bluuebunny/crossref_metadata_2025_split huggingface dataset:
MCM4 as a prognostic biomarker of early-stage lung cancer.
Authors: Sriuranpong Virote , Luangdilok Sutima , Chantranuwatana Poonchavist , Leeladejkul Nussara , Pornpatanarak Nopporn , Benjacholamas Vichai , Sitthideatphaiboon Piyada , Vinayanuwattikun Chanida - , Pisitkun Trairak 
Published: May 2020

e21033 Background: Prognostic biomarker in early-stage lung cancer is less well defined. Despite early detection, one-third of patients with completely resected early-stage lung cancer without lymph node involvement have a recurrence. Our main objective is to investigate potential biomarkers useful in classification and predicting prognosis of this early-stage lung cancer, particularly in lymph node-negative subgroup. Methods: In discovery phase, we performed proteomic profiling on 60 lung cancer tissues to distinguish solid versus non-solid adenocarcinoma. Relative protein quantification was analyzed using Tandem Mass Tag mass spectrometry. In validation phase, tumor tissues from an additional cohort were analyzed by immunohistochemistry in conjunction with quantitative image analysis to confirm the differential expression of significantly altered proteins, including MCM2, MCM4, MCM6, SCAMP3, DPP4 and MYH11. Prognostic potentials of each biomarker were analyzed with univariate and multivariate analyses. Results: Quantitative proteomic analysis of predominantly solid versus non-solid adenocarcinoma tissues showed 30 differentially expressed proteins consisting of 13 increased and 17 decreased proteins found in solid compared with non-solid adenocarcinoma. Four most increased proteins (MCM2, MCM4, MCM6, and SCAMP3) and two most decreased proteins (DPP4 and MYH11) were selected for immunostaining in the validation cohort of 204 patients with resected adenocarcinoma without lymph node involvement. 57 out of 204 (27.9%) patients had recurrent disease. The high expression level of MCM4 was the strongest signature for disease recurrence (HR 4.85, 95%CI 2.78-8.47, p < 0.0001) and remained significant under multivariate analyses adjusted for TNM stage, histologic subtypes, lymphovascular invasion, tumor necrosis, and adjuvant chemotherapy. Recurrence-free survival (RFS) was significantly shorter in patients with high MCM4 compared with low MCM4 (5-y RFS 50% vs 84%, p < 0.0001) and remained highly significant within stage IA (5-y RFS 69% vs 93%, p < 0.0001), or stage IB and II (5-y RFS 36% vs 69%, p = 0.001). High expression of MCM4 correlated with other poor prognosis factors including smoking (p = 0.001), stage (p = 0.003), lymphovascular invasion (p = 0.036), visceral pleural invasion (p = 0.005), tumor necrosis (p < 0.0001) and solid histology (p < 0.0001). Conclusions: High MCM4 expression serves as an important prognostic biomarker predicting recurrence in early-stage node-negative lung adenocarcinoma.
A nomogram for predicting overall survival in resected non-small cell lung cancer with chemotherapy.
Authors: Zeng Yuan , Liang Wenhua , He Jianxing 
Published: May 2020

e21064 Background: Chemotherapy is very common for resected Non-Small-Cell Lung Cancer (NSCLC) patients. However, models for predicting the survival outcomes of resected NSCLC patients with chemotherapy are scarce. The aim of this study was to develop a clinical nomogram for predicting overall survival in these patients. Methods: A total of 16661 resected NSCLC with chemotherapy were cases extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the prognostic factors to build a nomogram.The model was subjected to bootstrap internal validation with the SEER database and external validations with 1108 patients from China. The predictive accuracy and discriminative ability were illustrated by calibration, concordance index (C-index) and risk group stratification. Results: On multivariate analysis independent factors for OS were age, sex, examined lymph node count, extent of surgery, N stage, T stage and grade which were then integrated into the nomogram. The calibration curves for probability of 1-, 3-, and 5-year OS showed excellent agreement between nomogram prediction and actual observation. The C-index of the nomogram was higher than that of AJCC 8th edition system for predicting OS (training cohort, 0.61 vs. 0.58; P < 0.01; validation cohort, 0.66 vs. 0.63, P = 0.56). The stratification into different risk groups allowed significant distinction between survival curves. Conclusions: We established a nomogram that can provide individual prediction of OS for resected NSCLC patients with chemotherapy. This practical prognostic model may help clinicians for treatment planning and to guide future studies.
Radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC): A prospective, observational study.
Authors: Berg Janna , Bengtson May-Bente , Halvorsen Ann Rita , Haugstvedt Jon Olav , Brustugun Odd Terje , Helland Aslaug 
Published: May 2020

