bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential intravenous chemotherapy with drug-eluting bead bronchial arterial chemoembolization for the treatment of stages III and IV lung squamous cell carcinoma: A retrospective controlled clinical study.
Authors: Tu Jianfei , Lai Lingqiang , Zhang Dengke , Ying Xihui , Chen Li , Wu Jiahao , Chen Jie 
Published: June 2023

8548 Background: To determine the differences in efficacy and safety between drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) combined with intravenous chemotherapy and systemic chemotherapy alone for the treatment of stages III and IV lung squamous cell carcinoma (LSCC). Methods: 136 patients with stages III and IV LSCC were retrospectively recruited between January 2018 and August 2021 and divided into group A (chemotherapy-only, N = 95) and group B (DEB-BACE combined with intravenous chemotherapy, N = 41). The short-term efficacy, hemoptysis and dyspnea remission rates, and incidence of adverse reactions were compared between the two groups. Survival estimation was performed by Kaplan-Meier, and the Log-rank test was performed to compare survival differences between groups. Results: The One-month DCR (90.2% vs. 49.5%) and ORR (75.6% vs. 38.9%) were better in group B than in group A (both P < 0.05). Progression-free survival (PFS) was 8.0 months in Group B and 6.0 months in Group A, a statistically significant difference (P < 0.05). The PFS rates at 6, 12, and 24 months were 63.4%, 24.4%, 0.0%, 43.2%, 13.7%, and 0.0% in groups B and A, respectively, this difference was significant (P < 0.05). The median overall survival was better in group B than in group A (19.0 vs 14.0 months, P < 0.05). The OS rates at 6, 12, and 24 months were 100%, 85.4%, 26.8%, 78.9%, 56.8%, and 22.1% in groups B and A, respectively, with statistically significant differences (P < 0.05). The hemoptysis and dyspnea remission rates were better in group B than in group A within one month after treatment (P < 0.05), however, in terms of the incidence of adverse reactions, incidences, such as post-treatment fatigue and bone marrow suppression, were significantly lower in Group B than in Group A during the follow-up period (P < 0.05). Conclusions: DEB-BACE combined with intravenous chemotherapy is effective for the treatment of advanced LSCC, with lower adverse reactions, and significant improvement in patients' hemoptysis and dyspnea symptoms, which is worthy of clinical application.
Association of circulating CD103+ T cells with major pathological response in a randomized phase 2 trial of neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer.
Authors: Walsh Zachary , Melms Johannes C , Rogava Meri , Caprio Lindsay , Ager Casey , Amin Amit Dipak , Ho Patricia , Malbari Murtaza , Mittal Vivek , McGraw Timothy , Altorki Nasser K. , Izar Benjamin 
Published: June 2023

8550 Background: We previously reported results of a randomized phase 2 study, demonstrating a higher rate of major pathological response to durvalumab in combination with stereotactic body radiotherapy (SBRT) compared to durvalumab alone in patients with localized (stage I-IIIA) non-small cell lung cancer (NSCLC). Biomarkers of response in NSCLC are poorly understood. To address this, we evaluated sequentially collected peripheral blood mononuclear cells (PBMCs) from study participants to identify easily accessible biomarkers associated with major pathological responses. Methods: PBMCs were obtained from study participants at defined pre-treatment, peri-operative, and post-operative timepoints. We performed 25-marker spectral flow cytometric analysis of the T cell compartment in these samples and used dimensionality reduction and clustering programs to identify populations of interest. Results: Our analysis of these samples revealed populations of both CD4+ and CD8+ T cells with hallmarks of prior antigen exposure and tissue residency (CD103+, CCR7-, CD45RA-), suggesting tumor-experienced T cells circulating into the blood. Greater pre-treatment frequency of these T cell populations was associated with major pathological responses to neoadjuvant therapy. This observation was consistent when evaluating patients with major pathological responses across both treatment arms, and within the durvalumab plus SBRT group, where we had enough patients with major pathological responses. Maturation of disease-free survival data from this trial will enable us to evaluate the association of these biomarkers with long-term survival. Conclusions: Together, these data reveal an unexpected population of T cells in the peripheral blood with features of tissue-residency, which are associated with major pathological responses, and suggest that re-circulation of tumor-experienced T cells may represent a predictive biomarker for neoadjuvant treatment of NSCLC.
Genomic comparison of MET exon 14 skipping and MET amplified non-small cell lung cancer.
Authors: Minne Rachel , Luo Natalie , Traynor Anne M. , Huang Minxuan , De Tullio Luisina , Godden Jen , Stoppler Melissa Conrad , Kimple Randall J. , Baschnagel Andrew 
Published: June 2023

