bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine in elderly pre-treated patients with metastatic non-small-cell lung cancer.
Authors: Li Lin , Yuan Yue , Gao Jiayi , Zhang Ping , Wu Xiaonan , Tang Min , Nie Xin , Ma Di , Zhao Zhe , Tian Yumeng 
Published: July 2024

e20556 Background: The subsequent therapy of elderly non-small cell lung cancer (NSCLC) without driver oncogene has always been a challenge due to the poor performance status and multiple comorbidities, especially in those who acquired resistance to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] blockade. Metronomic chemotherapy (MCT) is the frequent administration of chemotherapy drugs at lower doses each time which shows a better safety profile, antitumor angiogenesis, and immune modulatory effects compared with traditional chemotherapy. Here we designed an observational study to evaluate the efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine(mOV) in elderly pre-treated metastatic NSCLC. Methods: Patients aged 65 years and above who had been histologically or cytologically confirmed unresectable stage III and IV NSCLC were recruited for this study. All the pts had no EGFR mutation, ALK fusions, or ROS1 fusions and received at least one systematic treatment. Pts received PD-1 inhibitors combined with mOV (30mg, TIW1, day 1-3-5 per week) for 6 cycles, followed by PD-1 inhibitors maintenance until disease progression or intolerable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: From May 2020 to June 2023, 23 pts were enrolled in the study. The median age was 70 with 18(78%) males. Median follow-up time was 22.8 months (range 3.9months-41.9months). The median PFS was 5.13 months (95%Cl: 3.1 months-7.1 months) and the median OS was 28.1 months (95%Cl: (15.2 months-NA). The ORR and DCR were 13% (95%C1: 1.44%-27.6%) and 69.6% (95%Cl: 49.2%-89.9%), respectively. The PFS (p = 0.459, HR = 0.671 95%CI 0.233-1.932) and OS (p = 0.483, HR = 1.607 95%CI 0.426-6.056) were similar between those pts who previously received immunotherapy (N = 16, 69.5%) and not. PD-L1 TPS didn’t affect the patient’s PFS (<1% vs≥1%, p = 0.078, HR = 2.648 95%CI 0.895-7.835 ) and OS(<1% vs≥1%, p = 0.306, HR = 2.202 95%CI 0.485-9.989). Adverse events (AEs) of any grade were observed in 20(86.9%) pts of which grade III-IV AEs occurred in 4 (17.4%) pts. These grade III-IV events consisted of interstitial pneumonia, pulmonary infection, leukopenia, and neutropenia. Immune-related adverse events (irAEs) occurred in 4 (17.4%) pts, of which grade III irAEs occurred in 2 (8.7%) patients with interstitial pneumonia. No grade 4 irAEs and grade 5 adverse events even occurred. Conclusions: The regimen of PD-1 inhibitors plus mOV for the subsequent therapy showed good overall survival benefits and safety in elderly patients with metastatic NSCLC without driver oncogene which suggests it is worth further exploration.
Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRASG12C mutation in China and the US.
Authors: 朱 亚宁 , Zhāng Peng , Xu Nong 
Published: July 2024

e20567 Background: Sotorasib was used for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with KRASG12Cmutation who had received at least one systematic therapy, showing good antitumor activity and safety. However, it was unclear whether the high-cost sotorasib was cost-effective. Methods: A Markov model was developed to compare the lifetime cost and efficacy of sotorasib to treat non-small cell lung cancer with KRASG12C mutation from the CodeBreak 200 randomized placebo-controlled trial, which included 345 patients with previously treated non-small cell lung cancer with KRASG12C mutation. Incremental cost-effectiveness ratio(ICER), quality-adjusted life-year (QALY), incremental QALY were calculated for the 2 treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagram was used to verify the model stability, probabilistic sensitivity analysis was performed by Monte Carlo simulation, random factors were introduced into the model to simulate a certain number of large samples, and the results were presented as cost-effectiveness acceptable curves. Results: This economic evaluation of data from the CodeBreak 200 randomized trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compwered with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than WTP, so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50 /QALY, which was low than WTP, indicating that the increased cost of sotorasib was acceptable. Conclusions: Sotorasib had cost effect from the perspective of the US. Howere, sotorasib had no cost effect from the perspective of China, and only when the willingness to pay(WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0 to 49%.
Characteristics, treatment patterns, and prognostic factors in small cell lung cancer transformation of advanced non-small cell lung cancer with epidermal growth factor receptor mutation after tyrosine kinase inhibitor therapy.
Authors: Liao Ying-Ting , Chiang Chi-Lu , Sun Ruei-Lin , Yeh Yi-chen , Huang Hsu-Ching , Shen Chia-I , Tseng Yen-Han , Luo Yung-Hung , Chen Yuh-Min , Whang-Peng Jacqueline 
Published: July 2024

