Browsing Over 400 Presentations
Invited Discussant 143PD and 144PD
- Els Wauters (BE)
- Els Wauters (BE)
98P - Trends in and impact of hospital-acquired adverse events in patients with lung cancer undergoing lung resection
- Arjun Gupta (US)
- Arjun Gupta (US)
- Kristin C. Mara (US)
- Kemp Kernstine (US)
- Sahil Khanna (US)
- David E. Gerber (US)
Abstract
Background
Hospital-acquired adverse events are a measure of quality of care delivered and may adversely impact patient outcomes. It is unknown if there been a change in the rates and impact of these adverse events with their increasing recognition as quality measures. We analyzed hospital-acquired adverse events in patients with lung cancer undergoing lung resection using the National Hospital Discharge Survey (NHDS) database from 2001 to 2010.
Methods
NHDS collects clinical information on patients dismissed from non-Federal short-stay United States hospitals. Demographics, diagnoses, procedures, and dismissal information were abstracted using ICD-9 diagnosis (162.X) and procedure codes (32.9, 32.3X, 32.4X, and 32.5X). The Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs) were utilized to identify hospital-acquired adverse events. Weighted analyses were performed using SAS version 9.4.
Results
An estimated 585,408 patients with lung cancer underwent lung resection during the study period and were included in the analysis; 58.3% were >65 years, 49.1% women, 66% white. Of these, 153,609 (26.2%) suffered from ≥1-PSI event during their hospitalization. The proportion of patients suffering from ≥1-PSI event consistently increased from 22.0% in 2001–2002, to 34.8% in 2009–2010, p value <0.01. Compared to those with no PSI, patients with ≥1-PSI experienced higher in-hospital mortality (2.2%, vs 15.7%, adjusted odds ratio, 7.8, 95% CI 5.1–11.8), and prolonged length-of-stay (7.8 days, vs 12.5 days, adjusted mean difference, 4.6 days, 95% CI 3.7–5.5), p value for both <0.01.
Conclusions
There was a substantial increase in the frequency of potentially avoidable adverse events in this national database of lung cancer patients undergoing resection, associated with worse outcomes. Although this may in part be due to increasing recognition, interventions are required to prevent these potentially avoidable events.
Clinical trial identification
Not applicable
Legal entity responsible for the study
Arjun Gupta
Funding
Has not received any funding
Disclosure
All authors have declared no conflicts of interest.
The relevance of pre-resection transcervical lymphadenectomy in lung cancer
- Sergi Call (ES)
- Sergi Call (ES)
153P - EGFR T790M co-exists with sensitive mutations in the same cell group in lung adenocarcinoma patients
- Xiaohua Shi (CN)
- Xiaohua Shi (CN)
- Shafei Wu (CN)
- Hanping Wang (CN)
- Zhiyong Liang (CN)
- Xuan Zeng (CN)
Abstract
Background
EGFR TKI targeted therapy has improved lung adenocarcinoma patients’ prognosis tremendously, but almost all of patients inevitably develop acquired resistance to these agents, and EGFR T790M mutation is the major contributors. Previous work has shown that after TKI therapy, lung adenocarcinoma patients kept the sensitive mutation and acquired resistance mutation simultaneously by sequencing methods or in vitro cell line experiments. Whether the two different type mutations are in the same cell group or in two different cell groups is unknown.
Methods
RNA in situ hybridization methods was employed to examined EGFR T790M and L858R mutation in lung adenocarcinoma cancer tissues which was obtained before and after TKI therapy. EGFR expression was examined by immunohistochemistry. EGFR mutation were detected by ARMS PCR methods.
