bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial differences in incidence, outcomes, and genomic alterations in small cell lung cancer.
Authors: Bayat Leyla , Fu Pingfu , Cao Shufen , Dowlati Afshin 
Published: June 2021

8514 Background: While the incidence of small cell lung cancer (SCLC) has been decreasing in recent years, an increasing proportion of our patients are younger African American (AA) women. There have been no studies describing these changes as well its impact on outcome and potential genomic differences amongst white and AA populations. Methods: We maintain a clinical/genomic/pathological database of all patients with SCLC treated at our comprehensive cancer center starting from 1998. We compared the baseline characteristics and outcomes (Overall survival [OS] and progression-free survival [PFS]) between AA and white patients, and between females and males. In addition, we looked at genomic alterations in >350 cancer-related genes and compared the frequency and types of mutations in our study population. Results: A total of 917 patients with SCLC were included (median age 66 years, 486 female, 179 African American). Amongst the African American patients, 67.6% were female, a striking difference compared to the white population, where only 49.1% were women (P<0.001). In multivariable analysis, there was no association between gender or race with OS or PFS (P> 0.05). There was an increase in mutational frequency in AA women compared to both AA men and white patients. PIK3CA and KIT mutations were more frequent in females while APC mutations were more frequent in males (P=0.041 for all comparisons). There was a trend toward increased mutational frequencies in TP53, PTEN, and NOTCH1 in AA patients. The relative frequency of gene alterations is shown in the table. In univariable analysis, NOTCH1 mutation was associated with improved OS (HR 0.24 [0.06-0.96], P=0.04). Conclusions: In this large cohort of patients with SCLC followed over 2 decades, there was a striking 2-fold higher incidence of SCLC in AA females than in AA males, although there were no differences in OS or PFS by sex or race. Several genomic alterations occur in higher frequencies in AA patients and AA women, in particular, have higher mutational frequencies.[Table: see text]
Driver mutations to predict for poorer outcomes in non-small cell lung cancer patients treated with concurrent chemoradiation and consolidation durvalumab.
Authors: Liu Yufei , Zhang Zhe , Rinsurongkawong Waree , Le Xiuning , Gay Carl Michael , Ning Matthew S. , Heymach John , Zhang Jianjun , Lin Steven H. 
Published: June 2021

8528 Background: The use of durvalumab after chemoradiation in locally advanced non-small cell lung cancer (NSCLC) patients significantly improves overall survival. However, it is unclear whether this benefit applies to all genetic subtypes of lung cancer. We hypothesize that patients with driver mutation NSCLC may derive less benefit from consolidation durvalumab. Methods: Using the Genomic Marker-Guided Therapy Initiative (GEMINI) database at MD Anderson, we identified 134 patients who were treated with chemoradiation followed by durvalumab for NSCLC. We segregated patients with driver mutations to targetable (EGFR, ALK translocation, ROS1 fusion, MET exon 14 skipping, RET fusion, and/or BRAF) (N = 24) and those driven by canonical KRAS mutations (N = 26). The rest (N = 84) had none of these mutations. We gathered demographic, treatment, and outcome data and compared progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. We used multivariate regression analysis to account for demographic and treatment variables. Results: For our cohort, median age at diagnosis was 64.8, 52% were female (n = 70), and median follow up was 1.5 years. 86% of patients have a history of smoking (n = 115). 21% had squamous cell histology (n = 28). 2 patients had stage IIA disease, 6 had stage IIB, 48 had stage IIIA, 56 had stage IIIB, 13 had stage IIIC, and 9 had stage IV. 73 patients had progression after durvalumab and 37 patients died. Patients with driver mutations had significantly worse median PFS compared to those without driver mutations (8.9 mo vs 26.6 mo; HR 2.62 p < 0.001). Patients with KRAS mutations had particularly poor PFS (Median 7.9 mo, HR 3.34, p < 0.001), while patients with targetable driver mutations trended to worse PFS (Median 14.5 mo, HR 1.96, p = 0.056). The median OS for the cohort was 4.8 yrs with no significant differences based on driver mutation status. On multivariate analysis, only driver mutation status was associated with PFS, but not OS. For patients with first progression, we found the targetable driver group to have significantly improved time to second objective progression (PFS2) compared to the KRAS (HR 0.28, p = 0.011) or non-mutated group (HR 0.38, p = 0.025). All patients in the targetable driver group received targeted therapy after first progression. Conclusions: Our results suggest that patients with driver mutations have worse PFS compared to patients without these mutations after chemoradiation. However, patients with targetable oncogene driver mutations have significantly improved prognosis after initial progression compared to the other groups, likely due to targeted therapy, suggesting that these therapies, including novel approaches towards KRAS mutants, should be further explored in this setting.
Patients with early-stage (T1-2N0) adenosquamous lung cancer have worse long-term survival compared to patients with early-stage lung adenocarcinoma or squamous cell histology.
Authors: Shagabayeva Larisa , Heer Patel B. , Yang Chi-Fu Jeffrey , Lanuti Michael 
Published: June 2021

