bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic evaluations of adjunctive osimertinib treatment in surgically resected epidermal growth factor receptor positive (EGFR+) non-small cell lung cancer (NSCLC): Analysis for stage 3A disease.
Authors: Obeng-Kusi Mavis , Choi Briana M , Abraham Rachel B , Aqel Osama , Calamia Matthias , Halawah Hala , Tugay Deniz , Alamer Ahmad , McBride Ali , Abraham Ivo 
Published: June 2022

e20505 Background: Patients with surgically resected EGFR+ NSCLC remain at risk of recurrence after surgery. Osimertinib, a tyrosine kinase inhibitor, had been assessed clinically as adjunctive therapy in surgically resected EGFR+ NSCLC including stage 3A. We conducted a cost effectiveness/utility analysis of adjunctive osimertinib therapy in stage 3A surgically resected EGFR+ NSCLC. Methods: We specified a two state partitioned survival model of disease free survival (DFS) versus disease recurrence and death in a), with a 5 year time horizon (US payer perspective). DFS and overall survival curves were extrapolated per parametric functions. A 3% discount rate was utilized to costs and utilities beyond year 1. Costs of therapies (wholesale acquisition cost), adverse events (AE; grade 3/4; all grades for immunotherapy related AEs), and monitoring costs were based on Redbook, publications, and Physician Fee Schedules, respectively (US $2021). Costs, DFS life years (DFSLY) and DFS quality adjusted life years (DFSQALY) were used to determine the incremental cost effectiveness/utility ratios (ICER/ICUR) of the additional cost needed to gain (g) a DFSLY and DFSQALY in base case (BSA) and probabilistic sensitivity analyses (PSA). Results: Exponential regression was used to extrapolate the Kaplan-Meier curves of osimertinib and placebo,. As shown in the table, the BCA (PSA) estimated the incremental cost at $669,369 ($670,274). The incremental DFSLY was 1.895 (1.899), yielding ICER of $353,125/DFSLYg ($352,963/DFSLYg). The incremental DFS QALY was 1.35, yielding an ICUR of $497,905/DFSQALYg ($497,676/DFSQALYg). Conclusions: In stage 3A surgically resected EGFR+ NSCLC, adjunctive osimertinib therapy showed incremental benefits of 1.895 (1.899) DSFLYg and 1.344 (1.349) QALYg compared to placebo, however at marked incremental cost. As adjunctive osimertinib treatment is indicated in EGFR+ NSCLC disease stages1B and 2, the present stage 3A cost effectiveness/utility results should be compared to those for stages 1B and 2.[Table: see text]
The age-adjusted rates and treatment of typical carcinoid tumors of the lung.
Authors: Valluri Anisha P , Voland Rick , Varlotto John M. , Shweihat Yousef Michael , Cooper Mark Michael , Zander Dani 
Published: June 2022

e20507 Background: Pulmonary typical carcinoid tumors(TC) are rare and the treatment of these tumors has not been well studied. The purpose of our investigation is to find whether or not these tumors are increasing in frequency and to assess the value of different treatment options. Methods: The National Cancer Database was queried from the years 2004-2015 for those patients who underwent a surgical resection((bi)lobectomy(L+) or sub-lobar resection(L-)) of TC. Multi-variate analysis for overall survival (OS) in surgical patients was used for propensity matching to determine the benefits of (L-) vs (L+) and to assess the role of chemotherapy or radiation in node positive disease(N+). SEER-18 was used to estimate the age-adjusted rates of TC and the percentage of N+ tumors during the years of our study. Results: With a median follow-up of 62.1 months, 16337 patients underwent surgical resection of TC of which 7846, 7538, 644, 302, and 7 patients had NX, N1, N2, and N3 disease. The rate of TC per 100,000 population progressively and significantly increased from 3.2 to 5.4 while the rate of node positivity remained flat at 0.3-0.4/100,000 population. Adjuvant therapy was given to 155 patients with radiation and 945 with chemotherapy. In the total population, a significant OS benefit was noted in those undergoing a L+ compared to L- (HR = 1.35 p < 0.0001), which was not seen in patients with node negative tumors < 2cm, but was seen in node negative tumors > 2cm (HR = 2.00, p 0.0088) and N1(HR = 3.2, P < 0.0001) and N2 disease(HR = 4.2, p < 0.0001. N2(HR = 2.25, p < .0001 and N1 disease(HR = 1.53 p = 0.0021) had a significant lower OS than N0 disease which were not improved not with radiation therapy(p-value 0.4055) and worsened with both adjuvant chemotherapy(median OS HR p value = < 0.0001). Conclusions: Typical carcinoid tumors are increasing in the US population and should undergo a lobectomy when the size > 2cm or when node positive disease is present. Despite the worse prognosis of patients with node positive disease, radiation did not improve and chemotherapy worsened OS.
The critical role of histone modifications in lung adenocarcinoma based on novel molecular subtypes.
Authors: Wang Bo , Zhang Lianbin , Tang Wei , Deng Jianqing , Mu Tianhao 
Published: June 2022

