bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment and outcomes of primary pericardial mesothelioma: A systematic review.
Authors: McGehee Elizabeth , Reisch Joan , Dowell Jonathan , Gerber David E. 
Published: September 2018

e20027 Background: Primary pericardial mesothelioma (PPM) is a rare cancer, for which there is no consensus on treatment. We performed a retrospective systematic review of recently published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Methods: Published literature from 2000-2016 was searched using the terms “primary pericardial mesothelioma”, “pericardial mesothelioma” and “malignant pericardial mesothelioma”. T-tests, Chi-square, and multivariable stepwise logistic regression were employed to correlate demographics, disease characteristics, and treatment with mortality. Results: We identified 6 case series and 84 case reports for a total of 103 PPM cases. Median age at diagnosis was 55; age range was 19 to 87. 39% were female and 61% were male. The mean time from diagnosis to death was 5.6 months. Tobacco exposure and asbestos exposure were reported in 15% and 25%, respectively. Neither exposure was predictive of mortality. 46% of patients underwent surgery, 8% received radiation, 37% received chemotherapy and 23% received no treatment. For 13% of patients, the treatment received, if any, was unknown. Radiation treatment was not associated with a mortality benefit (p = 0.54). A mortality benefit was seen for patients who had resection of their tumor (46% alive at last follow-up, p = 0.0061) but not in patients who had pericardiectomy (25% alive at last follow-up, p = 0.44). A mortality benefit was noted in those who received chemotherapy (p = 0.0022), specifically pemetrexed (p = 0.0038) or platinum agents (p = 0.003). Gemcitabine was not associated with a mortality benefit (p = 0.101). Conclusions: To the authors’ knowledge, this is the first comprehensive analysis of published PPM cases in the modern era. In this retrospective systematic review, a mortality benefit was seen with tumor resection and chemotherapy. Selection bias may account for some of this effect. However, given the inability to perform prospective studies in this population due to small patient numbers, it seems reasonable to offer surgical and medical therapy to eligible patients with PPM.
Age as a determinant of overall survival (OS) and progression free survival (PFS) in patients with stage III lung carcinoma: A Cleveland Clinic experience.
Authors: Seepana Jyothirmai , Mohapatra Suryanarayan , Khalid Sidra , Subramaniam Subanandhini , Spiro Timothy Peter , Daw Hamed , Haddad Abdo S. 
Published: September 2018

e20036 Background: Stage III NSCLC is defined as loco-regionally advanced disease due to primary tumor extension into the extra-pulmonary structures(T3 or T 4 ) or mediastinal lymph node involvement without evidence of distant metastasis. Methods: Retrospective study with 561 patients during study period 2003-2014. The most common method used for staging was contrast enhanced CT (97.5%) followed by PET(94.1%). The patients were further stratified into three subgroups < 65 years, 65-75 years and > 75 years. The overall median age was 66, and the median age for the groups was 57, 69and 79 years respectively. 33.9% patients received surgery; 43% patients received concurrent/sequential chemo-radiation, 7.8% patients received chemotherapy only, and 10.1% received radiotherapy only. In terms of type of chemotherapy, 21.4% had adjuvant chemotherapy, 8.8% had neo-adjuvant chemotherapy and 12.9% had both. 24.7% patients had target therapy and 3.7% had immunotherapy. The median survival was 57 months (95% CI). The two-year survival rate was 98% ± 0.7%, and the five-year survival rate was 47.3% ± 4.0%. 387 patients had relapsed. Relapse and death were both treated as PFS events, and the median PFS was 14 months (95%CI). The two-year PFS was 40% ± 0.23%, and the five-year PFS was 14.2% ± 1.7%. Results: see table. Conclusions: No difference was found for OS between < 65 versus 65-75 age groups, neither between 65-75 versus ≥75 age groups. PFS was not different between < 65 versus 65-75 age group. However PFS was marginally significantly different between 65-75 versus > 75 age groups (p = 0.088). [Table: see text]
Multiregion whole exome seuquencing of pre- and early neoplastic lung lesions.
Authors: Zhang Jianjun , Su Dan , Fujimoto Junya , Ying Lisa , Chow Chi-Wan , Sun Wenyong , Zhang Jianhua , Hu Jinlin , Behrens Carmen , Antonoff Mara , Ostrin Edwin Justin , Godoy Myrna , William William N. , Swisher Stephen , Lee J. Jack , Wistuba Ignacio Ivan , Hong Waun Ki , Futreal Phillip Andrew ,   Pre/Early Lung Neoplasm Study Team: Jaime Rodriguez Canales, Marcus Coyle, Curtis Gumbs, Jun Li, Latasha Little, Neda Kalhor, Xizeng Mao, Edwin R. Parra Cuentas, Xingzhi Song, Rebecca Thornton, Ara Vaporciyan, Annikka Weissferdt, Chang-Jiun Wu, Jiexin Zha
Published: September 2018

