bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of intratumor heterogeneity (ITH) on survival outcomes in patients with non-small cell lung cancer (NSCLC) with high tumor mutational burden (TMB-H).
Authors: Fridland Stanislav , Kim Hye Sung , Chae Young Kwang 
Published: July 2024

e20519 Background: Heterogeneity among cancer cells within a tumor significantly impacts cancer development and resistance to treatment. Currently, no standard measure exists for assessing ITH in routine clinical settings. In this study, we applied a quantitative metric to assess intratumor genetic diversity in NSCLC, using a large, multicenter database. Methods: We accessed the Tempus database for next-generation sequencing results from patients with NSCLC who underwent immune checkpoint inhibitor (ICIs) monotherapy as their first-line treatment. We calculated the mutant-allele tumor heterogeneity (MATH), defined as the ratio of the distribution's range to the median of mutant-allele fractions across tumor-specific mutated loci. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Results: A total of 160 pembrolizumab Significant differences in PFS between high and low MATH groups (MATH-H and MATH-L, respectively), using the 50th percentile as the cutoff, were observed among patients with stage 4 adenocarcinoma who had TMB-H above the 25th percentile (Table). In this subgroup, with 27 patients in the MATH-H/TMB-H group and 22 in the MATH-L/TMB-H group, the MATH-H/TMB-H group showed improved PFS (median PFS 5.19 vs. 1.61 months; p = 0.02). Differences in PFS were also observed among patients with TP53, KEAP1, and MET mutations (p < 0.001, p = 0.02, and p = 0.004, respectively). TP53 mutations were found in 27.6% of the MATH-H group and 27.8% of the MATH-L group, KEAP1 mutations in 8.2% and 10.1%, respectively, and MET mutations in 5.1% and 8.9%, respectively. No significant PFS differences were found in groups with low TMB, other stages, or squamous histology. Conclusions: Our findings suggest that higher genetic diversity within stage 4 TMB-H lung adenocarcinoma, as quantified by MATH, might be linked to improved clinical outcomes among those who receive pembrolizumab as first-line therapy and supports further exploration of MATH as a predictive/prognostic biomarker. [Table: see text]
Health outcomes of pembrolizumab plus chemotherapy in non-small cell lung cancer.
Authors: Marin Pozo Juan Francisco , Cao Viña Vanesa , Plaza Arbeo Ainoa , Morales Rivero Begoña , Ortega Granados Ana Laura , Lopez Lopez Jose Antonio 
Published: July 2024

e20527 Background: Pembrolizumab (PEM) is a standard of treatment for advanced or metastatic non-small cell lung cancer (m-nSCLC) in tumors without biomarker actionable. The clinical practice protocol for m-nSCLC in our hospital includes PEM monotherapy if PD-L1 ≥50% and PEM+chemotherapy (PEM+CT) if PD-L1 1-49% or negative. The aim of this study is to determine the effectiveness results of PEM+CT in m-nSCLC in real clinical practice. Methods: It was designed a single center, observational and retrospective study. We included all patients (pts) treated with PEM+CT as first line of therapy with m-nSCLC of September-2019 to August-2023 at a hospital from south Spain, cut-off date 11/30/2023. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The results were analyzed for population and by subgroups (histology, ECOG, previous localized disease (LD) and other), using Kaplan-Meier method. Results: 103 pts were enrolled (89% men), mean age was 66.2 years, 48.5% of pts had ECOG 0, 40.8% ECOG 1 and the rest ECOG 2-3. The tumors were 64.1 % non-squamous histology. 28.2% pts were treated for previous localized disease and 39.8% pts received radiation therapy at some point during treatment. At start of therapy the mean WBC count with PEM+CT was 10.0 x10(9)/L (sd=6.2). With a median follow-up of 10.8 months (m) the median for treatment duration was 5.7 m [95%CI 4.3-7.2].PFS was 7.2 m [IC95% 5.9-8.6] for all pts, 6.6 m [IC95% 4.6-8.7] for non-squamous and 8.2 m [IC95% 4.6-11.7] for squamous histology, p=0.158. OS was 14.2 m [IC95% 10.2-18.2] for all pts, 13.1 m [IC95% 7.6-18.6] and 14.2 [IC95% 9.3-19.2] by non-squamous and squamous histology, respectively, p=0.396.We found statistically significant difference in OS between: pts with ECOG 0-1 (median 15.1 m [IC95% 11.6-18.7]) vs pts with EOCG 2-3 (median 6.6 m [IC95% 1.6-11.6]), p=0.046 and pts previously treated pts of LD (median 21.7 m [IC95% 2.5-40.8]) vs pts with advanced or metastatic disease at onset (median 10.5 m [IC95% 5.2-15.9]), p=0.025. Another subgroup analysis is shown in table. Conclusions: The effectiveness of PEM+CT was similar in OS and PFS values to that of the pivotal trials. In contrast to these, our results were slightly better in squamous histology. The OS was better in pts with ECOG 0-1 and previously treated of localized disease, highlighting the importance of early diagnosis. [Table: see text]
Effect of first-line bevacizumab on prognosis of second or later-line immunotherapy in patients with advanced non-squamous non-small cell lung cancer: A retrospective analysis.
Authors: Chen Qian , Yuan Shumin , Liu Ni , Wang Huimin , Shang Xiaoling , Ma Xinchun , Sun Ying , Wei Chenxi , Liu Lian , Wang Xiuwen , Liu Yanguo 
Published: July 2024