e20569 Background: Small cell lung cancer transformation in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation following tyrosine kinase inhibitor (TKI) therapy poses a challenging clinical scenario. This study aims to explore the characteristics, treatment patterns, and prognostic factors associated with this transformation. Methods: A total of 41 patients with transformed SCLC (tSCLC) were included. Patient characteristics, treatment details, and laboratory data were collected. Re-biopsy specimens and subsequent treatments were analyzed. Statistical analyses were conducted to identify factors associated with treatment response and survival outcomes. Results: The median age of the patients was 61.7 years old, with a median time from TKI treatment to small cell transformation of 22.2 months. The majority were female (58.5%), never smokers (80.5%), with 53.7% having stage IVB disease prior to EGFR-TKI treatment. The most prevalent initial EGFR mutation was exon 19 deletion (56.1%), and afatinib (46.3%) was the most commonly used EGFR-TKI. EGFR mutation analysis was performed in 68.3% of the tSCLC specimen, and acquired T790M was detected in 7.1% of the patients. Treatment patterns after transformation included various systemic therapies, with the most (63.4%) receiving etoposide plus platinum (EP) based chemotherapy in the first line setting. Among all the patients, 56.1% received EGFR-TKI and 22% received immune checkpoint inhibitors (ICI) throughout the post-transformation treatment course. Anemia (Hgb < 10g/dL) and ever use of EP were significant factors associated with post-transformation survival. The median progression-free survival (PFS) of the first line treatment was 3.27 months, and the overall survival (OS) was 10.43 months post transformation. Conclusions: Small cell lung cancer transformation in advanced NSCLC with EGFR mutation after TKI therapy is associated with diverse clinical characteristics and dismal outcomes. We presented the complexity of managing these cases in real-world practice. Anemia and ever use of EP affected post-transformation survival. Further research is warranted to optimize therapeutic strategies for this unique subset of patients.
Dermatologic adverse events in EGFR-TKIs: A real-world analysis.
Authors: Paton Emily , Friedman Ryan Jeremy , Cetnar Jeremy Paul 
Published: July 2024

e20572 Background: Dermatologic adverse events (DAEs) affect a significant number of patients with non-small cell lung cancer (NSCLC) who are treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). While many DAEs have been identified during clinical trials and included in FDA drug labels, patients have raised concerns about experiencing unexpected DAEs. This study reviews the FDA Adverse Events Reporting System (FAERS) to identify DAEs in EGFR TKIs approved in NSCLC that are not included in drug labels. Methods: FAERS was queried for DAEs between 2003 – 2023 for osimertinib, afatinib, ertlotinib, gefitinib and mobocertinib. The reporting odds ratio (ROR) was calculated to compare DAEs between these EGFR-TKIs and all other drugs in the database. DAEs were considered statistically significant if the lower limit of the ROR 95% confidence interval (CI) was > 1 and if there were ≥ 3 reported adverse reactions. Results: 67,480 adverse events were reported for the 5 EGFR-TKIs studied. DAEs constituted 30.3% (20,426) of all adverse event reports. We identified skin (skin fissures, eczema, lip swelling, and skin infection), nail (onychalgia and onychomadesis), and hair (abnormal hair growth and hair disorder) DAEs not previously included in EGFR-TKI drug labels. RORs with 95% CIs are summarized in the table. Conclusions: Real-world FAERS data complements clinical trial data in identifying specific DAEs affecting NSCLC patients treated with EGFR TKIs. Our findings highlight DAEs that were previously not described, aiding clinicians in educating patients about side effects and giving patients a more nuanced understanding of what to expect before undergoing treatment. [Table: see text]
PD-(L)1 inhibitors plus bevacizumab and chemotherapy as first-line therapy in PD-L1 negative metastatic lung adenocarcinoma: A real-world data.
Authors: Ge Yihui , Sun Yuping , Gao Aiqin , Li Juan , Wang Dahai , Wu Jiake , Sun Yanxin , Sun Haifeng , Sun Haodong , Li Jie 
Published: July 2024

