bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of decision-support system and guideline treatment concordance on response rate in advanced lung cancer.
Authors: Liang Jun , Tang Chuanhao , Wang Xiangyi , Guo Ziwei , Ni Jun , Xu Weiran , Dankwa-Mullan Irene , Willis Van , Chen Alan , Jackson Gretchen Purcell , Rhee Kyu , Li Tianle 
Published: March 2020

e20006 Background: Clinical decision-support systems (CDSS) provide up-to-date evidence to practitioners overwhelmed by the deluge of clinical findings. Few studies, however, have evaluated their impact on patient outcomes. This cross-sectional retrospective study was conducted to: 1) measure concordance of real-world clinical decisions with therapeutic options from the IBM Watson for Oncology (WfO) CDSS and the Chinese Society of Clinical Oncology (CSCO) guidelines, 2) the effect of concordance on objective response rate (ORR). Methods: Health records from patients receiving 1stline treatment at Peking University International Hospital Oncology Center in China between January 2016 and December 2018 (69 stage IV NSCLC, 30 with SCLC) with documented tumor progression after 2+ cycles of treatment, were reviewed to determine concordance of actual treatment with WfO therapeutic options and CSCO guidelines. Patients’ treatments were grouped as concordant with: WfO+CSCO, WFO only, CSCO only, or neither. ORR, defined as partial or complete response after 2+ treatment cycles (RECIST criteria)was determined for each group. Results: For NSCLC, ORR ranged from 21.4% for discordance with both WfO and CSCO to 100.0% for WfO only concordance. For SCLC, ORR ranged from 37.5% for CSCO only concordance to 73.3% for WfO+CSCO concordance (Table). The main reasons for discordance were: 1stgeneration TKIs like Gefitinib and Erlotinib (vs. Osimertinib) are standard of care for EGFR mutant patients in China, (2) Local CSCO guideline drugs like Lobaplatin and Icotinib are not included in WfO. Conclusions: This study provides preliminary evidence to suggest that treatment concordance with WfO may be associated with improved ORR in some cases of NSCLC (WfO only) and SCLC (WfO + CSCO). ORR in NSCLC patients who were discordant with both WFO and CSCO guidelines was the lowest at 21.4%. Larger studies are needed to understand the effect of guideline and WfO concordance on ORR. [Table: see text]
Evaluation of tumor infiltrating lymphocites (TILs) and survival in patients with resected non-small cell lung cancer.
Authors: Cárdenas Quesada Nuria , Ortega Granados Ana Laura , Márquez Lobo Bélgica , Rosa Garrido Carmen , Sanchez Rovira Pedro , Núñez Torres María Isabel 
Published: March 2020

e20010 Background: Due to the prognosis of non-small cell lung cancer (NSCLC), even at initial stages we need to characterise better our patients in order to know their prognosis. The purpose of our study is to find some prognostic factors to help us to choose the best therapeutic approach. We found some data about histology and tumor lymphocytic infiltration. Methods: We followed outcome of 94 patients diagnosed of initial stage NSCLC that underwent surgery in our institution between 2010-2013, for more than 5 years, and related survival with findings in tumor samples. Results: Tumor samples were classified in order to establish 4 variables related to tumor lymphocitic inflltration (TILs, as it was established by Brambilla et al): absent, mild, moderate and intense. 20 (21.3%) patients were considered TILs intense, 36 (38.3%) moderate, 33 (35.1%) mild and 5 absent (5.3%). We found some significative differences in disease free survival (DFS, more favorable for TILs absent group), but none for overall survival (OS). Conclusions: TILs and tumor stage could be part of an immunoscore to classify initial stage NSCLC, this score should be validated in future studies [Table: see text]
Identification of MET Exon 14 skipping by targeted RNA-based next-generation sequencing in Chinese Patients with NSCLC.
Authors: Che Nanying , Xu Ziguang , Dong Yujie , Cheng Peng , Gao Yun , Yu Yang , Fu Shijun , Gao Min , Kong Lingfei 
Published: March 2020