e20570 Background: Previous studies have demonstrated that anti-angiogenic agents have the capacity to regulate tumor microenvironment and may affect the clinical effect of immune checkpoint inhibitors (ICIs). However, the impact of previous anti-angiogenic agents on clinical outcomes of non-squamous non-small cell lung cancer (nsqNSCLC) patients treated with ICIs remains unclear. Methods: In the present study, we incorporated POPLAR, OAK, and BIRCH trials with a total of 912 non-squamous NSCLC patients. Using Vivli data-sharing platform, we have obtained specific clinical information about individual patients. The progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier analysis with a log-rank test, and the corresponding hazard ratio (HR) and 95% confidence interval (CI) were estimated using the Cox proportional regression model. Chi-squared test was used to compare proportions between different groups. All statistical analysis and plotting were done in R version 4.1.1 and SPSS R26.0.0.2. P less than 0.05 was considered statistically significant. Results: In the overall cohort, PFS (2.77 months vs. 2.83 months; hazard ratio [HR],1.1; 95% confidence interval [CI], 0.9 to 1.3; p = 0.43) and OS (15.1 months vs. 14.3 months; HR,1.0; 95% CI, 0.8 to 1.3; p = 0.86) in patients treated with bevacizumab before atezolizumab (pre-bevacizumab group) and patients treated without bevacizumab before atezolizumab (no pre-bevacizumab group) were not statistically different. Merely in patients with KRAS mutation, no pre-bevacizumab group had an improved PFS (4.04 months vs. 1.64 months; HR,1.7; 95% CI, 1.0 to 2.7; p = 0.04) as compared to the pre-bevacizumab group. Longer use of bevacizumab (≥1.43 months) before atezolizumab suggested a longer PFS compared with shorter use of bevacizumab ( < 1.43 months) (20.07 months vs. 2.75 months; HR,0.40; 95% CI, 0.17 to 0.95; p = 0.03). Conclusions: In conclusion, our study demonstrated that whether or not first-line bevacizumab is given has no effect on PFS or OS of second-line or later-line immunotherapies. Patients with longer duration of first-line bevacizumab use have a longer PFS on later immunotherapy. The more appropriate timing and sequence of administration of anti-angiogenic agents and ICIs will help us achieve a better therapeutic effect in the clinical practice of patients with advanced NSCLC.
Response to first-line therapies in metastatic lung adenocarcinoma with low PD-L1 expression: A multi-center retrospective study.
Authors: Ge Yihui , Gao Aiqin , Sun Yuping , Li Juan , Wang Shuyun , Wang Jian , Wei Xiaojuan , Wang Leirong , Cheng Qinglei , Wang Xiufen , Zhang Jian , Fu Xuebing 
Published: July 2024

