bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety analysis of immune checkpoint inhibitors plus angiogenesis inhibitors for treatment of advanced driver-negative NSCLC in elderly patients: A retrospective study.
Authors: Zhang Jian , Wang Hao , Zhou Jundong , Zou Zhonghua , Tan Jie , Shi Jianping , Yang Hui , Xue Jing 
Published: June 2023

e21044 Background: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic drugs may have synergistic effects in elderly patients with advanced driver-gene wild-type non-small cell lung cancer (NSCLC), but its true efficacy remains unclear. In addition, the chemotherapy tolerance of elderly NSCLC patients is poor, and the precise identification of the population who can benefit from ICIs combined with angiogenesis inhibitors is also the focus of current research. Methods: We retrospectively compared the clinical efficacy and safety of ICIs combined with or without antiangiogenic agents in elderly patients with advanced driver-gene negative NSCLC who were ≥65 years old in the Cancer Center of the Affiliated Suzhou Hospital of Nanjing Medical University. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs). Results: A total of 36 patients in the IA group（Immune checkpoint inhibitors plus angiogenesis inhibitors group) and 43 patients in the NIA group（Immune checkpoint inhibitors without angiogenesis inhibitors group) were enrolled in the study between January 1, 2019 and December 31, 2021. The median follow-up time for patients in IA group and NIA group was 18.2 months (95%CI: 14 - 22.5 months) and 21.4 months (95%CI: 16.7 -26.1 months), respectively. The median PFS and median OS were longer in the IA group compared to the NIA group（8.1 months vs 5.3 months；HR for PFS: 0.778, 95%CI: 0.474-1.276, P = 0.32; NA vs 30.9 months; HR for OS: 0.795, 95%CI: 0.396-1.595, P = 0.519). Subgroup analysis showed that patients in the IA group had significantly longer PFS in the subgroup with PD-L1 expression ≥50% (P = 0.017), and the relationship between treatment regimens and outcomes was still discrepant in different PD-L1 expression levels (P for interaction = 0.002). There was no significant difference in ORR between the two groups (23.3% vs 30.5%, P = 0.465). The incidence of adverse events in IA group was lower than that in NIA group (39.5% vs 19.4%, P = 0.05), and the cumulative incidence of treatment interruptions due to adverse events was significantly reduced (P = 0.045). Conclusions: In elderly patients with advanced driver-gene wild-type NSCLC, the addition of antiangiogenic agents to ICIs therapy did not provide significant clinical benefit, but the incidence of treatment interruptions due to adverse events was significantly reduced. In the subgroup analysis, we found that the clinical benefit of this combination therapy was observed in patients with PD-L1 expression ≥50%, which warrants further exploration. Clinical trial information: NCT05688046 .
Epidemiology and survival trends of lung carcinoids in the veteran population.
Authors: Tehzeeb Javaria , Mahmood Fatima , Gemoets Darren , Azem Amin , Mehdi Syed Arzoo 
Published: June 2023

e21049 Background: Lung carcinoids (LC) continue to increase in prevalence and existing data shows a female predominance of these tumors, but relevant epidemiologic data for heterogeneous populations is limited. In this study, we describe the epidemiology of LC in the United States (US) Veteran population. Methods: In this retrospective study, we searched Veteran Affairs Cancer Cube Registry (VACCR) for LC cases diagnosed between 2000 and 2017 and their baseline characteristics. Survival rates were analyzed across all baseline characteristics to identify important prognostic factors and results were compared with Surveillance, Epidemiology, and End Results cancer database (SEER). Data was analyzed via chi-square and Fischer exact probability tests (level of significance at < 0.05). Results: We identified 846 LC cases in VACCR (91% males), and 8,851 LC cases in SEER (32% males). Compared to SEER, VACCR data had more black patients (12% vs 8%), less cases with loco-regional disease (56% vs 84% in SEER) and same proportion of lower lobe tumors (40%). The annual incidence rate of LC among all lung cancers in Veterans tripled from 2000 to 2017 (0.3% to 0.9%). No racial disparities in treatment were noted among the Veterans. Male-specific 5-year survival rate was 18% lower in VACCR compared to SEER (61% vs 79%). Univariate analysis of both databases showed a statistically significant association of survival with age, primary tumor site and gender (p < 0.05 for all) (Table 1), with advanced age, upper lobe LC and male gender associated with worse survival. SEER subgroup analyses also showed lower 5-year survival rates for males across all baseline characteristics. Overall, black race appeared to be associated with worse prognosis, but the results did not reach statistical significance for VACCR data. Conclusions: Our study showed that US Veteran population, consisting of older males with more comorbidities, LC have lower survival rates than SEER population with more female LC cases. Advanced age, upper lobe predominant disease, and advanced stage were associated with worse survival. Both SEER and VACCR data suggest that male sex is a poor prognostic factor for LC. [Table: see text]
Gut microbiota profiling and clinical response in patients with metastatic non-small cell lung cancer receiving endothelial growth factor-tyrosine kinase inhibitors (EGFR-TKI).
Authors: Zhao Jing , Rao Jie , Li Qianxia , Yang Lin , Hu Guangyuan 
Published: June 2023

