for this purpose. Among them, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) should be especially considered. Different…

MA04.03 Lung Tumorspheres Characterization Reveals Cancer Stem-Like Cells Potential Targets and Prognostic Markers in Non-Small Cell Lung Cancer

Valoración clínica del estado dental y periodontal en un grupo de pacientes oncológicos, previo inicio de la quimioterapia

Objetivos: Valorar el estado bucodental en 88 pacientes con cánceres corporales, previo al inicio de su tratamiento quimioterápico. Diseño del estudio: Estudiamos 88 pacientes con cánceres de diferentes localizaciones corporales y los comparamos con un grupo control. Analizamos la placa dental (mediante el índice de Silness y Löe), el estado dental (mediante el índice CAO.D) y el estado periodontal (índice CPI modificado). Resultados: En el grupo de pacientes oncológicos, la media del índice de placa de Silnness y Löe fue de 1,28±0,11. Los pacientes presentaban múltiples ausencias dentarias, siendo la media de dientes ausentes por caries de 7,55±0,80. También se observó que la media de cari…

Oxidative stress in bisphosphonate-related osteonecrosis of the jaws

Objectives To analyze whether oxidative stress (OS) changes are present in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus controls. Materials and Methods Oxidative stress was analyzed in serum and unstimulated saliva of three groups: Group 1 consisted of 24 patients who had been treated with intravenous bisphosphonates (ivBPs) and developed BRONJ, group 2 consisted of 20 patients who had received ivBPs and did not develop BRONJ, and group 3 comprised 17 control subjects. Reduced glutathione (GSH), malondialdehyde (MDA), oxidized glutathione (GSSG), and 8–oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) levels, as well as the GSSG/GSH ratio, were measured. Results Me…

Development of an MCDA framework for evaluation and positioning of oncological treatments in clinical practice.

95 Background: Ensuring that effective innovations are accessible in a timely and affordable manner to all cancer patients is a challenge that stakeholders face today. Several oncology frameworks (ASCO, ESMO, ICER, NCCN) have been developed to define and quantify the value of oncological therapies to support clinicians and patients at the time of selection and as a basis for decision-making. However, current frameworks only define treatment value in terms of clinical benefit, creating a need for one that allows holistic evaluation of treatments and supports decision-making in clinical practice. The ECO Foundation led this study to develop a reflective multi-criteria decision analysis (MCDA…

Impact of burn-out syndrome in oncology staff and its improvement through specific interventions.

249 Background: Burn-Out Syndrome (BOS) is defined by: emotional and physical exhaustion; cynicism and depersonalization; and no personal nor professional fulfillment. With increasing incidence, it impacts negatively in the patient attention quality and the quality of institutional processes. Few experiences reported about its incidence and impact in Medical Oncology. Lack of resources for its diagnosis and management. Our objective was to determine the incidence of the BOS in our workers, analyze its causes and try to reduce in 20% the percentage of workers suffering or at risk of suffering BOS. Developed as a Quality Training Program (ASCO - ECO Foundation) project. Methods: 23 nurses/nu…

New generation of cancer stem cells inhibitors in non-small cell lung cancer.

e20545Background: Lung cancer is the commonest tumor worldwide of which the most frequent type is non-small cell lung cancer (NSCLC) that represents a large proportion of cancer deaths and is chara...

Delphi Consensus on the Follow-up of Cancer Patients with Breakthrough Pain Under Opioid Treatment

e23135 Background: Breakthrough cancer pain (BTcP) is one of the most common symptoms related with the disease and its treatment. Its management differs from that of chronic pain but there is not a wide consensus about fundamental aspects of BTcP definition, diagnosis, follow-up, and management. The objective of this study promoted by ECO Foundation, is to reach a consensus on the follow-up of patients with BTcP under opioid treatment. Methods: This work was conducted using a modified Delphi method organized in two rounds and involving a panel of 84 medical oncologists. A questionnaire of 66 items was developed. The items proposed to reach a consensus included the following topics: 1) When…

