bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of cisplatin, doxorubicin, and cyclophosphamide (PAC) compared to other regimens for patients with unresectable or metastatic thymic carcinoma: A single-institution retrospective analysis.
Authors: Wuthrich Brice , Maniar Rohan , Heldman Emily , Laniak Louis , Davis Hannah , Ardeshir-Larijani Fatemeh , Spittler Aaron John , Kesler Kenneth , Loehrer Patrick J. 
Published: June 2023

e20650 Background: Thymic Epithelial Tumors (TETs) are uncommon tumors of the anterior mediastinum comprised of thymomas and Thymic Carcinomas (TC). Given the rarity of these tumors, little data exists regarding the comparative effectiveness of various combination therapies. Platinum-based treatment regimens in combination with anthracyclines (e.g., PAC), taxanes (e.g., carboplatin plus paclitaxel (CT)) or etoposide (PE) have demonstrated efficacy in TETs in the front-line setting (although current NCCN guidelines recommend only CT for the treatment previously untreated advanced TC). We sought to characterize the efficacy of these regimens for TCs in a real-world setting. Methods: We conducted a single-institution, retrospective database analysis of 164 TC patients seen at the IUSCCC from 1996 - 2020. Of those patients, 42 met the study criteria as having a de novo diagnosis of TC treated with front-line systemic chemotherapy and available outcome data. Chemotherapeutic intervention and demographic/clinical variables were evaluated in this study. Data was compiled and collected using descriptive statistics and the Kaplan Meier method for survival analysis via GraphPad Prism software. Results: Of the 42 patients identified to have sufficient data, the median age was 55.6 years (range, 21 - 82). The median follow-up for patients was 23 months. Metastatic sites of disease included the pleura (11%), lymph nodes (11%), bone (10%) and lungs (5%). Multi-site involvement accounted for 36% of cases. Squamous cell carcinoma (SCC) was found in 52.3% (n = 22) of the patients, while 26.2% (n = 11) had rare TC subtypes, including, SCC with basaloid features, SCC with neuroendocrine features, and neuroendocrine (21.4% of cases were classified as TC only). Most patients received first line treatment with PAC (n = 16), CT (n = 13) or PE (n = 9). There was no difference in progression free survival (PFS) for TC patients treated with PAC or CT (10.5 v. 7.5 months, respectively, NS). PE was associated with inferior outcomes compared to PAC (4.5 vs. 10.5 months, ***p = 0.0005) and CT (4.5 vs. 7.5 months, *p = 0.0158), respectively. A subgroup analysis of rarer histologic subtypes revealed a trend towards improved PFS for patients who received PAC compared to CT (9.5 v. 4.5 months, NS). Conclusions: The results of our study support PAC combination chemotherapy as a reasonable alternative for patients with previously untreated advanced TC. Further studies to correlate the genomic differences of common and uncommon TC subtypes will be crucial to optimize the role of conventional and targeted systemic therapies in this rare malignancy.
Genomic biomarker testing and treatment in advanced NSCLC: Practice patterns and barriers in a global survey of oncology point-of-care mobile app users.
Authors: Jacobson Anne , Pozniak Eugene , Bambury Kevin Dan , O'Carroll Eoin , George Renita , Banna Giuseppe Luigi 
Published: June 2023