e20042 Background: The widespread use of CT for lung cancer screening and other reasons has resulted in a dramatic increase in the number of indeterminate ground glass opacities (GGOs). While many of GGOs can be resected with minimal morbidity, the cost has been called into question. Furthermore, multifocality is a relatively common, which makes decisions on extent of surgical resection and potential benefit less clear. Chemoprevention is a theoretically appealing approach to reduce lung cancer incidence and mortality. However, randomized trials have been disappointing to date. This may be due to the constellation of many factors including lack of reliable biomarkers to identify high-risk patients, lack of appropriate molecular targets and appropriate drugs because of our rudimentary knowledge on early carcinogenesis of lung cancers. It has been postulated that atypical adenomatous hyperplasia (AAH) represents preneoplastic lesion that can progress to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and further to frankly invasive adenocarcinoma (ADC). However, the biology of these lesions is poorly understood and the definition and management of these lesions remain controversial. Methods: Study on early carcinogenesis is hampered by the small size of lesions and challenge of obtaining longitudinal samples at different stages of disease progression. Multiregion sequencing can depict genomic events relative to molecular time with early events ubiquitously present in all regions and late mutations confined to spatially separated regions of lesions. Using this approach, our recent work has reported that 20/21 canonical cancer gene mutations were early genetic events. Results: With intent to delineate the pivotal molecular events driving early carcinogenesis of lung cancer, we have collected 154 resected GGOs with including AAH (N = 40), AIS (N = 39), MIA (N = 55) and ADC (N = 20) based on the IASLC/ATS/ERS classification from 89 patients including 38 patients presenting with multifocal GGOs and 18 patients carry more than one type of pathology. Two to five spatially separated regions from each of the 154 lesions are subjected to whole exome sequencing. Conclusions: The data will be ready to present at the meeting.
The PI3K-Akt signaling leads to synergy of erlotinib and crizotinib in wild-type NSCLC.
Authors: Rolfo Christian Diego , Van Der Steen Nele , Pauwels Patrick , Reclusa Pablo , Peters Godefridus J. , Giovannetti Elisa 
Published: September 2018

e20043 Background: Targeted therapies caused a revolution in treatment of non-small cell lung cancer (NSCLC). Response to Epidermal Growth Factor Receptor such as erlotinib, can be predicted by the presence of sensitizing mutations in EGFR. In case of cMET, amplification or exon 14 skipping serve as biomarkers for response to cMET-TKIs, crizotinib. Methods: In this study, we investigated the combination of erlotinib and crizotinib on several squamous NSCLC cell lines wild-type for EGFR and cMET. Growth inhibition was determined using the sulforhodamine B-assay. Combination indexes (CI) were calculated based on the method of Chou and Talalay. A CI below 0.8 was considered synergistic, between 0.8 and 1.2 was considered additive and above 1.2 was considered antagonistic. The influence of treatment on the cell cycle, cell migration, 3D cell cultures and phosphorylation was studied. Results: The H1703 cell line gave an antagonistic (CI = 1.20±0.15), the Calu1 (CI = 0.81±0.04), H520 (CI = 0.87±0.06) and SKMES1 (CI = 0.81±0.02) were additive and LUDLU (CI = 0.39±0.07) was synergistic. A G1 phase arrest occurred after treatment with erlotinib (38 to 76%), whereas crizotinib caused a G2/M phase arrest (13 to 64%). In the combination, the effect of crizotinib was dominant (13 to 52%). A decrease in p-ERK1/2 (Thr202/204), p-PRAS40 (Thr246) and p-GSK3 β (Ser9) was observed. Phospho-PRAS40 showed a decrease after treatment with erlotinib or crizotinib, whereas combination treatment almost abolished p-PRAS40. In the SKMES1 cell line, p-PRAS40 only decreased after the combination, whereas H1703 cells showed no change in p-PRAS40 levels. Phospho-PRAS40 activity is strongly linked to PI3K/Akt signaling. Her3 is able to heterodimerize both with EGFR and cMET, thus activating downstream PI3K/Akt signaling. No expression of Her3 in the antagonistic cell line was detected. In the LUDLU, levels of p-Her3 were not detectable after erlotinib treatment and in the combination, whereas in the SKMES1 levels of p-Her3 slightly decreased only after combination treatment. Conclusions: To conclude, the simultaneous inhibition of both EGFR and cMET leads to a strong inhibition of PI3K/Akt signaling, leading to synergy in the LUDLU wild-type squamous NSCLC cells.
One year experience of MET gene exon 14 skipping analysis in lung cancer: Identification of 18 cases by NGS.
Authors: Dubbink Hendrikus J , Geurts-Giele Willemina , Meijssen Isabelle , van der Leest Cor , Peric Robert , Von Der Thusen Jan , Aerts Joachim , Dinjens Winand N.M. 
Published: September 2018

