bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant effusion aspirate for use in constructing organoids model to assist individualized treatment of advanced non-small cell lung cancer.
Authors: He Qiong , Yu Xinmin , Chen Zhenhua , Xie Cuiwei , Xiao Hongjiang 
Published: July 2024

e20526 Background: Organoids derived from cancer patients are considered to represent the overall appearance of the original tumor in lung cancer. With the in-depth study of molecular mechanisms and the development of new drugs, the survival time of advanced non-small cell lung cancer has been greatly extended. However, when it comes to the back-end treatment, they often have limited amounts of fresh tissue samples or cannot complete puncture, which affects the successfully establishment of organoids. Some patients often have malignant pleural effusion (MPE) requiring repeated aspiration, so it is clinically easy to obtain. Our goal was to culture organoids from malignant effusion of advanced NSCLC patients (LCO), and explore and analyze the consistency of drug sensitivity with clinical practice. Methods: In this study, malignant pleural effusion specimens of 39 patients with NSCLC were collected and complete clinical information was obtained.The partially paired successfully modeled organoids and the original malignant effusion were sequenced by WES(N = 7) and RNA(N = 6) for genetic background consistency.All successfully cultured organoids were subjected to drug sensitivity test, and the drug sensitivity results were compared with the actual therapeutic effect of clinical patients. Results: We successfully established 34 LCOs with a success rate of 87.2% . LCOs retained the mutation spectrum of the matching primary tumor. TP53 and EGFR were the most frequently mutated genes, occurring in 83.3% (5 of 6) and 66.7% (4 of 6) of effusion samples. On average, LCOs retained an 93.2% overlap of the most frequently lung cancer gene mutational variants from the parental MPE samples.The gene expression in the paired LCOs and effusion samples were compared, demonstrating an average 80% overlap in gene expression between the LCOs and the matching effusion samples.The clinical outcomes of the 25 patients (27 rounds of treatment) and their LCOs pharmaco-phenotyping results are analyzed. Notably, 94.7% of the treatments, which include at least one drug that was tested to be sensitive or moderately responsive by LCOs, achieved partial response or stable disease. However, 62.5% of the treatments, which do not include any drug that was tested to be sensitive or moderately responsive by LCOs, developed progressive disease. Overall, the LCO pharmaco-phenotyping results are highly correlated with clinical outcomes, with 85.2% accuracy (95% CI, 67.5–94.1%), 85.7% sensitivity (95% CI, 62.6–96.2%), and 83.3% specificity (95% CI, 36.5–99.1%). Conclusions: The effusion and LCOs have high concordance of genomic profiling. Organoid culture from malignant effusions of lung cancer can be used as a platform for drug sensitivity testing. These LCOs may be helpful in individualized treatment of NSCLC.
Efficacy and safety of second-line immunotherapy in patients with advanced non-small cell lung cancer.
Authors: Sánchez Escudero Laura , Cobelas Cartagena Stephanie S. , Sánchez Esperilla María , Bayo Juan L. 
