bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of lung cancer in renal transplant recipients.
Authors: Sridhar Arthi , Yohannan Binoy , Kaur Harmanpreet 
Published: June 2023

e20592 Background: Renal transplant recipients (RTRs) are at a higher risk of developing malignancies primarily due to prolonged immunosuppression. Lung cancer while rare in RTR, is associated with significant morbidity and mortality. The primary objective of our study is to analyze the clinical characteristics and outcomes of RTRs who developed lung cancer at our institution. Methods: We retrospectively reviewed 1998 RTRs who underwent transplantation between January 1, 1999, and December 31, 2019, at our institution and identified patients who were diagnosed with lung cancer after transplant. Baseline demographic variables and information related to the renal transplant, the diagnosis and management of lung cancer were collected. Results: Among 1998 RTRs, 10 patients (0.005%) developed lung cancer. A majority of the lung cancer patients identified as male (n = 8), and the median age was 62.5 years. The races of the patients were white (30%, n = 3), African American (50%, n = 5), Hispanic (10%, n = 1), and Native American (10%, n = 1). Concomitant liver transplant was performed in 2 patients, and a concomitant heart transplant was performed in 1 patient. Median time to lung cancer diagnosis after transplant was 67.5 months (range, 12-168). The histology of the lung cancers found were adenocarcinoma (n = 4), squamous (n = 4), and small cell (n = 2). All patients had a history of smoking, with 90% reporting a > 15 pack-year history of smoking and none of them received lung cancer screening. Among the patients with non-small cell lung cancer (NSCLC), 87.5% (n = 7) had early-stage disease, and 12.5% (n = 1) had locally advanced disease (Stage IIIB). Both patients diagnosed with small cell lung cancer had extensive-stage (es-SCLC) disease at the time of diagnosis. Among patients with NSCLC, 2 had genomic tumor profiling performed. Among patients with early-stage NSCLC, 57% underwent upfront surgery, 14% received radiation alone, 14% received neoadjuvant chemotherapy, and 14% received adjuvant chemotherapy. Around 71% (n = 5) remained alive at the last follow up recorded. The patient with stage IIIB NSCLC received chemotherapy and concomitant radiation but had an overall survival (OS) of only 6 months; that patient died of complications related to cancer progression. Both patients with es-SCLC received front-line chemotherapy with carboplatin and etoposide. To our knowledge, 40% (n = 4) of these patients retained their renal graft function. At 1-year from diagnosis, 40% of patients diagnosed with lung cancer were still alive. Conclusions: Lung cancer in RTRs is rare but is associated with significant morbidity and mortality. With the improving life expectancy of RTRs, the incidence of de novo malignancies including lung cancer is likely to increase. Annual screening for lung cancer in high-risk individuals is an important step for early diagnosis. Surgical resection and chemotherapy are well tolerated in patients with lung cancer.
Establishment of a nomogram predictive model for survival and prognosis of 97 patients with different subtypes of lung adenocarcinoma after radical resection.