8553 Background: In non-small cell lung cancer (NSCLC), the MET tyrosine kinase receptor can be dysregulated by mutations and/or gene amplification. The most common MET mutation is in exon 14 (METex14), leading to impaired receptor degradation and increased MET-mediated signaling causing sustained tumor proliferation. MET amplification also leads to continued MET signaling and oncogenesis and can be a mechanism of resistance to targeted therapy. We sought to compare the genomic landscape of METex14 and high-level MET amplified tumors, both of which can be targeted with tyrosine kinase inhibitors. Methods: We analyzed 18,047 NSCLC tumors (any stage/subtype) sequenced with Tempus xT assay (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq). Tumors were queried for METex14 mutations, high MET amplification (METamp), defined as copy number gain (CNG) ≥10, and other MET mutations (METother). Immuno-oncology (IO) biomarkers were compared across MET-altered and MET wild-type (METwt) groups. The prevalence of somatic gene alterations was compared similarly with the false-discovery rate (FDR) adjustment. Results: A total of 276 (1.53%) METex14, 138 (0.76%) METamp, 27 (0.15%) METother, and 17,606 (97.56%) METwt tumors were identified. Across groups, patients with METex14 were older, more likely to be female, and nonsmokers. METex14 exhibited the lowest tumor mutational burden (TMB) and lowest neoantigen tumor burden (NTB). PD-L1 positivity rates were higher in METex14 tumors compared to METamp and METwt tumors. MET log10 gene expression was highest in METamp. METamp exhibited the lowest proportion of CD4 T cells and the highest proportion of NK cells. Compared to METex14, METamp exhibited increased prevalence of TP53 (83% vs 37%), TFEC (46% vs 1.1%), CFTR (37% vs 1.4%), EGFR (31% vs. 7.6%), WNT2 (11% vs 0.4%), KEAP1 (14% vs 0.7%), and STK11 (8% vs 1.4%), and decreased prevalence of MDM2 (4.3% vs. 14%), and FRS2 (2.9% vs. 12%). Conclusions: In this large population-based analysis of MET-altered NSCLC, METex14 tumors exhibited differences in IO biomarkers and the somatic landscape compared to non-METex14 NSCLC tumors. Variations in immune profiles may affect immunotherapy selection in MET-altered NSCLC and require further exploration. [Table: see text]
Development of a novel blood-based RNA gene expression platform for early-stage lung cancer diagnosis.
Authors: Keiser Martin J , Cormier-May Elizabeth , Alderdice Matthew , Kavanagh Joy N , Stiles Brendon Matthew 
Published: June 2023

8557 Background: Blood-based methods using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) are under development for early and less invasive detection of lung cancer, although detection of the earliest stage cancers (stages 0-II) using these modalities is suboptimal. We hypothesized that a machine learning approach using RNA gene expression may offer important information on the biology of the patient, allowing for gene expression profiles to be used as a surrogate measurement of cancer disease phenotype and as a promising direction for early detection of lung cancer. In a previous study, 23 miRNA biomarkers were successfully discovered and validated for the non-invasive diagnostic classification of lung adenocarcinoma, achieving 97.7% sensitivity, 98.7% specificity in blood obtained from 383 clinical subjects. The aim of this study was to train a machine learning algorithm, from the 23 miRNA features, to test the signature for early lung cancer detection. Methods: A large and diverse clinical cohort was obtained from the NIH Gene Expression Omnibus database, GEO Accession Number GSE137140 ( n=3,744), comprised of miRNA extracted from serum samples consisting of subjects with pre-operative lung cancer ( n=1,566) and non-cancer controls ( n=2,178). Our analytic plan leveraged machine learning methods derived from XGBoost classification, a popular supervised-learning algorithm that uses sequentially built shallow decision trees to provide accurate results and avoidance of overfitting. The algorithm was trained using XGBoost 1.4.1.1 R library programmed with R v3.6.3. Results: The lung cancer cohort was heavily weighted towards early-stage lung cancer (87.7% stage I/II), including representation across prevalent histologic types (adenocarcinoma 77.8%, non-adenocarcinoma 22.2%) and those who self-reported as never smokers (37.9%). The 23-miRNA signature achieved 98% sensitivity, 89% specificity in the held-out test set (Table). When incorporating age and gender, the 23-miRNA signature achieved 95.5% sensitivity, 90.3% specificity. Conclusions: A machine learning approach using RNA gene expression in patient serum achieved high sensitivity and specificity in a large, predominantly early-stage, lung cancer cohort. A multi-analyte, multimodal approach that leverages machine learning algorithms with RNA gene expression profiles and available demographics and clinical risk-factors, represents the possibility to accurately detect lung cancer in the earliest stages. This approach has successfully been translated from microarray to PCR instrumentation, with further validation of this machine learning method and approach currently underway. [Table: see text]
Benefit of post-operative radiation therapy for incompletely resected stage I-IIIA non-small cell lung cancer: An analysis of the National Cancer Database.
Authors: Iska Sindu , Mohanna Mohamed , Sabbagh Saad , Dominguez Barbara , Itani Mira , Liang Hong , Arteta-Bulos Rafael , Nahleh Zeina A. , Alley Evan W. 
Published: June 2023