Published: July 2024

e20571 Background: Patients (Pts) with advanced non-small cell lung cancer (NSCLC) face limited treatment options. Immunotherapy (IO) has revolutionized the treatment of NSCLC in this setting. The objective of our study is to evaluate the efficacy and safety of atezolizumab (Az) in Pts with advanced NSCLC in the second-line setting following progression on platinum-based chemotherapy (CT) in the Huelva area. Additionally, we aim to compare the results with those obtained in the phase 2 POPLAR and phase 3 OAK clinical trials. Methods: This is a descriptive and observational study conducted on patients with advanced NSCLC who received second-line IO with atezolizumab 1200 mg/1680 mg every 3 or 4 weeks, from 2015 to 2023 in the Huelva area (Spain). SPSS Statistics 22 was used for data analysis. Results: 26 Pts were treated, median age 67 years and 88.5% men. ECOG PS 0-1 in 92.3%. According to smoking habits, 42.3% were ex-smokers and 38.5% were active smokers. Regarding histology, 53.8% were non-squamous. 73.1% were inicial stage IV and 23% were stage III. Depending on the expression of PDL-1, PDL-1 was < 1% in 34.6% (9 Pts) of the sample, between 1-49% in 53.8% (14 Pt) and unknown in 3 Pts. 26.9% of patients achieved disease stability and 11.5% achieved partial response. The response has not been evaluated in 38.5% because these patients maintain treatment. The adverse effects (AE) suffered by patients treated with Az in the second line were 53.8% grade (G) 1- 2 and 7.7% G 3-4. The most frequent were asthenia (48%), pruritus and arthralgia in 15.4%, both cases, and skin toxicity in 11.5%. In the case of the 2 Pts with G 3-4 toxicity, they were due to autoimmune anemia and asthenia with subsequent to grade 1, so treatment did not have to be interrupted. The median progression-free survival (PFS) was 2.7 months (m) (95% CI 0-6.8) and the median overall survival (OS) was 5.2 m (95% CI 0.5- 9-9). In both cases the results were not statistically significant. According to PDL1, no statistically significant differences were found in the subgroup analysis. Conclusions: Based on our results and those of the Phase 2 POPLAR and Phase 3 OAK studies, we consider that Az has an acceptable safety profile, with fewer G 3-4 side effects compared to CT, so a lower percentage of Pts drop out the treatment. Although the PFS was similar to the phase II-III studies, the OS was lower, probably due to the percentage of Pts with rapid progression and patients currently continuing to receive treatment, being a limitation in our study along with the small sample size. Despite this, our results are encouraging regarding the benefit of IO in Pts. Therefore, we conclude that the use of IO in these Pts falls within good clinical practice, offering them a clearly effective therapy and thus avoiding treatments with greater toxicity such as CT.
Lung cancer in females from nonsmoker families in India: Observations and inferences in 5 years.
Authors: Udupa M. S. Namratha 
Published: July 2024

e20610 Background: Incidence in lung cancer in last two decades has been changing drastically in terms of gender, age, smoking behaviour of patients, stage at presentation, histopathology, genetic abnormalities, operability at presentation and survival. More perplexing is the increase in its occurrence in females from non smoker families, mitigating the sole importance of the traditional risk factors of tobacco and smoking in the recent times. This highlights the need to investigate other risk factors like radon exposure from indoor pollution where females stay most of the time, exposure to arsenic and other chemicals in daily life, particle pollution, physical inactivity and inflammatory diseases of airways. Methods: It was an observational study of patients who were diagnosed and treated at a high volume cancer centre in Karnataka state of India. 89 never smoker female patients under 50 years of age from non smoker families with no obvious exposure to second hand or third hand smoke were enrolled from October, 2018 to June, 2023. It was a longitudinal prospective cohort study where the demographic data, symptoms with duration, histopathology including genetic abnormalities, treatment details and survival were noted. Results: 89 never smoker females from non smoker families with ages ranging from 36 to 50 years had a median age of 46 years. About 70% of the ladies were from houses closely associated with farm in past or present. 55% of them had overweight and obese body habitus. Most common presenting symptom was dry cough with median duration of about 3 months in about 89%. Other symptoms were pleuritic chest pain(39%), breathlessness (19%), generalized body ache(9%) and jaundice(2%). Stage of disease was IV(69%), IIIC(12.3%), IIIB(11.2%), IIIA(5.6%) and II in just one patient. Most common sites of metastasis were contralateral lung(45%), bone(20%), liver(20%), adrenal glands(10%) and brain (15%). Most common histopathology was adenocarcinoma(87.6%), adenosquamous carcinoma(7.8%), squamous cell carcinoma(3.3%), large cell neuroendocrine carcinoma in just one patient. EGFR was mutated in 56(62.9%) with deletion 19( 33%) and L858R(21%) being the most common abnormalities. ALK rearrangements and ROS1 fusion were seen in about 9(3.3%) and 3(3.3%) patients respectively. Surgery was done in only 3 patients and chemoradiation after neoadjuvant chemotherapy was given in 8(8.9%) patients. Median overall survival was about 42 months in stage IV patients. Conclusions: Changing demographic profile of lung cancer warrants more research into the other causes of lung cancer. More stage IV disease highlights the emphasis on prevention and screening for the disease.