Results
Twenty-four patients were enrolled in this study which were divided into 3 groups. Group 1: 4 patients who had concurrent primary T790M and sensitive EGFR mutation. Group 2: 14 patients who acquired T790M mutation after receiving TKI therapy. Among them, 6 patients had biopsy tissues before and after TKI therapy. 8 patients only own tissues after TKI therapy. Group 3: 6 patients who had sensitive EGFR mutation and received TKI therapy, but re-biopsy tissues didn't have EGFR T790M. We found that the results of RNA ISH and ARMS PCR methods was identical in the majority of the examined tissues. Only one repeated biopsy tissue didn't identify EGFR T790M after TKI therapy by PCR in group 3, while the RNA ISH method detected T790M in this tissue which contain only 100 tumor cells. In the serial cut slides, we observed that T790M and L858R mutations were in the same cell group, not only in the primary resistance cases, but also in the acquired resistance cases. For the two cases which had tissues available after receiving third generation TKI therapy, we observed that T790M disappeared in the repeated biopsy specimen, leaving the sensitive mutation which existed from the beginning.
Conclusions
EGFR sensitive mutation and T790M co-exist in the same cell groups. EGFR sensitive mutation is a trunk and drive mutation, while T790M is a passenger mutation during the treatment process by TKI therapy.
Legal entity responsible for the study
Peking Union Medical College Hospital
Funding
Peking Union Medical College Youth Fund, the Fundamental Research Funds for the Central Universities (Project NO. 3332016002). Pathology Research Centre of the China Academy of Medical Sciences (Project No. 2016ZX310176-2)
Disclosure
All authors have declared no conflicts of interest.
Combination of immunotherapy with targeted therapies
- Lizza Hendriks (NL)
- Lizza Hendriks (NL)
177P - Clinicopathologic characteristics in large cell neuroendocrine carcinomas of the lung (LCNCL): The experience of one center
- Michael Vaslamatzis (GR)
- Michael Vaslamatzis (GR)
- Apostolos Laskarakis (GR)
- Theodoros K. Tegos (GR)
- Michail G. Pavlakis (GR)
- Theodoros Argyrakos (GR)
- Nektarios Alevizopoulos (GR)
- Charalambos Zoublios (GR)
- Edvin Vasili (GR)
- Ekaterini Gioti (GR)
- Kalliopi Athanasiadi (GR)
Abstract
Background
LCNCL is a newly recognized clinicopathologic entity, characterized by the cell morphology and the immunohistochemical evidence of neuroendocrine markers. The optimal treatment for LCNCL is not yet established. The aim of our study was to describe the clinicopathologic findings, the outcome and treatment toxicity in LCNCL patients (pts).
Methods
Twenty-five pts (4%), smokers (>40 pack/year), with LCNCL, among 585 with small cell lung cancer (SCLC), were admitted & treated consecutively in our Unit between 1/1996–12/2017. Patients’ characteristics are shown in the
Results
All pts received Cisplatin-Etoposide ± mediastinal ± cranial RT. Response Rate was documented in 20 (80%), median PFS was 8 (2-93+) months (mo) and OS 12 (4-93+) mo. In median follow up of 1 (1+−93+) mo, 22 (88%) died. Still alive are 3 (12%) patients. One (4%) patient, pT2N2 IIIA underwent left upper lobectomy & then received adjuvant chemotherapy + mediastinal RT + prophylactic cranial irradiation (PCI). He is still alive after 93+ mo. The other 2 with stages IIIA and IV with limited bone disease are in very good partial response for 33+ and 36+ mo. The mPFS and mOS for stages ≤ IIIA and IIIB + IV are 9 vs 3 and 16 vs 6 mo. Grade III & IV febrile leukopenia, thrombocytopenia & anemia had 4, 2 and 2 patients respectively.