8558 Background: The presence of micro-residual (R1) or macro-residual (R2) disease in non-small cell lung cancer (NSCLC) is associated with a higher risk of recurrence. The benefits of post-operative radiation therapy (PORT) in incompletely resected NSCLC is not clear. The purpose of this study is to compare median overall survival (mOS) of treatment modalities in the post-operative setting for resected stage I-IIIA NSCLC with residual disease (R1/R2) and to determine if PORT provides benefit in this patient population using the National Cancer Database (NCDB). Methods: From the NCDB dataset for the years of 2006-2016, we extracted patients diagnosed with stage I-IIIA NSCLC and who had incomplete resection with residual disease (R1/R2). Kaplan-Meier analysis was performed to differentiate the effect of different post-operative treatment modalities, concurrent chemo-radiotherapy (CCRT), sequential chemo-radiotherapy (SCRT) and chemotherapy (CT) alone on mOS. Subsequently, univariate Cox regression was used to identify statistically significant variables, then multivariate Cox regression was performed to establish variables that contributed to the survival. Lastly, multinomial logistic regression was utilized to establish association of the independent factors. SAS version 9.4 was used to analyze the data. Results: Among the 2701 patients who met inclusion criteria, the average age was 64.1, 64.8 and 65.9 year old for CCRT, SCRT and CT, respectively. Male's constituted 53.6% and white's were 88.1%, and patient's were distributed equally across clinical stages. The majority of patients received SCRT (51.7%) followed by CT alone (39%), and CCRT (9.2%). There were no statistically significant differences in mOS between the different treatment modalities (p=0.220). Patients with R2 were 177% more likely to receive CCRT than CT compared to R1 (OR 2.77, CI 1.86-4.13 and p<0.001). Male's were 28% more likely to receive SCRT than CT compared to females (OR 1.28, CI 1.08-1.52 and p=0.0041). Nodal involvement was associated with decreased mOS with N2/N3 having 37% lower mOS compared to N0 (HR=1.37, CI 1.19-1.57 and p<0.0001). Patients who had R2 disease had a 38% lower mOS compared to those R1 (HR 1.38%, CI 1.19-1.62, p<0.0001). Conclusions: Despite the risk of unfavorable outcomes for patients with residual disease after surgery for NSCLC, the addition of radiotherapy, either concurrently or sequentially, to CT did not offer statistically significant mOS benefit compared to CT alone. Given the known toxicities of radiation, and the lack of impact on survival, the benefit of post-operative radiation is questionable among patients with residual disease after resection.
Large scale evaluation of pulmonary nodule workup: A real-world study of over 150,000 patients in New York State.
Authors: Velcheti Vamsidhar , Klump Erika , Long Andrew , Green Hadrian , Williams Tessa , Van Vleck Tielman , Wong Hesper , Legg Randall , Apple Jon , Arelli Bobby , Arslan Ilker 
Published: June 2023