Authors: Aosiman Aliya , Aerxiding Patiguli , Nuermaimaiti Gulinuer , Zheng Yang , Meng Yuan 
Published: June 2023

e20596 Background: Postoperative recurrence and metastasis of lung adenocarcinoma (LUAD) is a major obstacle to long-term survival, and how to identify patients at high risk of recurrence / death after surgery and those likely to benefit from adjuvant therapy is currently a clinically relevant question. In this study, we investigated the survival characteristics of patients with different subtypes of LUAD after radical resection and established predictive prognostic models to inform postoperative management, recurrence prediction and risk management in lung cancer patients. Methods: A retrospective analysis of 97 patients who underwent concurrent genetic testing for LUAD radical resection at The Affiliated Tumor Hospital of Xinjiang Medical University between December 01, 2014 and December 30, 2017 was performed. A COX proportional risk regression model was used to construct a prognosis model for patients with LUAD after surgery and visualization of the model was performed using column diagrams. The performance of the model was evaluated using C index, calibration curve, and ROC curve. Results: (1)46 patients (47.42%) were included and 51 patients died (52.58%), with a median survival of 78 months (95% CI: 63-93). Twenty of these patients had a good prognosis (20.62%) and 77 had a poor prognosis (79.38%), with a median survival time of 88 months (95% CI: 81-95). The overall survival rate was 98.9%, 78.3% and 59.7%, respectively, and the cumulative disease-free survival rate was 77.3%, 37.1% and 20.6%, respectively, for 1, 3 and 5 years. Pathologic types were lepidic, acina/papillaryand solid/micropapillary with 87.50%, 56.90% and 58.80% OS and DFS, respectively. 37.50%、80%、11.80%. (2)26 patients (26.8%)had recurrent metastasis,the main site of metastasis was extrapulmonary, and multiple metastases were more common. (3)Univariateand multivariate analysis showed that TNM stage III, pathological classification as solid/micropapillary, tumor diameter ≥ 3cm, and gene mutation positivity were independent risk factors for prognosis in patients with lung adenocarcinoma after surgery. Based on the above risk factors, the Nomogram prognostic model was established with a C index of 0.687 (95% CI: 0.622-0.752) and calibration curves and ROCs for the 1, 3, and 5 year models, respectively, with AUC values of 0.742, 0.752, and 0.820 > 0.7, suggesting that the model is within the acceptable range of partitioning and accuracy, with the highest AUC for the 5-year DFS prediction. Conclusions: High TNM staging, pathotyping of micronipples or entities, ≥ 3cm tumor diameter, and mutant positivity were independent risk factors for recurrence and metastasis in patients with LUAD. The Nomogram predictive model based on patient risk factors after LUAD radical resection is effective in predicting long-term survival and guiding personalized treatment.
Comprehensive genetic characteristics of multiple primary lung cancer in patients in China.
Authors: Pei Guotian , Yang Yingshun , Li Mingwei , Ma Xiaoxue , Qin Jiayue , Cao Shanbo , Liu Qiang , Wang Shuai , Huang Yuqing 
Published: June 2023

e20597 Background: With the development of molecular biology and next-generation sequencing (NGS), researchers have been exploring the use of genomic technologies for the classification of lung cancers. The aim of this study was to investigate genetic characteristics of multiple primary lung cancer (MPLC) to facilitate precise diagnosis and therapy by NGS. Methods: A total of 271 lesions from 92 patients with MPLC (225 lesions) and 20 intrapulmonary metastasis (IM, 46 lesions) which were diagnosed by American College of Chest Physicians (ACCP) guidelines, were sequenced by Acornmed panel with 808 cancer-related genes. Results: The most frequent mutation in 225 lesions was EGFR (46.7%), followed by RBM10 (19.6%), BRAF (16.4%) and KRAS (15.1%) among MPLC while IM lesions showed high TP53 (63.0%) mutation frequency. Further analysis showed that MPLC patients had higher proportion of private mutations, and lower proportion of shared mutations and branch shared mutations than IM (p < 0.0001). In our cohort, 95.7% (88/92) of MPLC patients had at least one driver alteration, and EGFR and KRAS comprised 57.4% and 18.0% of 183 driver mutations, respectively. Further analysis showed that only 19.6% (18/92) of MPLC shared the same driver mutation in each patient and 61.1% (11/18) of co-driver mutation was EGFR L858R which was commonly detected in lung cancer. In contrast, 95.0% (19/20) of IM shared the same driver mutation in each patient. MPLCs were associated with a high frequency of T > C transitions (p < 0.001), while T > G transversions (p < 0.001) were more frequent in tumors from IM. MPLC had significantly higher intratumor heterogeneity (ITH) (17.1 vs 4.05, p < 0.001) and lower weighted-genomic integrity index (wGII) than IM (0.01638 vs 0.18321, p < 0.001). Besides, MPLC had lower percentage of clonal mutations (p < 0.001) than IM. However, IM had higher arm-level somatic copy number variations fraction (p < 0.001) than MPLC. Conclusions: Our analysis reveals that patients with MPLC have distinct molecular characteristics different from IM, which may increase the understanding of MPLC. In addition, the molecular features of MPLC may provide new opportunities to distinguish MPLC from IM by broad panel NGS.
CT based radiomics signature for phenotyping histopathological subtype in patients with non-small cell lung cancer.
