bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective evaluation of locally advanced thymoma and thymic carcinoma: Factors influencing the prognosis after local treatment modalities.
Authors: Yalçintas Arslan Ülkü , Geredeli Caglayan , Özdemir Nuriye , Ciltas Aydin , Sonmez Ozlem , Kucukoner Mehmet , Karaca Halit , Gok Durnali Ayse , Boruban Melih Cem , Zengin Nurullah , Buyukberber Suleyman , Suner Ali , Seker Mesut , Alkis Necati , Oksuzoglu Omur Berna 
Published: March 2020

e18510 Background: Aim of the study was to determine the relationship between clinicopathologic characteristics and treatment modalities for locally advanced thymic malignancies(TM). Methods: We retrospectively reviewed medical records of 107 patients(pts) who treated from 1992 to 2012 in medical oncology service of 7 tertiary hospital. 21 pts who presented metastatic disease and 31 pts who had early stage at the time of diagnosis were excluded. Results: A total of 55 patient’s data were analyzed. Median age was 46(17-73) years. Median follow-up was 33(1-103) months(mts). 65% of pts was male. Histopathologic diagnosis were as follows: thymoma type A-B2 ( TA-B2) 29 , thymoma type B3 (TB3) 10 and thymic carcinoma (TC) 16. 42 of pts underwent surgery, but total resection of the tumor have been achieved at only 28 pts(6 TC and 22 TA-B2 or TB3).30 pts have stage III diasease (mostly thymoma 23/30). 43 pts treated with mediastinal radiotherapy ( 21 adjuvant, 22 primary). A cisplatin containing regimen has been received 23 pts in the adjuvant setting. 31 pts were given as primary chemotherapy (ADOC, PAC and EP). Overall response rate was 81.6% with first-line chemotherapy. There was no apparent response in 3 pts(3/23) with thymoma and 4 pts(4/8) with TC. 20 pts have experienced a disease progression and 27 pts died ( 8 of these cases died from other unrelated causes). Median progression free survival was 45 (30-59)mts. Kaplan-Meier survival analysis estimated that overall survival of the pts with stage III disease were relatively longer than stage IVA ones, but it can not reach statistical significance (median 78 vs 45 mts,p=.11). Prognosis of TC pts were considerably worse than TB3 and TA-B2 (median 17 vs 45 vs 76 mts respectively,p=.01). Although there was no a statistical difference between pts who underwent total tumor removal and who did not, we have seen a trend toward better survival in pts who were suitable to triple modality therapy(median 79 vs 45 mts,p=.27). Conclusions: Cisplatin based chemo plus mediastinal radiotherapy may provide a chance of achieving a long-lasting remission in locally advanced TM. But, complete surgical removal of the tumor are still the mainstay of treatment.
ERCC1 as a predictor of response to induction therapy for stage III non-small cell lung cancer.
Authors: Marra Alessandro , Kemming Dirk , Krueer Thomas , Bosse Ulrich , Netchaeva Maria , Wagner Wolfgang , Koch Olaf M. , Vogt Ulf , Hillejan Ludger 
Published: March 2020