e20510 Background: Studies revealed the pathogenesis and exploring the treatment of lung adenocarcinoma (LUAD), but overall survival (OS) of LUAD patients still remains low in the recent years. Methods: This study analyzed the relationship between gene expression and histone modifications, and discussed the prognostic value of these findings in patients with LUAD. Four types of histone modifications including H3K9me3, H3K27me3, H3K27ac and H3K4me3 were included. Promoters and enhancers in protein coding genes (PCGs) were selected as targeted analyzing regions. Unsupervised consensus clustering was performed to identify molecular subtypes. Cox regression analysis and stepwise Akaike information criterion (stepAIC) were applied to construct a prognostic model. Results: A large number of epigenetic abnormal genes in lung adenocarcinoma were found by comparing the histone modifications and methylation regions on the elements including. We identified 699 epigenetic dysregulated genes specific to LUAD. Finally, based on these epi-PCGs, we constructed three molecular types of LUAD and identified 5 epi-PCGs as prognostic markers for LUAD patients. Conclusions: Our research provided a better understanding that the abnormal epigenetic regulation of PCG expression contributes a lot for the progress of gene regulation in LUAD. These novel molecular subtypes and the prognostic model could serve as guiders to assist decision-makings for LUAD treatment.
The gain of somatic copy number alteration in both primary and lymph node metastases predict poor prognosis of non-samll cell lung cancer.
Authors: Wan Renping , Jing Zhongying 
Published: June 2022

e20511 Background: Lung cancer is the leading cause of cancer-related mortality among the world, and distant metastases is still the main cause of poor prognosis and cancer-related deaths. Lymph nodes nearby primary tumor is the most commonly metastases. More than 90% NSCLC patients were diagnosed at II or higher stage. Although more and more prognosis molecular biomarkers have been identified, it’s still hard to completely understand the metastases mechanism of NSCLC. Here we work on evaluation whether molecular divergence or common mutational characters in matched primary and lymph node metastases of NSCLC could predict patient’s prognosis. Methods: Within MSKCC(MSK-IMPACT-2017) datasets, 12 matched primary and lymph node metastatic samples were gotten. Molecular divergence and similarity were analyzed between matched samples, including SNVs, fusion mutations, CNA, TMB, signature, concordance between primary and metastatic lymph nodes and relate it to patient’s overall survival. Results: Cox survival analysis results proved that the gain of CNA in both primary and lymph node metastases would be a poor prognosis biomarker for NSCLC. 3/3 NSCLC patients with CNA in both primary and metastases occurred death within 10 months, median OS was 7.76 month. Only 1/9 of the others occurred death at 14 months, other NSCLC patients did not reach the end point of this study. HR for OS with CNA in both matched samples versus the others was 0.07 (95% CI 0.0067-0.67), log-rank p value was 0.0028. Conclusions: The gain of CNA in both primary and lymph node metastases could be a poor prognosis predictor for NSCLC patients.
EGFR gene aberrations in non-small cell lung cancer patients in the Crimea Republic.
Authors: Timoshkina Natalya N. , Petrusenko Natalia A. , Rashed Al-Nsour , Gvaramiya Astanda K. , Gappoeva Madina A. , Savchenko Dmitriy A. , Kit Oleg I. , Kutilin Denis S. 
Published: June 2022