| No of pts | 25 |
| Median (m) age | 66 (33–77)ys |
| Men/Female | 19/6 |
| ECOG | |
| 0 | 4 (16%) |
| 1 | 14 (56%) |
| 2 | 3 (12%) |
| 3 | 4 (16%) |
| 4 | 0 (0%) |
| Histology | |
| pure LCNCL | 21 (84%) |
| Mixed LCNCL-SCLC | 4 (16%) |
| cStage | |
| Ib | 1 (4%) |
| IIa | 1 (4%) |
| IIb | 1 (4%) |
| IIIa | 4 (16%) |
| IIIb | 1 (4%) |
| IV | 17 (68%) |
| Ki-67 (%) | 60 (40–90%) |
| NSE (+) | 25 (100%) |
| TTF-1 (+) | 24 (96%) |
| Chromogranine/Synaptophysin (+) | 24 (96%) |
| CK7 (+) | 25 (100%) |
| CD56 (+) | 25 (100%) |
Conclusions
(1) LCNCL is an unusual type of lung carcinoma with strong correlation with smoking. (2) Surgery seems to be beneficial for early stage disease, but on it's own it doesn't appear to be sufficient & adjuvant chemotherapy consisting of Cisplatin/Etoposite±RT is considered mandatory.
Legal entity responsible for the study
Vaslamatzis Michael Head of the Oncology Department Evangelismos General Hospital
Funding
Has not received any funding
Disclosure
All authors have declared no conflicts of interest.
Clinical oncologist’s perspective on biomarker testing by next generation sequencing
- James Chih-Hsin Yang (TW)
- James Chih-Hsin Yang (TW)
232TiP - Lanreotide autogel/depot in lung neuroendocrine tumours: The randomized, double-blind, placebo-controlled, international phase 3 SPINET Study
- Xuan Mai Truong Thanh (FR)
- Xuan Mai Truong Thanh (FR)
- Diane Reidy-Lagunes (US)
- Matthew Kulke (US)
- Edward Wolin (US)
- Simron Singh (CA)
- Diego Ferone (IT)
- Dieter Hoersch (DE)
- Aude Houchard (FR)
- Martyn Caplin (GB)
- Eric Baudin (FR)
Abstract
Background
Treatment options for advanced lung neuroendocrine tumours (NETs) are limited. The phase 3 CLARINET study demonstrated antitumour efficacy of the somatostatin analogue (SSA) lanreotide autogel/depot (LAN) 120 mg/28 days vs. placebo for metastatic gastroenteropancreatic grade 1/2 (Ki-67 < 10%) NETs, but prospective data on SSAs in advanced lung NETs are lacking. This study evaluates antitumour efficacy and safety of LAN 120 mg in patients with advanced lung NETs.
Trial design
SPINET is a large double-blind, placebo-controlled phase 3 study. Main inclusion criteria are adults with well-differentiated typical/atypical, metastatic and/or unresectable lung NETs, at least one measurable lesion on CT/MRI imaging (RECIST v1.1), positive somatostatin receptor imaging, ECOG PS0–1. Patients have a maximum of two previous courses of cytotoxic chemotherapy, molecular-targeted therapy or interferon. A total of 216 patients from 80 sites across the USA, Canada and Europe will be randomized 2:1 to either LAN 120 mg/28 days or placebo, both with best supportive care, until progressive disease (PD)/death or unacceptable toxicity. Patients experiencing PD on placebo may opt to receive LAN 120 mg in an open-label extension. All patients experiencing PD will be followed to document survival, quality-of-life (QoL) and subsequent treatment. Recruitment began in July 2016. The primary endpoint is progression-free survival (PFS, time from randomization to PD/death; central review, RECIST v1.1). Main secondary endpoints include, objective response rate, overall survival, time to treatment failure, change in chromogranin A, QoL, and safety. SPINET is the first prospective randomized trial designed to assess LAN 120 mg in typical/atypical carcinoid lung NETs.
Clinical trial identification
NCT02683941; EudraCT: 2015-004992-62
Legal entity responsible for the study
Ipsen
Funding
Ipsen
Disclosure
X-M. Truong Thanh, A. Houchard: Employee of Ipsen. D. Reidy-Lagunes: Honoraria from Novartis; Consultancy and speakers’ bureau fees from Ipsen, Novartis, and Pfizer; Research funding from Novartis. M. Kulke: Consultancy fees from Ipsen, and Novartis. E. Wolin: Consultancy and advisory fees from Ipsen, and Advanced Accelerator applications. D. Ferone: Renumeration for services from Novartis, Ipsen, and Pfizer. D. Hoersch: Fees from Lexicon; Grants, personal fees and other from Novartis, Ipsen, and Pfizer. M. Caplin: Honoraria, consultancy and speakers’ bureau fees from Ipsen, Advanced Accelerator Applications, and Novartis. E. Baudin: Remuneration for services (advisory board or board of directors; corporate-sponsored research; consulting fee; research investigator; speaker) from Ipsen, Novartis, Pfizer, and Advanced Accelerator Applications. All other authors have declared no conflicts of interest.