e18511 Background: Neoadjuvant platinum-based chemotherapy in stage III NSCLC offers the chance to eradicate occult metastases and decrease tumor volume, thus improving curative surgical resection rates. A remission after induction therapy is correlated with prolonged survival. However, only 40-50% of patients respond to therapy since there is still no validated predictor for the benefit of platinum based chemotherapy. As DNA repair mechanisms are related with resistance of lung cancer cells to platinum-based chemotherapy, aim of the study was to compare ERCC1 level in lymph node metastases with the degree of pathologic tumor regression after induction treatment and surgery. Methods: From July 2004 to June 2009, 46 NSCLC patients with clinically staged IIIA (N = 32) or IIIB (N = 14) NSCLC underwent at least two cycles of platinum-based induction chemotherapy and combined radio-chemotherapy. After restaging radical surgery was performed. ERCC1 was determined from pretreatment samples of metastatic nodes taken on mediastinoscopy. Real time RT-PCR assays were performed to determine ERCC1 mRNA expression. Tumor regression has been classified on surgical specimen using an score system ranging from grade I (pCR) to grade VI (non-responder). The samples were categorized into three groups according to their ERCC1 expression values and in two groups according to their chemotherapy response (either pCR or non-pCR). Results: A significant correlation between the ERCC1 expression level and the chance to achieve a pCR during a platinum-based chemotherapy could be demonstrated in our samples (P<0.05). Furthermore, the median overall survival in the pCR group was 44 vs. 29 month in the non-pCR group (HR 0.33 [95%-CI: 0.02-1.15]; P=0.06). However, no direct correlation between ERCC1 expression and local or distant metastasis formation could be found. Conclusions: Assessment of ERCC1 mRNA expression in pretreatment tumor tissue is feasible in the clinical setting and predicts response to platinum-based induction therapy. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to redefine induction protocols on an individual basis, thus enhancing response rates and perhaps outcome.
The relation between neutrophil lymphocyte ratio and survival in patients with small cell lung cancer.
Authors: Inanc Mevlude , Bozkurt Oktay , Kiziltepe Melih , Karaca Halit , Berk Veli , Duran Ayse Ocak , Ozkan Metin 
Published: March 2020

e18516 Background: Neutrophil-lymphocyte ratio (NLR) is not an only inflammation marker, but also used as a prognostic index of various malignancies. Small cell lung cancer (SCLC) is considered metastatic at time of diagnosis, and survival is quite short. There is no any study evaluating the relationship between NLR and survival in SCLC. In this study, we aimed to determine the effect of NLR on overall survival. Methods: The study included 200 patients with SCLC. Survival times of patients, clinicopathological data and the results of a complete blood count at diagnosis were evaluated from patient archive files retrospectively. Patients were randomized into two groups according to NLR 5< or 5≥. Results: The median age of patients was 56 (36-80) years. One hundred and eighty one (90.5%) patients were male and 19 (9.5%) were males. Sixty-eight (34%) patients had dyspnea, 36 (18%) of cases had cough, 22 (11%) patients had back pain, and 14 (7%) of the cases had chest pain. While the duration of symptoms longer than 3 months in 90 (45%) patients, 110 (55%) patients had symptoms shorter than 3 months. Seventy-two (36%) patients had limited disease, 128 (64%) patients had extensive disease at the time of diagnosis. Twenty-one (10.5%) patients had brain metastasis initially. The median neutrophil count was 5.46 (1.02-20.2) 103 µl, and the median lymphocyte 1.69 (0.27 to 21.9) 103 µl, and median NLR was 3.19 (0.04 to 37.63) respectively. NLR overall survival rate was lowering in patients with greater than or equal to 5 group (5 ≥ group=7 months, 5< group=10 months) (p = 0.004). Conclusions: NLR is an important prognostic index that emphasis on the relationship between cancer and host in SCLC. However, a blood test is cheap and easy to use. This study was concluded that survival was shorter in patients with NLR ≥ 5 in SCLC.
Preoperative serum CA125 as an independent predictor for recurrence and death in operable patients with non-small cell lung cancer.
Authors: Feng Jianguo , Xu Haiyan , Wu Hanmo , Luo Min , Mao Weimin , Su Dan 
Published: March 2020

e18520 Background: The role of serum CA125 in the prognosis of non-small cell lung cancer (NSCLC) remains controversial, especially in early stage patients. The aim of this study is to analyze the prognostic value of CA125 in operable NSCLC. Methods: We retrospectively analyzed 645 patients with non-small cell lung cancer (NSCLC) who underwent curative surgical resection for lung cancer at Zhejiang Cancer Hospital of China from 2006 to 2011. Micropartical enzyme immunoassay was used to measure preoperative serum CA125. Pearson’s chi test was used in univariate analyses and a multivariable proportional hazard Cox regression model was applied to assess the prognostic significance of the different covariates. Kaplan-Meier was used to analyze survival curve. Results: The positive rate of preoperative serum CA125 was 18.9% (126/667) in all patients, and elevated CA125 concentration was associated to poorly differentiated tumor and advanced clinical stage. Moreover, CA125 was closely related to patient outcomes. The Kaplan-Meier survival curves were shown patient with normal CA125 concentration had significantly longer DFS (median DFS, not reach vs 21 months, p=0.000) and OS (median OS, 61 vs 29 months, p=0.000) than those with positive CA125. Multivariate Cox analysis indicated patients with positive CA125 had an elevated risk of disease recurrence or death compared with those who had negative one. The adjusted hazard ratio (HR) was 1.74 for replase (95% confidence interval [CI], 1.25-2.41, p=0.001) and 1.79 for death (95% CI, 1.34-2.41, p=0.000) after adjusted by age, gender, grade, stage, histology and smoking status. Conclusions: CA125 seems to play an important role in disease progression and it may be an independent predictive marker for prognosis in patients with NSCLC. [Table: see text]
Effect of the load versus capacity unbalance on the sensitivity of malignant pleural mesothelioma cells to proteasome inhibitors.
Authors: Jocolle' Genny , Numico Gianmauro , Cerutti Fulvia , Laura Oliva , Cenci Simone , Donati Giovanni , Cascio Paolo 
Published: March 2020