8550 Background: Survival outcomes for patients with adenosquamous carcinoma of the lung are not well understood by virtue of reduced prevalence. The objective of this study is to compare the long-term survival among patients with adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma of the lung. Methods: Overall survival of all patients with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma who received guideline-concordant treatment for T1-2N0M0 from 2004-2017 in the National Cancer Data Base was assessed using Kaplan-Meier analysis, multivariable Cox proportional hazard analysis, and propensity score-matched analysis. Results: Among patients who met study criteria (N = 88,983), there were 2,469 (2.77%) patients with adenosquamous, 60,148 (67.59%) with adenocarcinoma and 26,366 (29.63%) with squamous cell carcinoma histology. In patients who had T1-T2 N0 M0 disease, adenosquamous carcinoma was associated with significantly worse 5-year overall survival (58.9% [95%CI:56.6%-61.1%]) when compared with adenocarcinoma (72.4% [95% CI:72.0%-72.8%]) and squamous cell carcinoma (62.6% [95% CI:61.9%-63.3%]). In multivariable Cox proportional hazards analysis, adenocarcinoma (HR 0.81 [95% CI:0.76-0.87], p < 0.001) and squamous cell carcinoma (HR 0.86 [95% CI:0.80-0.92], p < 0.001) continued to be associated with significantly better survival when compared to adenosquamous carcinoma histology. A propensity score-matched analysis of 1,854 adenocarcinoma and 1,854 adenosquamous patients who were well matched by 17 common prognostic covariates (including tumor size and comorbidities) found that adenosquamous histology (57.2% [95% CI:54.7%-59.6%]) was associated with worse survival when compared to adenocarcinoma (63.0% [95% CI:60.6%-65.4%]). An additional propensity score-matched analysis of 1,852 squamous cell carcinoma and 1,852 adenosquamous patients matched by the same covariates demonstrated that adenosquamous carcinoma (57.1% [95%CI:54.6%-59.6%]) was associated with worse survival when compared with squamous cell carcinoma (64.0% [95% CI:61.5%-66.4%]). Conclusions: Early stage adenosquamous carcinoma of the lung is associated with worse overall survival compared to its individual histologic components of adenocarcinoma or squamous cell carcinoma. These observations in both the unmatched and propensity matched patient cohorts invoke consideration of multimodality therapy for these early tumors.
A phase II study of palbociclib for recurrent or refractory advanced thymic epithelial tumor (KCSG LU17-21).
Authors: Ahn Myung-Ju , Jung Hyun Ae , Kim Miso , Kim Joo-Hang , Choi Yoon Hee , Cho Jinhyun , Park Ji Hyun , Park Keon Uk , Park Sehhoon , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Park Keunchil 
Published: June 2021