16P - Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression
- Chen Qinnan (CN)
- Chen Qinnan (CN)
- Wang Zhaoxia (CN)
Abstract
Background
Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD (lung adenocarcinoma) remains unknown.
Methods
Quantitative reverse transcription PCR (qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24 (interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24.
Results
LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD.
Conclusions
Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.
Legal entity responsible for the study
The Second Affiliated Hospital of Nanjing Medical University
Funding
National Natural Science Foundation of China (No. 81472198), the Key Clinical Medicine Technology Foundation of Jiangsu Province (No. BL2014096), the Medical Innovation Team Foundation of the Jiangsu Provincial Enhancement Health Project (No.21), “333 high class Talented Man Project” (No. BRA2016509)
Disclosure
All authors have declared no conflicts of interest.
38P - Survival of lung cancer: Bangladesh perspective
- Rahnuma Parveen (BD)
- Rahnuma Parveen (BD)
- Parveen S. Akhtar (BD)
- Nazrina Khatun (BD)
- Md J. Islam (BD)
Abstract
Background
Lung cancer, the most common and the leading cause of cancer death in the world, is increasingly being recognized in Bangladesh. Comprising one third of all male cancers, it is mostly presented at later stages. This study aimed at finding out the survival of lung cancer patients and also the important prognostic factors behind survival who were registered and treated in National Institute of cancer Research & Hospital.
Methods
This study was done from Jan 2012 to June 2015 at Dept. of Medical Oncology, NICRH. The lung cancer patients attending NICRH in two years (from Jan 2012 to Dec 2013) were selected. After thorough evaluation, symptomatic and supportive management as well as chemotherapy and/or radiotherapy were given on priority basis. The patients were followed up every 4–8 weekly up to survival or maximum 42 months whichever was earlier. The patients were assessed during each visit by clinical status, investigations and treatment response. All events of death were documented properly.
Results
Out of 2264 lung patients who were registered and treated during the period of Jan'12 –Dec'13, 1067 were in contact and eligible for the study. The male female ratio was 4.2:1 (862 male and 205 female). Female patients were younger (mean age of male 58.24 years and female 52.18yrs), 80% of all cases belonged to poor and lower middle-class families with 54% illiterate and 26% had primary education. Their performance status was mostly ECOG grade 2 & 3 (>80%). Male patients were smokers (90%) and females were mostly betel nut and/or tobacco chewers (66%) and also smokers (27%). All cases were at stage III and stage IV diseases with 86% non-small cell carcinoma and 14% small cell carcinoma. About 50% patients survived six months. One year survival of all cases was 27%; female 32% and male 25%. Mean survival of male and female patients was respectively 7.82 and 16.63 months. Survival of female patients was significant (P value-0.001) and survival of younger patients (<40 years) were also significant, 10.06 months (P value-0.001).
| Survival in months according to gender and age | |||
|---|---|---|---|
| Gender | Mean Survival Time (months) | 95% confidence interval | P-value |
| Male | 7.820 | 7.300–8.341 | 0.001 (HS) |
| Female | 16.638 | 14.153–19.124 | |
| Overall | 8.780 | 8.237–9.322 | |
| Age group | |||
| <=40 | 10.063 | 7.723–12.403 | 0.001 (HS) |
| 41–50 | 9.630 | 8.369–10.891 | |
| 51–60 | 9.481 | 8.527–10.435 | |
| 61–70 | 7.642 | 6.736–8.547 | |
| >70 | 6.171 | 4.944–7.399 | |
| Overall | 8.780 | 8.237–9.322 | |
Conclusions
Lung cancer patients mostly presented at advanced stage (inoperable), with poor performance status. After supportive, symptomatic and anticancer treatment (chemotherapy and radiotherapy), one year survival of lung cancer was 27%. Female and young age <40 years patients’ survival was significantly higher than male and aged patients (>40yrs).