e18522 Background: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that originates from the mesothelium of the pleural cavities. Due to its resistance to all chemotherapies available, news therapies against MPM are urgently needed. Bortezomib is a potent Proteasome Inhibitors (PI) that induces apoptosis in different cancers and it was recently approved for treatment of Multiple Myeloma (MM). Since in MM an unbalance between a reduced proteasomal activity (capacity) and an increased proteins degradation (load) was shown to determine apoptotic sensitivity to PI, we challenged this paradigm also in MPM. Methods: Four different MPM (MM98, REN, MMB, MSTO) and a normal (TERT) pleural lines were treated with increasing doses (from 1 to 1000 nM) of Bortezomib and after 24h apoptosis was assessed by flow cytometric analysis of AnnexinV and propidium iodide positive cells. Levels of polyubiquitinated proteins were evaluated by immunofluorescence microscopy and western blotting with the specific monoclonal Ab Fk2 (BIOMOL International). The three main proteasome activities were measured in continuoin cellular extracts at 37°C with a Carry Eclipse spectrofluorometer (Varian, Palo Alto) by means of specific fluorogenic substrates (Suc-LLVY-amc, Bz-VGR-amc, Suc-YVAD-amc). Results: The sensitivity towards Bortezomib greatly differs between the 5 pleural lines analyzed. Specifically the EC50value was higher for the TERT line (130 nM) while for MPM lines ranged between 17 nM (MM98) and 71 nM (MSTO). Importantly, for all the 5 lines analyzed enhanced sensitivity to Bortezomib perfectly correlates with increased levels of ubiquitinated proteins and reduced proteasome specific activity. Conclusions: Our results prove that MPM lines are significantly more sensitive towards the pro-apoptotic effect of Bortezomib than normal pleural cells. Moreover, as in MM, also in MPM PI-sensitivity stems from an unbalance of the load/capacity ratio. Our data, therefore, establish a rationale for the use of Bortezomib (and new second generation PI) in MPM and indicate that combinatorial therapies with other drugs active on the proteostasis network (like HSP inhibitors) might be highly effective against this cancer.
Prognostic factors affecting survival in malignant pleural mesothelioma.
Authors: Komurcuoglu Berna Eren 
Published: March 2020

e18535 Background: Determining the pre-treatment prognostic factors in malignant pleural mesothelioma (MPM) is of importance in terms of both estimating the course of disease and determining the patients who are candidate to multimodal therapy. Aim of the current study was to determine the prognostic factors affecting survival in the patients with MPM. Methods: One hundred and twenty five patients who had been diagnosed histologically as having MPM over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC), serum lactate dehydrogenase (LDH) values, their histology, performance scores and stage of disease were examined. Results: Advanced clinical stage, N2 nodal involvement and presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be poor prognostic factor independently of other factors. Conclusions: We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate multimodal treatment and estimating the prognosis.
Prediction of skip mediastinal lymph node metastasis in surgical patients with clinical N0 non-small-cell lung cancer.
Authors: Nakahara Rie , Suzuki Haruko , Matsuguma Haruhisa , Igarashi Seiji 
Published: March 2020

