bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are the results of clinical trials in patients with NSCLC reflected in real life? The Registurk-Lung study.
Authors: Artac Mehmet , Yildirim Mahmut Emre , Sümbül Ahmet Taner , Ozturk Akin , Karadurmus Nuri , Koral Lokman , Demirci Umut , Arslan Cagatay , Gumus Mahmut , Kefeli Umut , Ercelep Ozlem , Celik Sinemis , Bozkurt Oktay , Oven Bala Basak , Cubukcu Erdem , Karaca Mustafa , Bilici Ahmet , Tural Deniz , Harputluoglu Hakan , Dane Faysal 
Published: July 2024

e20512 Background: Evaluation of real-world data together with data in clinical studies is very important in the evaluation of treatment algorithms. In real life, treatments are applied to the elderly, patients with poor performance and unusual groups with comorbidities. Determining these treatment results is important in the creation of treatment algorithms. Methods: In our country, within the scope of the Registurk-Lung observational study (NCT05254119), a total of 4250 patients without driver mutation, metastatic non-small cell lung cancer were recorded between December 2021 and December 2023 in 42 centers representing the whole country. The demographic, histopathological, molecular and clinical data of the patients were recorded. The relationship between progression-free survival (PFS) time and overall survival (OS) time with these characteristics was investigated. Results: 4250 patients were evaluated. The median age was 64 (26-90) years and 15.1% of the patients were female. The proportion of patients who never smoked was 10.4 %. Histopathologically, 36.4% of the patients were diagnosed with squamous cell carcinoma. PDL-1 level was higher than 50% in 24.0% of patients and < 1 in 40.4% of patients. Only 11.8 percent of patients received single agent immunotherapy or chemoimmunotherapy. Other patients had received only a combination of doublet chemotherapy. The PFS was 6.9 months (95% CI: 6.4-7.3) and OS 14.6 (95% CI: 12.3-16.8) months in the whole patient group. Compared to the group that received chemotherapy alone, PFS and overall survival were longer in the group that received chemoimmunotherapy. This difference between the two groups was found to be statistically significant (p:0,001 and 0,031 respectively). Conclusions: As shown in clinical studies, immunotherapy alone or chemoimmunotherapy according to PDL-1 expression status provides a significant survival contribution compared to chemotherapy alone.
Real-world effectiveness and safety of amivantamab for exon 20 EGFR-mutant non-small cell lung cancer (NSCLC) in French early access program: Amexon 20 GFPC.
Authors: Pierret Thomas , Guisier Florian , Daniel Catherine , Descourt Renaud , Galland Loick , Molinier Olivier , Decroisette Chantal , Cortot Alexis B. , Moreau Diane , Bigay-Game Laurence , Wislez Marie , Cloarec Nicolas , Curcio Hubert , Delberghe Nicolas , Cadranel Jacques , Duchemann Boris , Toffart Anne-Claire , Moreau Lionel , Greillier Laurent , Auliac Jean-Bernard 
Published: July 2024

e20529 Background: Amivantamab is a bispecific EGFR/MET antibody approved for patients with NSCLC with EGFR exon 20 insertions. In France, early access has made it possible to use it as a second or further-line treatment after at least one line of chemotherapy. Methods: This is a retrospective multicentric cohort of consecutive patients with an adenocarcinoma and EGFR exon 20 insertions, who received at least one dose of amivantamab as part of the French early access program from September 3th, 2021 (date of approval in the French early access program) until April 30th, 2022. Patients gave consent for the data collection and were enrolled in 28 sites. Primary end point was Real world Progression free Survival (Rw PFS) and secondary endpoints were description of clinical characteristics, best response, duration of treatment, overall survival (OS), CNS activity, toxicities and subsequent treatment. Results: Thirty-nine patients received amivantamab in early French access. Median age was 60 years [39-83]; 64 % of patients were female and 54% never smoker; 33% had PS 2 or more and 66 % had brain metastasis at inclusion. Amivantamab was administered as a second or third line and more in 30% and 70% of patients respectively. Patients received a median number of 10 injections [1-47]. Overall, 37 patients were evaluable for response; response rate was 35 % and disease control rate (DCR) was 62%. After a median follow-up of 11.3 months [8-16.7], median Rw PFS and OS were 3.5 months [2.6-5.8] and 11.3 months [8-17.8] respectively. Rw PFS and OS at 6 months were 33.3% and 74.4% respectively. Duration of response was 5.8 months [2.3-11.9]. Overall, 23 patients were evaluable for CNS response; 26 % had CNS response and CNS DCR was 69%. Main sites of progression were lung (43%), bone (28%), liver (12.8%) and brain (10%). Grade III/IV adverse events were reported in 11 patients (28.2%), mainly skin toxicity (n = 5), infusion reaction (n = 2), digestive disorders (n = 1), interstitial pneumonia (n = 1), neurological disorders (n = 1), fever (n = 1). Amivantamab was permanently discontinued due to toxicities in 4 patients (10.3%). Subsequent treatment was administered to 21 patients (53.8%) after amivantamab, mostly consisting of mono chemotherapy (n = 13). Conclusions: Our real-world multicenter analysis showed that amivantamab was an effective monotherapy treatment in second line and after for patients with EGFR exon 20 insertions. No new toxicities were reported.
