bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of advanced NSCLC patients with at least 6 months erlotinib treatment duration in Czech Republic.
Authors: Coupkova Helena , Skrickova Jana , Hejduk Karel , Zbynek Bortlicek , Kadlec Bohdan , Salajka Frantisek , Pesek Milos , Kolek Vitezslav , Koubkova Leona , Sixtova Dimka , Zatloukal Petr , Roubec Jaromir , Zemanova Milada , Vyzula Rostislav , Spelda Stanislav 
Published: March 2020

e18062 Background: Erlotinib is approved for NSCLC treatment in Czech Rep since 2005. This analysis was performed to analyze the profile of pts treated with erlotinib longer than 6 months. Methods: This retrospective analysis evaluates data from Czech Tarceva Registry of pts treated outside clinical trials. Survival (mOS, mPFS) was evaluated by the Kaplan-Meier method, survival comparison was performed by Log Rank test. Results: Up to October 2011, 430 out of 2121 pts with completed data in registry were treated with erlotinib for 6 months and longer. Median age 65 years, 54.4% men; 29.8% smokers, 37.9% former smokers, 32.3 % non-smokers; 77% pts ECOG PS 0-1. 74.7% stage IV pts, 21.4% stage IIIB. 43.5% adenoca, 31.9% squamous ca,11% non-specific NSCLC, 6% bronchioloalveolar ca. Erlobinib administered as 1st line treatment in 13% pts, 2L in 50.9%, 3L in 34.9%. Till October 2011, 322 pts (74.9%) finished the treatment, 108 pts (25.1%) still on erlotinib therapy. Treatment discontinued due to progression in 75% pts, death in 15%, toxicity in 3%. The entire group results (n=430): CR in 2.3%, PR in 17.7%, SD in 65.8%, PD in 2.6%. mPFS and mOS from erlotinib initiation 12.4 and 21.4 months respectively. mOS from diagnosis was 43.5 months. Statistical difference in mOS (from the erlotinib initiation) was observed between groups with PS ECOG 0-1 and PS 2-3, 22.0 vs 16.4 months (p=0.001), although there was no difference in both groups in mPFS (12.9 vs. 10.6 months). mPFS and mOS in pts with adenoca (n=187) from erlotinib initiation 14.4 and 23.7 months respectively. mOS from diagnosis was 45.6 months. mPFS and mOS in pts with squamous ca (n=137) from erlotinib initiation was 11.3 and 17.6 months respectively. mOS from diagnosis was 42.2 months. Conclusions: This analysis documented good activity of erlotinib in both adeno and squamous cell carcinoma. The difference in mOS and mPFS between both groups was statistically significant when measured from erlotinib initiation (mOS: p= 0.017, mPFS: p=0.022), however not statistically significant when measured from the date of diagnosis (p=0.361). Patients with PS 0-1 have statistically significantly greater mOS than patients with worse PS (p=0.001).
Differences in utilization of ALK rearrangement FISH analysis and EGFR assay.
Authors: Lathan Christopher S. , Lynch Julie Ann 
Published: March 2020

e18067 Background: This study examined institutional and regional factors associated with use of ALK rearrangement FISH diagnostic test compared to the EGFR assay. Previous research presented at AACR Cancer Disparities conference illustrated substantial underutilization of the EGFR assay. Disparities existed in access by institutional and regional factors. Methods: We linked proprietary industry data for clinical diagnostic assays (EGFR mutation and ALK rearrangement) provided by Genzyme Genetics and Abbott Molecular to public datasets which provided institutional and regional characteristics of US hospitals. Individual orders were aggregated and summarized to the hospital. Each hospital’s Medicare provider number (known as the OSCAR number) was obtained and recorded. OSCAR number and zip code were used to link the proprietary and public datasets. Public datasets included Census files, CMS/NCI Provider of Service (POS) files, among others, all current as of 2011. Logistic and multiple regression analysis were conducted. Results: Initial analysis of data suggests higher utilization of the ALK rearrangement FISH analysis when compared to EGFR Assay. However, even with incorporation of both assays into clinical practice guidelines, significant institutional and regional differences existed in access to tumor tissue analysis. 7800 EGFR assay tests were sold in 2010. First 5 months post approval; approximately 12,000 Vysis tests were sold. A reasonable approximation of the testable population of NSCLC patients, given histology and tissue availability is approximately 114,000 patients. This suggests a 7% penetration rate for the EGFR mutation analysis and a 10% penetration rate for ALK rearrangement assay, though EGFR mutations have a 15% incidence rate compared to 5% incidence rate of EML-ALK4 rearrangement. Conclusions: Uptake of the ALK rearrangement assay is likely higher due to the linkage of crizotinib to the FISH diagnostic test. Utilization patterns show regional underutilization that could contribute to disparities.
Evaluation of relationship between progression-free survival and overall survival in first-line treatment of advanced non-small cell lung cancer.
Authors: Buzoianu Manuela , Hong Dr Shengyan , Shi Li , Viner Jaye 
Published: March 2020

