bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal trends in small cell lung cancer: Analysis of the U.S. Surveillance, Epidemiology and End Results (SEER) database.
Authors: Cohen Sean , Brennan Ben , Banerjee Mousumi , Kalemkerian Gregory Peter
Published: June 2023

e20641

Background: Prior studies reported that the incidence of small cell lung cancer (SCLC) had decreased, while overall survival (OS) had improved, from 1973-2002. In 2019, immunotherapy was integrated into the standard therapy for patients with extensive-stage (ES) SCLC based on studies demonstrating an improvement in OS. This study aims to provide an update on SCLC incidence and survival at the dawn of this new therapeutic age. Methods: We analyzed data on all patients with primary lung cancer in the SEER17 database from 2000-2019. Patients with ICD-O codes 8002 and 8041-8044 were classified as SCLC. Incidence rates were calculated based on the standard U.S. population. OS was calculated based on censored time to death or last follow-up, whichever occurred earlier. Temporal trends in incidence and OS were evaluated using the Mantel-Haenszel chi-square statistic. Results: Of 847,747 patients with primary lung cancer, 111,263 (13.1%) had SCLC. The incidence rate of SCLC steadily declined from 8.8/100,000 in 2000 to 4.8/100,000 in 2019. Over this time, the incidence rate decreased among both males (10.7 to 5.1/100,000) and females (7.5 to 4.6/100,000), and among all examined races (NHW: 10.1 to 6.0/100,000, NHB: 8.3 to 4.7/100,000, NHA/PI: 3.5 to 1.6/100,000, Hispanic: 4.0 to 1.9/100,000). The proportional incidence of SCLC relative to NSCLC also continued to decline, from 14.5% in 2000 to 11.8% in 2019. The male:female ratio of SCLC patients decreased from 1.14:1 in 2000 to 0.93:1 in 2019. The percentage of patients with limited-stage (LS) SCLC decreased from 31.1% in 2000 to 26.4% in 2019. The majority of patients with LS-SCLC were female throughout the study period (53.9%), while most of those with ES-SCLC were male (51.8%). Among patients with LS-SCLC, 2-year OS increased from 26.7% in 2000 to 36.7% in 2017, while 5-year OS increased from 11.3% in 2000 to 15.6% in 2014. Among patients with ES-SCLC, 2-year OS increased from 6.4% in 2000 to 8.4% in 2017, while 5-year OS increased from 2.2% in 2000 to 2.9% in 2014. Both 2-year and 5-year OS increased in LS-SCLC over the study period in both males and females (M: 2-year: 23.4% to 36.2%, 5-year: 9.9% to 15.2%; F: 2-year: 29.9% to 37%, 5-year: 12.8% to 16.0%). In ES-SCLC, 2-year OS increased in both males and females (M: 5.8% to 7.3%, F: 7.0% to 9.5%), while 5-year OS increased in females (2.2% in 2000 to 3.9% in 2014), but remained stable in males (2.3% in 2000 to 2.0% in 2014). Conclusions: Both the incidence and proportional incidence of SCLC have continued to decline in the U.S. over the past 20 years. The male:female ratio also declined, with women now accounting for the majority of patients with SCLC. The percentage of patients with LS-SCLC decreased, likely due to improvements in staging procedures. Overall survival has continued to improve, with greater gains seen in LS-SCLC than in ES-SCLC prior to the integration of immunotherapy.
Investigation of the prognostic significance of CD5, CD117, EZH2, POU2F3, MTAP and BAP1 in thymic carcinoma.
Authors: Naso Julia R. , Jenkins Sarah M. , Vrana Julie A. , Koepplin Justin W. , Olivier Kenneth R. , Cassivi Stephen D. , Molina Julian R. , Roden Anja C.
Published: June 2023

