bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative efficacy and safety of immunotherapy for advanced NSCLC: A systematic review and network meta-analysis.
Authors: Xu Bin , Zhao Chen , Zhong Hao , Lei Tianyu , Zhang Huibo , Wu Jie , Li Lan , Yao Yi , Song Qibin 
Published: June 2022

e21028 Background: Advanced non-small cell lung cancer (NSCLC) patients responded differently to checkpoint inhibitors (ICIs) therapy, leading to the confuse of choosing the optimal regimens for patients. Therefore, we performed this network meta-analysis to compare different agents across clinical trials. Methods: We searched databases, including EMBASE, PubMed, ClinicalTrials and etc, for abstracts, full-text articles and minutes of the annual meetings published from database inception through Oct 01, 2021. Phase 3 randomized clinical trials (RCTs) of first-line immunotherapy or combinations for adcanced (stage III/IV or recurrent) NSCLC were included. We selected 26 trials evaluating different ICIs (Atezolizuma (atezo), Pembrolizumab (pem), Nivolumab(nivo), Durvalumab (durva), Camrelizumab (camre), Tislelizumab (tisle), Sintilimab (sint), Sugemalimab (suge), Toripalimab (tori), Cemiplimab (cemip)) and combinations based on them. Primary outcomes of interests were overall survival (OS) and progression-free survival (PFS). Secondary outcomes of interests were objective response rate (ORR), and adverse events (AEs). Hazard ratio (HRs) and 95% confidence intervals (CI) were used to represent the results of OS and PFS. The subgroup analysis (pathological type, PD-L1 expression, gender, smoking history, ECOG score, metastasis status and ethnicity) was performed and the treatments were ranked in it and overall population. Results: In our study, all ICIs-based regimens had benefit in OS and PFS compared with chemotherapy. The network meta-analysis for OS showed the combination of Camre-Chemo ranked 1st in overall population, and most of dual ICIs-based regimens, except Nivo-Ipi-Chemo, showed minor improvement in OS while possess more safety concerns compared with other regimens. Atezo-Beva-Chemo (ranked 1st in PFS, 20th in safety), has shown good efficacy but was revealed with lower safety. Sint-Chemo demonstrated promising efficacy in PFS, but it remains to be seen whether the effectiveness could be transformed into OS benefit due to the lack of related data. Pem-Chemo (ranked 1st in ORR) demonstrated the best response to tumors in all treatments regardless of PD-L1 expression. In subgroup analysis, for patients with poor health conditions (≥65 years or with ECOG = 1), multi-drug combination regimens, such as Nivo-Ipi-Chemo and Atezo-Beva-Chemo, showed better benefits in PFS and OS compared with only chemo but had no significant advantages than any other treatments. Conclusions: In our study, we provide relative comprehensive results for latest researches of first-line ICIs. Overall, Care-Chemo, Pem-Chemo, Sint-Chemo, are prior to be recommended according to our study.
Pattern of disease progression amongst veterans with stage IV non-small cell lung carcinoma (NSCLC) on immunotherapy.
Authors: Mahmood Fatima , Azem Amin , Gemoets Darren , Thalody Vimala , Mehdi Syed Arzoo 
Published: June 2022

e21032 Background: Use of immune checkpoint inhibitors against advanced stage NSCLC is associated with significant reduction in overall morbidity and mortality. However, despite the survival benefit, tumors invariably relapse. We aim to study pattern of disease progression and assess baseline or tumor specific associations. Methods: We performed a retrospective review of 74 Veterans with Stage IV NSCLC who received ≥2 immunotherapy cycles between 2015-2021 at Albany Stratton VA Medical Center. IRB approval was obtained. Fisher Exact Probability Test was used to analyze data, level of significance at < 0.05. Results: Baseline characteristics of 74 male veterans revealed median age 67 years (IQR 62.5-72.5). Common tumor histology included squamous cell carcinoma (SCC; n = 38, 51.3%) and adenocarcinoma (n = 32, 43.24%), PD-L1 expression > 50% in 33.8% of population. Molecular testing positive for EGFR in 1 patient and otherwise negative for EGFR, ALK, BRAF, ROS, KRAS translocations in all patients. Treatment regimen was either immunotherapy alone or concurrent chemoimmunotherapy. Disease status prior to starting immunotherapy was classified as M1a (25.7%), M1b (50%) and M1c (24.3%). Out of total study population, progression of disease was noted in 48 patients (56.4%) further divided into progression at initial site only 20.8%, new site only 31.2%, or combined 48%. Most common sites of progression included local and distant LNs, brain, bone, and liver. Using Kaplan Meier Survival Analysis, median progression free survival (PFS) from start of immunotherapy till evidence of progression was 8.4 months. Our data revealed that progression at initial, new, and combined sites was noted in both adenocarcinoma and SCC. Use of immunotherapy as first line therapy and smoking history > 50ppd were also associated with risk of progression. Other characteristics such as ECOG score (p = 0.50), initial metastatic status (p = 0.30), type of immunotherapy (p = 0.60) and PD-L1 score (p = 0.27) did not reveal significant association. We did not find any association between baseline characteristics and improved PFS. Conclusions: We conclude that certain baseline characteristics can be associated with progression of Stage IV NSCLC on immunotherapy amongst Veteran population. We recommend further studies with a larger study population to analyze the pattern of disease progression and associated factors. This will allow physicians to modify and personalize therapy regimen to improve PFS.[Table: see text]
AI in NSCLC: PET-CT & histology model.
Authors: Batra Ullas , Nathany Shrinidhi , Nath Swarsat Kaushik , Jose Joslia T , Sinha Robin , P Preeti , Sharma Trapti , Pasricha Sunil , Sharma Mansi , Bansal Abhishek , Rawal Kamal 
Published: June 2022