e21004 Background: Appropriate molecular testing and oncogene-directed treatment planning are essential best practices for managing patients with advanced non-small cell lung cancer (aNSCLC) who are potential candidates for targeted therapy. Understanding real-world practices and challenges among oncology health care professionals (HCPs) is necessary to inform the development of digital tools and other initiatives that support optimal care. Methods: From 12/2022 to 01/2023, 142 HCPs who treat aNSCLC completed an online survey related to NSCLC genomic biomarker testing and treatment planning. Participants were recruited from a global cohort of HCPs who are active users of an oncology point-of-care mobile app following the launch of an NSCLC decision-support tool and educational intervention. Results: Participants included medical oncologists (87%), surgical oncologists (3%), pulmonologists (2%), and nurses (4%) from 62 countries. Most (72%) reported providing care for ≥5 pts/month with aNSCLC; 27.5% provide care for ≥20 pts/month. HCPs reported testing the following genomic biomarkers in 100%, 50-99%, 1-49%, and 0% of patients with aNSCLC, respectively: EGFR (44%, 23%, 27%, 4%), ALK (41%, 20%, 29%, 8%), ROS1 (32%, 19%, 23%, 22%), BRAF (23%, 20%, 23%, 31%), NTRK (12%, 14%, 22%, 47%), HER2 (11%, 17%, 27%, 42%), KRAS (23%, 15%, 25%, 33%), RET (13%, 13%, 25%, 44%), MET exon 14 (15%, 12%, 27%, 42%). Reported barriers varied in frequency (Table 1), with the most common involving biomarker test turnaround time. The majority of HCPs reported often or sometimes feeling that “results take too long,” and they (80%) and/or their patients (81%) are eager to start treatment. HCPs also commonly reported often or sometimes not being sure about which tests to order (45%), when to test (43%), which 1st-line therapy to select (45%), which 2nd- or later-line therapy to select (57%), and how to manage adverse events of oncogene-targeted therapy (50%). Conclusions: In current real-world practice, the majority of HCPs report suboptimal testing for targetable genomic alterations ( EGFR, ALK, ROS1, BRAF, NTRK, HER2, KRAS, RET, and MET exon 14) in patients with aNSCLC. Identified common barriers represent opportunities for future interventions to improve biomarker-directed NSCLC care. [Table: see text]
Impacts of androgen pathway manipulation on patients with lung cancer.
Authors: Lee Po-Hsin , Tseng Jeng-Sen , Huang Yen-Hsiang , Hsu Yu-Wei , Hsu Kuo-Hsuan , Yang Tsung-Ying , Lin Ho 
Published: June 2023

e21010 Background: Sex hormone may play a role in lung cancer pathophysiology. We aimed to evaluate if androgen pathway manipulation (APM) is associated with better survival in patients with lung cancer, and how finasteride, a 5-alpha reductase inhibitor, impacts androgen receptor (AR) activation and growth of lung cancer cells. Methods: In this retrospective hospital-based cohort study, we screened all men with lung cancer diagnosed during the period from January 2006 to December 2021. APM exposure was defined as using antiandrogens, 5-alpha reductase inhibitors, or gonadotropin-releasing hormone agonists for > 30 days after lung cancer diagnosis. The in vitro study was conducted on A549 lung cancer cells; while the tumor xenograft model was conducted on BALB/c nude mice. Results: Among 4744 men with lung cancer, 98 (2.1%) were identified as having APM exposure. The majority of patients (73.5%) received 5-alpha reductase inhibitors. The patients with APM exposure were older (71.5 vs. 67.0, p < 0.001), had a higher proportion of having prostate cancer (27.6% vs. 1.4%, p < 0.001), and had a smaller proportion of having metastatic lung cancer (41.8% vs. 54.0%, p = 0.003), compared to those without APM exposure. In multivariable Cox proportional hazards analysis, patients with APM exposure experienced better OS compared to those without exposure (Hazard ratio 0.57; 95% CI, 0.44–0.73, p < 0.001). In in vitro study, we illustrated that AR protein stimulated the cell proliferation of A549 cells. Finasteride reduced the AR protein expression and inhibited A549 cell growth. Finasteride promoted ubiquitination and degradation of AR protein and therefore interfered the stability of AR protein. Furthermore, finasteride inhibited cell cycle progression and promoted apoptosis of A549 cells. The in vivo results also supported the inhibition effect of finasteride on lung cancer growth. Conclusions: APM was associated with better OS in male patients with lung cancer. Finasteride interfered with the stability of AR and inhibited A549 lung cancer cell growth. Our findings indicated an oncogenic role of AR on lung cancer which may provide potential therapeutic and targets for lung cancer. The inhibition effect of finasteride on lung cancer might be of benefit for future treatment strategies, prevention and control.[Table: see text]
A comparative analysis of next-generation sequencing based on plasma cfDNA and tumor tissue DNA in patients with advanced lung cancer.
Authors: Li Tian , Lin Jingmin , Peisu Suo , Li Yingmei , Chen Shifu , Wang Yunfan 
Published: June 2023