e18073 Background: There is increasing interest in assessing progression-free survival (PFS) as a potential surrogate for overall survival (OS) in many tumor types. However, such an assessment has yet to be adequately performed for non-small cell lung cancer (NSCLC). We assessed the relationship between 1st line treatment effects on PFS or OS in advanced NSCLC utilizing published data from clinical trials. Methods: The estimated PFS hazard ratio (HR) and OS HR from 43 randomized trials published between 2000 and 2010 were used to estimate Pearson correlation coefficient and to model the linear relationship between PFS HR and OS HR. Three approaches were considered in fitting the linear model, reflecting different ways of handling the variability of HR estimates used in the model fitting. The analysis was performed on add-on trials and head-to-head trials separately as well as jointly. Results: For add-on trials, the Pearson correlation coefficient r was 0.831 based on the observed HR data weighted by trial size. The R2 was 0.791 for the linear model after Bayesian adjustment of variability in the observed HR data. All showed strong relationship between PFS HR and OS HR for add-on therapies. The relationship is weak for head-to-head therapy (r=0.288 and R2=0.202). The overall relationship, when jointly considering add-on and head-to-head therapies, is moderate (r=0.653 and R2=0.577). Conclusions: Our analysis supports the use of PFS as a reasonable surrogate for OS if an add-on therapy is developed, but not if a head-to-head therapy is developed as 1st line treatment of advanced NSCLC.
Comparison of bevacizumab versus pemetrexed in combination with platinum-based doublets in first-line treatment of advanced non-small cell lung cancer.
Authors: Pereira Augusto Akikubo Rodrigues , Martins Sandro José , Lessa Rafael Costa , Pinto Flavio Augusto Ismael , Gagliato Debora De Melo , Santos Elizabeth S. , Rodrigues Newton Augusto Ferreira , Freitas Paulo Henrique Aires , Padua Fernando Vidigal , Alves Marclesson S. , Lima Geraldine Eltz , Fanelli Marcello Ferretti , Rinck Jose A. , Dettino Aldo A. , Nicolau Ulisses Ribaldo , Pereira Jose Rodrigues , Cruz Marcelo Rocha De Sousa , Lima Vladmir C. 
Published: March 2020

e18078 Background: First-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with platinum-based doublets, including pemetrexed (P) or bevacizumab (B), has achieved more than 12 months of survival. At the moment, there are no phase III head-to-head comparisons of these combinations. Methods: We retrospectively analyzed, from 05/2007 to 02/2011, in a single institution, all pts with stage IIIB or IV nonsquamous NSCLC treated with B or P combined with platinum compounds in first-line treatment to determine differences in OS, PFS, ORR and toxicity. We performed multivariate analysis to identify prognostic factors for survival. Results: Of the 82 pts included, 40 pts (48,8%) received carboplatin/paclitaxel or cisplatin/gemcitabine combined with B (BEV group), while 42 pts (51,2%) received cisplatin or carboplatin combined with P (PEM group). BEV had significantly fewer pts with age > 70 years (p=0,01) and CNS metastases (p<0,001) than PEM. Maintenance therapy was administered in 65,0% and 52,4% of pts in BEV and PEM groups, respectively (p=0,17). Significantly more pts in BEV received second-line treatment (72,5% vs. 52,4%; p=0,04) than in PEM, prevailing P as drug of choice (79,3%). ORR (60,0% vs. 35,7%; p=0,04) and median survival (26,4 vs. 16,4 months; p=0,009) were significantly superior for BEV. Median PFS were not different between BEV and PEM (10,5 vs. 7,7 months; p=0,06). In multivariate analysis, ECOG 2 (p=0,005), bone (p=0,01) and adrenal metastases (p=0,005) were independent prognostic factors for worst survival, while treatment with BEV did not reach statistical significance (p=0,07). Grade 3-4 neutropenia (27,5% vs. 9,5%; p=0,03) and neuropathy (17,5% vs. 0%;p=0,005) were more frequent in BEV. Conclusions: First-line treatment of advanced nonsquamous NSCLC patients with platinum-based doublets combined with B resulted in better ORR and higher rate of toxic effects as compared with P-based regimens. ECOG 2, bone and adrenal metastases were independent prognostic factors for poor survival. Although there was a survival benefit at univariate analysis, use of B combination was not an independent prognostic fator.
KRAS mutation in lung cancer patients: A poor prognostic factor but not a predictive factor of EGFR-TKI and chemotherapy?
Authors: Guan Jilin , Zhong Wenzhao , An Shejuan , Su Jian , Chen Zhihong , Huang Ying , Huang Zhimin , Zhang Xuchao , Yang Jinji , Wu Yi Long 
Published: March 2020