The impact of online CME on clinicians’ ability to utilize immunotherapy in unique populations of patients with NSCLC.
Authors: Worst Michelle Arielle , Small Andrew , Furedy Amy , Zhang Cong , Yuan Meng , Bahra Sukhbir , Liu Stephen V. , Weiss Jared 
Published: July 2024

e21004 Background: Immunotherapy (IO) has become a standard of care in the management of advanced non-small cell lung cancer (NSCLC). However, treatment with IO-based regimens may not always be straightforward, particularly in unique clinical scenarios and patient populations. As such, members of the multidisciplinary care team, including oncologists and pulmonologists, may lack experience in utilizing IO in these instances. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of oncologists and pulmonologists with respect to recognizing strategies that facilitate the safe and effective use of IO in patients with advanced NSCLC. Methods: The educational analysis consisted of 2 online, CME-certified activities. Educational impact was assessed with repeated pre-/post-education including multiple choice knowledge/competence questions and 5-point Likert scale confidence questions. Data from all oncologists and pulmonologists who completed pre- and/or post-education assessments were aggregated across activities and stratified by learning theme. Relative changes in percentage of correct responses and clinicians who were confident (value of 4 or 5) were used to measure improvement in knowledge, competence, and confidence. A McNemar’s test assessed significant levels of changes reported with P values <.05 considered statistically significant. The first activity in the analysis launched October 2023 and the last launched November 2023; data were collected until January 2024. Results: The educational series resulted in improvements in oncologists’ (N=119) and pulmonologists’ (N=49) knowledge, competence, and confidence after education. Conclusions: This analysis demonstrates that oncologists’ and pulmonologists’ knowledge, competence, and confidence regarding the safe and effective use of IO in patients with advanced NSCLC improved after education. Despite these improvements, additional educational activities are needed to address residual gaps and further increase clinicians’ ability in these dynamic and challenging clinical settings. [Table: see text]
The effect of an online micro CE/CME on the multidisciplinary care of patients with nonmelanoma skin cancer.
Authors: Worst Michelle Arielle , Small Andrew , Middleton Deborah , Yamaguchi Yoji , Yuan Meng , Bahra Sukhbir , Patel Vishal A. 
Published: July 2024

e21006 Background: Nonmelanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC), are the most common malignancies diagnosed in the US and worldwide. While most are successfully cured with local therapies or surgery alone, immunotherapy agents have been added to the arsenal for advanced tumors that are unresectable or unlikely to be cured with surgery alone. Thus, the multidisciplinary care model in this clinical setting has numerous advantages; however, many healthcare professionals (HCPs) may not fully recognize the role of their colleagues and their value in caring for affected patients. The objective of this study was to assess the educational impact of an online micro continuing [medical] education (CE/CME) activity on the knowledge and competence of HCPs’ with respect to the role and value of the multidisciplinary team in the optimal care of patients receiving immunotherapy for NMSC. Methods: The educational activity consisted of a collection of six online video-based micro-CE/CME-certified chapters, presented by six respected NMSC experts, allowing learners to choose their chapters for participation. Educational impact was assessed with repeated paired pre-/post-assessment study design, where individual participants served as their own control. A McNemar’s test assessed significant levels of changes reported with P values <.05 considered statistically significant. The activity launched September 2023; data were collected until January 2024. Results: The educational activity resulted in overall statistically significant improvements in HCPs’ knowledge and competence after education by chapter and by HCP audience type ( P < .01), including oncologists, dermatologists, surgeons, nurses, and pharmacists. Results presented below highlight the improvements in HCPs’ knowledge and competence by chapter. Conclusions: This analysis demonstrates the success of an online CE/CME activity with micro video chapters on improving HCPs’ knowledge and competence related to the value of the multidisciplinary team members in the comprehensive care of patients receiving immunotherapy for the treatment of NMSCs. Despite these significant improvements, additional educational activities are needed to address residual gaps and further increase HCPs’ ability and comfort in providing care in this clinical setting. [Table: see text]
Hidden advertisements included in cancer information posts: Insights from social listening.