8576 Background: Thymic epithelial tumors (TETs) are rare but the most common tumor of the anterior mediastinum. Platinum-based combination chemotherapy is standard of care which is associated with a 50%-90% overall response rate (ORR) in metastatic disease. However, there is no standard chemotherapeutic option after failure of platinum-based combination chemotherapy. Genetic alterations associated with cell cycle including pRB, p16INK4A, and cyclin D1 are commonly observed in TETs. Based on these results, we conducted a phase II trial to evaluate the efficacy and safety of palbociclib in patients with recurrent or refractory advanced TETs. Methods: This is a phase II multicenter, open-label, single arm study of palbociclib monotherapy in patients with recurrent or metastatic advanced TETs who failed one or more cytotoxic chemotherapy. Patients receive oral palbociclib 125mg daily for 21 days followed by a 7-day break. The primary endpoint was the progression-free survival (PFS) rate at 6 months (H0 = 30% vs H1 = 48%). Results: Between August 2017 and October 2019, 48 patients were enrolled. The median number of previous chemotherapy was 1 (range: 1-4) and 21 (43.7%) of 48 patients received thymectomy. By WHO classification, Type A (n = 1), Type B1 (n = 2), Type B2 (n = 8), Type B3 (n = 13), Type C (n = 23), and unknown (n = 1). With medial follow-up of 14.5 months (range 0.8-38.2), the median cycle of palbociclib was 10 (range 1-40). The PFS at 6 months was 60% and the median PFS was 11.0 months (95% CI: 4.6-17.4). Six of 48 patients (12.5%) achieved partial response. The median overall survival was 26.4 months (95% CI: 17.4-35.4). The most common adverse events of any grade included neutropenia (62.5%), anemia (37.5%) and thrombocytopenia (29.1%). Conclusions: Palbociblib monotherapy is well tolerable and encouraging efficacy in patients with TETs who failed platinum-based combination chemotherapy. Updated results will be presented. Clinical trial information: NCT03219554.
METex14 ctDNA dynamics & resistance mechanisms detected in liquid biopsy (LBx) from patients (pts) with METex14 skipping NSCLC treated with tepotinib.
Authors: Paik Paul K. , Veillon Remi , Felip Enriqueta , Cortot Alexis , Sakai Hiroshi , Mazieres Julien , Thomas Michael , Reinmuth Niels , Raskin Jo , Conte Pier Franco , Garassino Marina Chiara , Iams Wade Thomas , Griesinger Frank , Kowalski Dariusz M. , Stroh Christopher , Juraeva Dilafruz , Scheuenpflug Juergen , Johne Andreas , Le Xiuning 
Published: June 2021

9012 Background: In the VISION study, tepotinib in METex14 skipping NSCLC pts (Cohort A) had robust and durable clinical activity. Serial LBx samples were collected for biomarker analyses, presented herein. Methods: LBx samples taken at baseline (BL), Week 6, 12, & end of treatment (EOT) were analyzed using Guardant360® CDx (73 genes). Investigator (INV)-assessed clinical outcome was evaluated per BL biomarker profiles and by molecular response (MR; defined as > 75% depletion from BL in METex14 variant allele frequency [VAF] ctDNA confirmed in 2 consecutive samples) or molecular progression (MP; defined as VAF increase > 0 from BL). Acquired resistance was investigated in EOT samples, following progression per INV. Results: LBx pts (n = 99) had a median age of 72 yrs (range 49–88), 53% were male, 44% never smokers, 85% had adenocarcinoma. INV ORR was 53% (95% CI 42, 63); ORR in 1L (n = 44) was 59% (43, 74) & ≥2L (n = 55) was 47% (33, 61). 94 pts had BL biomarker profiles; these were similar in 1L and ≥2L pts, except EGFR amp: 1/43 1L [2%] vs 8/51 ≥2L [16%]. Outcomes were not impacted by location/type of METex14 alteration. 1 pt with concomitant MET M1250T mutation had a PFS of 17.3 months. A trend towards better efficacy was seen in pts with concomitant MET amp (6 responses in 8 pts). Response to tepotinib occurred both in pts with wt or mutant TP53; however, there was a trend for longer mDOR in pts with wt TP53 (18.3 [95% CI 9.7, ne] vs 7.1 [4.7, 10.9] months) and mPFS (9.5 [6.7, 19.7] vs 5.1 [2.8, 6.9] months). Concomitant oncogenic mutations were rare, with no responses in 3 pts with KRAS, NRAS alterations and 3 responses in 5 pts with PI3K/AKT alterations. 65 pts had 2 consecutive on-treatment samples: 46 (71%) had confirmed MR, 5 (8%) had confirmed MP, 14 (22%) had no change in VAF or lacked confirmation. MR was associated with clinical response and MP was associated with no response/short PFS (Table). 52 pts with progression had EOT LBx samples. Emerging MET resistance mutations (Y1230H/C & D1228H/N) occurred in 7 (13%) pts, all responders and 5/7 had PFS > 10 months. Analyses on non-MET-driven resistance mechanisms will be presented. Conclusions: LBx biomarker analysis from the largest on-treatment data set for a MET inhibitor in METex14 skipping NSCLC, showed that ctDNA depletion in METex14 VAF is associated with improved clinical response in pts treated with tepotinib. This suggests serial LBx could help us to monitor response/non-response, understand resistance, and guide trials that test escalation/de-escalation strategies to improve outcomes and maximize QOL. Clinical trial information: NCT02864992. [Table: see text]
Effect of antibiotic therapy on immunotherapy outcomes for non-small cell lung cancer: Analysis from the Veterans Health Administration Database.
Authors: Stokes William A. , Behera Madhusmita , Jiang Renjian , Gutman David , Giuste Felipe , Burns Abigail , Sebastian Nikhil , Ramalingam Selvi , Sukhatme Vidula , Lowe Michael C. , Ramalingam Suresh S. , Sukhatme Vikas , Moghanaki Drew 
Published: June 2021