e18090 Background: At present, prognostic and predictive value for KRAS mutation in lung cancer patients remains to be controversial. Biases in disease stage, treatment regimens and small scale patient population led to inconsistent results in previous studies. Methods: we collected 91 consecutive lung cancer patients with KRAS mutation detected in Guangdong Lung Cancer Institute from January 2007 to may 2010. And each patient with mutant KRAS was paired randomly to a patient with KRAS/EGFR wild-type and a patient with mutant EGFR according to the identical TNM stage. All patients were followed up for treatment regimes, tumor response, progression-free survival (PFS) and overall survival (OS). Results: The patients with KRAS mutation were associated with a significantly shorter overall survival compared with patient without KRAS mutation (P=0.0005), and the same trend of disease free survival was also found in R0 resected lung cancer patients (P=0.039). Multivariate analyses proved the status of KRAS mutation was an independent prognostic factor (HR=2.69, 95%CI: 1.91-3.80, P=0.0005). No difference was found in PFS and tumor response between the first or second line EGFR-TKI treated patients harboring KRAS mutation and KRAS/EGFR wild-type (The first line: P=0.23, 0.82; The second line: P=1.00, 0.48). In the first and second line chemotherapy, there was no significant difference for PFS among the three groups (P=0.15, 0.52). Conclusions: KRAS mutation was a poor prognosis factor, but not an independent predictive factor for EGFR-TKI and chemotherapy in lung cancer patients. EGFR wild-type is major reason for resistant to EGFR-TKI in patients with KRAS mutation.
Survival patterns by line of treatment of stage IIIb/v NSCLC patients from community U. S. oncology practice.
Authors: Chaugule Shraddha , Foltz Boklage Susan H , Kreilick Charles , Sullivan Sean D , Ramsey Scott David , Haislip Sally , Gilmore James W. , Szabo Stephen , Sarma Syam , Asche Carl V , Seal Brian S. 
Published: March 2020

e18097 Background: Lung cancer is the most common cause of cancer-related death in men and women worldwide. 80% of the lung cancer patients are diagnosed with NSCLC. Patients have varying survival results from multiple lines of treatment. The objective of this study was to evaluate in a real world context, treatment patterns with survival, and the impact of adding a third line of chemotherapy to a stage III/IV NSCLC population. Methods: The Georgia Cancer Specialist database (2005-2011) was used. Patients with stage III or IV primary NSCLC and treated with chemotherapy were followed from initial NSCLC diagnosis until death, study end or lost to follow-up. Patients were stratified into lines and type of protocol for treatments. Kaplan-Meier curves were used to compare the overall survival results between lines of therapy. Results: A total of 291 patients with advanced NSCLC were identified and included in the primary analysis. Of these, 40 patients received third line therapy. The most commonly used treatment regimens in third line were Pemetrexed with 11 patients (3.8%), Docetaxel with 10 patients (3.4%), Gemcitabine with 4 patients (1.4%), Vinorelbine with 3 patients (1%) Cisplatin/Gemcitabine/Bevacizumab with 2 patients (0.7%). No single treatment regimen was predominantly used in third line. No association of survival gain was seen in patients who received third line therapy over those who received second line therapy (Log-Rank test P=0.4926) Conclusions: In a large EMR physician practice based database of advanced NSCLC patients, we failed to find a difference in the median overall survival of patients who received third line therapy compared to those who received second line therapy. Limitations include a small sample size and no standardized timing of diagnosis and treatment. The lack of a standard of care in third line therapy necessitates the need of further randomized controlled clinical studies to establish a benefit for a particular combination.
Is conventional chemotherapy effective in advanced sarcomatoid lung cancers?
Authors: Vieira Thibault , Cazes Aurelie , Pierre Bonnette , Zemoura Leila , Monnet Isabelle , De Cremoux Hubert , Chouaid Christos , Duruisseaux Michael , Giroux Leprieur Etienne , Belmont Laure , Lavole Armelle , Cadranel Jacques , Wislez Marie 
Published: March 2020