e21065 Background: RP is a clinically challenging side effect following SBRT. The reported incidence of RP varies from 2.2% to 46.8%, depending on study design and different grading systems. We evaluated the grading systems for RP and identified possible predictive tests for RP. Furthermore, we estimated the correlation between RP and dosimetric measurements from the radiation therapy. Methods: Medically inoperable patients, n = 44, with peripherally located NSCLC stage I-II, were treated with SBRT, with a total dose of 45–56 Gy in 3–8 fractions. Median age was 75 years, 43.2% were female and 60% had moderate to very severe COPD. Follow up included physical examination by pulmonologist, spirometry and single-breath lung diffusing capacity (DLCO) and CT evaluation at baseline and 1.5, 3, 6, 9 and 12 months after SBRT. Results: We constructed three groups for grading RP based on CTCAE version 5.0 and imaging changes according to EORTC (LENT-SOMA) Non-RP (asymptomatic or mild symptoms and slight imaging changes, n = 19, 43%), Asymptomatic, radiology-only RP (asymptomatic or mild symptoms, increased density imaging changes, n = 17, 39%) and Symptomatic and radiology-detected RP (moderate and severe symptoms and increased density imaging changes, n = 8, 18%). Active smokers and patients with emphysema were overrepresented in non-RP group. In the symptomatic RP group, DLCO and FEV1 dropped almost 5% 4-6 weeks after SBRT, before symptoms and imaging changes, and DLCO, FVC and FEV1 dropped significantly at 3 months (table). Development of RP was associated with critical dose-volume parameter 1000ccm and 1500ccm. Several dosimetric parameters significantly negative correlate with FVC-drop at 1 and 3 months only in symptomatic RP. Conclusions: Active smokers and patients with emphysema have less propensity of RP. Symptomatic RP is seen with a presymptomatic drop in FEV1 and DLCO occurring 4-6 weeks after SBRT. Critical dose-volume parameter is important parameters for RP. Correlation between dosimetric parameters and FVC-drop in symptomatic RP. Clinical trial information: NCT02428049 . [Table: see text]
Comparison between T1 with lymph node metastases and T3-4 without lymph node metastases in patients with non-small cell lung cancer.
Authors: Liang Naixin , Cao Lei , Cao Zhili , Bing Zhongxing , Gao Chao , Wang Yanyu , Wang Yadong , Jia Ziqi , Yang Xiaoying , Li Chengcheng , Gong Fuyu , Wang Guoqiang 
Published: May 2020

e21074 Background: Patients with small tumor size but lymph node metastases (T1N1-N3, T1N1+) and patients with large tumor size but without lymph node metastases (T3-4N0, T3+N0) mainly belong to stage IIB to IIIA according to the 8th version TNM staging. However, whether the contradictory between tumor size and lymph node may influence the survival and the underlying genomic differences have not been fully studied. Methods: Whole-exome sequencing and RNA sequencing data for 1001 patients with NSCLC including 514 lung adenocarcinoma (LUAD) and 487 lung squamous cell carcinoma (LUSC) were downloaded from TCGA. The prognosis between patients with T1N1+ and T3+N0 has been investigated. The DNA sequencing data and RNA sequencing data from TCGA were used to study the underlying mechanism. Results: Patients with T3N0+ consisted of 80.2% Stage IIB and 17.4% Stage IIIA and patients with T1N1+ consist of 66.7% Stage IIB and 25.9% Stage IIIA. There were no differences in race, age, staging or neoadjuvant history between T1N1+ and T3+N0 cases. T1N1+ patients were more frequent among females (P = 0.02) and were more likely to be adenocarcinomas (P = 0.01) compared to T3+N0. Patients with T1N1+ was associated with a prolonged disease-free survival (DFS) (HR, 0.47; 95% CI, 0.28-0.79; P < 0.05) and progression-free survival (PFS) (HR, 0.31; 95% CI, 0.17-0.56; P < 0.001) than patients with T3+N0. In the multivariable cox proportional hazards regression model including stage, patients with T1N1+ still had increased PFS (HR, 0.45; 95% CI, 0.26-0.82; P = 0.009) and DFS (HR, 0.38; 95% CI, 0.16-0.95; P = 0.04) compared to T3+N0 cases. Moreover, patients with T1N2, belong to Stage IIIA according to AJCC 8th edition TNM staging, had a superior DFS (P = 0.01) and PFS (P = 0.04) compared with the patients with T3N0, who are in Stage IIB. Further investigation revealed that the tumor mutation burden was no significant difference between two groups (P > 0.05). There was no difference in genomic alterations between groups in LUSC and LUAD. GSEA analysis revealed that gene expression involved in DNA repair signaling was enriched in T1N1+ patients in LUSC and LUAD. Conclusions: Patients with T1N1+ shows a longer DFS and PFS compared with patients with T3+N0, especially T1N2 cases who belong to Stage IIIA show a better prognosis compared with T3N0 patients who are in Stage IIB, indicating the AJCC 8th edition TNM staging need to be refined. Moreover, the better prognosis in T1N1+ patients may be related with DNA repair signaling genes enrichment.
Predictive value of the Lung Immune Prognostic Index (LIPI) in locally advanced non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) in the multicenter retrospective study.
Authors: Oya Yuko , Saito Go , Tamiya Akihiro , Kawachi Hayato , Fujimoto Daichi , Iwasawa Shunichiro , Suzuki Hidekazu , Niitsu Takayuki , Matsumoto Hirotaka , Miyauchi Eisaku , Yokoi Takashi , Mitsui Miho , Uenami Takeshi , Sakata Yoshihiko , Nakachi Ichiro , Okada Asuka , Hara Satoshi , Teraoka Shunsuke , Kokubo Masaki 
Published: May 2020