e21050 Background: Pre-clinical mouse models have suggested that gut microbiota in immune relates with inflammation and modulates tumor response, while it remains uncertain in lung cancer patients with EGFR mutation. We aimed to evaluate the relationship between gut microbiota and early tumor response after EGFR-TKI treatment in metastatic non-small cell lung cancer (NSCLC) patients. Methods: NSCLC patients haboring EGFR exon 19del or 21L858R mutation were enrolled in this study in Tongji Hospital, Wuhan, China. Early response was assessed at 12 weeks after EGFR-TKI initiation per RECIST 1.1, and patients were categorized as responders (CR+PR) and non-responders (SD+PD). Stool sample was collected prior to EGFR-TKI treatment. The V3–V4 region of the 16S rRNA gene was amplified for the characterization of the gut microbiota profiling. Data were analyzed on the online tool of Majorbio Cloud Platform to compare microbiota community structure and abundance at α- and β-diversity levels. Linear discriminant analysis with effect size (LEfSe) was used to to identify biomarkers using a taxonomic bar chart. PICRUSt2 was used to predict the functional profiling of microbial communities. P-values < 0.05 were considered statistically significant. Results: From June 2020 to Sep 2022, 24 patients were included. CR, PR, SD and PD were recorded in 2 (8.3%), 14(58.3%), 6(25%) and 2(8.3%) patients, respectively. The four most abundant bacteria at phylum level were Firmicutes (64.4%), Bacteroidota (15.1%), Proteobacteria(14.7%), and Actinobacteriota (4.6%). The relative abundance of Actinobacteriota counts were significantly higher in responders than those with no-responders ( p= 0.032). There was a significant difference in the Sob index (α-diversity) between responders and no-responders (60.062 vs. 86.250, p= 0.043). β-diversity was similar between the two groups ( p= 0.087). Differential analysis using LEfSe identified that genus Rothia was significantly enriched in responders; phyla Actinobacteria and Deinococcota, genera Ruminococcus, Collinsella, Holdemanella were significantly enriched in non-responders. PICRUSt2 based on KEGG prediction identified that Transketolase and Carbamoyl-phosphate synthase were significantly enriched enzymes in non-responders compared with responders, the p values were 0.019 and 0.022, respectively. Conclusions: The early response of EGFR-TKI was associated with alteration of specific genera and metabolic function of gut microbiota. Further research with larger cohorts is needed to validate this pilot study. [Table: see text]
Efficacy and safety of immune checkpoint inhibitor without pemetrexed for first-line maintenance therapy in advanced lung adenocarcinoma.
Authors: Gao Ming , Yang Wenyu , Wang Chunyu , Wang Ting , Jing Fangfang , Zhang Fan , Tao Haitao , Ma Junxun , Hu Yi , Wang Lijie 
Published: June 2023