8559 Background: Around 1.6 million patients in the US annually have a pulmonary nodule (PN) found on imaging. Previous studies suggest 1-12% of PNs represent an underlying malignancy at a potentially curative stage. PNs ≥6mm are considered higher risk. Despite guideline availability, only about one-third of commercially insured patients with a PN receive recommended workup, which may include further investigation via imaging or surgery. In addition, patients and providers may delay workup of PNs identified during COVID-19. We aimed to describe variations in PN workup for different patient demographic and clinical characteristics at 7 healthcare institutions in New York (NY) state. Methods: We used a retrospective cross-sectional design in which structured demographic and unstructured clinical data were used to analyze patient documents from a NY state health information exchange from January 2018 to February 2022. Clinical features were abstracted using a clinical natural language processing platform, CLiX unlock. Results: 58 million documents from 5.5 million unique patients were analyzed. Of the overall 151,436 patients with PNs, workup was found in 47% (71,071). Across institutions, workup ranged between 24% and 52%; 40% (60,749) had evidence of a PN in the upper lung location. We found 52,789 patients (35%) had a maximum PN ≥6mm and of those, 55% (28,958) had a workup (Table). For patients with a PN ≥6mm, workup for non-English speaking patients was 9% lower than for English speaking patients (47% vs 56%), 17% lower for patients 18-44 years than patients 45-90 years (39% vs 56%), 47% lower for patients presenting with a chest injury rather than cancer screening (28% vs 75%), and 9% higher for patients with initial imaging via chest computed tomography (CT) rather than other CT (58% vs 49%). After the start of the COVID-19 pandemic (January 2020), overall workup decreased 3.8% and prevalence of symptoms such as dyspnea and chest pain increased. Conclusions: The descriptive findings of this analysis demonstrate gaps and variations in workup for patients with PNs across different demographics and clinical scenarios. A subsequent project is underway to explore strategies for improvement in adherence to guideline-recommended care to benefit patients by diagnosing lung cancer at an earlier, potentially curative stage. [Table: see text]
Mortality benefit of a blood-based biomarker panel for lung cancer and the PLCO cohort.
Authors: Fahrmann Johannes , Irajizad Ehsan , Ostrin Edwin J. , Vykoukal Jody , Dennison Jennifer , Long James Patrick , Do Kim-Anh , Feng Ziding , Hanash Samir M , Marsh Tracey 
Published: June 2023

8560 Background: A 4-protein biomarker panel (4MP) combined with the validated PLCOm2012 clinical risk model has been shown to improve lung cancer risk estimation over either metric alone. We investigated whether these panels in combination could also identify individuals at high risk of harboring a lethal lung cancer. Methods: We used data from an established logistic regression combining the 4MP and the PLCOm2012 risk model, which were assessed in pre-diagnostic sera from 552 lung cancer cases and 2,193 non-cases from the Prostate Lung Colorectal and Ovarian (PLCO) cohort. Of the 552 lung cancer cases, 387 (70%) died from lung cancer. Cumulative incidence of lung cancer death as well as sub-distributional and cause-specific hazard ratios were calculated based on 4MP+PLCOm2012 risk scores at a pre-defined 1.0% and 1.7% 6-year risk thresholds, which correspond to the 2013 and 2021 US Preventive Services Task Force lung cancer screening criteria, respectively. Results: When considering cases diagnosed within 1 year of blood draw and all non-cases, the AUC estimate of the 4MP+PLCOm2012 model for risk prediction of lung cancer death was 0.88 (95% CI: 0.86-0.90). Among cases, the cumulative incidence of lung cancer death was statistically significantly higher in individuals with 4MP+PLCOm2012 scores above the 1.0% 6-year risk threshold (modified χ2: 5.42, P: 0.02). Corresponding sub-distributional and lung cancer death-specific hazard ratios for test-positive cases were 1.69 (95% CI: 1.07-2.66) and 1.80 (95% CI: 1.15-2.82), respectively. Conclusions: The blood-based biomarker panel in combination with PLCOm2012 identifies individuals at high risk of a lethal lung cancer.
Impact of SARS-COV2 infection on the clinical outcomes in patients with lung cancer compared to all other cancers.
Authors: Deenadayalan Vaishali , Dasgupta Mona , Baloch Ali Shahbaz , Swarna Siri Chandana , Kim Junglee , Gupta Shweta 
Published: June 2023