Authors: Kim Dalyong , Lim Joo Han , Choi Wonyoung , Lee Hyun Woo , Yoon Ho Young , You Kyung Han , Lee Sang-Cheol 
Published: July 2024

e21017 Background: Access to cancer information on the Internet has proliferated, yet ensuring the accuracy and reliability of such information remains a challenge. The abundance of online content necessitates a comprehensive understanding of the prevailing landscape of cancer information dissemination. Methods: Cancer-related information was retrieved from search engine results pages of NAVER and Google, the most frequently used websites for information search in South Korea, during September and October 2023. Promoted posts and overt advertisements were excluded from the dataset. Posts featuring more than 50% of advertising content were categorized as fully hidden advertisements (HA), while those with lesser proportions were classified as partially HA. In cases where there was no advertising content but the hospital name or contact information was indicated for promotional purposes, it was classified as a simple HA. Topic modeling techniques were employed to analyze the content of HA posts, identifying prevalent themes and keywords indicative of promotional intent. Results: Of the collected posts, 48.6% were classified as HA. The publisher of the HA was 26.8% of oriental medicine/care hospitals, followed by general hospitals (25.3%), non-professional (21.3%), and small and medium-sized private hospitals (17.4%). In HA, 40.3% were full advertisements, 36.75% were partial advertisements, and the remainder were simple displays. By cancer type, 65.3% of posts about breast cancer were advertising posts, 55.2% were about colon cancer, and 53.7% were about stomach cancer. In the topic modeling analysis of HA, despite containing basic and theoretical information about cancer, HA subtly directs users towards advertising content, featuring terms related to private insurance and complementary medicine. Conclusions: The study elucidates the prevalence and characteristics of HA within cancer-related information available online, highlighting the need for heightened awareness. While it may not be inherently wrong, HA can impact user perception and decision-making processes. Additional research is underway to determine whether information classified as HA can be trusted. Addressing issues such as HA within cancer information will likely require cooperation between search engine platforms and government agencies.
Longitudinal circulating tumor DNA kinetics and correlation with patient outcomes in metastatic melanoma.
Authors: Tummala Ramya , Tummala Sirisha , Kuzel Timothy , Tan Alan 
Published: July 2024

e21538 Background: Previous studies have shown circulating tumor DNA (ctDNA) to be an accurate noninvasive method for detecting minimal residual disease and predicting therapeutic response. This study aims to investigate if positive ctDNA and subsequent clearance kinetics may be used as a predictive and prognostic tool in patients with stage IV metastatic melanoma. Non-clearance of ctDNA may be associated with poorer outcomes for progression-free survival (PFS) and overall survival (OS). Methods: In this retrospective analysis of preexisting data from a cohort of 27 patients with stage IV melanoma treated at Rush University, longitudinal ctDNA plasma samples collected between 05/01/2020 and 01/01/2024 were analyzed. A tumor-informed ctDNA assay (SignateraTM, reported in mean tumor molecules per mL (MTM/ml), low limit of detection of 0.01% variant allele frequency) was used for detection and quantification of ctDNA in plasma samples. Progression was determined based off of radiographic studies, overall survival was determined by time from stage IV diagnosis to patient death. Results: A total of 192 ctDNA timepoints were analyzed. The median number of ctDNA timepoints per patient was 5 (range 1-26). 8 patients were identified whose initial ctDNA result was negative and remained negative throughout their treatment course; 5/8 of these patients had baseline negative values available prior to the initiation of treatment. 19 patients had at least 1 positive ctDNA result at any given time; 1/19 of these patients was ctDNA-negative at baseline, 7/19 were positive at baseline, and 11/19 did not have baseline values available. The PFS rate was higher for ctDNA-negative patients compared to ctDNA-positive patients (62.5% vs. 57.9%). The OS rate was also higher for ctDNA-negative patients compared to ctDNA-positive patients (75% vs. 52.6%). Of the ctDNA-positive patients, those who achieved persistent clearance or had decreasing values of ctDNA had higher PFS rates when compared to ctDNA-positive patients who neither downtrended nor achieved clearance (71.4% and 66.7% vs. 22.9%). Patients who achieved persistent clearance or had decreasing values of ctDNA also had higher OS rates when compared to ctDNA-positive patients who neither downtrended nor achieved clearance (71.4% and 100% vs. 33.3%). Conclusions: Within the limitations of a small sample size, our data suggests that for patients with stage IV melanoma, a positive ctDNA result is associated with poorer outcomes for PFS and OS, when compared to patients with negative ctDNA results. Additionally, ctDNA-positive patients who achieved persistent clearance or downtrending ctDNA values showed more favorable outcomes for PFS and OS than ctDNA-positive patients who did not. [Table: see text]
Exploring the correlation between high HRD status and immunotherapy response in melanoma.