e20514 Background: Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and remains the most commonly diagnosed human neoplasm with a poor prognosis. Significantly improving the clinical course of NSCLC, EGFR tyrosine kinase inhibitors are effective only against tumors carrying activating mutations in the EGFR gene, and their frequency varies depending on the patient population. The aim of the study was to analyze a retrospective group of Crimean patients with advanced NSCLC for the presence of EGFR gene aberrations and association with clinical outcome. Methods: We used DNA samples from FFPE blocks of tumor and non-tumor tissues of 72 European-type patients (aged 46-78 years, median 64 years, 82% - men, 18% - women) diagnosed with lung cancer (T1-1aN0-2M0-1, stage I-IV). The relative copy number of the EGFR gene was assessed by RT-qPCR using GAPDH and B2M as reference genes. Mutations (9 deletions in exon 19, L858R, T790M, L861Q, G719S/A/C, 3 insertions in exon 20, S768I) in the EGFR gene were determined using the Therascreen EGFR RGQ PCR Kit (Qiagen, Germany). Results: For Crimean population patients, the squamous subtype of NSCLC was more common (57%). EGFR copy number evaluation in patients with adenocarcinoma showed locus amplification in 9 patients (30%), no loss of copy number was recorded. In the squamous cell carcinoma group, locus amplification prevailed in 25 of 42 samples (59.6%) and a decrease in copy number was noted in 4 samples (9.5%). Differences in the frequency of aberrant changes in the relative copy number of EGFR in adenocarcinoma and squamous cell lung cancer groups were statistically significant (χ2 = 11.04 at p = 0.003). The activating mutation frequency in adenocarcinoma samples was 9.7% (ex19del), which was lower than the frequency recorded in European adenocarcinoma patient populations (14.4%, p = 0.036). No EGFR mutations were found in cases of squamous cell lung cancer. The presence of mutations and/or changes in EGFR copy number were associated with shorter overall survival in patients who did not receive targeted and immune therapy (p = 0.034). Conclusions: The ex19del activating mutation of the EGFR gene frequency in adenocarcinoma samples was 9.7%. A more frequent EGFR alteration was detected when assessing the locus copy number in the tumor relative to the non-tumor tissue: changes were recorded for 30% of adenocarcinoma cases and 69.1% of squamous cell lung cancer.
Experimental photodynamic therapy in the treatment of lung tumor.
Authors: Komarova Ekaterina Fedorovna , Engibaryan Marina A. , Ulianova Yulia V. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Pustovaya Irina V. , Chertova Natalia A. , Goncharova Elena G. , Gvaramiya Astanda K. , Maldonado Mary L. , Cherkes Maria A. , Komarova Elizaveta , Goncharova Anna S. , Kurbanova L. Z. 
Published: June 2022

e20515 Background: Study of the effect of photodynamic therapy (PDT) with Photoditazine using a high-energy laser at various periods after tumor transplantation on the dynamics of growth of experimental Lewis lung carcinoma in mice. Methods: The study included 176 male C57Bl6 mice weighing 18-20 g with Lewis lung carcinoma (LLC) transplanted subcutaneously. The animals received experimental PDT sequential overlapping of fields of influence (662 nm, 3 W, Photoditazine 25 mg/kg, 300 J/cm2). Animals received PDT on day 11 after the transplantation (experimental series I) and on day 21 (experimental series II). Experimental groups were divided in dependence on the exposure area (to the primary tumor -1gr, thorax (area of metastases)-2 gr and to both zones-3 gr). Animals with tumors without PDT were used as controls. Results: PDT with Photoditazine using the 3W laser stimulated the growth of primary tumor node. The degree of stimulation depended on the time of PDT. Increase in tumor sizes differed already on day 7 after PDT at various periods of the LCC growth. During PDT on the 11th day from the moment of tumor inoculation, the percentage of growth on the 7th day after the end of treatment was 60.7; 69.6 and 86.7% in groups 1, 2 and 3, respectively. In the groups of animals that underwent PDT on the 21st day of the growth of the grafted tumor on the 7th day after the end of treatment, the percentage of tumor growth was 20; 35.6 and 24.4% in groups 1, 2 and 3, respectively. Increase in the median survival was registered in experimental animals with PDT on 22.6% compared to control. A smaller increase in tumor volume was observed in animals receiving PDT to the primary tumor, and the group receiving therapy to both areas was in between. Conclusions: The study was shown that with an earlier initiation of PDT, a greater stimulation of tumor growth was revealed than with therapy at a later date. The revealed characteristics of the development of experimental LLC at PDT exposure allows further selection of parameters for photodynamic therapy regimens.
Clinical analysis of patients (pts) with Lung cancer treated with anti-PD1/PDL1 therapy.
Authors: Tian Kaihua , Wang Xintong 
Published: June 2022