e20577 Background: Chemotherapies combined with immune checkpoint inhibitors (ICIs) and/or bevacizumab (named IC, BC and IBC respectively) are the preferred first-line options for PD-L1 negative and oncogenic driver wild-type metastatic lung adenocarcinoma. However, the optimal strategy is still undetermined. Methods: This retrospective real-world study enrolled PD-L1 negative metastatic lung adenocarcinoma patients from four cancer centers between January 1, 2018 and June 30, 2022. All the patients received IC, BC, or IBC as the first-line therapies. The efficacy and safety were evaluated. Results: A total of 205 patients were included, with 60, 83, and 62 patients in IC, BC, and IBC groups, respectively. Patients receiving IBC obtained the highest objective response rate (ORR) (43.5%) and disease control rate (DCR) (100%) relative to those receiving IC (40.4%, 84.2%) or BC (40.5%, 96.2%). Compared with the IC (6.74m) or BC (8.28m) group, IBC group improved significantly median progression-free survival (mPFS) (9.53m, P = 0.005). However, the difference in overall survival (OS) were not observed among the three groups. When analyzed based on different clinical and molecular information, we found that male gender, ever smoking, wild-type genes, and adrenal metastasis predicts superior PFS benefit when treated with IBC. In patients with liver metastasis, IBC or BC treatment achieved better PFS compared with IC. No additional adverse reactions were observed in IBC group compared with other two groups. Conclusions: Combined IBC treatment achieved superior DCR and PFS compared with IC or BC treatment in patients with PD-L1 negative metastatic lung adenocarcinoma, while did not increase the adverse events.
Pre-treatment CT radiomics for predicting immunotherapy response in non-small cell lung cancer(NSCLC): RECIST vs. irRECIST criteria.
Authors: Yadav Monica , Lee Jeeyeon , Kim Haseok , Lee Seyoung , Um Taegyu , Lee Salie , Djunadi Trie Arni , Chung Liam IL-Young , Yu Jisang , Rodrigues Darren , Gennaro Nicolo , Kim Leeseul , Nam Myungwoo , Kim Yuchan , Hong Ilene , Jang Jessica , Kang Grace , Cho Amy , Velichko Yury , Chae Young Kwang 
Published: July 2024