Authors: Nassief George , Adeyelu Tolulope Tosin , Zhou Alice Yao , Keller Jesse W. , Abdulla Farah R. , Vanderwalde Ari M. , Gibney Geoffrey Thomas , Park Soo J. , Ansstas George 
Published: July 2024

e21541 Background: Homologous recombination deficiency (HRD) status demonstrates DNA instability in tumor cells and has been implicated as a response marker for immune checkpoint inhibitors (ICI). Here, we explore the correlation between high HRD status and ICI response biomarkers, homologous recombination repair (HRR) mutations, and the prognostic advantage of high HRD status following ICI in cutaneous melanoma patients. Methods: Melanoma samples (N = 2158) were profiled for genomic loss of heterozygosity (LOH) by NGS at Caris Life Sciences (Phoenix, AZ). As a surrogate for HRD, LOH-high was defined as LOH at ≥ 16% of the segments analyzed (up to 552). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) was tested by IHC/NGS.Tumor mutational burden (TMB)-high was defined as ≥ 10 mutations/Mb. interferon gamma (IFN-g) and T-cell inflamed scores. Real-world overall survival (rw-OS) information was obtained from insurance claims data, with Kaplan-Meier estimates calculated from the start of immunotherapy until the last date of contact. Mann-Whitney U, Chi-square, and Fisher exact tests were applied where appropriate, with p-values adjusted for multiple comparisons. Results: Melanoma patient samples include - cutaneous: 1853; acral: 130; mucosal: 175, with LOH-high observed in 8.3% of cutaneous specimens, 13.1% of acral, and 30.9% of mucosal. Firstly, most biomarkers associated with response to ICI (PD-L1, TMB-high, total neoantigen load, IFN-g score, T-cell inflamed level, and dMMR/MSI-H) were not significantly different between LOH-high and LOH-low cohorts in all melanoma subtypes. However, TMB-high was significantly more prevalent in LOH-low cutaneous melanoma patients (54.9% vs 63.3%, p = 0.039). Prevalence of HRR gene mutations was not significantly different between high and low LOH groups in all cohorts, except for the ATRX gene which exhibited a significantly higher prevalence in the high LOH cutaneous (8.6% vs 1.3%, p < 0.001) and mucosal (28.8% vs 2.5%, p < 0.00001) melanoma specimens. Analysis of rw-OS showed no improvement in the treatment of LOH-high cutaneous melanoma patients with ICI compared to LOH-low (HR: 1.397 [95% CI: 0.759- 2.569], p = 0.281). Conclusions: This study demonstrates that HRDness reflected by the high-LOH status in melanoma did not correlate with mutations in HRR genes. In addition, melanoma specimens with high HRD status did not exhibit an overall higher prevalence of biomarkers associated with ICI response. Our study did not demonstrate improved survival outcomes in patients with high HRD status following anti-PD1 therapies. Future investigation is needed to assess other therapeutic approaches for these patients such as PARP inhibitors.