e21058 Background: Currently, the standard first-line treatment for driver gene-negative advanced lung adenocarcinoma (LUAD) is chemotherapy plus immune checkpoint inhibitor (ICI) therapy followed by pemetrexed and ICI. However, pemetrexed is prone to certain adverse reactions and needs to be pretreated. At present, there is no relevant study on the efficacy between pemetrexed combined with ICI and ICI monotherapy in maintenance treatment. The object of this study is to explore the efficacy and safety of ICI as maintenance therapy in such patients. Methods: The study retrospectively analyzed patients with driver gene-negative advanced LUAD in PLA General Hospital from January 2019 to June 2022. These patients had received pemetrexed and platinum-based chemotherapy combined with ICI for 4-6 cycles. Patients who didn’t progress were subsequently entered into maintenance stage. The primary endpoint was progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was objective response rate (ORR) and safety. Results: A total of 93 patients with advanced LUAD who received first-line chemotherapy combined with ICI were collected, including 39 patients receiving pemetrexed plus ICI of maintenance therapy, 30 patients receiving ICI maintenance therapy, and 24 patients who failed to enter the maintenance treatment. Baseline characteristics of ICI group and pemetrexed plus ICI group were as follows: median age, 61.5 (42~81) years vs. 63 (35~74) years; male, 66.7% (20/30) vs. 79.5% (31/39); Smoking history, 63.3% (19/30) vs. 74.4% (29/39); Brain metastases, 10% (3/30) vs. 23.1% (9/39). ORR was 60.0% (95%CI 42.5-77.5) in the ICI monotherapy group and 69.2% (95%CI 54.7~83.7) in the pemetrexed plus ICI group. By November 30, 2022, the median follow-up time was 19.2 months. The median PFS of the two groups were 15.8 months (95%CI 9.84-21.70) in ICI group and 22.8 months (95%CI 4.57-40.97) in pemetrexed plus ICI group and there was no statistical difference between the two groups (P = 0.50). Neither group achieved OS. The incidence of all grade treatment-related adverse events (TRAEs) was 90.0% (27/30) in ICI monotherapy group and 92.3% (36/39) in pemetrexed plus ICI group. Grade 3/4 TRAEs occurred in 23.3% (7/30) and 23.1% (9/39) of each cohort and no grade 5 TRAE occurred. Conclusions: ICI maintenance therapy without pemetrexed showed great therapeutic efficacy in first-line maintenance stage and can be a feasible regimen in advanced lung adenocarcinoma.
Pretreatment radiomic biomarker for immunotherapy responder prediction in IB-IV stage NSCLC: A multi-center retrospective study.
Authors: Wu Shaowei , Zhou HaiYu , Xie Daipeng , Yao Lintong 
Published: June 2023

e21060 Background: The current biomarker of immune checkpoint inhibitors (ICIs) efficacy is not sufficient. This study investigated the correlation between radiomic biomarker and immunotherapy responder in patients with IB-IV stage non-small-cell lung cancer (NSCLC), including its biological explanation for ICIs treatment response prediction. Methods: CT images from 319 pretreatment NSCLC patients receiving immunotherapy between January, 2015 and November, 2021 were retrospectively collected and were distributed into a discovery (n = 214), independent validation (n = 54), and external test cohort (n = 51). 851 features were extracted from both tumoral and each peri-tumoral VOIs. The reference standard is the durable clinical benefit (DCB) and the crucial exclusion criteria are missing pretreatment CT scans. The predictive value of combined radiomic signature (CRS) was assessed in a cohort of 98 resectable NSCLC patients receiving ICIs. The association of radiomic features and tumor immune landscape on the online dataset (n = 60) was also evaluated. A clinical model was constructed and incorporated with radiomic signature to improve performance further. Results: CRS discriminated between DCB and non-DCB patients in the training cohort (area under the curve (AUC): 0.82, 95% CI: 0.75 to 0.88)) and independent cohort (AUC: 0.75, 95%CI: 0.62 to 0.88). In this study, the predictive value of CRS was better than PD-L1 expression (AUC of PD-L1 subset: 0.59, 95%CI: 0.50 to 0.69) or clinical model (AUC of validation cohort: 0.66, 95%CI: 0.51 to 0.81). When predicting pathological response, CRS divided patients into a major pathological response (MPR) and non-MPR group (AUC: 0.76, 95%CI: 0.67 to 0.81). Moreover, CRS showed a promising stratified ability on overall survival (OS; HR: 0.48, 95%CI: 0.27 to 0.89; p = 0.020) and progression-free survival (PFS; HR: 0.43, 95%CI: 0.26 to 0.74; p = 0.002). Biological pathway analysis on online dataset revealed that dysregulation of Hedgehog and Hippo signaling pathways got involved in the prediction of radiomic features. Conclusions: By analyzing both tumoral and peri-tumoral regions of CT images in a radiomic strategy, we developed a non-invasive biomarker distinguishing responder from ICIs therapy, which might inform clinical decisions on the use of ICIs in advanced as well as resectable NSCLC patients.
Post-double lung transplantation survival outcomes of bilateral lung cancer and incidence of post-transplant lung cancer.
Authors: Lee Jeeyeon , Yu Jisang , Schellenberg Samuel , Chung Il-Young , Bharat Ankit , Chae Young Kwang 
Published: June 2023