Anti-cancer activity of NTAX-44 (bioprocessed arsenic trioxide) on lung cancer.
Authors: Bendale Yogesh Narayan , Shastry Padma , Pujari Radha , Nagre Surendra , Khot Nandinee , Kadam Avinash 
Published: July 2024

e20573 Background: In contemporary allopathic medicine, intravenous administration of Arsenic trioxide is extensively investigated for its diverse applications in cancer treatment. However, the associated adverse effects demand exploration of alternative formulations. In present study, we propose the patented green technology-based compound “oral Arsenic Trioxide” (NTAX-44), in its unique form that can be administered orally, thereby reduces cost of treatment. This product presenting itself as a promising candidate for cancer therapy. Despite the ethnopharmacological uses of arsenicals in medicine, comprehensive understanding of their safety and efficacy remains limited. Thus, present study is proposed to investigate anticancer potential of NTAX-44 in lung adenocarcinoma cancer cell line A549. Methods: The effect of oral NTAX-44 was assessed on the viability of cell lines grown as 2D monolayers by MTS assay and 3D multicellular spheroid (MCS) model. Anti-metastatic potential of NTAX-44 was studied by using migration and colony formation assay while, expression of PD-L1 in A549 cell line treated with Arsenic Trioxide was checked by flow cytometry. The anti-metastatic capacity and cytocompatibility testing of Arsenic Trioxide was evaluated by in ovo chick embryo yolk sac membrane (YSM) angiogenesis assay and MTS assay using PBMCs respectively. Results: NTAX-44 is found to be effective to inhibit viability of A549 cell line (IC50 21.47±1.7 μg/ml for 48 hr and 14.65±0.92 for 72 hr of treatment); exhibiting its anti-proliferative activity. The A549 spheroids showed comparatively more resistance with loss of viability at higher concentration (50 and 100 µg/ml). Statistically significant decrease in scratch repair rate was observed at 24 hr and 72 hr of treatment and showing anti-migratory activity in A549 cells. In colony formation assay, complete inhibition of the colonization of A549 cells was observed after 48 hr of treatment; the survival fraction identified as 0%. NTAX-44 at 25µg/ml concentration inhibited PD-L1 expression in A549 cells, suggesting its potential to decrease expression of PD-L1 on tumor cells resulting in reversal of immune suppressive tumor microenvironment. Treatment of YSM with NTAX-44 resulted in approximately 40% inhibition in formation of quaternary blood vessels comparable to Bevacizumab (Avastin®). This significant anti-angiogenic potential is suggestive of its in vivo anti-metastatic effect. Notably, cytocompatibility testing of NTAX-44 at concentrations up to 200μg/ml was well-tolerated in PBMC cells emphasizing its favourable biocompatibility profile, providing crucial insights into its safety. Conclusions: Inhibitory effect of NTAX-44 on cell proliferation serves as a noteworthy attribute in context of its potential therapeutic utility against lung cancer. Its cytocompatibility further indicates application of arsenic trioxide as a candidate for clinical application.
Effects of lack of access to cancer medication on survival of patients with lung cancer.
Authors: El-Halabi Laura Nasser , Hodroj Mohammad Hassan Mahmoud , Rammal Firas , Ghais Ali , Tfayli Rami , Bou Orm Abdallah , Charafeddine Maya , Tfayli Arafat H. 