Authors: Liu Yan , Zerka Fadila , Bodard Sylvain , Felfli Mehdi , Voyton Charles , Thinnes Alexandre , Jacques Sebastien , Iannessi Antoine 
Published: June 2023

e20599 Background: The determination of the histopathology of non-small cell lung cancer (NSCLC) is crucial for guiding the appropriate therapeutic strategy, affecting prognosis and recurrence rates. In addition, targetable oncologic mutations are highly correlated to histological subtypes. Conventional methods such as biopsy or surgical excision are the primary methods for histology determination but are invasive, costly, and have limitations such as sampling error. Computed tomography (CT) scans, widely used for NSCLC diagnosis and follow-up, offer a non-invasive alternative through radiomics-based models that provide comprehensive analysis of the entire tumor and surrounding tissue, improving patient selection and stratification in clinical trials and enhancing the development of molecularly targeted drugs. The goal of this study was to evaluate the ability of a CT-based radiomics model to predict the subtype histopathology of NSCLC patients. Methods: A total of 678 patients with advanced-stage NSCLC with at least one measurable lung lesion (≥10mm) were selected from multicenter institutions; 531 were used for training and 147 for independent testing. The test set originates from centers unique from the training cohort. Semi-automatic segmentation of the lung lesions was performed and the segmentations were retrospectively reviewed by an experienced radiologist with > 20 years of experience. A total of 1246 radiomics features were extracted using the Pyradiomics package. Ten Robust features were selected first by removing all features with variances near zero, then by applying Maximum Relevance — Minimum Redundancy to the remaining features. All selected features were standardized before modeling. A support vector machines classifier was trained using a five-fold cross-validation and Random Over-Sampling Examples to classify the histology of NSCLC patients (Squamous vs. Non-Squamous). Results: The model trained with the radiomics features achieved a mean area under the curve (AUC) of 0.80 (95% CI, ±0.05) on the cross-validation and an AUC of 0.77 (95% CI, ±0.05) on the test set. Conclusions: Results showed that the model was able to accurately classify the histology of NSCLC patients as squamous vs. non-squamous in a multicenter setting. It highlights the promise of CT-based radiomics in determining the histopathology or other molecular biomarkers of NSCLC, offering a more efficient, cost-effective, and less invasive alternative to traditional tissue analysis methods. Our findings suggest that this non-invasive method has the potential to improve patient selection and stratification and enhance the development of molecularly targeted drugs. These results underscore the importance of incorporating advanced imaging techniques and machine learning algorithms into oncology practice for better patient outcomes.
Somatic aberrations detected in tumor tissue and plasma in Chinese patients with stage I single-lesion and multi-lesions lung cancer.
Authors: Pei Guotian , Yang Yingshun , Li Mingwei , Ma Xiaoxue , Qin Jiayue , Cao Shanbo , Liu Qiang , Wang Shuai , Huang Yuqing 
Published: June 2023

e20600 Background: Recent studies show that the use of circulating tumor DNA (ctDNA) has potential to guide precision medicine and transform the management of early-stage lung cancers. We aim to investigate whether plasma is suitable for detecting tumor‐derived DNA in patients with stage I single-lesion lung cancer and multifocal lung cancer which has rarely been investigated. Methods: Matched tumor tissues (n = 114) and plasma samples (n = 95) from Chinese patients with stage I lung cancer (n = 95), including 80 patients with single-lesion and 15 patients with multiple primary lung cancer (MPLC) diagnosed by American College of Chest Physicians (ACCP) guidelines, were analyzed by Acornmed panel with 808 cancer-related genes. Results: Using tumor tissue-based results as the gold standard, we performed variant-level assessment of the ctDNA tests. In patients with single-lesion, sequencing detected alterations in 98.8% (79/80) ctDNA and 9.3% (74/797) of variants in ctDNA were detected by corresponding tDNA. Among them, 31.3% (25/80) patients had at least one overlapping variant called by tDNA and ctDNA, and 5% (4/80) patients shared EGFR in both tDNA and ctDNA. Meanwhile, we identified 2 mutated EGFR in ctDNA that were not detected in tissues. As for multiple primary lung cancers, 86.7% (13/15) of MPLC patients had ≥1 alteration in ctDNA. In addition, 7.4% (9/122) of variants in ctDNA were detected by corresponding tDNA in MPLC. The overall concordance for all variants detected in both ctDNA and any tDNA of patients was 53.3% (8/15) in MPLC, with EGFR and KRAS as the most two frequent mutations. Furthermore, mutations consistent with ctDNA were detected in 29.4% (10/34) of the lesions in MPLC. Conclusions: Our analysis showed that plasma with high mutation detection rate and considerable concordance rate with tDNA maybe a powerful complement to tissues for molecular testing in lung cancer. Furthermore, ctDNA detection not only may be able to overcome the heterogeneity of tumors but also more comprehensively reflect the disease state of patients with multifocal lung cancer.