e21044 Background: Almost 70% of cases of lung cancer are diagnosed at advanced stage, albeit with sophisticated imaging modalities available. Of these, 35% are tiny nodules that are often missed at initial radiological screening, owing to limitations of resolution of human vision.Dramatic shift in therapeutic paradigm in the management of lung cancer in the last decade has ushered an era of stratified medicine. In India, one-third population inhabits rural lands;lack of awareness for molecular medicine poses challenges to treating oncologists. AI-based cancer detection and prediction of potential oncogenic driver at diagnosis, will help alleviate patient anxiety caused due to diagnostic delays, aiding in prompt initiation of optimal therapy.Here, a comprehensive deep-CNN based diagnosis of lung adenocarcinoma (LUAD) was implemented using both PET/CT and histopathology images of 100 patients. Methods: Data collection: 143 whole-slide images were downloaded from Dartmouth Lung Cancer Histology Dataset from Biomedical Informatics Research and Data Science website and PET/CT dataset-A Large-Scale CT and PET/CT Dataset for Lung Cancer Diagnosis (Lung-PET-CT-Dx) from The Cancer Imaging Archive. This comprises 251,135 images from 355 participants across 436 studies. Creation of Deep-CNN model: Residual Neural Network - 18 was used for histopathlogic classification followed by Detectron2’s region-based deep-CNN for detection of presence of tumours in lung PET/CT images. Properties such as size, morphology, attenuation, malignancy, and spiculation were also measured. The 18-layer deep network, ResNet-18, detected the histologic patterns using whole-slide histopathology images. Results: Results for 100 patients whose PET/CT images, histopathology images, and mutational status of three genes (EGFR, ALK, ROS) were readily available. The histologic patterns of tumour cells appear to be related to the mutational status of genes. The ResNet-18 CNN could predict various histologic patterns (Acinar, Lepidic, Papillary, Micropapillary, and Solid patterns). Conclusions: CNN models can help in early diagnosis and prompt treatment of lung cancer, if fairly accurate. Larger datasets are needed to improve the same. The final validation of the model is underway and will be reported in near future.[Table: see text]
The association between BIM deletion polymorphism and treatment efficacy of PD-1/PD-L1 inhibitors in advanced NSCLC.
Authors: Zhang Dai , Li Xuanzong , Huang Caimei , Fan Xinyu , Qin Wenru , Yang Linlin , Wang Linlin 
Published: June 2022