e21021 Background: Although liquid biopsy based on plasma cell-free DNA (cfDNA) provides a non-invasive detection method for cancer patients, tissue biopsy is still the gold standard for molecular subtyping. The concordance of these two techniques has been evaluated in certain cohorts. The comparison of plasma cfDNA and tissue DNA NGS ina large Chinese cancer cohort is yet to be analyzed. Methods: We retrospectively reviewed HaploX's genomic sequencing data from July 2021 to December 2022 to assess the concordance between plasma cfDNA and cancer tissue DNA. A total of 589 advanced lung cancer patients with matched tissue and plasma sample were included in the study. Tissue and peripheral blood was collected at the same time during surgical operation or biopsy. Tissue DNA and plasma cfDNA were isolated and prepared for the NGS with commercially available kits. The positive percent agreement (PPA) between plasma cfDNA sequencing and tissue sequencing, the negative percent agreement (NPA), positive predictive value (PPV), negative predictive value (NPV), and overall percent agreement (OPA) were calculated and compared. Results: The positive percent agreement (PPA) of plasma cfDNA sequencing compared with tissue sequencing were 78% (EGFR, 82%; KRAS, 71%; HER2 mutation, 76%; BRAF V600E mutation, 75%; ALK fusion, 74%; RET fusion, 60%; ROS1 fusion,33.3%; MET exon14 skipping, 50%). EGFR mutations included EGFR p.L858R,19del, p.C797S, p.L861Q, p.T790M, KRAS mutations included p.G12X and p.Q61X.， HER2 mutations included gain-of-function mutations；NPA was 92.4%，PPV was 93.8%，NPV was 74.4%，OPA was 84%. Conclusions: The positive mutation detection consistency of plasma cfDNA sequencing and tissue sequencing in advanced lung cancer patients is 78%, indicating that liquid biopsy based on plasma cfDNA is reliable in most advanced lung cancer patients, but there are some limitations in gene fusion and MET exon 14 jumping detection. Liquid biopsy based on plasma cfDNA can meet most clinical genomic testing needs in general, especially when tissue is not available, but physicians need to be more cautious with negative results. Keywords: Liquid biopsy, Next-generation sequencing (NGS), Concordance Analysis, Lung Cancer.
Identification and characterization of karyopherin a-2, a nuclear export protein in lung adenocarcinoma.
Authors: Kim Seoree , Lee Heejin , Yoon Jung-Sook , Jeong Joon Won , Lee Ji Hyun , Chun Sang Hoon , Won Hye Sung , Hong Soon Auck , Kang Keunsoo , Ahn Young-Ho , Ko Yoon Ho , An Hojung 
Published: June 2023

e21025 Background: It is emerging that the Karyopherin a-2 (KPNA2), a nucleocytoplasmic transport protein, regulates the nuclear import of macromolecules and contributes to carcinogenesis and changes in cellular phenotype. In particular, it can be a poor prognostic marker by causing aberrant subcellular localization of DNA damage response proteins or OCT4-c MYC pathway molecules depending on the type of carcinoma and inducing anticancer resistance. In some carcinomas, an association with the p53 oncogenic pathway has been reported, showing good prognostic values. We aimed to investigate the clinical significance and metabolic pathway of stable cancer associated fibroblast (CAF) and cancer cells for KPNA2. Methods: We retrospectively analyzed the data extracted from EMR for NSCLC patients receiving curative surgical resection in Uijeongbu and Bucheon St. Mary’s Hospitals (n = 165). Immunohistochemistry staining was performed on the tumor microarray samples using antibodies against KPNA2. The functional assay and gene silencing was conducted. Results: Based on the TMA staining, mean KPNA2 score was 36.5 [0-240] and median value was 10. The clinical and pathological information of the experimental group is as follows. Table 1. Scatter plots and correlation between KPNA2 expression levels and tumor invasiveness markers reveals that high KPNA2 expressor was related to lymphatic invasion (p = 0.00782), advanced stage (p = 0.0202) and current smoker (p = 0.0074). KPNA2 expression was higher in squamous cell carcinoma(SqCC) histotype than in adenocarcinoma (SqCC ratio (%), 13.5 vs 43.4 in Low exp vs High exp; p = 0.007). Patients with high expression of KPNA2 showed shorter survival than other patients (median OS (months), 72.8 vs 42.2, P < 0.0001; median RFS (months), 72.8 vs 32.1, P < 0.0011) and relevant to high recurrence (recurrence rate (%), 24.7 vs 44.7, p = 0.007). Further, high KPNA2 expression was associated with poor survival outcomes. To test the effect of KPNA2 on cancer cell invasion, we knocked down Kpna2 via shRNA. Spheroids composed of H1299, Calu-6, A549, HCC827 lung cancer cells with either Kpna2-overexpression or Kpna2-knockdown, and spheroid invasion was then monitored for two days. Eminently, the 3-D invasion of spheroids was suppressed via Kpna2 knockdown. In addition, Kpna2-overexpressing cells promoted cancer invasion to a greater extent than control. Conclusions: In conclusion, our results suggest that KPNA2 protein expression has a poor prognostic association, revealed by its association with survival outcome or invasiveness markers. Its clinical significance as an oncogenic target molecule is emerging, and further evaluation using an organoid model is in progress.
Prognostic impact of TP53 mutations in metastatic non-squamous non-small-cell lung cancer.
Authors: Mathiot Laurent , Nigen Benoît , Goronflot Thomas , Hiret Sandrine , Doucet Ludovic , Pons-Tostivint Elvire , Bennouna Jaafar , Denis Marc G. , Herbreteau Guillaume , Raimbourg Judith 
Published: June 2023