e20522 Background: Characterization of Lung cancer treated with anti-PD1/PDL1 therapy was an approach to predict the clinical benefit. this research is a prospective and observational study of long-term immunization therapy safety in routine clinical practice in lung cancer. Methods: This study obtained 395 Chinese patients lung cancer patients who underwent surgical resection or biopsies from January 2020 to January 2022. It is aimed to evaluated the value of TMB,MSI,and PD-1 expression in the pts subset that was therapy at anti-PD1/PDL1 therapy(n = 47),other anticancer therapies (n = 348) included chemoradiation therapy(55%), docetaxel(18%), EGFR-TKIs (16%), pemetrexed (5%) etc. Results: In this cohort, lung cancer pts treated with anti-PD1/PDL1 therapy had a higher proportion of MSI-H than others (7.7% vs 3.4%). PD-L1 High expression in two groups (anti-PD1/PDL1 therapy vs others) about in 19.1%(n = 9) vs 10.6% (n = 37), and low expression in 8.9% (n = 31) vs 10.6% (n = 5) pts. Median TMB was 13 mut/Mb from anti-PD1/PDL1 therapy and 9.6 mut/Mb from other therapy. Conclusions: Lung cancer pts were integrated after immunotherapy vs other therapy, most pts received multiple subsequent anticancer therapies. In this study, immune-related biomarker analysis of lung cancer populations with multiple treatment methods may help improve the efficacy of precise treatment in lung cancer.[Table: see text]
The prognostic value of Sprouty2 protein in nonsmall cell lung cancer.
Authors: Acikgoz Yusuf , Yildirim Fatma Unal , Ergun Yakup , Ucar Gokhan , Aktürk Esen Seli̇n , Bal Oznur , Uncu Dogan 
Published: June 2022

e20524 Background: We represent Sprouty 2 (Sprty2) protein expression analysis and its association with key pathological and clinical features of pts with NSCLC as the largest ex-vivo data series. Methods: All IHC stainings were performed using a fully automated IHC staining device (Ventana BenchMark XT, Ventana Medical Systems, Tucson, AZ). Sprouty2 (Clone: AB_2720609, Cat. Number: PA5-7688; Dilution:1/100, ThermoFisher-Invitrogen) primer antibodies were used in IHC examination. Lung alveolar epithelium and bronchial mucosa were used as positive controls. Staining intensity [0 (no reaction), 1+ (weak reaction), 2+ (moderate reaction), 3+ (strong reaction)] and percentage of positively (PP) stained cells [0 (0%), 1 (< 10%), 2 (11-50%), 3 (51-90%), 4 (> 90%)] were analyzed together to calculate immunreactivity score (IRS) values ranging from 0 to 12. Results: 41 pts' sample were analyzed in this study. Sprty2 staining intensity and percentage were statistically significantly lower in tumor tissue (p < 0.0001). The number of pts with positive Sprty2 expression was 17 (42%) and negative was 24 (58%). The ratio of smoking status, brain and lypmh node metastasis were higher in Sprty2 positive group (Table). OS for patients with Sprty2 positive was lower than those with Sprty2 negative in metastatic patients (6.9 mo vs 13.6 mo, p = 0.023). Sprty2 positive pts had inferior survival compared to Sprty2 negative pts among those with AC histology (7.0 mo vs NR, p = 0.003). Conclusions: Sprty2 expression was decreased in tumor tissue compared to normal lung parenchyma. Paradoxically, Sprty2 positive patients had lower survival in certain subgroups (metastatic disease, AC) compared to those with negative pts. Sprty2 protein may be a new target especially for pts without druggable targets. [Table: see text]
Caloric restriction ketogenic diets (KR) in relation to radiotherapy responses in lung cancer xenografts
Authors: Lyu Jiahua , Xiao Ling , Liu Yudi , Wang Yuan , Zhang Rongke , Chen Taiyu , Zhang Hangyue , Tang Chunhan , Pan Shiyi , Nie Xinyu , Zhang Min , Li Tao 
Published: June 2022