e21076 Background: PD-L1 inhibitor, durvalumab has been approved since the PACIFIC study showed its efficacy as consolidation therapy after CCRT for locally advanced NSCLC. But predictive factor for the efficacy of CCRT on this post PACIFIC era have not been known. LIPI has been proposed as a new biomarker for the anti-PD-1 therapy of advanced NSCLC. In this study, we investigated the usefulness of LIPI as a predictive marker in multicenter cohort of patients with locally advanced NSCLC who received CCRT as initial treatment. Methods: 219 patients with available baseline LIPI were reviewed. The progression free survival (PFS) was estimated by the Kaplan-Meier method, and LIPI were calculated at baseline. Kaplan-Meier estimates of PFS and recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox and logistic regression models, respectively, adjusted for age, sex, ECOG-PS, smoking, histology, TNM stage, chemotherapy regimens, Body mass index (BMI), PD-L1 status, EGFR or ALK mutation, and baseline LIPI. Results: 62.5% (n = 137) of the patients had a good (0 factors) LIPI, while 37.5% (n = 82) had intermediate (1 factor) and poor (2 factors) LIPI respectively. In multivariable analysis, good LIPI (0 factors) were significantly associated with longer PFS (HR = 0.46, 95% CI 0.28-0.75; P < 0.01) as did ECOG-PS0 (P < 0.01), ≤stageIIIA (P < 0.01), being treated with durvalumab after CRT (P = 0.04). There were no difference in the patient characteristics between good LIPI and intermediate/poor LIPI, significantly. Higher LIPI (1 or 2 factors) were strongly prognostic factor for recurrence after CCRT in multivariate analysis (P = 0.04), along with ECOG-PS1≤ (P < 0.01), stage IIIB≤ (P < 0.01). Conclusions: The good LIPI predictive value for PFS and disease control in patients treated with CCRT was confirmed. Although a strong statistical significance, we needs to be confirmed further with longer follow-up and prospective study.
KRAS G12C mutation associated outcomes among patients with locally advanced non-small cell lung cancer.
Authors: Qian David , Behera Madhusmita , Steuer Conor Ernst , Pakkala Suchita , Carlisle Jennifer W , Owonikoko Taofeek Kunle , Fischer-Valuck Benjamin Walker , Kesarwala Aparna Hemant , Bradley Jeffrey , Curran Walter J , Ramalingam Suresh S. , Higgins Kristin Ann 
Published: May 2020