Published: July 2024

e20585 Background: Lung cancer is the leading cause of cancer-related death. The treatment has evolved with the introduction of immunotherapy. During the economic crisis in Lebanon, cancer medications became unavailable forcing oncologists to adjust treatment protocols. This study aims to assess the effect of medication shortage on the progression-free survival (PFS) of lung cancer patients treated at a tertiary care center in Lebanon. Methods: A retrospective analysis of patients with metastatic NSCLC treated during the period of drug shortage (October 2021-December 2022) as compared to those treated in 2019-2020. The primary end point was progression-free survival (PFS) on first line of therapy and its association with dose density ratio (dose density given/standard dose density). Electronic medical records of 117 patients were reviewed and data of 83 eligible patients were collected and analyzed using IBM SPSS software. Results: The mean age at diagnosis was 68 years. Of the total, 63.5% were male. Additionally, 14.4% of the patients received chemotherapy, 39.7% received immunotherapy, and 42.1% received a combination of chemotherapy and immunotherapy. In total, 49 patients were eligible in the 2019/2020 category. 84% of the patients had the opportunity to receive immunotherapy. In contrast, 25 patients were eligible in the 2021/2022 category, and only 73% of them had the opportunity to receive immunotherapy. The median PFS of the 2019/2020 category was 11.2 months, compared to 5.4 months in 2021-2022 (p-value of 0.339). PFS was studied based on the dose density ratio for immunotherapy. Twenty-two patients received a full immunotherapy dose with a ratio of 1, and their PFS was 5.43 months. Twelve patients received a dose density ratio ranging from 0.01 to 0.50 and had a PFS of 10 months. Twenty-nine patients received a dose density ratio of 0.51-0.99 and had PFS of 12.8 months. Contrary to our initial expectations, we did not observe a statistically significant difference between the dose density of immunotherapy and PFS values with a p-value of 0.107. Conclusions: Despite significant shortages in immunotherapy medications, our study suggests that this has no significant detrimental effect on PFS. This unexpected discovery challenges the conventional notion that full immunotherapy doses are necessary and prompts further exploration of the complex relationship between dosage and treatment outcomes in patients.
Genomic profiling of lung adenocarcinoma and squamous carcinoma in Indian patients: Implications for precision oncology.
Authors: Prabhash Kumar , Kumar Prashant , Jha Prerana , Joshi Asim , Mishra Rohit , Limaye Sewanti , Kanakasetty Govind Babu , Batra Ullas , Malik Prabhat Singh , Menon Nandini Sharrel , Shah Minit Jalan , Patil Vijay Maruti , Rauthan Amit , Kuriakose Moni , Noronha Vanita , Venkataramanan R 
Published: July 2024

e20599 Background: Lung cancer, the leading cause of cancer related mortalities, remains a significant global health burden. Despite advances in next generation sequencing technologies, the genomic landscape of non-small cell lung cancer (NSCLC) in the Indian patients remains underexplored. In this study, we aimed to elucidate the genomic landscape of lung adenocarcinoma and squamous carcinoma among Indian patients using targeted sequencing data of over 400 lung cancer patients. Methods: Utilizing targeted sequencing of 50 established cancer-related genes, we conducted a comprehensive analysis of the genomic alteration profiles in 325 lung adenocarcinoma and 81 lung squamous carcinoma samples from Indian patients. Further, we employed robust statistical methodologies to delineate correlations between genomic alterations and clinical characteristics including age, gender, extent of disease, habits and PD-L1 status. Furthermore, our investigation revealed distinctive genomic signatures of NSCLC specific to the Indian population through comparative analyses across various ethnicities. Results: EGFR mutations were detected in 45.8% of lung adenocarcinoma and a notable 18% of lung squamous carcinoma cases among Indian patients, showing significant prevalence among females and non-smokers. Alongside EGFR, lung adenocarcinoma patients exhibited frequent alterations in TP53 (27.4%), ALK (11.4%), and KRAS (10.2%), while lung squamous carcinoma cases predominantly showed mutations in TP53 (40.7%), PIK3CA (17.3%), and CDKN2A (8.6%). Remarkably, 68% of lung adenocarcinoma cases deemed eligible for NCCN-approved targeted therapies. Additionally, it was observed that 60% of PD-L1-negative squamous carcinoma patients harbored TP53 alterations, indicating intriguing therapeutic implications. Overall, we observed alterations in 88% lung adenocarcinoma and 70% lung squamous carcinoma patients. Conclusions: Our study unveiled distinct genomic variations present in both adenocarcinoma and squamous carcinoma patients from India, revealing crucial insights for precision medicine and clinical management of lung cancer. Our findings provide a significant lead for designing clinical trials aimed at evaluating EGFR inhibitors in lung squamous carcinoma patients, potentially expanding therapeutic options for Indian lung cancer patients.