e21033 Background: TP53 is the most common mutated gene in lung cancer, with a wide range of different mutations. It is unclear whereas TP53 mutations impact the prognosis of patients treated in first-line for advanced or metastatic non-squamous non-small-cell lung cancer (nsNSCLC). Methods: In this retrospective study, we studied the hypothetical impact of TP53 mutations in patients treated in first-line for advanced or metastatic nsNSCLC on overall survival (OS) and progression-free survival (PFS). Secondary objectives were to explore OS and PFS according to treatment received among the two groups. Results: From January 1, 2018 to May 31, 2021, 222 patients were included, 129 in the mutTP53 groups and 93 in the wtTP53 group. Estimated median follow-up time was 26.4 months (95% CI, 24.5-33.5) for mutTP53 group and 24.2 months (95% CI, 20.3-27.5) for wtTP53 group. Median OS (mOS) was 17.5 months (95% CI, 11.3-21.5) in the mutTP53 and 9.5 months (95% CI, 7.3-13.4) in the wtTP53 group, with a significant difference ( p= 0.039). Median PFS was 6.19 months (95% CI, 5.3-7.39) in the mutTP53 and 3.16 months (95% CI, 2.26-5.23) in the wtTP53 group, with a significant difference ( p= 0.011). In multivariable analysis, after adjusting for confounders, the risk of death over the study period appears to be lower in the mutTP53 group than in the wtTP53 group, although this result is not significant (HR 0.74, 95% CI 0.51-1.07, p= 0.11). In subgroup analysis by treatment received (chemotherapy, immune checkpoint inhibitors (ICI) or combination), only patients in the mutTP53 group treated with ICI had a significant improvement in OS compared to patients in the wtTP53 group. The mOS was 24.7 (95% CI, 20.8-NR) vs 10.6 months (95% CI, 4.5-NR) (HR 0.30, 95% CI 0.14-0.64, p= 0.002) for ICI group, and mOS was 20.5 (95% CI, 8.8-NR) vs 16.8 months (95% CI, 8.1-NR) for combination group (HR 1.73; 95% CI, 0.61-4.91, p= 0.3). Conclusions: TP53 mutations is associated with a better OS and PFS than wtTP53 in patients treated with ICI, but we found no difference for patients treated with chemotherapy or combination of chemotherapy and ICI. WtTP53 patient had a short OS on ICI and improved when ICI is combined with chemotherapy. This study emphasizes the importance of evaluating in prospective study the prognostic and predictive role of TP53 mutations in advanced or metastatic nsNSCLC.
Differential efficacy of tyrosine kinase inhibitors (TKIs) according to the types of EGFR mutations and agents in non-small cell lung cancer (NSCLC): A real-world study.
Authors: Choi Yong Won , Kim Tae-Hwan , Ahn Mi Sun , Lee Hyun Woo , Kang Seok Yun , Choi Jin-Hyuk 
Published: June 2023