e20018 Background: MET (mesenchymal-epithelial transition) exon14 skipping mutations have been reported to represent a clinically unique molecular subtype of NSCLC. The prevalence rates of MET exon 14 skipping in lung adenocarcinoma are quite different, from 0.9% to 4.0% in Asian populations. Since some somatic variants not covering the MET exon 14 splice sites might also induce MET exon 14 skipping, we believed that RNA-based sequencing is the most accurate method to detected exon 14 skipping. Methods: A total of 951 NSCLC patients from two hospitals were enrolled in this study. We detected MET exon14 skipping using both targeted DNA- and RNA-based next generation sequencing and elucidated the driver gene mutation profile of Chinese NSCLC patients. Results: The overall estimated prevalence of MET exon 14 skipping was approximately 1.8% (14 of 772) in adenocarcinomas and 1.7 % (16/951) in NSCLCs. Furthermore, we compared the detection rate of MET exon 14 skipping from different specimen source, including surgical resection, percutaneous transthoracic needle biopsy (PTNB) and transbronchial lung biopsy (TBLB). Notably, the detection rate of MET exon 14 skipping from surgical resection specimen is 2.3% in NSCLCs and 2.0% in adenocarcinomas, respectively. MET exon 14 skipping was identified in 7.1% of EGFR/KRAS/ALK/ROS1/RET negative adenocarcinomas (13 of 196). In addition, PD-L1 trended to be highly expressed in NSCLC patients harboring MET exon 14 skipping (55.6% vs 17.3%, p = 0.022). Conclusions: In this study, the prevalence of MET exon14 skipping in lung adenocarcinomas in East Asian population was very close to that of West population using RNA-based NGS. The NSCLC patients with Met exon 14 skipping tended to be older than patients with other oncogenic driver mutations, such as EGFR, ALK, ROS1. In addition, PD-L1 trended to be highly expressed in NSCLC patients with MET exon 14 skipping.
Haematological biomarkers of pathological response on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA non-small cell lung cancer (NSCLC) patients.
Authors: Laza Briviesca Raquel , Cruz Bermudez Alberto , Barquin Miguel , Nadal Ernest , Insa Amelia , Garcia-Campelo Rosario , De Dios Alvarez Noemi , Domine Manuel , Massuti Bartomeu , Majem Margarita , Rodriguez-Abreu Delvys , Martinez Marti Alex , Cobo Manuel , Lopez-Vivanco Guillermo , del Barco Elvira , Bernabé Reyes , Vinolas Nuria , Barneto Isidoro , Viteri Santiago , Provencio-Pulla Mariano 
Published: March 2020

e20026 Background: PD1/PDL1 treatments have become the main therapy in advanced stages of NSCLC due to its significant increase in overall survival (OS), but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described the neutrophil-to-lymphocyte ratio (NLR) and platelets-to-lymphocyte ratio (PLR) as indicator of systemic inflammation, that could be use as biomarker of response to immunotherapy. In our study, we described the effect of neoadjuvant chemo-immunotherapy in Complete Blood Count (CBC) parameters and evaluated their relationship with pathological responses. Methods: Immune cell populations of 46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response assessed in the resection specimen: complete response (pCR), mayor response (< 10% viable tumour) and incomplete response (> 10% viable tumour). Wilcoxon and Mann-Whitney U statistic test were used to evaluated differences between pre and post treatment and between pathological responses groups respectively. Results: From 46 patients, 5 patients did not undergo surgery, so they were excluded from the analysis. Absolute numbers (x103cells/µl) of CBC were significantly reduced after neo-adjuvant treatment in patients, leucocytes (8.80 vs 6.64), Eosinophil (0.22 vs 0.15), Monocytes (0.72 vs 0.62), Neutrophils (5.53 vs 3.53), Haemoglobin (35.82 vs 29.68), Platelets (292.44 vs 227.22), NLR (2.73 vs 1.71) and PLR (143.34 vs 115.85) except Lymphocytes (2.22 vs 2.25) and Basophils (0.06 vs 0.05). Moreover, when the analysis was done by subgroups of pathological responses, PLR variation was significantly different between pCR and incomplete response (-21.33 vs -76.98) whereas NLR and the rest of the immune populations were no different between subgroups. Conclusions: In our study, NLR is not associated to chemo-immune neo-adjuvant treatment response. Nevertheless, in our cohort a higher decrease on PLR post neo-adjuvant treatment is associated to an incomplete pathological response.
Impact of resectable lung adenocarcinoma pathological subtypes on patients prognosis and surgical strategies determination: A SEER population-based data analysis.
Authors: Lu Di , Yang Jianjun , Feng Siyang , Liu Xiguang , Dong Xiaoying , Wang Zhizhi , Wang He , Shi Xiaoshun , Wu Hua , Cai Kaican 
Published: March 2020