e20574 Background: For metastatic lung adenocarcinoma with low PD-L1 expression (tumor proportion score:1-49%), chemotherapy in combination with immune checkpoint inhibitors (IC), with bevacizumab (BC), or with both (IBC) have been established as standard first-line options. However, the optimal scheme is still undetermined. Methods: This retrospective study enrolled 125 metastatic lung adenocarcinoma patients with low PD-L1 expression from four cancer centers. All the patients received IC, BC, or IBC as the first-line therapies. Propensity score matching (PSM) with a ratio of 1:1:1 was used to balance the inter-group clinical characteristics. Efficacy, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), as well as safety were evaluated. Results: 35 of the 125 patients received IBC, 37 received BC, and 53 received IC. After PSM, a total of 35 pairs of patients were enrolled in the analysis. Patients receiving IBC (ORR: 57.1%, DCR:100%) or IC (ORR: 57.1%, DCR: 91.4%) obtained superior ORR and DCR in relative to those receiving BC (ORR: 45.7%, DCR: 82.9%). However, only IBC (median PFS: 20.47m; median OS: not research) rather than IC (median PFS: 10.0m; median OS: 21.36m) treatment generated significantly prolonged PFS and OS compared with BC (median PFS: 9.43m, P = 0.007; median OS: 23.2m, P = 0.048). We further analyzed the survival benefit based on different clinical and molecular features. We found patients with female gender had more significant OS benefit from IBC treatment over IC or BC treatment. In addition, non-smokers benefit more from IBC compared with IC. The occurrence of adverse events (AEs) was more frequent in IBC (74.3%) and IC (85.7%) group in relative to BC group (42.8%). Meanwhile, ≥ grade 3 AEs (22.9%) was markedly higher in IBC group compared with that in BC group (5.7%). However, leukopenia and neutropenia represent the most common ≥ grade 3 AEs, which are easy to be clinically managed. Conclusions: For metastatic lung adenocarcinoma patients with low PD-L1 expression, IBC is the preferred first-line therapy in terms of survival. However, the AEs should be carefully concerned.
Real-world data analysis of first-line targeted therapy for patients with non-small cell lung cancer with different EGFR mutation status in a tertiary care hospital.
Authors: Peng Yang , Liao Ziyi 
Published: July 2024

e20586 Background: Lung cancer is still the malignant tumor with the highest incidence and mortality rate in the world, of which non-small cell lung cancer (NSCLC) accounts for about 85%. The EGFR mutation rate in Asians is 30%-60%, with exon 19 deletion mutations and exon 21 L858R point mutations accounting for about 90% of EGFR mutations, which are the classic EGFR mutation types. The two have significant differences in clinical characteristics, and some clinical trials have shown differences in efficacy between different subgroups, but whether they exist in the real world needs to be further confirmed. Meanwhile, the efficacy of first-line targeted therapy in patients with coexisting mutant NSCLC harboring different EGFR classical mutations and whether there is a difference in different subgroups has not been conclusively determined. Methods: To collect general clinical data and their genetic test reports of NSCLC patients diagnosed with gene mutations who attended the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2021 for follow-up, with a follow-up date of June 30,2023, as the end date. Kaplan-Meier survival analysis and log-rank test were applied to compare:1)the median PFS in different subgroups of patients with no co-mutation classic EGFR mutation;2)the median PFS in patients with co-mutation classic EGRR mutation and no co-mutation classic EGFR mutation;3)the median PFS in different subgroups of patients with no co-mutation 19-Del/L858R and with co-mutation 19-Del/L858Rpatients;4)median PFS of patients between co-mutated 19-Del and L858R subgroups. Results: The median PFS of 19Del was significantly better than that of L858R in different subgroups of EGFR classical mutations (14.0 months vs. 8.1 months, p = 0.004 < 0.05). The median PFS of EGFR classical mutation was significantly better than that of EGFR classical mutation with co-mutation,11.1months vs. 5.8 months, respectively, p < 0.001. In different subgroups,19Del median PFS was superior to 19Del co-mutation (14.0 months vs. 6.1 months, p = 0.001 < 0.05),and L858R median PFS was superior to L858R co-mutation (8.1 months vs. 5.8 months, p = 0.449 > 0.05). 19Del co-mutation and L858R co-mutation median PFS were not observed in the analysis of the same simple 19del first-line targeted therapy survival benefit was significantly better than the similar survival benefit of L858R, whose median PFS was 6.1 months vs. 5.8 months, respectively, p = 0.449>0.05, the difference was not statistically significant. Conclusions: The survival benefit of first-line targeted therapy for 19Del in the real world is superior to that of L858R, while the clinical benefit of first-line targeted therapy is poor for classical mutations in EGFR with co-mutations, and combinations with other therapeutic modalities should be considered.
Prognostic factors for survival in NSCLC treated with immunotherapy: An institutional analysis.
Authors: Huang Judy , Khullar Rohit , Bhattacharya Moinak , Keresztes Roger , Prasanna Prateek , Sher Amna Falak 
Published: July 2024