Differentiating ensartinib from lorlatinib and alectinib for first line use in an ALK+ non-small cell lung cancer preclinical model (ResCu).
Authors: Gadde Manasa , Hill Lindsay , Schwabe Elizabeth , Bulow Christopher 
Published: June 2023

e20607 Background: The objective of this study was to determine whether Ensartinib with its high potency and resistance suppressing properties creates a more favorable treatment profile when used as first-line therapy in ALK+ non-small cell lung cancer compared to two other ALK inhibitors, Alectinib and Lorlatinib. Methods: The ResCu system, a novel culturing system, allows for long term culture of cells without the need for passaging, allowing determination of treatment resistance that can develop over time in a physiologically relevant system that conserves the resistance pathways found in patients. Two ALK-dependent lung adenocarcinoma cell lines, H3122 and H2228 were used to derive starting populations for this study. Using ResCu, we drove resistance to three ALK inhibitors: alectinib, lorlatinib, and ensartinib by using a clinically equivalent dose. The evolved cells were characterized for cross-sensitivity and resistance to a representative panel of 21 drugs. Cell viability was assessed by luminescence after 7 days of exposure to these secondary drugs. Additionally, BulkRNA Seq and WES were performed on the resistant evolved cells. Results: The ResCu system developed resistant cell populations by evolutionary steering of H3122 and H2228 cell lines treated with ensartinib, alectinib, and lorlatinib. Genetic background had a significant effect on which ALKi exhibited the most durable response. The H2228 derived cell population became resistant to alectinib and lorlatinib by 14 days while ensartinib remained effective for at least 42 days. In contrast, H3122 derived cells became resistant to all ALK inhibitors tested by 14 days. Rate of cross-resistance generation also varied between ALK inhibitors. Alectinib led to the highest levels of cross-resistance to other ALKi, approximately 3x higher. Lorlatinib led to highest levels of cross-resistance to other drug classes. Treatment with lorlatinib led to resistance in 13 other drug classes. Ensartinib led to least cross-resistance to ALKi and other drug classes. While the H3122 derived cells more rapidly evolved ALKi resistance, first line treatment with ensartinib sensitized them to lorlatinib, extending overall response to ALKi. Conclusions: The ResCu system developed two ALKi resistant cell populations from distinct genetic backgrounds under physiologically relevant conditions. In one of the two genetic background ensartinib response was durable for greater than 42 days compared to 14 days with alectinib and lorlatinib. Alectinib led to the most cross-resistance to other ALKi while lorlatinib led to the most cross-resistance to other drug classes in both backgrounds. Biomarkers of ALKi escape and cross-resistance were derived from RNA-seq, and we are currently validating these alterations against clinical samples.
Molecular profiling in a Peruvian population with advanced non-small cell lung cancer assessed by NGS.