e20035 Background: The prognosis difference among lung adenocarcinoma patients with different pathological subtypes remains controversial. Furthermore, the appropriate surgical plan according to each subtype for early-staged adenocarcinoma patients is undetermined. Methods: We retrospectively analyzed patients with solid, papillary and acinar lung carcinoma from 2004 to 2015 using SEER*Stat 8.3.4. The primary readout of this study were overall survival (OS). The Kaplan–Meier method was used to determine OS. Results: 2282 patients with lung adenocarcinoma were finally included (solid, N = 117, papillary, N = 739, acinar, N = 1426). For patients received radical resection (lobectomy/bilobectomy, radical and extended pneumonectomy), those with acinar adenocarcinoma had the best survival (median OS: solid, 59 months, papillary, 91 months, acinar,102 months, solid VS papillary, P = 0.258, solid VS acinar, P = 0.014, papillary VS acinar, P = 0.008). For early diagnosed patients in stage I, those with acinar adenocarcinoma who received radical resection had a better OS compared to those received partial resection (wedge resection and segmentectomy) (median OS: wed&seg, 88 months, radical 106 months, P = 0.024). Particularly, patients underwent radical resection or segmentectomy had a better OS compared to those received wedge resection (mean OS of seg: 99.175±5.336 months; median OS: wed, 67 months, radical, 106 months, wed VS radical, P = 0.001, wed VS seg P = 0.026, seg VS radical, P = 0.353), while those treated with radical resection had comparable prognosis compared with patients with segmentectomy. As for patients with stage I papillary adenocarcinoma, those who received partial resection tended to have a worse prognosis compared to those who received lobectomy, although no significant difference was detected (median OS: wed&seg, 74 months, radical 111 months, P = 0.151. N of patients: wed, N = 72, seg, N = 20, radical, N = 415). Conclusions: Patients with acinar lung adenocarcinoma have a better prognosis than solid and papillary adenocarcinoma patients after radical resection. For patients with stage I acinar adenocarcinoma, segmentectomy and radical resection have similar therapeutic effects. For patients with stage I papillary adenocarcinoma, radical resection is the first option.
The cross talk between the molecular alterations and tumor immunity in the microenvironment in non-small-cell lung carcinoma.
Authors: Zhou Chengzhi , Chen Yanhui , Hu Ying , Liu Yang , Zhang Henghui 
Published: March 2020

e20043 Background: The previous study indicated that the biomarkers of molecular alterations and tumor immunity in the microenvironment could predict the response of immunotherapy in NSCLC patients. However, the cross talk between the two factors is unclear. This study was designed to investigated the features of tumor immunity in the microenvironment of deferential molecular characterization in NSCLC patients. Methods: Tumor tissue and matched blood samples from 62 patients with NSCLC were collected. The mutation profiles were sequenced by a cancer gene-targeted NGS panel. The PD-L1 expression and immune cells infiltrated in tumor microenvironment were detected by multiplex immunofluorescence staining. Results: The distinct of molecular alterations showed the different tumor microenvironments in terms of immune cell composition and of PD-L1 expression by tumor cells in NSCLC. KRAS-mutated tumors were characterized by higher level of PD-L1 expression and lower NK cells infiltrated in tumor area than KRAS-wild type tumor. TP53-mutated tumors were characterized by higher CD8+T cell and lower NK cells infiltrated in tumor area. In contrast, EGFR-mutated tumors were characterized by lower level of PD-L1 expression and higher NK cells. Moreover, we found that the PD-L1 expression increased in MET gene CNV gain tumors than MET wild type tumors. Conclusions: The features of tumor immunity in the microenvironment changed in deferential molecular characterization in NSCLC. it may help to explain the phenomenon that the efficacy of immunotherapy changed in deferential molecular characterization of NSCLC.
Mutational landscape of early-stage non-small cell lung cancer patients using a 451 gene panel.
Authors: Mao Guanxian , Xuxing Peng , Hao Wu , Junbing Wang , Suyue Liu , Qiang Wu , Ying Liu , Ren Qiang , Liu Jixian , Melançon Charles E. 
Published: March 2020