e21079 Background: Recent progress in targeted therapy includes the demonstration of promising anti-tumor activity and safety of a KRAS inhibitor in patients with advanced malignancies harboring the G12C somatic mutation ( KRASG12C). KRAS mutations are present in one-third of all non-small cell lung cancers (NSCLCs), of which KRASG12C comprises about 40%. In this study we characterize the outcomes of patients with stage III NSCLC who received radiotherapy, stratified by KRASG12C status. Methods: Level 3 data for NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA). Clinical and somatic mutation data were analyzed for the 118 NSCLC patients with stage III disease whose treatment included radiotherapy with or without chemotherapy. Overall survival (OS) and progression-free survival (PFS) were then compared between patients whose tumors possess versus lack KRASG12C using Cox proportional hazards regression. Results: This TCGA cohort study consists of 75 males and 43 females with stage III NSCLC (57 adenocarcinomas and 61 squamous cell carcinomas) enrolled between February 2010 and November 2014. Presence of KRASG12C was detected in 7 patients (6%) and conferred poorer OS (HR 3.14, 95% CI 1.12–8.84, P = 0.030) as well as PFS (HR 3.74, 95% CI 1.46–9.56, P = 0.0059) compared to absence of KRASG12C, with median survival of 9.0 versus 28.9 months and median time to progression of 8.5 versus 16.8 months. All 7 patients with KRASG12C had lung adenocarcinomas (ACs). Inferior survival of patients with KRASG12C persisted on subgroup analyses of AC and KRAS mutation status (Table). Conclusions: Among patients with stage III NSCLC in TCGA treated by radiotherapy, those with KRASG12C had significantly worse OS and PFS. Clinical trial of a KRAS inhibitor is a rational next step toward improving outcomes for this patient population, which has yet to be remarkably impacted by existing precision oncology approaches. [Table: see text]
APC fusions analysis in Chinese non-small cell lung cancer (NSCLC) using comprehensive NGS panel: A multicenter study.
Authors: Wang Liping , Xu Chunwei , Wang Wen xian , Zhu You-cai , Zhuang Wu , Huang Yun-jian , Fang Yong , Wang Hong , Zhang Yinbin , Wang Yafei , Chen Meifang , Li Jinluan , Cai Shangli , Fang Meiyu , Chen Gang , Lv Tangfeng , Song Yong 
Published: May 2020

e21086 Background: Currently, with the advances in detection techniques, such as next generation sequencing (NGS), more and more rare or atypical APC fusions had been identified. Such as APC-MCC, the importance of Wnt signaling in the pathogenesis of lung cancer and the efficacy of EGFR-TKI treatment had been demonstrated. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. To determine the frequency of the APC fusions in NSCLC and other tumors, we analyzed data from 2743 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, just two (0.07%) patients were identified with a APC fusion, including APC-MCC (1), APC-MRPL13 (1). The genes most frequently co-altered in patients with APC fusions were TP53 (100.00%), CCND1 (50.00%), ESR1 (50.00%), TNN (50.00%), MAP2K2 (50.00%) and POM121L12 (50.00%). Overall TMB in the APC fusions was low (median 2.16 mut/Mb). For treatments, both patients chose chemotherapy based on pemetrexed for first line, and a case example of advanced APC fusion NSCLC patients responding to anlotinib was actively being sought thru our database. Conclusions: The frequency of APC fusions in Chinese populations with NSCLC is extremely rare (0.08%). NGS can identify novel fusions and increase the list of actionable variants for patients. More patients can benefit from targeted treatment. In addition, for short-or long-term responses to TKI treatment, we can use the NGS assay to explore differential gene expression in the future.
Real-world data in limited-disease small-cell lung cancer: Results from a retrospective nationwide population-based cohort study in Korean HIRA database.
Authors: KIM Seoree , Kim In-Ho , Hong Ji Hyung , Sung Soo-Yoon , KIM Yeo Hyung , Lee Hyun Woo , Lee Jung Soo , Ko Yoon Ho 
Published: May 2020