e20646

Background: Thymic carcinomas tend to be aggressive malignancies with variable patterns of immunostaining. We aimed to assess whether the outcome of patients with thymic carcinomas was associated with immunoreactivity for conventional and emerging immunohistochemical markers of thymic carcinoma versus thymoma. Methods: Scoring of CD5, CD117, EZH2, POU2F3, BAP1, and MTAP immunohistochemistry on whole slide sections was compared to overall survival (OS) and progression free survival (PFS) for 36 thymic carcinoma patients, 28 of whom had complete tumor resection and 8 of whom had incomplete tumor resection. Results: Positive CD5 staining (defined as staining in ≥50% of tumor cells) was present in 13/36 cases (36%) and was significantly associated with longer OS (P = 0.005, hazard ratio = 0.18, CI 0.03-0.63) but not PFS (P = 0.14, hazard ratio = 0.48, CI 0.16-1.26), whereas the other markers were not significantly associated with OS or PFS. Positive CD5 staining remained significantly associated with OS in squamous cell carcinoma subgroup analysis (n = 23, HR = 0.17, CI 0.03-0.65, P = 0.009), patients who did not receive neo-adjuvant treatment (n = 24, HR = 0.21, CI 0.03-0.85, P = 0.03) and after adjusting for incomplete resection (HR = 0.20, CI0.03-0.73, P = 0.01), M1 stage (HR = 0.19, CI 0.03-0.71, P = 0.01) or neoadjuvant treatment (HR = 0.19, CI 0.03-0.71, P = 0.01) in bivariate models. Positive CD5 staining was also significantly associated with age ≥60 years, absence of neoadjuvant treatment, and positive POU2F3 staining. Conclusions: CD5 staining in ≥50% of tumor cells was significantly associated with longer OS for thymic carcinoma patients. Our study supports the notion that CD5 immunohistochemistry may have utility as a prognostic marker for thymic carcinomas.
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.
Gaps and factors in patient awareness of biomarker test timing and purpose in non-small cell lung cancer (NSCLC): Baseline assessment for implementation of 4R Oncology model.
Authors: Mohindra Nisha Anjali , Trosman Julia R. , Houseknecht Stefanie , Feliciano Josephine Louella , Sacks Ruth Lauren , Cain Joan E. , Souter Benjamin , Waugh Wendi , Woodyard Jennifer , Martin Jeremiah , Schmidt Laura , Chang Cara , Rediske Anna , Zavala Sonia , Lycan Thomas William , Martin Nikki A. , Boehmer Leigh , Plotkin Elana , Lile Ashley , Weldon Christine B.
Published: June 2023

e21059

Background: Biomarker testing is necessary for optimal 1st line treatment selection in advanced NSCLC. Patient understanding of timing and purpose of biomarker testing is imperative for patient engagement in care, but is challenging to achieve (Martin Oncol Issues 2022). The 4R Oncology model of patient self-management and timely care delivery has been shown to improve patient knowledge of timing/sequence of care in breast cancer (Trosman JCOOP 2021) but has not been studied in NCLSC in relation to biomarker testing. 4R is being implemented at 5 centers (3 community and 2 academic) in NSCLC. We report baseline assessment of patient awareness of biomarker testing timing and purpose to inform 4R implementation. Methods: Pre-implementation surveys of patients with advanced NSCLC at 5 centers Aug – Dec 2022. Metrics are listed in Table. Results: Survey response rate: 46% (65/142). Respondents were 65% white, 42% high school educated or less, 46% with annual income ≤$30K. While all patients were aware of receiving non-biomarker tests, > 40% were not aware of receiving biomarker testing (Table). About half knew why or how long they needed to wait for results, but only 29% received this information from providers. Of those tested, the majority reported provider discussions of biomarkers or therapy selection and were clear about results or therapy selection. Awareness (eg knowing to wait for results before therapy) was associated with receiving printed NSCLC materials (45% vs 7%, p < .01), education above high school (69% vs 41%, p = .03) and income > $30K (67% vs 32%, p = .01). Willingness to wait for test results was associated with knowing how to prepare for treatment while waiting (89% vs 46%, p < .01). Race did not impact these metrics. Conclusions: Considerable gaps exist in patient awareness of timing and purpose of biomarker testing. We refined the 4R model to emphasize biomarker timing in printed visual material, facilitate patient-provider discussions and engage patients in health maintenance while waiting for results. We revised 4R to a lower literacy level. Results will be reported when available. [Table: see text]
Prognostic effects of TP53 variants co-occuring in patients with HER2-mutated non-small cell lung cancer (NSCLC).
Authors: Feng Jamie , Hueniken Katrina , Fan Zhen (Jason) , Corke Lucy , Leighl Natasha B. , Liu Geoffrey , Bradbury Penelope Ann , Sacher Adrian G. , Eng Lawson , Stockley Tracy , Tsao Ming Sound , Shepherd Frances A.
Published: June 2023