e20048 Background: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Methods: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Results: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0%)0/39) for BRAF,5.7% (2/35) and 0%)0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53. Conclusions: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0% )0/39) for BRAF,5.7% (2/35) and 0% )0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53.
Selection of patients for stereotactic body radiation therapy (SBRT) or (bi)lobectomy (L) for the treatment of cT1-T2N0M0 NSCLC by the risk of node involvement using readily available preoperative factors.
Authors: Griffin Molly , Hebert Christine , Voland Rick , Varlotto John M. , DeCamp Malcolm , Flickinger John Charles , Ali Suhail M. , Maddox Debra , McIntosh Lacey , Baima Jennifer , Uy Karl , Lou Ferian , Maxfield Mark , Oliveira Paulo , Emmerick Isabel M , Fitzgerald Thomas J. , Walsh William Vincent 
Published: March 2020

e20055 Background: Currently it is not known whether certain patients with early-stage non-small cell lung cancer(NSCLC) would be better served with stereotactic body radiation (SBRT) or surgery. The purpose of our investigation is to see if patients who are at higher risk of node involvement based upon pre-operative factors would be preferentially served with (bi)Lobectomy(L). Methods: The NCDB was queried for the years 2004-2014 to find patients with cT1-T2N0M0 NSCLC (excluding lepidic adenocarcinoma and their variants) < 5cm treated via L or SBRT(N = 16,722). Recursive partition analysis was used in the L group to develop high, medium, and low risk node involvement groups in those patients having complete node assessment (10 or more nodes examined) by American College of Surgeons commission on cancer quality care measures(ACOS coc), N = 83,890. The L and SBRT groups were then propensity matched based upon factors associated with OS to assess whether there was an OS benefit for either the L or SBRT treatments by node risk category. OS was calculated by log-rank testing. Results: The high, medium, and low risk categories had an average risk for node involvement of 20.12, 11.3, and 4.57%, respectively. The low risk group was defined as tumors < 21mm for all squamous cell carcinomas(SQ) and adenocarcinoma(AD) in the right upper lobe only. High risk categories were associated tumors > 21 mm in the RUL in white Hispanics; and ages < 60yr old for SQ, large cell ca, and NSCLC-NOS; and > 21mm with non-RUL location and < 55yr old. OS was significantly better in patients treated by L for the high, medium, and low risk groups with all p-values of < 0.0001. Conclusions: When patients undergo a complete lymph node dissection by the ACOScoc quality measures and have (bi)lobectomy, their OS is superior to patients undergoing SBRT whether they are at high, low or medium risk of lymph node involvement.
Use of surgery and stereotactic body radiotherapy (SBRT) in very elderly patients with early-stage non-small cell lung cancer (NSCLC): A national cancer database (NCDB) analysis.
Authors: Kharouta Michael , Grubb William , Podder Tarun Kanti , Biswas Tithi 
Published: March 2020

e20058 Background: SBRT treatment for very elderly ( > 80 years) patients with early stage NSCLC has been reported to be well tolerated with good short term efficacy. Using a large hospital based registry, we report a comparison of patterns of practice, outcomes, and prognostic factors for very elderly patients undergoing any treatment for early-stage NSCLC. Methods: The NCDB was queried for patients with clinical Stage I-IIA NSCLC with age ≥ 80 years diagnosed from 2001-2015 treated with surgery or SBRT alone. Patients were excluded if they received chemotherapy /immunotherapy or non-standard SBRT doses (i.e. > 5 fractions of RT, < 30 Gy or > 70 Gy total dose). Survival analyses were performed with propensity-matching, Kaplan-Meier estimates, Cox proportional hazards regression, and log rank testing. Results: 26039 patients met search criteria, median age 83 (80-90) years. 17141 (65.8%) patients underwent surgery, and 8898 (34.2%) underwent SBRT. Median follow up was 31 months. Median survival was 52 and 35 months for surgery and SBRT. Of patients receiving SBRT, 2044 (23%) had a contraindication to primary surgery due to patient risk factors. Age, clinical stage, tumor size, surgery type, CDCC score, BED, bronchial involvement, and type of treatment facility were predictive of median survival. BED > 154 Gy was associated with greater median survival (p < 0.01). Lobectomy was associated with greater median survival vs sub-lobar resection/pneumonectomy (p < 0.0001). For stage I tumors, surgery was associated with better median survival (56 vs. 35 months, p < 0.0001), but for stage IIA patients both modalities had similar median survival (30 vs 29 months, p = 0.04). Conclusions: Surgery remains the predominant treatment modality for early stage NSCLC in this very elderly population, and is associated with good outcomes for patients with stage I tumors. For elderly patients who are poor surgical candidates due to medical co-morbidities SBRT is associated with reasonable median survival. With limited information on patient comorbidities, more robust studies are needed to determine the effects of patient selection on treatment outcomes in this population.
Prognostic value of tumor infiltrating lymphocytes in epithelioid malignant pleural mesothelioma.
Authors: Adashek Michael , Chan Abigail Sy , Heath Johnathan , Fanaroff Rachel , Kallen Michael E , Friedberg Joseph S. , Culligan Melissa , Khashab Tamara , Miller Kenneth David 
Published: March 2020