e18554 Background: It has been reported that the prognosis of surgical non-small-cell lung cancer (NSCLC) patients with skip-N2 metastasis (without hilar lymph node metastasis) is generally more favorable than that of those with pathological N2 disease. Therefore, when a surgeon determines whether to perform mediastinal lymph node dissection, it is important to accurately predict skip-N2 metastasis in surgical patients without hilar lymph node metastasis. Methods: Of the patients who had undergone complete resection for NSCLC in our hospital between October 1986 and December 2010, 741 with cN0 NSCLC who had undergone mediastinal lymph node dissection were analyzed. The relationship between the lymph node metastasis status and clinicopathological parameters (age, gender, and serum CEA level, histological type, primary tumor location, tumor diameter, pleural invasion(pl), lymphatic invasion(ly), vascular invasion(v)) was analyzed, and factors that predict differences between pN0 and skip-N2 patients were identified. Results: Of the 741 patients, 609 had pN0 disease, 62 pN1 disease, and 70 pN2 disease. Of the pN2 patients, 23 had skip metastases to the mediastinal nodes alone. No significant difference was observed in the gender, age, or histological type between the N0 and skip N2 groups. However, the serum CEA level, tumor diameter, and pl(+) rate were significantly higher (p=0.0028), larger (mean, 3.7 cm, p=0.012), and higher (p=0.0064), respectively, in the skip-N2 group. Also, the ly(+) and v(+) rates were significantly higher in the skip-N2 group. Skip-N2 appeared more frequently with primary tumors in the lower lobes than with those in the upper lobes. Conclusions: Even if no hilar lymph node metastasis is found during surgery in patients with a high serum CEA level, large tumor diameter or lower lobe location, they may have skip-N2 lymph node metastasis. Although the p factor status becomes clear after surgery, patients with pleural indentation so marked as to raise the suspicion of pl(+) have a high probability of skip-N2 metastasis. Mediastinal lymph node dissection is preferable in these patients.
Significance of EGFR and KRAS gene mutation in small cell lung cancer.
Authors: Kurokawa Koji , Matsui Tomoharu , Ikeda Hideko , Nishikawa Shingo , Sone Takashi , Kasahara Kazuo 
Published: March 2020

e18564 Background: In non-small cell lung cancer, epidermal growth factor receptor (EGFR) and KRAS are known as driver mutations. However the association between these gene alteration and small cell lung cancer (SCLC) has been unclear. The aim of this study is to investigate the gene status of EGFR and Kras in SCLC. Methods: This retrospective study included 66 SCLC patients with available tumor tissue from primary lung tumor or metastatic and clinical data including survival. We evaluated for the presence of EGFR and KRAS mutation those patients using Scorpion-ARMS method. This study was approved by IRB. Results: Sixty-six patients (52 male,14 female median age 68 range 49-89, LD/ED 34/32, PS0-1/2-3 57/9, smoker/never smoker 64/2) were evaluated. Their median overall survival (OS) were 484 days, progression-free survival (PFS) were 217 days. Sixty-six samples were evaluated EGFR mutation test and 61 were evaluated KRAS mutation test by Scorpion-ARMs methods. SCLC patients with EGFR mutation were the only one patients (1.5%,1/66). KRAS mutation were also the only one patients (1.6%,1/61). A 54 years-old nevere-smoker female was already treated with EGFR tyrosine kinase inhibitor for non-small cell lung cancer, the patients with EGFR mutation had a transformation into SCLC. The KRAS mutation patient was combined SCLC with adenocarcinoma. Conclusions: This study suggested that EGFR and KRAS patients associated with SCLC is poor, these driver mutation is unnecessary for common SCLC.
Potential impact of different methodologies for detecting EGFR mutations in selecting chemotherapy for patients with lung cancer.
Authors: Bender Ryan P. , Ghazalpour Anatole , Tan Zheng , Gatalica Zoran , Paul Les , Reddy Sandeep K. , Castro Michael 
Published: March 2020