e21065

Background: TP53 variants are common in NSCLC and have been reported as prognostic of poor outcome. The impact of TP53 variants in ERBB2/HER2-mutated NSCLC is unclear. Methods: A total of 40 patients with HER2-mutated NSCLC at Princess Margaret Cancer Centre were identified retrospectively; next generation sequencing results were reviewed for TP53 variant status. Associations between TP53 status with patient and tumor characteristics, and outcomes (overall survival [OS] and progression-free survival [PFS]), were investigated. Median survival was computed by Kaplan-Meier estimator; differences between groups were assessed via Cox proportional hazards regression. Results: Co-occurring TP53 variants and HER2 mutations were found in 19/40 patients (47.5%). Median age was 64.5 years and most patients were female (65%), never-smokers (74%), and had adenocarcinoma (90%; Table 1). Median OS was 39.3 months (95% CI:31 months – not reached [NR]) in the TP53 wildtype (WT) cohort compared to 20.5 months (95% CI:3.7 months - NR) in the TP53 variant cohort (HR 2.65 (95% CI: 1.09-6.43; p = 0.03). Median PFS was 30.9 months [16.7-59.8] vs 15.9 months [10.2-NR], although not statistically significant (HR 1.86, 95% CI 0.83-4.18; p = 0.13). There was a tendency for presence of brain metastases at any point for those with TP53 variants (38% versus 63%, p = 0.11). Of the 29 de novo stage IV patients, 10 (36%) had first line targeted treatment. The rest had chemoimmunotherapy (29%), chemotherapy (25%) or immunotherapy (11%). Overall response rates were similar to first line palliative treatment (33% vs 38%, p = 1.00). Conclusions: Co-occuring TP53 variants with HER2 mutations are prognostic of shorter OS and PFS in NSCLC, and may be associated with a higher incidence of brain metastases. Our larger validation dataset with ~75 patients will be presented.[Table: see text]
Serum tumor biomarkers as a surrogate for radiographic assessment of non-small cell lung cancer.
Authors: Strum Scott , Vincent Mark David , Gipson Meghan , McArthur Eric , Breadner Daniel Adam
Published: June 2023