e20613 Background: Accurate prediction of how patients with non-small cell lung cancer (NSCLC) will respond to immunotherapy is essential for customizing individual treatment plans. This research explores the use of radiomics analysis from pre-treatment CT scans as a method to predict the effectiveness of immunotherapy in individuals with NSCLC. Methods: This IRB-approved retrospective study investigated radiologic and clinical data from 159 patients with stage III-IV NSCLC treated with immunotherapy. Imaging responses were assessed according to RECIST 1.1 and immune-related RECIST (irRECIST) criteria at least twice during a 24-week period. Responses were categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). 3D radiomics features were extracted from both the tumor and a 1 cm thick peritumoral region. A linear mixed-effect harmonization model was employed to correct for scanner-associated variations. A Random Forest algorithm was used to develop a classification model to predict response according to RECIST 1.1 or irRECIST. The dataset was split into training (70%) and test (30%) sets. The accuracy of predictions was evaluated using confusion matrix statistics and bootstrapping with 1,000 iterations for median and 95% confidence interval (CI). Results: Using RECIST 1.1 criteria, 41 patients (25.2%) achieved PR and CR(0.6), 62 (39.0%) achieved SD, and 56 (35.2%) achieved PD. IrRECIST criteria yielded slightly higher CR/PR rates with 52 patients (32.7%), while SD decreased to 65 (41.0%) and PD remained at 42 (26.4%). For predicting CR/PR and SD responses, the models achieved a sensitivity of 0.45 (95% CI: 0.38-0.50) and 0.64 (0.60-0.68) for irRECIST, compared to 0.34 (0.28-0.38) and 0.55 (0.52-0.60) for RECIST 1.1. The corresponding specificity was 0.85 (0.83-0.87) and 0.63 (0.59-0.67) for irRECIST, compared to 0.91 (0.89-0.93) and 0.67 (0.63-0.72) for RECIST 1.1. For predicting PD response, the models achieved a sensitivity of 0.49 (0.45-0.56) for irRECIST and 0.57 (0.52-0.62) for RECIST 1.1. The models' balanced accuracy for predicting CR/PR, SD, and PD were 0.65 (0.61-0.68), 0.64 (0.61-0.67), and 0.65 (0.63-0.69) for irRECIST, compared to 0.62 (0.59-0.64), 0.61 (0.59-0.64), and 0.62 (0.59-0.64) for RECIST 1.1, respectively. Conclusions: This study demonstrates the potential of pre-treatment CT radiomics to predict immunotherapy responses in NSCLC patients, offering insights into personalized treatment approaches. However, larger studies are needed to validate our findings.
Double lung transplantation in patients with recent history of malignancy.
Authors: Demir Tarik , Bharat Ankit , Chung Liam IL-Young , Woo Wongi , Moloney Carolyn , Jung Chan Mi , Tomic Rade , Chae Young Kwang 
Published: July 2024

e20614 Background: Recent history of malignancy has been considered as a contraindication for double lung transplantation (DLT) due to concerns for risk of cancer recurrence and worse outcomes. However, the relationship between the recent malignancy history and lung transplantation mortality remains unclear. Methods: Among patients treated with DLT between 09/2021 and 02/2024 in single institution, patients with a recent history of other cancers were included in this study. All patients had enrolled in cohort C of the DLT registry aimed for lung-limited malignancies (DREAM) study (NCT05671887). Exclusion criteria include extrapulmonary metastatic disease and medical ineligibility for DLT. All patients were followed up with computed tomography every 12 weeks. Results: Four patients were included; three (75%) patients with a histology of NSCLC (squamous cell, stage Ib-IIIb), and one (25%) with prostate adenocarcinoma (stage IIc). The median no-evidence-of-disease (NED) time was 19.5 months (0-41). Patients were aged 57-68, three (75%) were male. The indication for DLT was chronic obstructive pulmonary disease (1/4, 25%), interstitial lung disease (2/4, 50%), and idiopathic pulmonary fibrosis (1/4, 25%). All patients had high oxygen requirements before DLT. The median duration of the waitlist for DLT was sixteen days (3-61). There was no in-hospital mortality and the median hospital stay was 20.5 days (16-32). During a median follow-up of 2.5 months (range 0-9), rejection and post-transplant malignancy did not occur in any of the cases (Table 1). Conclusions: Four patients with history of cancers underwent DLT without significant complications. The median post-transplant follow-up was 2.5 months (0-9). Ongoing DREAM study cohort C will continue to investigate the role of DLT in patients with a recent history of malignancy. Clinical trial information: NCT05671887 . [Table: see text]
Sex influence on cancer immunotherapy efficacy and safety in advanced non-small cell lung cancer (NSCLC): A Canadian institution real-world experience.
Authors: Cohen Sara Frida , Cruiziat Diane , Naimer Jeremy , Cohen Victor , Kasymjanova Goulnar , Spatz Alan , Agulnik Jason Scott 
Published: July 2024