e21061 Background: To evaluate the role of double lung transplantation (DLT) for lung cancer, the survival outcomes of patients who underwent DLT for lung cancer and the incidence of lung cancer after DLT were assessed. Methods: Data from case series reported in the literature were pooled and collected from the Organ Procurement Transplantation Network (OPTN) and the International Society of Heart and Lung Transplantation (ISHLT) registries. We evaluated the recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) of patients who underwent DLT for lung cancer. Moreover, the incidence and OS of post-transplant lung cancer in patients who received transplants for the non-cancerous disease were examined. Results: Regarding patients who underwent DLT for lung cancer, in the pooled (n = 19), OPTN (n = 15), and ISHLT (n = 25) data, 5-year RFS was 52.6%, 66.7%, and 80.0%, and 5-year OS was 57.9%, 26.7%, and 36.0%, respectively. The median CSS was 48.0 (range, 6.0–144.0), 27.7 (range, 0.2–66.6), and 24.0 (range, 0.1–145.1) months. Additionally, the application of cardiopulmonary bypass was associated with lower tumor recurrence in the pooled data (p = 0.004). The incidence and 5-year OS post-transplant lung cancer in patients who underwent DLT for the non-cancerous disease were 0.8% and 47.3% in the OPTN data and 0.6% and 50.7% in the ISHLT data, respectively. Conclusions: We demonstrated that reasonable survival outcomes can be achieved with DLT in patients with bilateral lung cancer. Further studies are required to evaluate the risk of post-transplant lung cancer in patients undergoing DLT for bilateral lung cancer.
Clinical efficacy of frontline immunotherapy (IO) in ethnic-minority patients (pts) with metastatic NSCLC.
Authors: Lee Matthew , Liu Jianyou , Miao Emily , Wang Shuai , Zhang Frank , Wei John X , Chung Julie , Xue Xiaonan , Halmos Balazs , Hosgood Dean , Cheng Haiying 
Published: June 2023

e21063 Background: Since minority pts have been historically underrepresented in key IO trials, knowledge on the clinical use of IO in ethnic-minority pts with non-small cell lung cancer (NSCLC) remains limited. This study aims to evaluate race/ethnicity and other demographic, socioeconomic and clinical factors of pts with metastatic NSCLC treated with first-line IO. Methods: A retrospective cohort study of 5920 pts diagnosed with lung cancer within the Montefiore Health system from 1/1/2013 to 6/1/2022 was conducted. Pts with metastatic NSCLC without EGFR or ALK alterations and underwent first-line IO use were identified. The primary endpoint was overall survival (OS) with secondary endpoints of progression-free survival (PFS) and time to discontinuation (TTD) from the start of IO. Results: In total, 248 pts were identified with median follow-up time of 10.7 months (mons), median age of 66 years and 39.1% as Non-Hispanic Black (NHB), 30.2% as Hispanic and 30.7% as non-Hispanic White (NHW). OS (p = 0.39), PFS (p = 0.29) and TTD (p = 0.98) were similar among races/ethnic groups. ECOG < 2 at the start of IO was associated with longer OS summarized in Table 1. Significantly higher PFS and TTD were noted respectively in pts with Medicare insurance and PD-L1 status (TPS>1), while lower PFS and TTD with lower BMI. These results were remained after adjusting for biological sex, smoking status, histology, and IO regimen. Conclusions: Our study demonstrates that race/ethnicity does not impact the benefits of IO. However, factors such as ECOG status impact OS, and BMI, insurance and PD-L1 significantly impact PFS and TTD. These findings help identify potential factors that can be addressed to optimize outcomes and supportive care while undergoing IO.[Table: see text]
Real world EGFR testing practices for non-small cell lung cancer by thoracic pathology laboratories across Europe.
Authors: Hofman Paul ,   on behalf of the Pulmonary Pathology Working Group of the European Society of Pathology
Published: June 2023