e21076

Background: Conventional tumor markers are positioned to serve as a useful adjunct in lung cancer management. However, most studies in this field have been specific to a particular disease stage or treatment regimen. Thus, the purpose of this research was to assess whether three minimally invasive, low-cost serum tumor markers (CEA, CA19-9, and CA-125) held associations with radiographic and clinical outcomes in non-small cell lung cancer (NSCLC) patients who received systemic therapy in a more comprehensive patient population. Methods: This was a single-center retrospective study of NSCLC patients treated between January 2016 and August 2020. Serum tumor markers were statistically analyzed for differences in patients who responded or progressed (RECIST 1.1 or iRECIST criteria), associations with demographic and clinical characteristics, and all-cause mortality in pre-defined populations. Disease response was assessed radiographically using RECIST 1.1 criteria. Results: From 533 NSCLC patients screened, 165 met inclusion criteria. Of these, 50.9% were male and 49.1% female. 69.7% had stage IV disease at baseline. The proportion of patients with an elevated CEA, CA-125, and CA19-9 at baseline were 58.8%, 50.9%, and 30.3%, respectively. A subset of 92 patients had paired tumor markers and radiographic scans, from which median (IQR) fold-change in tumor markers from nadir to progression was 2.13 (IQR 1.24 - 3.02; p < 0.001) for CEA (n = 47), 1.46 (IQR 1.13 - 2.18; p < 0.001) for CA19-9 (n = 46), and 1.53 (IQR 0.96 - 2.12; p < 0.001) for CA-125 (n = 47). Median (IQR) fold-change in tumor markers from baseline to radiographic response was 0.50 (IQR 0.27, 0.95; p < 0.001) for CEA (n = 39), 1.08 (IQR 0.74, 1.61; p = 0.99) for CA19-9 (n = 35), and 0.47 (IQR 0.18, 1.26; p = 0.008) for CA-125 (n = 35). Lastly, an elevated baseline CEA was not associated with a difference in overall survival (HR 1.05, 95% CI 0.63-1.74, p = 0.84) in patients with stage IV disease within the total population. Conclusions: Serum CEA, CA-125, and CA19-9 levels were significantly different than nadir in patients who progressed. CEA and CA-125 were significantly different than baseline in those who responded. These cost-effective tumor markers may serve as an important adjunct to clinical decision making. Analysis within a controlled clinical trial is warranted.
The impact of cationic amphiphilic antihistamines on patients with lung cancer receiving immunotherapy.
Authors: Chiang Cho Hung , Chiang Cho Han , See Xin Ya , HSIA YUANPING , Peng Chun-Yu , Horng Chuan-Sheng , Chang Yu-Cheng , Wang Shih-Syuan , Chiang Cho Hsien , Peng Cheng-Ming , Shiah Her-Shyong
Published: June 2023

e21078

Background: H1-antihistamines are long-used medications for the treatment of allergies. In preclinical studies, antihistamines, particularly those with cationic amphiphilic properties, have been found to have anti-tumor effects. In observational studies, H1-antihistamines have been associated with improved survival in patients receiving immune checkpoint inhibitors (ICIs) in pan-cancer association studies. However, the impact of antihistamines on lung cancer is unclear. We aim to evaluate the effect of antihistamines on lung cancer patients receiving ICIs. Methods: We conducted a retrospective cohort study at two tertiary referral centers in Taiwan involving lung cancer patients receiving ICI therapy. Antihistamines were subclassified into cationic amphiphilic and non-cationic amphiphilic antihistamines according to their lipophilic properties. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Results: We identified 336 lung cancer patients receiving ICIs, of which 294 were antihistamine users (43 cationic amphiphilic and 222 non-cationic amphiphilic) and 42 were non-antihistamine users. Compared with non-antihistamine users, antihistamine users had a longer OS (median 24.4 vs. 6.4 months, p = 0.002) and PFS (median 8.2 versus 4.1 months, p = 0.049). Among antihistamine users, cationic amphiphilic antihistamine users had a longer OS (median 38.0 versus 17.8 months, p = 0.015) and PFS (median 17.5 versus 6.2 months, p < 0.001) than non-cationic amphiphilic antihistamine users. In Cox proportional hazard analysis, antihistamines and particularly cationic amphiphilic antihistamines were associated with a 30-55% lower risk of all-cause mortality and disease progression. Conclusions: The use of antihistamines, particularly those with cationic amphiphilic properties, was associated with improved outcomes among lung cancer patients undergoing immunotherapy.[Table: see text]
Efficacy and safety of dose-escalated alectinib in patients with metastatic ALK-positive NSCLC and CNS relapse on standard dose alectinib.
Authors: Cheung Justin Matthew , Kang Jiyoon , Yeap Beow Y. , Peterson Jenn , Do Andrew , Digumarthy Subba R , Gainor Justin F. , Lin Jessica Jiyeong
Published: June 2023