e20618 Background: Males and females differ in innate and adaptive immune responses. This difference may also be reflected in their response to cancer immunotherapies. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced NSCLC, however the impact of sex on treatment outcomes in these patients remains unclear. The aim of this retrospective cohort study was to evaluate sex-related differences in immunotherapy outcome in a real-world population of NSCLC patients treated with ICIs. Methods: Demographics, clinical, pathological and treatment characteristics were assessed. Treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes including response rates, PFS, OS and all-cause treatment discontinuation (TD) in relation to sex. Results: 152 advanced NSCLC patients receiving first-line immunotherapy, either alone or in conjunction with chemotherapy, were included in the study cohort. Females were younger age, were more likely to be non-smokers, have non-squamous tumors and had a higher prevalence of pre-existing autoimmune diseases compared to males. Disease control (CR/PR/SD) was achieved in 65.8% of patients. Median PFS was 12.0 mo in females and 14.1 mo in males. Median OS for all patients was 15.8 mo; 16.1 and 15.7 mo in females and males respectively. No statistical differences based on gender were observed in PFS and OS (P = 0.767 and P = 0.657). In regression analysis older age and presence of liver metastases were independent poor prognostic factors. Gender was not an independent prognostic factor in PFS and OS. Notably, 44 or 28.9% patients developed symptomatic immune-related adverse events (ir-AEs) that led to TD (Table 1). ir-AE-related TD occurred at a significantly higher rate in females compared with males (Table 1; 38.2% vs 19.7%, RR = 1.90; 95% CI: 1.12 to 3.26; p = 0.018). GI toxicity, including hepatitis and colitis was predominantly observed in females, whereas pneumonitis was the most frequent ir-AE leading to TD in males. Conclusions: Despite no significant differences based on gender were observed in PFS and OS, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic ir-AEs and TD. This finding indicates that broad-based sex differences in this context could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.[Table: see text]
Enhancing oncologist knowledge and skills through patient-centric medical education: A collaborative approach with LUNGevity.
Authors: Wilfong Kadrin , Beyer Michael , Basu Roy Upal Kunal , Martin Nikki A. , Liu Stephen V. , Wills Dana , Drew Heather 
Published: July 2024

e21007 Background: Patient centricity in healthcare delivery has evolved, driven by accumulating evidence of improved outcomes through patient empowerment. PeerView partnered with LUNGevity Foundation to develop multiple educational initiatives with a patient-centered approach to lung cancer care. Methods: 4 live events and 4 online enduring activities were developed to improve the knowledge and skills of oncologists and other healthcare professionals (HCPs) involved in the management of patients with small cell and non–small cell lung cancer. These initiatives followed a patient-centric approach, featuring: Learning objectives addressing incorporation of patient-centric approaches to provision of optimal and equitable lung cancer care in two of the activities; LUNGevity input on the co-creation and development of the activities, including curriculum planning, identifying faculty, highlighting advocacy resources, and incorporating the patient voice; Expert discussions framed with patient perspectives and illustrative case scenarios to highlight strategies for improving team-based collaboration, patient engagement, shared decision-making, and health equity in clinical care and research; Unique instructional elements, including patient focus group insights and video role play; and Tools designed to enhance clinician-patient communication, patient engagement in care, and shared decision-making Pre- and post-activity assessments included multiple choice questions to measure changes in knowledge and skills and Likert-style questions assessing intent to change practice. Responses from enduring activity participants were also compared with those from a matched sample of nonparticipants. Results: To date, 11,227 learners, including 8,112 oncologists, have participated in these activities. Substantial post-activity gains were consistent across all initiatives, with a 44-ppt average increase in knowledge and skills. Outcomes related to patient-centric care included increases of: 38 ppt in ability to implement team-based and patient-centric approaches to ensure timely and accurate diagnosis, appropriate biomarker testing, individualized treatment, and equitable care of all patients with NSCLC (43% to 81%); 44 ppt in ability to implement team-based and patient-centric approaches to ensure optimal and equitable use of immunotherapy in the care of all eligible patients with NSCLC (39% to 83%); and 15 ppt in intent to provide education, guidance, and resources to patients with lung cancer (68% to 83%). Conclusions: These initiatives demonstrated significant improvements in learner knowledge, skills, and confidence across all learning objectives. Furthermore, incorporation of patient-centric approaches represents an effective model for clinical education to increase HCPs’ compassion, empathy, and ability to provide effective and holistic patient care.