e18102 Background: Sarcomatoid lung cancers (SC) are associated with poor prognosis. A few studies suggest that these tumors are resistant to platinum-based chemotherapy. Methods: Between January 1994 and October 2011, all consecutive patients with SC were screened from six French centers. Patients with advanced disease and treated with first-line chemotherapy were included in this study. Clinical data, staging (TNM 2009 classification), drugs and response to chemotherapy (RECIST 1.1) at first tumor assessment were reported. Factors associated with progressive disease (PD) in univariate (p<0.2) were included in multivariate analysis. Results: 111 patients with SC were screened. 51 had advanced stage and were treated by a first-line chemotherapy. Among them, 27 (53%) had initial advanced disease and 24 (47%) had relapse after radical surgery or radiotherapy. Patients were 60.7±3 years old, 69% were male, 86% smokers and 86% were symptomatic. PS was 0 (57%), 1 (39%) 2 (4%). Stages at the diagnosis were I (15.5%), II (13.5%), IIIA (20%), IIIB (6%), IV (45%). Histological subtype were pleomorphic (70%), pure sarcoma-like (20%) unspecified (6%), carcino-sarcoma (4%). 38 (75%) received a platinum based-combination and 13 (25%) a monotherapy. Drug given alone or combined with platin were gemcitabine (23%), navelbine (16%), placlitaxel (16%), docetaxel (12%), pemetrexed (9.8%), ifosfamide (9.8%), vepeside (4%) and others (11%). At first tumor assessment, PD and disease control rates were 71% and 29%, respectively. Median progression free survival was 2 months IC95% [1.3, 2.7]. Median overall survival was 6 months [3.2, 8.8]. In univariate analysis, age, gender, smoking status, numbers of metastatic locations, histological subtypes, monotherapy vs platin-based combinations, relapse after radical treatment vs initial advanced disease were not associated with PD. In multivariate analysis, initial advanced disease was the only independent factor of PD (OR 4.59 [1.17, 18] p=0.03). Conclusions: Our series confirm that advanced SC are refractory to conventional chemotherapy. Molecular characterizations are needed to improve therapeutic strategy.
Assessment of EGFR mutations in patients diagnosed of squamous non-small cell lung cancer (NSCLC).
Authors: Lobo Francisco , Domine Manuel , Rojo Federico , Izarzugaza Yann , Leon Ana , Casado Victoria , Fernandez-Acenero Maria Jesus , Rubio Gustavo , Martin-Valades Jose Ignacio , Arranz Juan Luis , Serrano Gloria , Carames Cristina , Cordova Sharon , Madoz Juan , Zazo Sandra , Rincon Raul , Canadas Carmen , Perez-Gonzalez Nuria , Campos Angel , Garcia-Foncillas Jesus 
Published: March 2020

e18106 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better outcome to EGFR tyrosine kinase inhibitors than platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies with Caucasian patients have shown a prevalence of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in squamous-cell NSCLC patients from an area of influence of 500,000 habitants. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletion, 9 (50%) exon 21 mutations (7 L858R and 2 L861Q) and 3 (16.6%) cases exon 20 insertion. In the EGFR mutated population, 16 (88.88%) patients were diagnosed as adenocarcinoma and 2 (11.11%) as squamous cell carcinoma. The characteristics of these squamous cell cancer patients were: 2 male; 1 non-smoker, 1 former-smoker; 1 stage IV and 1 stage IB at diagnosis; one case exon 20 insertion and one exon 21 mutation (L858R). Conclusions: The EGFR mutation rate in squamous-cell NSCLC patients in our referral area is superior (11.17%) than previously reported, reinforcing the importance of including EGFR mutation testing in squamous-cell NSCLC population for selecting optimal therapy for these patients.
Statins (ASIs) may improve the outcome of erlotinib as second line treatment (tx) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC).
Authors: Maimon Natalie , Keizman Daniel , Gottfried Maya 
Published: March 2020