e20055 Background: Lung adenocarcinoma (LAC) is the most common histological type of non-small-cell lung cancer and is one of the malignancies with the most evolved personalized treatments based on molecular characteristics of the tumor. Mutations in EGFR, HER2 and BRAF, specific translocations of ALK, ROS1, RET and amplification of MET all have standard diagnostic importance and lead to specific treatment options for the individual LAC patients. Recently, in 2-4% of LAC MET gene mutations leading to skipping of exon 14 were found. These mutations were described to occur more frequently in tumors with sarcomatoid histology. LAC with MET exon 14 skipping mutations showed impressive, although temporary, responses to MET tyrosine kinase inhibitors (TKI) crizotinib, cabozantinib and capmatinib. We will present our experience with routine molecular diagnostic detection of the most common MET exon 14 skipping mutations. Methods: In January 2016 we included in our standard, DNA based, molecular diagnostics custom-made NGS analyses 4 amplicons for detection of MET skipping mutations. The analyses were performed on microdissected FFPE tissue sections or routine histology or cytology stained preparations. Nine different mutations were validated for their effect on splicing by RT-PCR on RNA isolated from the same tissue samples. Results: Between January 2016 and January 2017 676 routine molecular diagnostic analyses on LAC were performed. In 18 (2.7%) cases MET mutations were detected possibly resulting in exon 14 skipping. Nine out of 16 different mutations were tested by RT-PCR and all 9 were demonstrated to result in MET exon 14 skipping. Conclusions: MET exon 14 skipping mutations can reliably be detected in routine pathology tissue samples. These analyses can easily be included in routine molecular diagnostic NGS. When necessary, confirmation of the mutational effect on RNA splicing can be implemented as well. Routine identification of MET skipping mutations (2.7% of cases) adds substantially to the personalized targeted treatment strategies for LAC patients.
Outcomes of video assisted thoracic surgery compared with open thoracotomy in patients with early stage lung cancer.
Authors: Shaheen Shagufta , Jabo Brice , Kaur Manmeet , Senthil Maheswari , Mirshahidi Saied , Zaheer Salman , Mirshahidi Hamid R. 
Published: September 2018

e20061 Background: Video Assisted Thoracic Surgery (VATS) has become the recommended approach for treatment of early stage lung cancer; however, no large randomized clinical trial has been conducted to formally compare VATS to open thoracotomy (OT). The current study sought to assess differences in patients and tumor characteristics for VATS and OT. Additionally, treatment outcomes that included margin status, postoperative length of stay (LOS) and overall survival (OS) were also compared. Methods: A single institution retrospective charts review was conducted for patients diagnosed with stage I-III lung cancer and treated with VATS or OT from May 2005 - May 2015. Patients and tumor characteristics included age at diagnosis, sex, tobacco use, tumor location, stage, size and receipt of chemotherapy or radiotherapy. Chis-square and Wilcoxon-Mann-Whitney tests were used to compare demographic, tumor characteristics and LOS. Multiple logistic and Cox regressions were used to compute relative risk (RR) for positive margins and mortality hazards ratio along with 95 percent confidence interval limits (95%CI), respectively. Results: A total of 232 patients underwent lung resection for cancer diagnosis; VATS n = 99 and OT n = 133. Age at diagnosis, sex, tobacco use, tumor location, and size were not significantly different between the two groups. VATS was more frequently performed for stage I lung cancer compared to OT, p = 0.043. The risk of positive margin RR = 0.49 (95%CI = 0.15, 1.60) and mortality HR = 1.49 (95%CI = 0.90, 2.46) were similar between the two groups. However, the median LOS was significantly shorter (4 days) for VATS than OT (6 days), p = 0.001. Conclusions: Our results show that both short and long-term oncologic outcomes are comparable between VATS and OT. VATS results in shorter LOS and should be considered as the approach of choice for patients undergoing lung resection for cancer. [Table: see text]
Staging in multidisciplinary (MDC) v serial care (SC) lung cancer (LCa) patients (Pts).
Authors: Smeltzer Matthew , Faris Nicholas Ryan , Rugless Stewart Fedoria Elaine , Ray Meredith , Boateng Nana , Meadows Meghan Brooke , Foust Courtney , Jackson Bianca , Patel Anita , Fehnel Carrie , Houston-Harris Cheryl , Signore Raymond S , Robbins Edward T , Osarogiagbon Raymond U. 
Published: September 2018