e21055 Background: PD-L1 is a recommended biomarker for immunotherapy, but Some patients with high pD-L1 expression had poor clinical response. Considering the inconsistent correlation between PD- L1 expression and ICI efficacy, A more sensitive biomarker is needed to predict immunotherapy efficacy. B-cell lymphoma-2 (BCL2L11/BIM) belongs to the Bcl-2 family and is a key factor promoting apoptosis. BIM deletion polymorphism (BIM- del) may lead to BH3 deletion and thus hinder cell apoptosis. Loss and decreased expression of BIM may lead to resistance to tumor therapy. A study on patients with metastatic melanoma found that the high level of BIM in CD8+ T cells suggests a stronger PD-1 and PD-L1 interaction, which predicts clinical benefit in patients with metastatic melanoma receiving anti-PD-1 therapy.This study aims to evaluate the relationship between BIM deletion and PD-1/PD-L1 inhibitors efficacy in advanced NSCLC patients. Methods: Patients diagnosed with advanced stage NSCLC that treated with Immune checkpoint inhibitors (ICIs) at Shandong Cancer Hospital between March 2019 and January 2021 were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del. Results: A total of 61 patients with advanced NSCLC who received immunotherapy were enrolled, only 18.0% (11/61) patients were detected with BIM-del. Most of the patients were male (73.8%, 45/61), younger than 65 years (72.1%, 44/61), non- smokers (50.8%, 31/61), previous treatment lines 0-1 (90.2%, 55/61),had Eastern Tumor Cooperative group (ECOG) performance status (PS) 0-1 (98.4%, 60/61). There were no associations between the BIM-del and clinical characteristics. There was no difference in the objective response rate between patients with and without BIM-del (27.3% vs 30 %, p = 1.000).BIM-del is associated with shorter progression-free survival (PFS) (5.7 months vs12.0 months, p = 0.001). The median OS had not been reached. Multivariate analysis suggested that BIM-del was an negative independent prognostic factor for PFS in immunotherapy patients with non-small cell lung cancer, but not for OS. Conclusions: BIM-del may be a negative prognostic biomarker for patients with advanced NSCLC treated with immunosuppressive therapy. It is very important to find effective and accurate biomarkers to predict the PD-1/PD-L1 inhibitors Treatment efficacy, and further exploration is needed in the future.
Relationship between IFN-α, IL-1B, IL-5, IL-6 and effectiveness of the first-line with camrelizumab combined with chemotherapy in non small cell lung cancer.
Authors: Shi Jian , Duan Xiaoyang , Liu Rongfeng , Wang Zhen , Han Shan , Shan Baoen 
Published: June 2022

e21059 Background: Biomarkers of combination with immunotherapy therapy remains unknown. To explore prediction of efficacy in patients(pts) with non small cell lung cancer (NSCLC) without driver genes mutations which received Camrelizumab combined with chemotherapy. Methods: From Jan, 2020 to Dec, 2021, 28 pts with NSCLC without driver genes mutations who received Camrelizumab combined with chemotherapy for 4 cycles. According to RECIST1.1, all of these patients were assessed with benefit. IFN, TNF-α, IL (IL-1B、IL-2、IL-4、IL5、IL-6、IL-8、IL-10、IL-12P70、IL-17)in peripheral blood of all pts were measured using flow cytometry. Statistical analyses were performed with SPSS 23.0 software (Pearson’s correlation). Results: Before treatment, the mean values of IFN-α, IFN-γ, TNF-α and IL in pts with partial response (PR) were higher than in pts with stable disease (SD). There was no correlation with age, sex, stage and pathological type of pts ( P > 0.05). There was significant difference of IFN- α, IL-1B, IL-5 and IL-6 increased compared with the level before treatment in 28 pts ( P＜0.05). However, pts with PR compared with pts with SD, There were no significant differences of IFN-α, IFN-γ, TNF-α, IL compared with the level before treatment (P > 0.05). The IFN-α, IL-1B, IL-5, IL-6 Spearman correlation showed that before treatment, there was a correlation between INF-α and IL-5, INF-α and IL-1B, INF- α and IL-6, IL-1B and IL-6, respectively (r = 0.786, P = 0.036 < 0.05; r = 0.889, P = 0.007 < 0.05; r = 0.929, P = 0.003 < 0.05; r = 0.778, P = 0.039 < 0.05). In self-control before and after treatment, there was a correlation between INF-α and IL-1B, INF- α and IL-6, IL-1B and IL-6, respectively (r = 0.880, P = 0.009 ＜05; r = 0.936, P = 0.002＜ 0.05; r = 0.882, P = 0.023＜ 0.05). Conclusions: First-line chemotherapy combined with Camrelizumab in NSCLC without driver genes mutations can effectively improve the levels of IFN-α, IL-1B, IL-5, and IL-6, and the combined detection has certain predictive significance for the efficacy evaluation of patients. Further study is needed.
Managing cardiotoxicity in metastatic non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs).
Authors: Sukar Nabil , Walker Damaal , Dumais Katerine , Powery Hermán Wesley , Raez Luis E. , Aung Pyi Phyo 
Published: June 2022