Spectrum of HER2 alterations in NSCLC: Comparative analysis of tissue and liquid biopsies in lung cancer.
Authors: Choudhary R. K. , Koppaka Deepak , Vaid Ashok K , Kulkarni Shriniwas Subhash , Bose Chirantan , Morzaria Dr Disha , Apurwa Sachin , Vijayan Poornima , Bhatt Amit Dilip , Ranade Anantbhushan , Page Raymond , Patil Darshana , Akolkar Dadasaheb , Limaye Sewanti 
Published: July 2024

e20602 Background: Non-Small Cell Lung Cancer (NSCLC) exhibits a spectrum of molecular alterations that play a crucial role in understanding its heterogeneity and tailoring targeted therapies. Among these alterations, HER2 aberrations have gained significance as potential therapeutic targets. This study aims to explore the diversity of HER2 changes in NSCLC through tissue and liquid biopsies, providing valuable insights into the feasibility and accuracy of either method. Methods: Data from next generation sequencing of 799 tissues and 1380 liquid biopsy specimens was retrospectively analyzed. The study sought to elucidate the prevalence of HER2 alterations with these two methodologies, evaluating their respective strengths and limitations in detecting HER2 changes in NSCLC. Results: HER2 mutations were identified in 2.1% (17/799) of tissue, mirroring the prevalence observed in the TCGA cohort (2%). The liquid biopsy cohort identified Her2 mutations with similar prevalence and was positive for Her2 mutations in 2.2% (30/1380). Within Her2 mutations, HER2 exon 20 insertion mutations emerged as the predominant variant, accounting for all variants in tissue samples and 93.3% (28/30) in liquid biopsies. The most frequent HER2 exon 20 variant was p.Y772_A775dup variant (76.5% in tissue, 71.4% in liquid biopsy), followed by p.E770_A771insAYVM (17.6% in tissue and 7.1% in liquid). Less frequent HER2 mutations included p.G776delinsLC, p.G776delinsVC, p.V777_G778insGSP, p.A775_G776insYVMA. HER2 amplification was detected in 1.4% (5/352) of tissue and 1.3% (8/617) of liquid biopsy samples; concurrent HER2 mutation and Her2 amplification were detected in 3 liquid biopsy samples. 11/60 cases had concurrent targetable alterations in other targetable genes. Most common concurrent alterations were in EGFR followed by KRAS. Concurrent EGFR sensitizing alterations were observed in 7 patients ( 6 EGFR Exon 19 deletion and one EGFR L858R). Only 2/7 patients showed concurrent EGFR/HER2 alterations at baseline, the remaining 5/7 patients had received prior EGFR TKI therapy. Conclusions: Our results demonstrate equivalent Her2 alteration detection rate with liquid biopsy as compared to tissue molecular profiling in NSCLC. Our results support utility of liquid biopsy for Her2 profiling in the primary setting as well as to detect acquired Her2 alterations like in patients post EGFR-TKI therapy. It highlights that HER2mutations coexist with HER2 amplification in subset of advanced NSCLC patients. [Table: see text]
Unleashing deep features and radiomics to enhance best overall response prediction to immunotherapy in advanced non-small cell lung cancer.