e19006 Background: Mutation analysis of the kinase domain of EGFR (exons 18-21) is a standard recommended procedure for patients diagnosed with non-small cell lung cancer (NSCLC). NSCLC patients whose tumor harbors certain EGFR mutations have notable responses to EGFR inhibitors. Several different methodologies are available as published assays or commercially available kits and include Sanger Sequencing, allele specific PCR (ASP) and restriction fragment length polymorphism (RFLP). Differences in the design of these three assays dictate which clinically relevant mutations will be detected. Methods: Sanger Sequencing of EGFR found 518 potentially clinically actionable mutations and 45 variants of unknown significance of the 4307 samples tested. To assess which clinically relevant EGFR mutations will be detected by the ASP and RFLP, we performed an in silico analysis of all observed mutations against the design specification of the ASP and RFLP assays. The RFLP assay used in this assessment was developed in our laboratory and is designed to detect all G719 mutations, all exon 19 deletions, all exon 20 insertions and the specific mutations T790M, L858R, L861R and L861Q. A commercially available ASP kit designed to detect 29 mutations in the kinase domain was also analyzed in this study. Results: Based on the performance characteristics assumed by the RFLP and ASP assays, the analytical sensitivities for detecting clinically actionable mutations of the two methodologies are 98.8% and 86.7% respectively, when compared to Sanger Sequencing. It is notable that the RFLP assay missed the S768I mutation (0% detected) whereas the assay did not detect some G719 mutations, exon 19 deletions, and exon 20 insertions (76.3, 86.6 and 35.3% detected respectively). Conclusions: Sequencing is still the preferred method of mutation detection in EGFR for NSCLC as it is the most comprehensive. However, if tumor nuclei are limited a more sensitive method than sequencing is required; EGFR mutation detection by RFLP would identify more of the potentially clinically relevant mutations than ASP. The ASP method would produce false negative results in 13.3% of patients expected to respond to EGFR inhibitors.
Clinical application of targeted deep sequencing for predicting responsiveness to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in never-smoking lung adenocarcinomas (NSLA).
Authors: Han Ji-Youn , Lee Yeon-Su , Lee Geon Kook , Hwang Jung-Ah , Hong Seung-Hyun , Yoon Sung Jin , Lee Jin Soo 
Published: March 2020

e19019 Background: Most patients with EGFR-mutant lung adenocarcinoma response well to EGFR-TKIs. However, a subset of patients showed primary resistance to EGFR-TKIs. The routine conventional methods have limitation in predicting primary resistance among EGFR mutant lung cancers. We performed targeted deep sequencing to explore the accuracy and additional values in predicting responsiveness to EGFR-TKIs in NSLA. Methods: We performed direct sequencing to identify EGFR mutations in 48 NSLA received gefitinib or erlotinib for their recurrent advanced disease after surgery. The peptide nucleic acid (PNA) clamp polymerase chain reaction (PCR) was used to confirm the EGFR mutation status. To exclude well known causes of resistance, we analyzed KRAS, BRAF and PIK3CA mutations by PNA clamp PCR, ALK rearrangement by FISH, and RET and ROS-1 rearrangements by reverse transcriptase (RT)-PCR and quantitative real-time PCR. After screening, Ion Torrent Personal Genome Machine (PGM) was performed in 31 patients harboring EGFR exon 19 deletions (19DEL) or L858R mutations or none of above molecular changes. Results: The conventional screening found 25 EGFR mutations (10 19DEL; 9 L858R, 1 G719X, 4 double EGFR mutations, 1 concomitant L858R and PIK3CA mutations), 4 KRAS mutations, 3 ALK, 2 RET and 2 ROS-1 rearrangements. No mutation was found in 12 patients. After screening, samples were divided into 4 groups; 1) good responders to EGFR-TKIs with only 19DEL or L858R (n=15); 2) non-responder to EGFR-TKI with only 19DEL or L858R (n=4); 3) non-responders to EGFR-TKI without any mutation (n=8); 4) stable disease to EGFR-TKI without any mutations (n=4). With PMG, all conventionally detected mutations were confirmed, and some additional mutations were detected in a subset of samples; two KRAS and one PIK3CA mutations in group 3, one concomitant PIK3CA and L858R mutations in group 3, one PIK3CA mutation in group 2, and one 19DEL mutation in group 4. Conclusions: Targeted deep sequencing may improve the detection of clinically actionable genomic alterations and enable mutation-driven personalized approach in lung cancer patients.