e21064 Background: Testing for EGFR mutations is an essential recommendation in both the ESMO and ASCO guidelines for metastatic non-squamous NSCLC, and is considered mandatory in European countries. However, in practice, considerable challenges are often faced when performing routine biomarker testing, including access to testing, inadequate tissue samples, and long turnaround times (TATs). Methods: In order to evaluate the real-world EGFR testing practices of thoracic pathology laboratories across Europe, an online survey was set up and validated by The Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories across Europe. The retrospective survey focused on the laboratory organisation and daily practice of pathologists and molecular biologists between 2018 and 2021, and covered the clinical circumstances in which EGFR testing was performed, sample types used, molecular biology techniques performed, average TATs for determining EGFR status, annual EGFR testing rates, laboratory accreditation, and external quality assessment. Results: TATs varied greatly depending on different parameters (notably relating to testing practices and methods used) both between and within countries. TATs were slightly (but non-significantly) faster for liquid biopsy samples (Mean: 7 days, IQR 4.5-12.5) when compared to tissue samples (mean 7 days, IQR 5-15) but were reported to take as long as 20 or 30 days, respectively. Discrepancies in TATs may be due in part to reflex testing practices, as 20% (11/54) of laboratories performed EGFR testing only at the request of the clinician. Many laboratories across Europe still favour targeted sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques, and 45.1% indicated they used targeted sequencing followed by NGS, depending on the case. Reported testing volumes were consistent over time with no significant decrease in the number of EGFR tests performed observed in 2020, despite the increased pressure and difficulties faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42% of molecular biology laboratories for targeted sequencing, and by 42.3% for NGS. 92% (49/53) of laboratories indicated they regularly participate in an EQA scheme. Conclusions: The results of the survey highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there remains large variability in testing capabilities, reflex testing practice and laboratory accreditation, which stresses the urgent need to harmonize budgets and reimbursement in Europe, in addition to harmonization of the technologies and decision-making algorithms.
Genomic profiling in advanced NSCLC in Italy: First results of NERoNE (NSCLC Emilia Romagna Next Generation Sequencing Evaluation) project.
Authors: Bertolini Federica , Alberti Giulia , Petracci Elisabetta , Bettelli Stefania , Ulivi Paola , Cravero Paola , Guaitoli Giorgia , Zanelli Francesca , Burgio Marco Angelo , Andrikou Kalliopi , Pagano Maria , Verlicchi Alberto , Calistri Daniele , Flospergher Michele , Mastrodomenico Luciana , Maur Michela , Di Emidio Katia , Dominici Massimo , Pinto Carmine , Delmonte Angelo 
Published: June 2023

e21077 Background: The NERoNE Project evaluates the use of Next Generation Sequencing (NGS) in molecular profiling of advanced NSCLC (aNSCLC) patients (pts) in three Oncology Units (OU) of Emilia Romagna Region aiming to clarify the impact of such extensive tool in characterizing different NSCLC subpopulations. Methods: Since January 2020 to December 2022, 970 sequential aNSCLC pts from three OU (AUSL-IRCCS of Reggio Emilia, Modena University Hospital and IRST Meldola) were profiled by NGS. Samples from Modena and Reggio Emilia were analyzed at Modena University Hospital Molecular Pathology Lab using Myriapod IL- 56G, Cancer Panel DNA, Cancer Panel RNA, Oncomine DX Target Test Assay, Oncomine Focus Assay. Samples from IRST Meldola were processed at its Molecular Diagnostic Unit by Myriapod NGS cancer panel DNA e RNA, Oncomine Focus Assay and Oncomine Comprehensive Assay v3.We considered molecular alterations with available target therapies in Italy: EGFR mutations (mut) (exon 18,19,20,21), KRAS mut, BRAF V600E mut, ALK, ROS1, RET and NTRK rearrangements, MET exon 14 skipping mut, ErbB2 mut, FGFR 1-3 mut. PDL1 expression was assessed by standard immunohistochemistry on 486 pts. Results: Among 970 pts, 501 with at least one mut (52%) were considered for analysis: 266 were female (53%), mean age was 69 ± 11 years (min-max: 33-94) and 473 pts (94%) had adenocarcinoma. Molecular features are listed in table 1. Distribution of mut among ages, categorized as < 60, 60-70 and > 70 y, was similar, EGFR activating mut were most prevalent in females; KRAS mut (G12C and non G12C) were most prevalent in males; 41 pts had co-mutations (8.2%): the most frequent co-mut were EGFR mut (27%). PDL1 expression was < 1% 129 (27%), 1-49% 211 (43,4%) and ≥50% 146 pts (30%). The majority of pts with EGFR activating mut had PDL1 < 50%. Conclusions: NERoNE evaluates data from NGS profiling of three OU mapping key actionable molecular alterations in a large population of aNSCLC also accounting for PDL1 status. This preliminary analysis will be the starting point for further evaluations in order to improve the personalized approach to aNSCLC. [Table: see text]