3D printing novel in vitro cancer cell culture model systems for lung cancer stem cell study

Two-dimensional (2D) in vitro cell cultures and laboratory animals have been used traditionally as the gold-standard preclinical cancer model systems. However, for cancer stem cell (CSC) studies, they exhibit notable limitations on simulating native environment, which depreciate their translatability for clinical development purposes. In this study, different three-dimensional (3D) printing platforms were used to establish novel 3D cell cultures enriched in CSCs from non-small cell lung cancer (NSCLC) patients and cell lines. Rigid scaffolds with an elevated compressive modulus and uniform pores and channels were produced using different filaments. Hydrogel-based scaffolds were printed with…

1212P Exosomes cargo analysis as an approach to identify new biomarkers in NSCLC

Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer

Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by H-1-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC). We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids…

Potential treatment strategy for the rare osimertinib resistant mutation EGFR L718Q

Epidermal growth factor receptor (EGFR) L718Q is a rare resistant mutation which independently leads to third-generation tyrosine kinase inhibitor (TKI) resistance. Although a few studies have examined its resistance mechanisms, no effective treatment strategy has yet been proposed for patients with this mutation. Here, we report an effective treatment strategy for the rare EGFR L718Q mutation for the first time. A 44-year-old Chinese male patient initially presented with the sensitizing EGFR L858R mutation, and the progression-free survival (PFS) time after initial icotinib treatment was 9 months. When the progression of the disease (PD) and the EGFR T790M mutation were identified, he did …

Characterization of lung tumourspheres reveals cancer stem-like cells potential targets and prognostic markers in non-small cell lung cancer

Abstract Background Non-small cell lung cancer (NSCLC) is the first cause of death cancer-related worldwide mainly due to high therapeutic resistance. This resistance is related to cancer stem-like cells (CSCs), for which the identification of targets and markers is still ongoing. Methods Primary cultures from 8 NSCLC patients were established as tumorspheres and as monolayers. CSCs properties were tested for both conditions in vitro and in vivo. The expression of 50 CSCs-related genes was assessed by RTqPCR and proteins of significantly overexpressed genes were examined by immunoblot and immunofluorescence. The prognostic role of these genes was analyzed in a cohort of 661 NSCLC patients f…

Analysis of the prognostic impact of Treg-related genes in tumor and stroma in resectable NSCLC

11073 Background: Immunosuppressive regulatory T lymphocytes (Tregs) have been proved to play a critical role in immune tolerance to tumor. In this study we have analyzed the expression of 11 genes related to Tregs in both tumor and stroma samples of resectable NSCLC patients. Methods: Primary tumor tissues of FFPE samples from 125 early-stage NSCLC patients were used in this retrospective study. The most representative areas of tumor cells and tumor stroma of each sample were carefully micro-dissected. RTqPCR using hydrolysis probes (TaqMan, Applied Biosystems) was performed to assess the expression of Treg markers such as: CD127, CD25, FOXP3, CTLA-4, IL-10, TGFB-1, LAG-3, GITR and TNF-a …

Update on biomarkers for the detection of lung cancer

Patients at risk for lung cancer may have subclinical disease for years before presentation. The diagnosis of this disease is primarily based on symptoms, and detection often occurs after curative intervention is no longer possible. At present, no lung cancer early-detection biomarker is clinically available. This study reviews the most recent advances in early detection and molecular diagnostic biomarkers for the detection of lung cancer. This review includes an overview of the various biological specimens and matrices in which these biomarkers could be analyzed, as well as the diverse strategies and approaches for identifying new biomarkers that are currently being explored. Several novel…

Assessment and treatment of breakthrough cancer pain in Spain: A self-audit study.

e18785Background: Breakthrough cancer pain (BTcP) is a common condition, but its management may be often suboptimal. We aim to determine if physician’s perception of the management and characterist...