e20528 Background: Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth. Caloric restriction (CR) and ketogenic diet (KD) are often thought to limit tumour progression. The current study tests the hypothesis that caloric restriction ketogenic diets (KR) enhance radiotherapy responses in lung cancer xenografts. Methods: Mice bearing Lewis Lung Carcinoma xenografts were randomly divided into ad libitum diet group (AL), radiation group (RT), KR diet group (KR), or KR + RT group (KT). Mice in KR and KT group were fed a KR (KetoCal 4:1 fats: proteins+carbohydrates;70% of total energy). Mice in RT and KT group were treated with radiation (4Gy*3f). Mice weights, tumor size, blood ketone levels and survival were monitored. Results: Blood ketone levels were significantly higher for the mice consuming a KR diet compared to standard diet (3.2 mmol/L vs 0.8 mmol/L at week 3, P < .001). Some mice with KR diet lost a significant amount of weight (10%～15% of starting weight) by the end of the treatment.The KR diets combined with radiation resulted in slower tumor growth in Lewis Lung Carcinoma xenografts and longer survival time (P < 0.05), relative to radiation alone. The KR diet also slowed tumor growth and prolonged survival (P < 0.05), relative to control. Hematological and pathological examinations indicated that the KR diet was safe and well tolerated, and no significant cardiac, hepatic and renal toxicity was observed. Conclusions: These results showed that a KR diet enhanced radiotherapy responses in lung cancer xenografts. Further studies are needed to address the mechanism of this diet intervention.
High homology of carcinomatous component and sarcomatous component in pulmonary carcinosarcoma and heterogeneity of gene expression among different patients.
Authors: Wu Haixia , Xue Yingbo , Huang Ping , Wu Xiaoliang , Peng Xueqin , Liu Xin 
Published: June 2022

e20534 Background: Pulmonary carcinosarcoma (PCS) is a rare subtype of non-small-cell lung cancer (NSCLC) which is highly aggressive and currently has no optimal treatment. Previous studies have shown that some potential markers for targeted therapy and immunotherapy have been detected in PCS patients. A few studies and cases have used microdissection to separate the carcinomatous component (CaC) and sarcomatous component (SaC) component of PCS and performed DNA-based next-generation sequencing (NGS) and confirmed that the two components are highly homologous. There are no studies yet to analyze the differences between CaC and SaC in PCSs from multiple aspects including DNA, RNA, and protein expression assays. Methods: 10 tumor tissues from 5 PCS patients were divided into CaCs and SaCs by microdissection, DNA-based NGS with a 520 gene panel, RNA-based NGS with a 115 gene panel, and Immunohistochemistry (IHC) were performed on these samples. The same type of detection results for different components of the tumors were used for comparative analysis, and the overall DNA test results of the two components were used to compare with detection data of NSCLC and lung sarcoma in the TCGA database respectively. Results: No significant differences were found between CaC and SaC at both DNA, RNA, and IHC assays. The most commonly mutated genes in this cohort of patients were TP53 (10/10, 100%), KRAS (6/10, 60%), LRP1B (5/10, 50%), RBM10, PTPRT, AKT2 (both are 4/10, 40%). Notably, all the mutated genes detected were more similar to those detected in NSCLC rather than mutated genes commonly found in sarcomas. In addition, regardless of DNA or RNA sequencing, no landmark fusion variants were detected in the four available sarcoma tissues. Single sample gene set enrichment analysis (ssGSEA) was used to analyze the RNA results of the matched CaC and SaC of the three patients, no difference in RNA expression among different types of tissues in the same patient was found, but gene expression heterogeneity among the 3 patients was very high. IHC results showed that the positive rates of PD-L1, CD3 and CD8 in the 5 CaCs were 40%, 100% and 100%, while this value was 80%, 100% and 100% in the 5 SaCs. PD-L1 showed a trend of high expression rate in SaC tissues of PCS patients. Conclusions: This study showed that the CaC and SaC tissues of the same PCS patient were both highly homologous in terms of DNA, RNA and protein expression, but the RNA expression was highly heterogeneous among different patients. The landscape of genetic alterations revealed that PCSs are molecularly more likely to arise from NSCLC rather than lung sarcomas, which suggests that for these patients, it may be suitable to choose a treatment plan for the pathological type of the carcinomatous component.