e20591 Background: Immune check point inhibitors (ICIs) are the cornerstone of treatment for patients with advanced NSCLC. However, not all patients benefit from ICIs and some develop significant immune-mediated toxicities. There is limited data regarding prognostic factors in NSCLC patients treated with ICIs. Imaging features can complement clinical variables in predicting response to ICIs. This study aims to evaluate CEA, blood leukocyte markers, and novel CT-derived radiomic features as factors predictive of survival in this patient population. Methods: In this retrospective study, clinical data from patients with advanced stage NSCLC treated with ICIs at Stony Brook University Hospital from 2016 to 2021 were collected. Baseline and subsequent CEA (carcinoembryonic antigen), ANC (absolute neutrophil count), ALC (absolute lymphocyte count), NLR (neutrophil to lymphocyte ratio), AEC (absolute eosinophil count), and AMC (absolute monocyte count) were evaluated as independent prognostic factors. 3-D segmentation of ipsilateral lung lobe was obtained using U-Net and radiologist report of tumor location. 600 stable IBSI-standardized features were extracted from the region using PyRadiomics. The discriminative ability of clinical and image-derived variables was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Results: This study included 80 patients. Objective response rate (ORR) was 25.0% with 1-year OS of 58.0%. PD-L1 expression ≥ 50% was significantly associated with survival (p < 0.02). Decrease in CEA (p < 0.01) and 5% increase in AEC (p = 0.027) significantly correlated with survival. Age, sex, clinical stage, ANC, ALC, NLR, AMC did not significantly predict survival. Three image biomarkers that correlated with median enhancement of tissue on chest CT, and degree of tissue heterogeneity were significant predictors of mortality (p < 0.02). A multivariable model with clinical inputs outperformed one with radiomic features only (C-index 0.70 vs. 0.64). Clinical and radiomic inputs together performed well in predicting survival (C-index 0.76). Conclusions: Changes in CEA and AEC were the strongest predictors of survival in advanced NSCLC patients treated with ICIs. This study suggests that combined clinical and radiomic biomarkers (quantifying local lobar heterogeneity) can identify patients most likely to benefit from immunotherapy. [Table: see text]
Real-world KRAS testing and treatment utilization among patients with metastatic non-small cell lung cancer.
Authors: Blanc Simon , Vasudevan Anupama , Gart Mike , Sura Teena , Shrivastava Aryamaan , Varughese Prateesh , Scott Jeffrey A. 
Published: July 2024

e20593 Background: About 30% of patients with non-small cell lung cancer (NSCLC) have been reported to harbor gene mutations of Kirsten rat sarcoma oncogene homologue (KRAS). KRAS testing is recommended at metastatic NSCLC (mNSCLC) diagnosis and targeted treatment has shown better outcomes among KRAS-positive patients. This study aimed to understand KRAS testing rates among mNSCLC patients and utilization of targeted treatment among KRAS G12C positive patients treated in the community oncology setting. Methods: A random sample of 836 mNSCLC patients from the Integra Connect PrecisionQ de-identified database was included in this retrospective observational analysis, with additional information supplemented by chart curation. The database contains ~80% community oncology and ~20% academic practices with over 3 million cancer patients across 500 sites of care. Eligible patients were those aged ≥18 years, diagnosed with mNSCLC, and who initiated treatment in the second line (2L) setting between 01-May-2021 and 01-Jan-2024. KRAS testing rates and utilization of targeted treatment use were assessed and presented for this study. Results: The median (IQR) age of 836 mNSCLC patients was 68 (62,75) years; 52.9% were female; 73.8% identified as White, 11.7% as African American, 1.9% as Asian, and 12.6% as Other. Testing for KRAS was reported in 749 (89.6%) of the mNSCLC patients any time during the evaluation period, with most of them (738/749) tested before 2L treatment initiation; 186/749 (24.8%) of those patients were positive, and 74 were KRAS G12C positive. Of the KRAS G12C positive patients, 53/74 (71.6%) reported a targeted KRAS treatment in the 2L or greater setting. Conclusions: In this real-world setting, the testing rates for KRAS are almost 90%, with about 70% of the mutated patients receiving a targeted treatment. However, there is still a proportion of patients who did not receive KRAS testing or targeted treatment in this real-world setting. Appropriate and timely testing and utilization of the targeted treatment is necessary for better patient outcomes. [Table: see text]
Efficacy of systemic treatments in patients with metastatic lung invasive mucinous adenocarcinoma.
Authors: Demir Tarik , Araz Murat , Hendem Engin , Kocak Mehmet Zahid , Erman Mustafa , Bas Onur , Köstek Osman , Sever Nadiye , Zeynelgil Esra , Karakaya Serdar , Moloney Carolyn , Chung Liam IL-Young , Chae Young Kwang 
Published: July 2024