Safe neoadjuvant trastuzumab-based treatment in HER2 + inflammatory early breast cancer in a glucose 6-phosphate dehydrogenase-deficient postmenopausal woman: A case report and review of the literature

Introduction Glucose 6-phosphate dehydrogenase (G6PD) is a basic antioxidant pathway for erythrocytes, being its deficiency the most common gene mutation worldwide. As breast cancer is one of the most frequent tumors, many of these patients may present with G6PD deficiency prior treatment without notice. Case report We present the case of a woman deficient for G6PD with the diagnosis of Stage IIIB (cT4d cN1 cM0) HER2-enriched early breast cancer. Management and outcome The patient underwent neoadjuvance with trastuzumab and anthracycline-free chemotherapy, based on docetaxel (75 mg/m2, 120 mg) and carboplatin (AUC 5, 560 mg). She did not present hemolytic crisis and no blood transfusions we…

Genomic profiling in advanced stage non-small-cell lung cancer patients with platinum-based chemotherapy identifies germline variants with prognostic value in SMYD2

Abstract Objective The aim of the study was to investigate the relationship between germline variations as a prognosis biomarker in patients with advanced Non-Small-Cell-Lung-Cancer (NSCLC) subjected to first-line platinum-based treatment. Materials and Methods We carried out a two-stage genome-wide-association study in non-small-cell lung cancer patients with platinum-based chemotherapy in an exploratory sample of 181 NSCLC patients from Caucasian origin, followed by a validation on 356 NSCLC patients from the same ancestry (Valencia, Spain). Results We identified germline variants in SMYD2 as a prognostic factor for survival in patients with advanced NSCLC receiving chemotherapy. SMYD2 al…

Study on compliance with breakthrough cancer pain guidelines by medical oncologists in Spain.

e18260 Background: Breakthrough cancer pain (BTcP) has been shown to be a prevalent and poor prognostic factor for cancer patients, which remains undertreated and underdiagnosed. The Spanish Society for Medical Oncology (SEOM) developed a clinical practice guideline (CPG) for the treatment of cancer pain which specifically addressed the management of BTcP. Methods: With the objective of evaluate compliance with SEOM’ guideline, Fundación ECO designed a survey to identify awareness, perceptions, implementation and gaps, among Spanish medical oncologists. Results: A total of 83 oncologists with a median experience of 13 years responded. Although 87% of oncologists considered their clinical p…

Determination of DPYD polymorphisms before treatment with chemotherapy with a pyrimidine: Should we continue doing it?

Clinical assessment of patients with advanced non-small-cell lung cancer eligible for second-line chemotherapy

Purpose: Knowledge of prognostic factors for advanced non-small-cell lung cancer (NSCLC) patients eligible for second-line treatment is scarce. The aim of this study was to assess the prognostic role of a number of routinely collected clinical variables and to provide a summary index to discriminate patients according to probability of survival.Methods: individual data from nine randomised trials of second-line treatment in advanced NSCLC were analysed. Primary end-point was overall survival (OS). Cox model, stratified by trial, was used for multivariate analyses, and a prognostic index was provided and validated according to an internal/external procedure.Results: Out of 1239 patients, 119…

Analysis of the prognostic role of an immune checkpoint score in resected non-small cell lung cancer patients

[EN] Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm. Patients with higher expression levels of IL2…

Functional FLT1 genetic variation is a prognostic factor for recurrence in stage I-III non-small cell lung cancer

Background: We propose that single-nucleotide polymorphisms (SNPs) in genes of the vascular endothelial growth factor pathway of angiogenesis will associate with survival in non-small-cell lung cancer (NSCLC) patients. Methods: Fifty-three SNPs in vascular endothelial growth factor-pathway genes were genotyped in 150 European stage I-III NSCLC patients and tested for associations with patient survival. Replication was performed in an independent cohort of 142 European stage I-III patients. Reporter gene assays were used to assess the effects of SNPs on transcriptional activity. Results: In the initial cohort, five SNPs associated (q < 0.05) with relapse-free survival (RFS). The minor allele…

Abstract 3056: Lung tumor spheres as in vitro platform for testing new therapeutic strategies against cancer stem cells