e20079 Background: Multi-modal staging is associated with improved survival for pts with LCa. We evaluated the thoroughness of clinical staging within and outside a co-located MDC. Methods: Prospective cohort study comparing newly-diagnosed LCa patients in MDC to serially referred (SC) pts within the same healthcare system. Pts were enrolled before treatment began. Stage-confirmation was defined as invasive biopsy of a stage-defining lesion. Bimodal staging involved use of either PET scan or invasive biopsy with CT scan, trimodal staging involved all 3. We used the chi-square test and multivariable logistic regression. Results: From 2014-16, 162 pts were enrolled into MDC, 318 into SC. MDC pts were older (median age 69 v 66), more likely to be black (37% v 29%), and less likely to be commercially insured (36% v 43%) than SC pts. MDC pts had node positive disease identified by PET/CT in 70% of cases, but only 42% in SC (p=0.003). MDC pts were more likely to be clinical M0 (70% vs. 55%). M1b pts were biopsied in 45% of MDC v 36% of SC cases. MDC pts were more likely to have bimodal (90% v 73%) and trimodal staging (51% v 29%) (both p<0.0001, Table 1). The stage-confirmation rate (OR: 1.93 [CI 1.32,2.84]); p=0.0007) and mediastinal stage confirmation rate (OR: 2.16[1.46,3.18]; p=0.0001) were both significantly higher in MDC (Table 1). Adjusting for age, gender, clinical N stage, and histology, these results remained significant (aOR=2.13, p=0.0003); (aOR=2.35, p<0.0001). A subgroup of SC patients (N=64) was discussed at a tumor board. This group had a stage confirmation rate (48%) and mediastinal stage confirmation rate (44%) intermediate between MDC and pure SC (p=0.007, p<0.0001). Conclusions: MDC effectively reached a higher percentage of underserved persons based on age, race, and insurance status, while providing significantly more thorough clinical staging. A tumor board alleviated, but did not eliminate, the gap. Clinical trial information: NCT02123797. [Table: see text]
Dual time PET-CT for mediastinal nodal staging in patients diagnosed with non-small cell lung cancer in an area with high prevalence of infectious granulomatous disease (LACOG-0114).
Authors: Hochhegger Bruno , Tsukazan Maria Teresa Ruiz , Bortolotto Vanessa Rezende , Vieira Arthur , Fritscher Carlos Cezar , Zanini Mara Lise , Berdichevski Eduardo Herz , Vilas Eduardo , da Silva Vinicius Duval , Pinto José Antônio Lopes de Figueiredo , Fritscher Leandro Genehr , Hartmann Louise , Alba Marcos , Schneider Airton , Debiasi Marcio , Zaffaroni Facundo , Martínez-Mesa Jeovany , Barrios Carlos H. , Werutsky Gustavo 
Published: September 2018