e21079

Background: Central nervous system (CNS) metastases represent a common cause of morbidity and mortality in patients (pts) with ALK-positive (ALK+) non-small cell lung cancer (NSCLC), with limited therapeutic options. We previously reported re-induction of CNS responses using dose intensification of alectinib in two pts with metastatic ALK+ NSCLC who had experienced CNS progression on standard dose alectinib. However, this strategy has not been assessed in larger cohorts. Methods: In this retrospective study, pts were eligible if they had advanced ALK+ NSCLC with CNS relapse on standard dose alectinib (600 mg twice daily) and subsequently received dose-escalated alectinib (900 mg twice daily). Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events (trAEs) were graded per the CTCAE version 5.0. Results: 27 pts were eligible [male, 67%; median age at diagnosis, 53 (range, 31-69)]. Pts had previously received median 3 lines of systemic therapy (range, 1-12) and median 2 ALK TKIs (range, 1-4); all had received standard dose alectinib with CNS progression. 19 pts (70%) had received prior CNS-directed radiotherapy (RT) [median time from most recent RT to dose-escalated alectinib, 13.9 months (mos) (range, 0.2-52.3)]. The median duration of dose-escalated alectinib therapy in this cohort was 7.7 mos (95% CI, 4.8-10.9), with median overall progression-free survival (PFS) of 7.8 mos (95% CI, 4.9-13.7). Among 25 response-evaluable pts with baseline measurable or non-measurable CNS metastases, the CNS objective response rate (ORR) was 8.0% (95% CI, 1.0-26.0), with 2 pts having intracranial complete responses. CNS disease control rate (DCR) was 92.0% (95% CI, 74.0-99.0), with median CNS duration of response (DoR) of 5.3 mos (95% CI, 3.4-8.3) and median CNS PFS of 7.1 mos (95% CI, 4.4-13.7). Of 3 patients with baseline measurable CNS disease, all 3 had best intracranial response of SD, and median CNS PFS was 6.7 mos (95% CI, 6.2-not reached). Dose-escalated alectinib was well tolerated with no drug discontinuation due to trAE and no grade 3 or higher trAEs. One pt required dose reduction to 750 mg twice daily due to intolerable grade 2 fatigue. 23 pts (85%) experienced grade 1-2 trAEs. Grade 1-2 trAEs that occurred in 10% of pts were anemia (52%), fatigue (37%), constipation (26%), bilirubin increase (15%), alkaline phosphatase increase (15%), and peripheral neuropathy (11%). Conclusions: Dose intensification of alectinib demonstrated meaningful efficacy and tolerability in pts with metastatic ALK+ NSCLC who had experienced CNS disease relapse on standard dose alectinib, and may represent a viable therapeutic option for re-establishing CNS disease control.
Real-world assessment of treatment effectiveness in patients with advanced non-small cell lung cancer (aNSCLC) with MET exon 14 skipping (METex14).
Authors: Furqan Muhammad , Karanth Siddharth , Goyal Ravi K. , Shih Yu-Hsuan , Cai Beilei , Rombi Julien , Davis Keith L. , Caro Nydia , Saliba Teddy Rassem
Published: June 2023

e21112

Background: Capmatinib is approved for patients (pts) with advanced stage (a)NSCLC harboring METex14. However, there is limited data on capmatinib activity in comparison to other approved therapies. We assessed real-world (rw) clinical outcomes of pts with aNSCLC with METex14 who initiated treatment with capmatinib, immunotherapy (IO), or chemotherapy (CT) regimens. Methods: In a retrospective chart review, data were abstracted by a sample of oncologists invited nation-wide in the US who randomly selected prespecified numbers of charts, with larger sampling targets for capmatinib and IO therapies. Eligible pts were aged ≥18 years, had stage ≥IIIB NSCLC and METex14; received first-line (1L) systemic therapy after 1 January 2017 with follow up of ≥6 months after starting 1L therapy (except death) as of the data abstraction date; and did not receive MET inhibitors other than capmatinib. Clinical outcomes included best overall real world response rate (rwORR), progression-free survival (rwPFS), overall survival (OS), and time to treatment discontinuation (TTD). RwORR was assessed using rw-RECIST guided by RECIST 1.1 criteria or physician documentation. All measures were descriptively analyzed. Time-to-event outcomes were assessed per line of therapy via Kaplan-Meier methods. Results: In total, 287 eligible pts were identified. Median age was 63.3 years, 71% were male, 41% were non-White, and 49.5% were treated in community settings. 15 pts had brain metastasis at diagnosis. Pts who received 1L capmatinib had higher rwORR and longer rwPFS, OS, and TTD than pts who received 1L IO mono or CT alone or in combination (Table 1). Pts treated with second-line (2L) capmatinib had higher rwORR than other treatments but was a smaller pt population. Conclusions: Our analysis suggests that capmatinib in aNSCLC with METex14 yields numerically better clinical outcomes than IO or CT alone or in combination. These findings support use of capmatinib in this setting and may inform clinical decision making in routine practice. [Table: see text]
Comparative proteomic profiling of plasma exosomes in patients with lung cancer with brain metastasis and liver metastasis.
Authors: Li Sini , Qu Yan , Liu Lihui , Bai Hua , Wang Jie
Published: June 2023