e18108 Background: The EGFR inhibitor erlotinib is a standard second line tx for mNSCLC. Statins are used in the tx of hyperlipidemia. Pre-clinical and clinical studies in several cancer types have shown that they may inhibit tumor growth. Their effect on the outcome of erlotinib as second line tx in mNSCLC is poorly defined. We aimed to study the effect of statins on the outcome of erlotinib as second line tx for mNSCLC. Methods: We performed a retrospective study of an unselected cohort of pts with mNSCLC, who were treated continuously with 150mg of oral erlotinib. Pts were divided into 2 groups: (1) statins users and (2) statins naive. The effect of statins use on objective response, progression free survival (PFS) and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chisquare test and partial likelihood test from cox model. Results: Between 2005-2011, 107 pts with mNSCLC were treated with second line erlotinib. There were 51 statins users (group 1) and 56 nonusers (group 2). All users started statins before erlotinib tx initiation. The groups were balanced regarding the following known clinical prognostic factors: female gender, ECOG performance status, active smoking, anemia, adenocarcinoma histology type, EGFR mutation (positive vs negative + unknown). Objective response in group 1 vs 2 was partial response (PR) 41% vs 29% (p=0.15), stable disease (SD) 41% vs 25% (p=0. 11), and progressive disease (PD) 18% vs 46% (OR=2.5, p=0.07). Median PFS was 12 vs 3 ms (HR 0.44 in statins users, p=0.02). Median OS was 35 vs 19 ms (HR 0.63, p=0.1). Conclusions: Statins may improve the outcome of pts with mNSCLC that are treated with erlotinib as second line tx. This should be investigated prospectively, and if validated, applied in clinical practice and clinical trials.
Chemosensitivity and clinical features of EML4-ALK-positive patients with advanced non-small cell lung cancer.
Authors: Park Jangchul , Kondo Chiaki , Shimizu Junichi , Horio Yoshitsugu , Yoshida Kimihide , Mitsudomi Tetsuya , Yatabe Yasushi , Hida Toyoaki 
Published: March 2020

e18145 Background: Lung cancers that harbor EML4-ALK can be effectively treated with anaplastic lymphoma kinase (ALK) inhibitors. Recent reports showed that pemetrexed-based therapy might be an effective treatment in patients with ALK-positive NSCLC. However, the efficacy of other regimens is still not known. The purpose of this study is to investigate the clinical characteristics, the efficacy of the cytotoxic chemotherapy in the first and second line setting in EML4-ALK positive NSCLC with advanced stage. Methods: EML4-ALK fusion was screened with RT-PCR and immunohistochemistry. When positive results were obtained with either method, gene rearrangement of ALK was confirmed with fluorescent in-situ hybridization. The clinical efficacy of chemotherapy was evaluated retrospectively. Results: We evaluated 20 EML4-ALK positive patients with advanced stage. Twelve patients were without a history of smoking, and 6 light smokers and 2 smokers. Seventeen (85%) of 20 had stage IV disease. Nine cases were male, and 11 were female. The mean age was 46.3 years (range, 26-79 years). Most of the CT findings at the primary site were masses or nodules, while two cases showed air-space consolidation. In the first line chemotherapy, most of the treatment regimens included carboplatin or cisplatin in combination with one or more therapeutic agents, such as taxans, bevacizumab except one case who was treated only by S-1. In 13 cases which were evaluable, 7/13 (53.8%) had a PR, 4/13 (30.8%) had SD, and 2/13 (15.4%) had PD. The treatment regimens in the second line setting included one therapeutic agent such as docetaxel, pemetrexed, S-1 or an oral ALK inhibitor. Among 10 evaluable cases in the second line setting, 2/10 (20%) had a PR, 5/10 (50%) had SD, and 3/10 (30%) had PD. Two patients who had a PR were all treated by oral ALK inhibitor. Within 7 patients who were treated by cytotoxic agents, none had clinical response. Conclusions: Our study suggests that EML4-ALK positive patients may show relatively favorable response to cytotoxic drug in the first line setting, but low response in the second line setting. These data might be helpful for further clinical trials including EML4-ALK positive patients.