Legal entity responsible for the study
Prof. Parveen Shahida Akhtar
Funding
Has not received any funding
Disclosure
All authors have declared no conflicts of interest.
58P - Co-treatment of trametinib (MEK inhibitor) with TPX-0005 (Src/FAK/JAK2 inhibitor) synergistic in KRAS mutant NSCLC cell lines and CDCP1 acts as a biomarker in KRAS mutant patients (p)
- Carles Codony-Servat (ES)
- Carles Codony-Servat (ES)
- MARIA Llanos Gil Moreno (ES)
- Jillian Bracht (ES)
- Ilaria Attili (IT)
- Chiara Lazzari (IT)
- Vanesa Gregorc (IT)
- Masaoki Ito (JP)
- Santiago Viteri (ES)
- Niki Karachaliou (ES)
- Rafael Rosell (ES)
Abstract
Background
KRAS mutant lung adenocarcinoma has a dismal prognosis. In the current study, we identified combination targets for trametinib, a MEK inhibitor, which acts downstream of KRAS to suppress signaling through MAPK cascade. However, we have previously shown that selumetinib (MEK inhibitor) in KRAS mutant NSCLC cells caused a rebound of ERK, AKT and STAT3, as well as YAP phosphorylation (Y357), NOTCH3 and activation of RTKs, AXL and MET. We hypothesize that, in KRAS mutant NSCLC, suppression of MAPK could lead to activation of Src-YAP1-AXL-MET. Since CUB domain-containing protein 1 (CDCP1) activates Src, we consider that CDCP1 could be a biomarker of Src activation.
Methods
Cell viability assay, colony formation assay and western blotting were performed to assess the treatment of trametinib plus TPX-0005 in a panel of 8 NSCLC cell lines: A549, Calu6, H23, H460, H2009, H2030, H441, H727. Synergy between trametinib and TPX-0005 was assessed via the Chou-Talalay method to estimate the combination index (CI). CI values <0.7 were considered synergistic, with decreasing CI values indicating greater synergy. We examined tumor samples of 32 KRAS mutant NSCLC p for CDCP1 mRNA levels.
Results
The combination of trametinib with TPX-0005 was synergistic or additive in all cell lines tested. H23 and Calu6 were the most synergistic, followed by H441 and H2030. In the majority of cell lines examined, the colony formation assay resulted in an almost complete abrogation of tumor cell colonies, particularly in the H23 and A549. Western blotting indicated that the combination of trametinib with TPX-0005 abolished the phosphorylation of STAT3 (Y705), paxillin (Y118), a readout of FAK, and Src (Y416). The median PFS of 32 KRAS mutant NSCLC p was 2.5 months and the overall survival was 13.4 months. According to CDCP1 levels, the median PFS was 3.5 months for those with low CDCP1 and 1.4 months for those with high CDCP1 (P = 0.012). The median survival was 16.3 months for p with low CDCP1, and only 3.2 months for those with high CDCP1 (P = 0.023).
Conclusions
The combination of trametinib plus TPX-0005 shows significant in-vitro activity in the majority of KRAS mutant NSCLC cell lines and the mRNA levels of CDCP1 could be a biomarker in KRAS mutant NSCLC p, indicating the activation of Src-YAP signaling. Clinical trials with the combination of MEK inhibitors with TPX-0005 are warranted.
Legal entity responsible for the study
IGTP, Germans Trias i Pujol Research Institute, Badalona, Barcelona, Spain
Funding
Fundació Obra Social “La Caixa”
Disclosure
All authors have declared no conflicts of interest.