e21123

Background: Brain or liver metastases are the main causes of lung cancer-related death. Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging, but important for early patient intervention. Accumulating evidence has suggested that circulating exosomes in the blood could mediate cancer metastasis by transferring specific proteins to the target cells. Methods: Using liquid chromatography-MS/MS, we analyzed the proteomic profiles of plasma exosomes derived from 42 metastatic lung cancer patients (including 26 solitary brain metastasis (BM) and 16 solitary liver metastasis (LM)), 25 local advanced (LA) lung cancer patients without metastasis, and 5 healthy controls (HC), and explored organ-specific proteomic biomarkers. Results: 120 and 143 differentially expressed exosomal proteins were found to be the dysregulated candidates in BM and LM of lung cancer (BM-DEEPs, LM-DEEPs), as compared to the LA lung cancer samples, respectively. The bioinformatics analyses indicated the homogeneity and heterogeneity in BM-DEEPs and LM-DEEPs. In terms of homogeneity, they were mainly involved in the protein activation cascade, collagen-containing extracellular matrix, and ECM-receptor interaction. In terms of heterogeneity, the BM-DEEPs were significantly enriched in S100 protein and calcium-dependent protein, while the LM-DEEPs were mainly enriched in integrin, lipoprotein, heat shock protein and proteoglycans. Moreover, our study also revealed the heterogeneity in plasma-derived exosome proteomics in patients with non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), which partly explained the different metastatic characteristics of NSCLC and SCLC. Additionally, we found that MUC5B and SELL could be used as a reliable diagnostic marker of BM, while APOH, CD81 and CCT5 could help to diagnose LM in lung cancer patients. Conclusions: For the first time, we revealed the comprehensive and comparative proteomic profiles of plasma-derived exosomes from lung cancer patients with solitary brain and liver metastasis. We further proposed some potential biomarkers and pathological mechanisms, which could serve as excellent resource for further studies investigating lung cancer metastasis.
Analysis of significant weight gain in patients using alectinib for ALK-positive lung cancer.
Authors: Sikkema Barend Joël , de Leeuw Simon , Pruis Melinda , Mohseni Mostafa , Veerman Geerten Dieuwert Marijn , Paats Marthe , Dumoulin Daphne W , Smit Egbert F. , Schols Annemie M.W.J. , Mathijssen Ron H.J. , Van Rossum Elisabeth , Dingemans Anne-Marie C.
Published: June 2023

e21138

Background: Alectinib is standard of care for metastatic anaplastic lymphoma kinase positive (ALK+) nonsmall cell lung cancer (NSCLC). Weight gain is an unexplored side effect reported in ~10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. Methods: Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were quantified using sliceOmatic software on computed tomography (CT) images at baseline, three months (3M) and one year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with > 10 kg weight gain were referred to Erasmus MC Obesity Center for in-depth analysis (dietary habits, metabolic/endocrine assessment). Results: Mean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p < 0.001) in 1Y. SAT increased 18.8 cm2 (12.4%, p < 0.001) in 3M and 45.4 cm2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis showed increased appetite in two patients and metabolic syndrome in all four patients. Conclusions: Alectinib caused significant increased abdominal obesity, sarcopenic obesity, SAT and VAT quickly after initiation. This may lead to serious metabolic disturbances in long-surviving patients.[Table: see text]