Abstract Background: Treatment resistance is related to cancer stem cells (CSCs), a highly tumorigenic subpopulation of cells capable of growing and forming tumor spheres under non-adherent conditions. This study aimed to isolate and characterise CSCs from resected non-small cell lung cancer (NSCLC) patients' tumor-tissue and cell lines like tumor spheres and to use them as an in vitro platform for drug screening. Methods: The study was performed on tumour cells from 8 resected NSCLC patients and 12 NSCLC cell lines grown in monolayer and as spheres. The expression of 60 genes, including CSC-markers, pluripotency inducers, cell cycle regulators and components of the Notch, Wnt and Hedgehog …

TMPRSS4: a novel tumor prognostic indicator for the stratification of stage IA tumors and a liquid biopsy biomarker for NSCLC patients

Relapse rates in surgically resected non-small-cell lung cancer (NSCLC) patients are between 30% and 45% within five years of diagnosis, which shows the clinical need to identify those patients at high risk of recurrence. The eighth TNM staging system recently refined the classification of NSCLC patients and their associated prognosis, but molecular biomarkers could improve the heterogeneous outcomes found within each stage. Here, using two independent cohorts (MDA and CIMA-CUN) and the eighth TNM classification, we show that TMPRSS4 protein expression is an independent prognostic factor in NSCLC, particularly for patients at stage I: relapse-free survival (RFS) HR, 2.42 (95% CI, 1.47&ndash

ctDNA levels before treatment predict survival in non-small cell lung cancer patients treated with a tyrosine kinase inhibitor.

9542 Background: Currently there is an intense debate concerning therapeutic strategies in EGFR positive NSCLC patients with advance disease. Osimertinib is superior to standard EGFR Tyrosine Kinase Inhibitors (TKIs) as first line treatment. However, it is yet unclear whether this option is superior to sequential treatment of a 1st or 2nd generation TKI followed by osimertinib. In order to clarify this issue it is important to identify which patients are at high risk of progression disease. Methods: This is a prospective, multicentre, cross-sectional study promoted by Spanish Lung Cancer Group. 698 plasma samples from 196 advanced NSCLC patients with tumors harboring an EGFR activating mut…

A gene expression signature to characterize human lung adenocarcinoma cancer stem cells.

e20547Background: Treatment resistance is linked to cancer stem cells (CSCs), a highly tumorigenic subpopulation of cells with the ability to grow as spheres in non-adherent conditions. The aim of ...

Non-clinical needs of cancer patients in Spain under different perspectives: A comparative study.

e18266 Background: Patients with cancer and their caregivers express unmet needs beyond the clinical approach to cancer. The ECO Foundation (Quality and Excellence in Oncology) and the Spanish Association Against Cancer (AECC) have promoted a qualitative research study with the objective to compare the perceptions of newly diagnosed and 2-3 years after diagnosis cancer patients, caregivers, oncologists, nurses and social workers in relation to a set of non-clinical needs expressed by cancer patients and caregivers, and to obtain concrete and feasible proposals for improvement aimed at satisfying these needs. Methods: A multidisciplinary group of experts developed a questionnaire containing…

Isolation and characterization of lung cancer sphere-forming cells as platforms for the development of new therapeutic strategies

e22190 Background: Resistance to treatment is one of major causes influencing the high mortality of lung cancer. This feature seems to be dependent of a minority of cancer cells with special charac...

Ratios between VEGF ligands and receptors in tumor and stroma have impact on the outcome in resectable NSCLC.

e22147 Background: In tumor angiogenesis there is a complex interplay between endothelial, stromal and tumor cells. Some key regulators of this process are the members of the vascular endothelial growth factor (VEGF) family of ligands and receptors and the neuropilins (NRP). This study analyzes the correlations between the expression of these angiogenic factors in tumor cells and tumor stroma, and their prognostic role in tissue samples from resected non-small cell lung cancer (NSCLC) patients. Methods: Representative tumor and stroma areas from FFPE tissue samples of 125 early-stage NSCLC patients were carefully micro-dissected. RNA isolated from the samples was retrotranscripted and prea…