e20609 Background: Invasive mucinous adenocarcinoma (IMA) is a relatively rare histological subtype of lung adenocarcinomas that differs in its clinical behavior, radiologic features, histopathological, and genomic characteristics than invasive non-mucinous adenocarcinomas (INMA). Methods: We retrospectively investigated medical records of patients diagnosed with lung IMA at four oncology centers in Turkey. Patients who were ≥18 years of age, pathologically diagnosed with lung IMA, and who received at least one course of treatment for metastatic or inoperable disease were included in the study. Results: Forty-one patients were included in the study. The median follow-up was 16.6 months. Among the included patients, 24 (58.5%) were male, 17 (38.5%) were female, and their average age was 62. Six (14.6%) patients had a targetable mutation. Three (7.3%) patients were epidermal growth factor receptor (EGFR), two (4.8%) anaplastic lymphoma kinase (ALK) mutation, and one (2.4%) neurotrophic tyrosine receptor kinase (NTRK2) fusion. Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. Of the patients who received cytotoxic chemotherapy, 9 (25.7%) had a partial response, 14 (40%) had a stable response, and 12 (34.3%) had progression. The median PFS was 8.24 months (95% CI: 5.9-10.5 months), and the median OS was 20.4 months (95% CI: 14.4-26.3 months) in all study populations. In those receiving cytotoxic chemotherapy, median PFS and OS were 8.11 months (95% CI: 5.02-11.2) and 17.5 months (95% CI: 11.7-23.3 months), respectively. While the PFS of two EGFR-positive patients were similar at 18.9 months and 20.6 months, the third patient's PFS was quite prolonged (66.5 months). The ALK-positive patients receiving brigatinib and crizotinib PFS were 15.8 months and 2.73 months, respectively. The PFS of the patient receiving entrectinib was only two months. Among the entire patient population, only one patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy. In this patient, who progressed after four cycles of gemcitabine and platinum first-line treatment, a partial response and 7.23 months PFS were achieved with second line XELOX. Conclusions: Standard-of-care treatments have the same efficacy in IMA and INMA patients. Targetable mutation is less common in IMA patients compared to INMA. 5-FU-based chemotherapies also appear to be effective in lung IMA patients.
The patient outcomes with EGFR-mutated advanced non-small-cell lung cancer receiving aumolertinib as first-line treatment.
Authors: Li Jisheng , Zhao Wen , Li Hongxin , Xuan Tiantian , Wang Chengjun , Zhang Rongyu , Yang Chuang , Wang Jian , Yi Cuihua 
Published: July 2024

e20619 Background: As a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), aumolertinib demonstrated superior progression-free survival and a well-tolerated toxicity profile to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. However, the real-world impact of aumolertinib in the first-line treatment on patients' HRQoL still remains unclear. Methods: Advanced NSCLC patients with sensitizing EGFR mutations treated with aumolertinib 110 mg daily in the first-line treatment were prospectively enrolled and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and EORTC Quality of Life lung cancer-specific module (QLQ-LC13) information were collected. Efficacy evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was also recorded here. Prespecified key symptoms were cough, hemoptysis, dyspnea, sore mouth or tongue, dysphagia, hair loss, tingling hands or feet, chest pain, arm or shoulder pain and pain of other sites. Results: Totally, 33 patients in the first-line treatment were included and 23 patients had efficacy information up to Jan 2024. The median follow-up time was 264 days (interval: 36-491 days). The objective response rate (ORR) and disease control rate (DCR) was 65.2% and 91.3%, respectively. All the patients haven’t reached the time to deterioration and the progression free survival(PFS) and overall survival is not reach. EORTC QLQ-LC30 showed general health status scale and functional scales increased and symptom scales decreased during aumolertinib treatment. Symptom scales assessed by EORTC QLQ-LC13 showed cough, sore mouth or tongue, chest pain, arm or shoulder pain and pain of other sites, were improved significantly after aumolertinib treatment (P < 0.05). Conclusions: General health status, functional status and key symptoms improved from baseline in patients with advanced NSCLC receiving aumolertinib as first-line treatment. The ORR and DCR in our study was comparable in those showed the AENEAS trial.