e21072 Background: Current guidelines for prevention and monitoring cardiac dysfunction in patients with cancer state there is insufficient evidence to support surveillance strategies for TKIs alone. Furthermore, risk stratification for baseline and frequency of monitoring remains unclear for various products. This study evaluates the current practice for screening and monitoring for cardiotoxicity in patients treated for NSCLC with TKIs and the adherence rate to the standards of care. Methods: A single-center retrospective chart review of 113 patients with metastatic NSCLC who received TKIs at a large academic-community cancer center was performed. The current practice for screening and monitoring for cardiotoxicity and the adherence rate to the suggested standards recommended by the prescribing information of each drug were analyzed. Total incidence of cardiotoxicity was also evaluated. Descriptive statistics were calculated for all demographic variables and clinical outcome endpoints. Incidence of cardiotoxic adverse events were reported as percentages. Results: A total of 113 metastatic NSCLC patients were identified with the majority of patients taking osimertinib (67.3%), alectinib (8.0%), or dabrafenib/trametinib (7.1%) at baseline. Total adherence rate for screening and monitoring for cardiotoxicity as recommended by the prescribing information for all agents was 54%. Cardiotoxicity occurred in 46 (40.7%) patients, presenting most frequently as hypertension and bradycardia. Cohort cardiotoxicity events are summarized in the table below. Decreased left ventricular ejection fraction (LVEF) ≥ 10% or to < 50% occurred in 6/76 (7.9%) patients on osimertinib; however, only 12 (15.8%) patients were able to be assessed due to lack of baseline data. Osimertinib was held and/or discontinued in 3 (3.9%) patients and 1 (1.3%) death resulted due to cardiomyopathy. QTc interval prolongation occurred in 2 (33.3%) patients on afatinib, 1 (20%) patient on crizotinib, and 1 (1.3%) patient on osimertinib. Three (3.9%) patients on osimertinib were diagnosed with atrial fibrillation. Conclusions: The results reported in this study show higher rates of decreased LVEF and similar rates of QTc prolongation with osimertinib compared to prior studies. The increased rate of hypertension observed may be associated with the high rate of uncontrolled blood pressure at baseline. Low adherence rates to the recommendations provided by prescribing information may contribute to increased risk of cardiac dysfunction.[Table: see text]
Temporal trends of lung cancer burden in India in comparison to global burden from 1990 to 2019: An observation analysis.
Authors: Jani Chinmay , Jani Ruchi Tusharkumar , Kurman Jonathan , Singh Harpreet 
Published: June 2022

e21081 Background: Lung cancer is the leading cause of cancer-related deaths worldwide and remains a significant health concern globally. There is limited understanding of the lung cancer epidemiology trends in India. This study compares lung cancer incidence, disability-adjusted life years (DALYs), and mortality in the Indian population with the global burden. Methods: The lung cancer incidence, DALYs, and mortality data were analyzed for males and females from 1990-2019 using the Global Burden of Disease (GBD) database. GBD is an open-source data repository managed by the Institute for Health Metrics and Evaluation research center, University of Washington. International Classification of Diseases (ICD) code C34 were used for data extraction. Temporal trends in lung cancer were evaluated using descriptive statistics. Results: India had a lower lung cancer-related disease burden than the global population. Incidence trends: In India, lung cancer age-standardized incidence rates (ASIRs) increased from 6.62/100,000 in 1990 to 7.7/100,00 in 2019. ASIRs increased from 10.36 to 11.16 in males and 2.68 to 4.49 in females. In contrast, overall and male ASIRs decreased globally from 28.39 to 27.66 and 46.22 to 40.44, respectively. But global lung cancer incidence in females increased from 13.77 to 16.83, mirroring the trends in the Indian female population. DALYs trends: In India, DALYs increased uniformly from 1990 to 2019. The overall DALYs (including males and females) increased from 166.66 to 190.16. In males, DALYs increase from 258.05 to 271.30, and in females DALYs increase from 68.80 to 112.90. Similarly, at the global level, DALYs in females increased from 311.7 to 327.57. However, overall and male’s global DALYs improved from 657.97 to 551.58 and 1053.25 to 802.86, respectively. Mortality trends: In the Indian population, there was only a slight overall increase in age-standardized mortality rates (ASMRs) from 7.04 to 8.06. A similar slight increase in mortality rates was observed in males (11.04 to 11.73). However, in females, there was a substantial increase from 2.85 to 4.70. In contrast, overall and male ASMRs decreased globally from 27.39 to 25.18 and 45.08 to 37.38, respectively. Similar females’ mortality trends in India, globally, females ASMRs increased from 13.04 to 14.96. Conclusions: Our study reports a lower lung cancer-associated health burden in the Indian population. However, there is an increase in the incidence, DALYs, and mortality in both males and females in the Indian population from 1990 to 2019. Similar worsening trends are observed in females at the global level. In contrast, there is a hint towards improvement in the incidence, DALYs, and mortality at the global level in general, primarily due to improvement in males’ disease burden. There is also a persistent gap in males and females epidemiology, where males have a higher lung cancer burden than females.
The comparison of chemotherapy and treatments according to NGS results in advanced lung adenocarcinoma patients resistant to EGFR-TKIs.
Authors: Jiang Kan , Lin Gen , Zheng Xinlong , Zheng Xiaobin , Long Feng 
Published: June 2022