8562 Background: The outbreak of 2019 Novel coronavirus disease (COVID) has led to various deleterious outcomes in cancer patients. Those with lung cancer were noted to have increased morbidity and mortality when infected with COVID. We aimed to study the outcomes of COVID infection in patients with lung cancer compared to those with all other types of cancer. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database-2020 was queried to identify all COVID patients with lung cancer and those with all other types of cancer excluding lung cancer. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included a diagnosis of thrombocytopenia (TCP), Acute Respiratory Failure (ARF), sepsis, anemia, pancytopenia and shock. Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 1,050,045 COVID-19 admissions in cancer patients were identified, of which 4,625 (8.7%) had lung cancer whereas 48,840 (91.3%) had other types of cancer other than lung cancer. Lung cancer patients were older (Mean age 72 vs 69 years, p < 0.01). There was a higher prevalence of lung cancer compared to other cancers in whites (71 vs 58%, p < 0.01), hispanics had a lesser prevalence of lung cancer (7 vs 17%, p < 0.01). Lung cancer patients has a higher Charlson Comorbidity burden ( > 2) compared to other cancers (91 vs 62%, p < 0.01). Lung cancer patients were less likely to have private insurance (14 vs 22%, p < 0.01). Among the comorbidity burden, lung cancer patients had a higher rate of dyslipidemia, COPD, Coronary artery disease, Smoking, venous thromboembolism (p < 0.05). A total of 8,135 cancer patients who were admitted with COVID died, among them 970 (11.9%) had lung cancer and 7,165 (88.1%) had other types of cancer making up 21% of all lung cancer admissions that died compared to 14.7% other cancer admissions (p < 0.05). On multivariate regression analysis, after adjusting for confounders those with lung cancer had a higher odds of all-cause mortality (aOR 1.37; 95% CI: 1.13-1.67,p = 0.002). Among lung cancer patients, adjusted LOS was reduced by 0.6 days (95% CI: -1.2 to -0.1, p = 0.017) and adjusted THC was decreased by $11,977 (95% CI: -19,010 to -4,943, p = 0.001). Among the secondary outcomes, lung cancer patients had lower rates of thrombocytopenia (6.5 vs 8.8%, p = 0.01) and anaemia (34.4 vs 38.5%, p = 0.02) compared to other cancer types. Conclusions: COVID-19 infection led to increased mortality in lung cancer patients compared to those with other types of cancer. The lower healthcare utilization was likely due to early mortality in the lung cancer cohort. This study calls attention to the increased vulnerability of lung cancer patients to the SARS COV2 infection than other cancer types.
Reevaluating the role of adjuvant chemotherapy in early-stage, resectable NSCLC with high-risk clinical and pathologic features.
Authors: Heiden Brendan , Eaton Daniel B. , Chang Su-Hsin , Yan Yan , Schoen Martin W. , Thomas Theodore Seth , Meyers Bryan F. , Kozower Benjamin D. , Puri Varun 
Published: June 2023

8572 Background: The preferred treatment for early-stage non-small cell lung cancer remains surgical resection with the consideration of adjuvant chemotherapy for tumors with certain high-risk features. It is commonly cited that such treatments confer a meager 5% 5-year survival benefit compared to observation alone. We sought to reassess the benefit of adjuvant chemotherapy using modern, real-world datasets. Methods: We performed a retrospective cohort study using a dataset from the National Cancer Database. All patients with early-stage stage NSCLC (3-5cm, node-negative) who would be eligible for adjuvant chemotherapy based on National Comprehensive Cancer Network guidelines were included (i.e., presence of at least 1 high-risk feature). High-risk clinical and pathologic features were defined as poor differentiation, tumor size (≥4cm), non-anatomic wedge resection, inadequate lymph node evaluation, vascular invasion, and visceral pleural involvement. We employed average treatment effect on the treated (ATT) weighting to match patients with similar demographic, tumor, and treatment-related variables to compare outcomes between chemotherapy versus observation groups. The primary outcome was overall survival. These findings were further validated in an independent cohort from the US Veteran Health Administration (VHA). Results: The study included 10,812 patients with early-stage NSCLC who had at least 1 high-risk feature. The frequencies of high-risk features were as follows: tumor size ≥4cm (n = 3,271, 30.3%), poor differentiation (n = 9,454, 87.4%), visceral-pleural invasion (n = 2,542, 23.5%), vascular invasion (n = 1,742, 16.11%), non-anatomic wedge resection (n = 781, 7.2%), and inadequate nodal sampling (n = 6,306, 58.3%). Despite the presence of high-risk features, only 1,427 (13.2%) patients received adjuvant chemotherapy. In the ATT weighted analysis, 1,261 (49.7%) patients received adjuvant chemotherapy and 1,278 (50.3%) patients received observation. The 5-year overall survival was 70.0% (95% CI 67.1-72.7) in the chemotherapy group versus 62.0% (95% CI 60.2-63.7%) in the observation group (absolute 5-year survival difference 8.0%). In the VHA cohort, 11.3% of patients received adjuvant chemotherapy. Similarly, the 5-year overall survival was 64.0% (95% CI 51.4-74.2) in the chemotherapy group versus 56.2% (95% CI 48.3-63.4) in the observation group (absolute 5-year survival difference 7.8%). Conclusions: These data suggest a notably larger benefit of adjuvant chemotherapy in eligible patients with high-risk clinical pathologic features compared to commonly cited statistics. With the addition of more robust treatment options in early-stage disease, adherence to adjuvant and neoadjuvant treatment guidelines may disproportionately improve early-stage NSCLC outcomes following curative-intent resection.