e20083 Background: The role of dual-time-point PET/CT acquisition for mediastinal node staging in non-small cell lung cancer (NSCLC) is still controversial. Interpretation of PET/CT results is challenging in areas with high prevalence of infectious granulomatous diseases, whereas the use of dual-time PET/CT could reduce the false-positive results. This study aims to evaluate the performance of dual-time PET-CT for mediastinal node staging in patients with NSCLC in an area with high prevalence of infectious granulomatous diseases (i.e. 99 cases of tuberculosis per 100.000 habitants). Methods: Patients diagnosed with clinical stages I-III NSCLC performed dual-time-point PET/CT (images acquired in hour 1 and 2) followed by mediastinal lymph node biopsy. Different cut-offs for SUV were evaluated to test accuracy in each time-point. Results: One hundred patients were enrolled, of which 85 had mediastinal node biopsy after PET-CT. Median age was 65 years (range 47-80), 49 (58%) were male, 80 (94%) were current or former smokers, and 1 (1.2%) had history of tuberculosis. Dual-time-point acquisition results were similar to those in single-time-point (Table 1). The highest sensitivity (87%) and NPV (90%) was achieved when a cut-off SUV > 0 was used. Conclusions: Dual-time point PET/CT did not improve accuracy of PET/CT-based LN staging in NSCLC in an area with high prevalence of infectious granulomatous diseases. [Table: see text]
First experience with osimertinib in patients with T790M mutation previously treated with EGFR – TKIs in Croatia.
Authors: Jakopovic Marko , Bitar Lela , Cucevic Branka , Plestina Sanja , Mazuranic Ivica , Seiwerth Sven , Hecimovic Ana , Vukic Dugac Andrea , Jankovic Mateja , Redzepi Gzim , Samarzija Miroslav 
Published: September 2018

e20518 Background: EGFR T790M mutation is responsible for around 60% cases of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in patients who have lung cancer with an activating EGFR mutation. Methods: We administered osimertinib 80 mg once daily in 8 patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with first and second-line EGFR tyrosine kinase inhibitors. Results: We treated 8 patients with osimertinib with stage IV lung adenocarcinoma. Four patients were males and four were females, median age 62 (raging from 54 to 82). Four patients were never smoker, and four were ex-smokers. All patients had initially deletion 19 in EGFR gene and then developed T790M mutation. In all patients T790M was proven from tumor tissue. Majority of patients were ECOG 1. All patients were previously treated with first or second line EGFR TKIs (erlotinib, gefitinib or afatinib) and had radiologically documented disease progression. Three patients were treated with osimertinib in third line setting, 2 in fourth, one in fifth, one in sixth and one even in tenth line setting. Median time to response was 4 weeks (raging from 3 to 7). All 8 patients had partial response (PR) with still no recorded disease progression. Duration of response is from 7 to 46 weeks and still ongoing. No significant side effects were observed. Conclusions: Osimertinib is highly active in patients with lung adenocarcinoma which harbor EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. There were no serious side effects of treatment.
Programmed cell death receptor ligand 1 (PD-L1) expression: Epidermal growth factor receptor (EGFR) and Kirsten RAS (KRAS) mutations in second-line therapy (2L) non-small cell lung cancer (NSCLC) patients—A Danish cohort study.
Authors: Cronin-Fenton Deirdre , Dalvi Tapashi , Hedgeman Elizabeth , Nørgaard Mette , Pedersen Lars , Hansen Hanh , Fryzek Jon , Lawrence David , Walker Jill , Mellemgaard Anders , Rasmussen Torben Riis , Shire Norah , Rigas James R. , Potter Danielle , Hamilton-Dutoit Stephen , Sørensen Henrik Toft 
Published: September 2018

e20523 Background: In NSCLC patients who received 2L therapy, we examined the association of PD-L1 expression, mutations in KRAS and EGFR and survival. Methods: 2L NSCLC patients diagnosed during 2001-2012 and with sufficient archival tumour tissue were selected from the Danish Lung Cancer Group Registry. We retrieved patient data from population-based medical registries, and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression using the Ventana IHC (SP263) validated assay (using 25% cutoff for positivity), and genotyped KRAS and EGFR via PCR-based kits. Follow-up was from the start of 2L therapy to death, emigration, or 31/12/2014. We used Cox regression to compute hazard ratios (HR) and associated 95% confidence intervals (95%CI) for PD-L1, EGFR and KRAS. Results: Among 368 patients, 204 (55%) were men, 250 (68%) were aged >60 years at diagnosis, and 95% were ever-smokers. 233 (63%) had adenocarcinoma, 90 (24%) had PD-L1 positive tumors, 28 (8%) had EGFR mutations, and 113 (31%) had KRAS mutations. In the PD-L1 positive tumors, 7% had EGFR and 37% KRAS mutations, respectively. In the PD-L1 negative tumors, 9% had EGFR and 32% KRAS mutations, respectively. Patients with KRAS mutations had shorter survival compared with wild-type patients. Survival was longer for patients with EGFR mutations compared with wildtype patients. PD-L1 expression did not correlate with survival (Table). Conclusions: Our findings suggest that EGFR and KRAS mutations, but not PD-L1 expression, correlate with survival in 2L NSCLC patients. [Table: see text]