Authors: Urbanos Gemma , Jiménez Pastor Ana , Lozano-Montoya Jose , Bellvís Bataller Fuensanta , Weiss Glen J. , Alberich-Bayarri Angel 
Published: July 2024

e20611 Background: Predicting immunotherapy response in advanced non-small cell lung cancer (NSCLC) through non-invasive means could be a groundbreaking advancement. Deep features extracted from medical images by deep Convolutional Neural Networks (CNNs) along with radiomics have demonstrated promising results in different oncologic diseases. However, the method for extracting these deep features influences the predictive capabilities of the model. Methods: A retrospective analysis of a multicenter study was conducted in advanced NSCLC patients with high PD-L1 expression with the aim of developing an imaging features-based model for the prediction of best overall response (BOR) to a checkpoint inhibitor immunotherapy. All visible lung lesions, beyond RECIST 1.1, were manually segmented in baseline CT scans. Radiomics features were extracted at lesion-level, and various preprocessing methods and CNN architectures were tested for deep features extraction. Radiomics and deep features were harmonized using ComBat methodology. A distinctive feature signature was created for each patient by calculating the mean across all lesions. Using this data, machine learning models were trained to predict treatment response, specifically distinguishing between complete response (CR) and partial response (PR) from stable disease (SD) and progressive disease (PD). The study compared the performance of different deep features extraction methods and assessed shapley additive explanations (SHAP) values of radiomics for interpretability. Results: In the cohort of 116 patients (mean age: 67, 93% ever-smokers, 73% male), 1024 to 5475 quantitative imaging features per lesion were extracted. Among these patients, 67 patients were CR+PR, and 49 were SD+PD. The top-performing predictive model, trained with radiomics and deep features from a deep convolutional autoencoder, achieved an average AUC of 85%. SHAP values showed that impactful radiomics features were correlated with intensity changes in adjacent pixels describing the tumor heterogeneity, along with shape features potentially associated with malignancy. Ultimately, combining both features demonstrated statistical significance, leading to a performance improvement of ~2-5% compared to models exclusively using deep features. Conclusions: Diverse techniques for extracting deep features were evaluated, revealing autoencoder training as the most effective strategy for predicting immunotherapy response. Consequently, the findings suggest that employing deep learning to extract imaging features from baseline CT scans, combined with radiomics, represents a promising non-invasive approach for the predicting immunotherapy outcomes in advanced NSCLC patients.
Ethnic disparities in biomarker testing of patients with metastatic NSCLC in the United States: A real-world analysis.
Authors: Jayram Diya , Bellur Shreyas S , Ozair Ahmad , Ahmad Shahzaib , Ganiyani Mohammad Arfat , Khosla Atulya Aman , McCracken Andrea , Marada Suresh , Hurmiz Charlie , Bowman Steven , Ahluwalia Manmeet Singh 
Published: July 2024

e20617 Background: National Comprehensive Cancer Network guidelines recommend biomarker testing prior to intervention in metastatic non-small cell lung cancer (mNSCLC). However, biomarker testing remains low, particularly in minorities, especially when targeted therapy against actionable driver mutations improves outcomes and quality of life significantly. We sought to determine testing rates and assess disparities between Hispanic and non-Hispanic Whites. Methods: A retrospective cohort study was conducted in accordance with "strengthening the reporting of observational studies in epidemiology" (STROBE) guidelines. All Hispanic and non-Hispanic White patients across a US oncology-focused hospital consortium (Guardian Research Network) were identified from 01/2018 to 01/2023. Socio-demographic details, clinical profiles, and details related to biomarker testing, treatment, and clinical outcomes were extracted. We also ascertained the area deprivation index (ADI) based on zip code as a surrogate for socio-economic stratification. We grouped patients into validated quintiles of ADI. We extracted testing details of the most common driver mutations – EGFR, ALK, KRASG12C, and PDL1. Data were analyzed using descriptive and inferential statistics. Results: Out of 4898 eligible patients with mNSCLC, 9.89% (n = 484/4898) were Hispanic, and 90.11% (n = 4414/4898) were non-Hispanic Whites. Overall testing rates for EGFR, ALK, KRASG12C and PD-L1 were 36.07% (n = 1767/4898), 33.60% (n = 1646/4898), 3.76% n = 184/4898) and 48.42% (n = 2372/4898). EGFR and ALK testing revealed significant differences showing reduced testing in the non-Hispanic White population (Table 1.) Multivariate logistic regression revealed no significant association between ADI, ethnicity and biomarker testing. Four hundred and eighty-three individuals underwent biomarker testing but did not receive treatment. Forty-three percent (n = 205/483) were alive at the time of data extraction, with 5.18% (n = 25/483) identified as Hispanic. Conclusions: Our analysis reveals that biomarker testing remains low in patients with mNSCLC, showing decreased testing rates of EGFR and ALK in non-Hispanic Whites when compared to Hispanic Whites. Purposeful strategies such as education and testing awareness campaigns are warranted to overcome low testing rates in patients diagnosed with mNSCLC.[Table: see text]