e20064 Background: Malignant Mesothelioma (MM) is an aggressive malignancy with survival of 4-12 mo. without treatment and 10% 5-year survival. The response of patients with MM to immunotherapy has increased interest in the tumor immune microenvironment. The purpose of this study was to determine if tumor infiltrating lymphocytes (TIL) are correlated with survival in epithelioid MM. Methods: Immunohistochemistry was performed on specimens from 27 patients with epithelioid mesothelioma using CD4, CD8, and CD68 antibodies. Infiltrate density was scored (0-3+) by pathologist estimate in intratumoral and adjacent tumoral tissue. ANOVA and regression analysis were performed. Overall survival (OS) for the entire group and time to progression (TTP) for nine patients with known time from surgery until tumor recurrence were also studied as a surgical resection subgroup (SRG). Results: For the small SRG the relationship between (TTP) and TIL score of CD8 at the edge of the tumor was significant (F[2,6]=5.64, P=.042) however TIL score of intratumoral CD8 cell infiltrates and TTP did not demonstrate statistical significance. The relationship between OS with CD8 infiltrate at the tumor edge, for the entire group, approached significance at (F [3,22]=2.93, P=0.056). TTP and OS and the TIL score of CD4, CD68 at both tumor center and tumor edge did not demonstrate statistical significance. Conclusions: CD8+ lymphocytes are an important component of host immune defense against cancer. We found that in epithelioid MM the cellular infiltrate of CD8 lymphocytes at the edge of the tumor (but not with intratumoral CD8) was associated with longer time to recurrence. TTP and OS were not associated with CD4 and CD68 within or at the tumor edge. The role of CD8 T-cells and the quantitative difference between CD8 at the edge of tumor and intratumoral CD8 should be further investigated in order to optimize immunotherapy.
Survival impact of thoracic cavity reduction during neoadjuvant chemotherapy in patients undergoing surgery for malignant pleural mesothelioma.
Authors: Kuroda Ayumi , Nakamichi Toru , Nakamura Akifumi , Hashimoto Masaki , Matsumoto Seiji , Kondo Nobuyuki , Hasegawa Seiki 
Published: March 2020

e20067 Background: It is difficult to predict prognosis for malignant pleural mesothelioma (MPM). The association of thoracic asymmetry and survival in patients with MPM was reported by Cho et al. in at the 18th World Conference on Lung Cancer. Here we investigated the survival impact of thoracic cavity reduction during neoadjuvant chemotherapy (NAC). Methods: The subjects were patients with resectable epithelioid MPM who underwent NAC with platinum and pemetrexed followed by surgery at the Hyogo College of Medicine from Jan 2009 to Aug 2018. The length of the ant-post and med-lat extent of both hemithoraces at the level of carina was measured before and after NAC. Asymmetric ratio (ASR) was defined as the product of the ant-post and med-lat extent of affected side divided by those of healthy side. Results: One hundred thirty-three patients were enrolled: median age 66 (16-79) years, M/F 112/21, R/L 70/63, extrapleural pneumonectomy 40 and pleurectomy/decortication 93. Significantly poor prognosis was associated with ≥ 10mm reduction of the med-lat extent of affected side during NAC and ≥ 10% reduction of the product of the ant-post and med-lat extent of affected side during NAC (p = 0.0021). ASR ≤ 0.9 before or after NAC was not associated with significantly poor survival. Conclusions: This study revealed that thoracic cavity reduction during NAC was associated with significantly poor prognosis of MPM.