e21082 Background: There were no relative researches referring to optimal treatment strategy after the resistance to the first/second-generation EGFR-TKIs without T790M mutation or the third generation EGFR-TKIs as the first or second line therapy. Methods: Retrospective analysis was performed on the clinical and sequencing data obtained from 129 patients with advanced EGFR-mutant lung adenocarcinoma and disease progression on the prior EGFR-TKIs.The patients were divided into Chemotherapy group or Personalized group according the the therapies after acquired resistance to EGFR-TKIs. Results: 36 patients were enrolled in Personalized group and 93 in Chemotherapy group. Personalized group：22 patients with MET amplification received the combination therapy of EGFR-TKIs and MET inhibitors; 6 patients with SCLC transformation received EP/EC chemotherapy; 2 patients with BRAF mutation were treated with the combination of EGFR-TKIs, dabrafenib and trametinib; 3 patients with ERBB2 amplification were added Trastuzumab in the therapy; 2 patients with RET fusion were accepted LOXO-292 therapy; 1 patient had the combination therapy of the 1st and 3rd EGFR-TKIs because of T790m and C797S mutations in trans allelic context.Chemotherapy group: 79 patients received pemetrexed plus platinum therapy, 14 patients received paclitaxel plus platinum therapy. 12 patients achieved PR and 11 patients achieved SD in Personalized group, 48 PR, 25 SD in Chemotherapy group. The median PFS was 5.5 months in Chemotherapy group and 3.5 months in Personalized group, No significant differences were observed in ORR(p = 0.13), DCR(p = 0.12) and PFS(P = 0.26) between two group. Conclusions: Chemotherapy maybe is the optimal choice to patients with advanced EGFR-mutant lung adenocarcinoma and disease progression on the prior EGFR-TKI in current medical conditions.
Cost of care in EGFR mutant versus wild-type non-small cell lung cancer.
Authors: Vusqa Urwat Til , Asawa Palash , Miller Katherine , Sethi Ashish , Rodriguez Robin Raquel , Friday Andrew , Finley Gene Grant 
Published: June 2022

e21084 Background: Lung cancer remains the most commonly diagnosed cancer in the United States, as well as the leading cause of cancer-related mortality. Approximately 84% of all lung cancers are non-small cell lung cancer (NSCLC). Most are diagnosed at an advanced stage when the prognosis is poorest. EGFR is the most common driver mutation in NSCLC with an incidence ranging from 20% in Caucasians, and up to 50% in Asians. Oral tyrosine kinase inhibitors (TKI) are the preferred treatment for EGFR mutant cancers as they provide better outcomes and lower toxicity than chemotherapy (Ch) or immunotherapy (ICI). Therefore, it is imperative to analyze NSCLC patients for these important driver mutations. Cancer care is expensive with the treatments and attendant costs for administration and management. We sought to compare cost of care (COC) in EGFR mutant vs wild-type NSCLC as the treatments and known toxicities differ markedly. Methods: We performed a retrospective COC analysis of NSCLC using claims data from the local BCBS affiliate Highmark (HM) members. Patients were selected based on NSCLC diagnosis codes between October 2016 and September 2018. COC was calculated from claims data to compare treatment of driver mutant NSCLC with targeted therapy versus treatment of wild-type NSCLC with ICI and/or ChT. Data used to compare COC analysis included overall medical costs defined as all medical claims incurred by a patient following start of respective therapy, oncology related medical claims, therapy costs, costs related to emergency room visits and tissue biopsies. Overall medical costs, oncology related costs and therapy costs were measured in per member per month (PMPM). We extracted cost related data at 6 months, 12 months, and 18 months into treatment. Results: Patients treated with ICI and/or ChT incurred $1000-2000 more in PMPM total medical costs than patients treated with targeted therapy. Additionally, chemoimmunotherapy patients were found to have a 5% higher emergency room admission rate along with a longer median length of stay of 1/3 day, when compared to targeted therapy patients. ICI and/or ChT patients showed a 20% higher rate of tissue biopsy and a 5-10% higher rate of repeat tissue biopsy which incurred an additional $300-$400 expense for chemoimmunotherapy patients. Conclusions: The use of targeted treatment with TKIs in EGFR mutant NSCLC patients is more cost effective than ICI and/or ChT in wild-type NSCLC. Routine screening of lung cancer patients with molecular profiling is essential, as identification of such critical driver mutations can alter the treatment plan to be more efficient, providing better care at lower cost.