Authors: Galvez-Nino Marco , Belmar-Lopez Carolina , Ruiz Rossana , Carrion Pamela , Diaz Diana , Chumpitaz Manuel , Gutierrez Jose Maria , Requena María , Pinto Joseph , Mas Luis 
Published: June 2023

e20612 Background: The use of next generation sequencing (NGS) both at diagnosis and disease progression has allowed us to detect changes in the genetic profile of patients that are potentially targetable. In this study we will describe the genetic profile of patients both at diagnosis and disease progression using NGS in tissue sample (TS) and liquid biopsy (LB). Methods: We evaluated 403 patients diagnosed with non-small cell lung cancer (NSCLC) referred to ONCOGENOMICS laboratory from 2016 to 2022 to somatic mutation testing. NGS was performed using the Ampliseq for Illumina FOCUS panel and run on the Illumina MiSeq. The panel targets single nucleotide variants (SNVs) and insertion/deletions (indels), copy number variation (CNVs), and gene fusions in 52 genes associate to solid tumors. Raw data were processed automatically on the BaseSpace Sequence Hub (Illumina) and aligned to the hg19 reference genome The default limit of detection (LOD) was set at 5% allelic frequency (VAF) in tissue samples and 0.5% VAF in ccfDNA samples. The Human Genome Variation Society (HGVS) nomenclature guidelines (http://varnomen.hgvs.org/) were used to annotate identified variants and the ClinVar database (www.ncbi.nlm.nih.gov/clinvar/) was used to determine the biological significance of all reported variants. Results: Of the 403 patients, 351 patients had NGS at diagnosis and 52 patients in disease progression. Regarding the genetic profile at diagnosis, we analyzed 328 tissue samples and 23 liquid biopsies, the most frequent alteration was the EGFR mutation, detected in 116 (33.1%) patients (detection rate TS 32.6% and LB 39.1%), followed by KRAS (15.4%), ALK (2.6%), BRAF (1.9%), and others (4.8%). In the disease progression setting, we analyzed 34 tissue samples and 18 liquid biopsies, the most frequent alteration was the EGFR mutation, detected in 28 (53.8%) patients (TS detection rate 29.4% and LB 44.4%), followed by KRAS (15.4%), ALK (3.9%), and others (3.9%). Conclusions: Peruvian patients are a population with a high mutation rate, in this cohort almost 50% of them had a target mutation, especially the EGFR mutation. Likewise, it was found that the detection rate of the EGFR mutation was higher with NGS in liquid biopsy than in tissue samples, both in the diagnostic and in the disease progression samples. On the other hand, it is important to mention that the frequency of KRAS mutations found is higher than previous Peruvian reports.
Prevalence of delta-like ligand 3 expression in small cell lung cancer.
Authors: Pundole Xerxes , Ju Chia-Hsin , Bylsma Lauren C. , Hooda Naushin , Movva Naimisha , Elkhouly Ehab , Bebb D. Gwyn , Fryzek Jon , Balasubramanian Akhila , Jandial Danielle , Dingemans Anne-Marie C. 
Published: June 2023

e20618 Background: Delta-like ligand 3 (DLL3), a ligand of the Notch-family, is a potential therapeutic target in small cell lung cancer (SCLC). High expression levels of DLL3 are observed in SCLC, however different methods and thresholds are used. A systematic literature review (SLR) was conducted to estimate the prevalence of DLL3 expression in SCLC. Methods: A comprehensive literature search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane Library databases, as well as on clinicaltrials.gov, using a pre-specified search strategy. This SLR was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD42022351119). Prevalence of DLL3 expression was evaluated overall and by method of DLL3 assessment and positivity threshold. Results: Of the 30 studies that met our study inclusion criteria, 22 (73.3%) were observational and 8 (26.7%) were clinical trials. Most studies (N = 21, 70%) evaluated less than 100 patient specimens (range: 20 to 1,362 patient specimens). Twelve studies (40%) were conducted in Asia, six (20%) in Europe, five (17%) in North America, five (17%) were multi-country, one in Brazil, and geographical location was not reported in one study. DLL3 testing methods varied across studies, with immunohistochemistry (IHC) being used in 26 (86.7%) studies. Two studies used real-time polymerase chain reaction, one used quantitative mass spectrometry, and one study did not report the testing method. Thirteen of the studies (13/26, 50%) that evaluated DLL3 expression by IHC used the Ventana SP347 assay. DLL3 expression was evaluated at various thresholds of tumor cell staining and showed a wide range of expression, across studies (Table). Conclusions: The SLR findings indicate that most studies assessing DLL3 in SCLC have relied on IHC methodology. Despite the range of thresholds used for evaluating positivity, DLL3 is notably expressed in SCLC. The frequency and impact of aberrant DLL3 localization was not addressed in these studies and minimal data on comparison of IHC with other methodologies exists. Results of this SLR also highlight the need to define a standardized method and threshold of evaluating DLL3 expression. [Table: see text]