e21096 Background: Small cell lung cancer (SCLC) is a highly proliferative and rapidly growing tumor with poor prognosis, even in limited disease (LD), and a timely and accurately high intensity therapy is necessary. During the concurrent chemoradiotherapy (CCRT), etoposide with platinum (EP) regimen is recommended, however, irinotecan with cisplatin (IP) regimen is also effective. Therefore, we performed a large-scale, retrospective and nationwide cohort study to analyze the efficacy of CCRT in patients with LD-SCLC Methods: The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2008, to November 30, 2016. Among 14,490 patients with SCLC patients who received chemotherapy, a total of 4,496 patients with LD-SCLC were analyzed. The primary objectives were to evaluate the survival outcomes of CCRT for LD-SCLC. Results: Patients who received EP-CCRT (n = 4,187) had better PFS of 11.233 months (95% confidence interval (CI) 10.900 – 11.667, P = 0.0477) and prolonged OS of 22.233 months (95% CI 21.233 – 23.333, P < 0.0001) than those who received IP-CCRT (n = 259; PFS = 9.567 months, 95% CI = 8.500 – 10.667; OS = 16.433 months, 95% CI = 14.467 – 18.333; P = 0.0477). After the failure of CCRT, we observed that dual chemotherapy (n = 925; OS = 9.133 months, 95% CI = 8.400 - 10.100) has better survival benefit (P < 0.0001) than single agent chemotherapy (n = 815; OS = 7.500 months, 95% CI, 6.933 – 8.133). IP chemotherapy demonstrated a better OS (9.567 months, 95% CI, 8.667 – 10.333 vs. 7.100 months, 95% CI, 5.100 – 10.400, P = 0.0170, respectively) than EP regimen in the platinum-resistant group; patients with PFS within 6 months after CCRT. However, in platinum sensitive group; patients who recurred after 6 months, the clinical benefit of EP regimen was superior to IP regimen (OS = 17.183 months, 95% CI, 13.033 – 25.633 vs. 6.617 months, 95% CI, 5.433 – 7.767; P < 0.0001). Cox proportional hazards regression analysis demonstrated that age, EP-CCRT, and dyslipidemia retained significant associations with OS after adjusting for all variables. Conclusions: In Korean population, concurrent thoracic radiotherapy with EP regimen had significantly favorable effects on OS and PFS. In addition, after the failure of CCRT, combination chemotherapy had clinical benefits over single agents. Among combination chemotherapy, IP combination regimen showed significantly favorable effects on OS and PFS, especially in the platinum-resistant group.
Weekly chemotherapy instead of best supportive care alone must be considered for patients of small cell lung cancer with poor performance status.
Authors: Shrivastav Gunjan , Gupta Alok , Sonthwal Neha , Singla Suhas Kirti , Mohindra Tarun , Chaturvedi Harit Kumar , Rohatgi Nitesh 
Published: May 2020

e21102 Background: Many patients of Small Cell Lung Cancer (SCLC) present with advanced age & comorbidities. Although chemotherapy may benefit these patients, therapy is denied due to treatment toxicities. We studied tolerability and efficacy of weekly Etoposide with carboplatin in patients unfit for 3-weekly regimen to analyze the hypothesis if small dose weekly chemotherapy can replace the current standard of care of best supportive care (BSC) alone in patients with poor performance status (PS). Methods: We retrospectively studied consecutive patients of SCLC treated between January 2015- December 2017. Based on team’s assessment, patients received either Etoposide100 mg/m2 (Day 1,2,3) + Cisplatin25 mg/m2 (Day 1,2,3) (or Carboplatin AUC5 Day 1) q 21 days OR Etoposide100 mg/m2 + Carboplatin(AUC2)q weekly OR BSC. Responses at 6-9 weeks of therapy and toxicities were studied according to RECIST 1.1 and CTCAEv4 criteria respectively. Results: 66 patients were diagnosed with SCLC. 24 patients received 3-weekly chemotherapy regimen (Group A). Of the 42 unfit patients, 21(50 %) received weekly chemotherapy regimen (Group B). Median age was higher in Group B ( 66 vs 61 yrs ) and Co-morbidities (≥ 2)were also more in Group B, 53 vs 33 %. Furthermore, Group B had more brain metastases (38 vs 21 %) but there was equal distribution of liver metastases and SVCO (4 patients each group). Altogether Group B had worse prognostic patients. In Group A the median number of chemotherapy cycles received were 4.5 (1-8) over a median duration of 3.37 months (0.75 - 6) while in group B the median number of chemotherapy cycles were 2 (1-5) over 1.5 months (0.5 - 3.75). G-CSF was required in 22(92%) in Group A and 15(71%) in Group B. Grade 3-4 toxicity and Febrile neutropenia were seen in 11(46%) and 7(29%) patients in Group A respectively and 8(38.1%) and 7(33%) patients in Group B respectively. Progressive disease was seen in 3(13%) and 6(29%) patients in group A and B respectively. Objective response was seen in 14(59%) and 9(43%) in Group A and B respectively. Clinical benefit rate (CBR) (Objective response + Stable disease) was 75% in Group A and 57% in Group B. Among patients with brain metastasis, CBR was 60% in Group A and 50% in Group B. This was better than most patients that are not offered treatment. Conclusions: Although 3 weekly doublet remains a better regimen, weekly etoposide and platinum is a valid option for patients unfit for standard regimen with no excess toxicity. Clinical benefit is seen irrespective of poor prognostic features.