e21040 Background: Both 1st and 2nd-generation (gen) EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data about the difference in the efficacy of EGFR-TKIs according to types of EGFR mutations and agents. Methods: This retrospective real-world study evaluated the outcome and clinicopathologic characteristics including the type of EGFR mutations in 237 advanced NSCLC patients (pts) treated with 1st or 2nd-gen (afatinib) EGFR TKIs as first-line therapy. Results: The median progression-free survival (PFS) and overall-survival (OS) of all pts were 11 months (M) and 25M, respectively. In univariate analysis, pts with exon 19 deletion (del) (n = 130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p = 0.047), without difference in PFS (p = 0.138). Pts treated with afatinib (n = 60) showed significant longer median OS compared to those treated with 1st gen TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p = 0.037). In pts with exon 19 del, there was no significant difference in median PFS (p = 0.868) and OS (p = 0.361) between pts treated with afatinib and those with 1st gen TKIs, while significantly better PFS (p = 0.042) and trend in OS (p = 0.069) were observed in pts receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p = 0.028), while age > 70 years (p = 0.017), ECOG performance status ≥2 (p = 0.001), primary metastatic disease (p = 0.007), and synchronous brain metastasis (p = 0.0026) were independent prognostic factors of poor OS. Conclusions: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC pts receiving first-line EGFR TKIs. Moreover, in pts with exon 19 del, first generation TKIs seem to be a reasonable option if osimertinib is unavailable.
Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China.
Authors: Yang Wenyu , Gao Ming , Wang Ting , Jing Fangfang , Zhang Fan , Tao Haitao , Ma Junxun , Hu Yi , Wang Lijie 
Published: June 2023

e21045 Background: Both pembrolizumab and sintilimab have been approved for the first-line treatment of patients with advanced squamous lung cancer in China. The differences of the two drugs in efficacy and safety are unclear. The aim of this study was to compare the efficacy and safety in advanced squamous lung cancer patients in real world. Methods: This was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The aim was to compare the objective response rate (ORR), disease control rate (DCR),progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Results: A total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P = 0.634). The DCR was 92.10% and 92.10% in two groups respectively (P = 0.991). The median PFS was 22.2 months in sintilimab group compared with 16.5 months in pembrolizumab group[ HR = 0.743; 95% CI: 0.479-1.152; P = 0.599]. Patients treated with sintilimab had a median OS of 30.7 months and a median OS did not achieve with pembrolizumab. The incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63)in the sintilimab group, and 90.1% (91/101) in the pembrolizumab group. Conclusions: Sintilimab and pembrolizumab were similar as a first-line treatment for patients with advanced squamous lung cancer in efficacy and safety. [Table: see text]
Effect of intrathecal pemetrexed on survival in patients with lung adenocarcinoma with leptomeningeal metastasis: A propensity score matching analysis.
Authors: Hong Yaping , Miao Qian , Zhuang Wu , Zheng Xinlong , Huang Zhangzhou , Xu Yiquan , Lin Gen 
Published: June 2023

e21048 Background: The effect of intrathecal chemotherapy (ITC) on the survival of leptomeningeal metastasis (LM) from lung adenocarcinoma (LUAC) has not yet been clearly defined. Methods: LUAC patients with cytologically or radiographically proven LM and receiving systemic pharmacotherapy after LM diagnosed were collected at the Fujian Cancer Hospital from July 2018 to March 2022. Patients were divided into intrathecal pemetrexed (IP) or non-IP groups and then propensity matched 1:1 into two groups. Among the matched cohort, the log-rank tests and multivariable Cox proportional hazards regression models were performed to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. Results: A total of 165 patients with LM were included; 83 were in the IP group and 82 were in the non-IP group. After PSM, 114 patients were identified in the matched cohort. There were no statistically significant differences between IP and non-IP groups in median overall survival (13.2 months versus 10.1 months; hazard ratio 0.84, 95% CI: 0.53 - 1.33; p = 0.49). In the multivariable Cox regression analysis, only ECOG PS was confirmed as an independent prognostic factor for overall survival in the matched cohort (hazard ratio 1.83, 95% CI: 1.04 - 3.23; p = 0.037). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (14.3 months versus 1.6 months; p = 0.002), but not in patients with good ECOG PS (12.8 months versus 12.6 months; p = 0.884). Conclusions: Our results indicated that IP may not bring survival benefit to all LUAC patients with LM, but may improve survival in patients with poor ECOG PS.