9017 Background: Dysregulation of the gut microbiota induced by antibiotic therapy (Abx) may alter the anticancer immune response. Multiple small studies have associated Abx use with inferior immune checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC). We aimed to study the impact of Abx in a larger population of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a nested cohort study of Veterans who were diagnosed with NSCLC between 2010 & 2018 and treated with ICI. Two exposures to Abx were specified and separately analyzed: prior Abx (pAbx) was defined as receipt of an Abx prescription within 30 days prior to initiation of ICI, and concurrent Abx (cAbx) was defined as receipt of an Abx prescription within 60 days following ICI initiation. A landmark analysis of 2 months from ICI start was applied to the cAbx analysis to exclude any Veterans with an OS event before that time point. OS was measured from start of ICI using Cox proportional hazard multivariate analyses (MVA). Results: 3,634 Veterans received ICI, mostly nivolumab (59.3%) or pembrolizumab (35.1%). Their median age was 69, and a plurality had male gender (97.0%), white race (73.0%), comorbidity count ≥1 (60.4%), adenocarcinoma (47.8%), and stage IV disease at diagnosis (40.9%). Of the 762 (21.0%) Veterans prescribed pAbx, beta-lactams, quinolones, and macrolides were the most common classes. These patients had shorter OS than those without pAbx (median 7 versus 10 months). Receipt of pAbx was also associated with lower OS on MVA (HR 1.31, p<0.01). In the propensity-matched cohort analysis, Veterans receiving pAbx had lower OS (HR 1.27, p<0.01) (Table top). For the cAbx analysis, 3,223 Veterans survived to the 2-month landmark, of whom 970 (30.1%) received cAbx. These Veterans had shorter OS than those without cAbx (median 7 versus 10 months). Lower OS with cAbx was also observed both on Cox MVA (HR 1.33, p<0.01) and in the matched cohort (HR 1.32, p<0.01) (Table bottom). Conclusions: In the largest analysis to date of Abx use in NSCLC patients receiving ICI, receipt of Abx within either 30 days before or 60 days after start of ICI was associated with lower OS. These findings suggest Abx therapy may have a detrimental effect on immunotherapy outcomes.[Table: see text]
Clinicogenomic real-world data analysis of patients (pts) with KRAS G12C-mutant advanced non-small cell lung cancer (aNSCLC) from the natural history cohort of the Blood First Assay Screening Trial (BFAST).
Authors: Dziadziuszko Rafal , Li Xiao , Anderson Eric C. , Zer Alona , Corrales-Rodriguez Luis , Cheema Parneet , Szczesna Aleksandra , Philco Manuel , Mathisen Michael , Paul Sarah M. , Bhagawati-Prasad Vijay , Pathria Gaurav , Shi Zhen , Hilton Magalie , zhang qing 
Published: June 2021

9023 Background: BFAST (NCT03178552) is a global, multicohort trial of targeted therapies or cancer immunotherapy (CIT) in treatment (tx)-naive aNSCLC. Pts are screened for the study using comprehensive blood-based next-generation sequencing (NGS). In the BFAST natural history cohort, data were collected for pts who received tx or care outside the study’s interventional cohorts. Here, we analyzed the subset of pts whose tumors have KRAS G12C mutations (mut). Methods: Pts eligible for blood-based NGS screening had unresectable aNSCLC, ECOG PS 0-2 and no prior systemic tx for aNSCLC. Pts without tissue samples were eligible. Key genomic and molecular features, including bTMB, PD-L1 and ctDNA concentration; cancer tx; tx response and survival data were collected and analyzed in an exploratory analysis. Results: In the full BFAST screening population through December 2020 (N = 5917), 23% of pts had tumors with any KRAS mut; 9% were KRAS G12C. Pts were enrolled in the natural history cohort from October 2018 to October 2020 (n = 1017); 63 pts had tumors with KRAS G12C mut. Median age was 68 y, 59% were male, 86% had ECOG PS 0-1 and 84% had non-squamous histology. Co-mut in TP53 (60%) and STK11 and/or KEAP1 (25%) were detected; 8% of pts had bTMB ≥16. High PD-L1 expression per local testing was reported in 32% of pts; 38% were not tested. Among pts with 1L tx (n = 50), 50%, 28% and 20% received chemo, CIT or CIT + chemo, respectively, with real-world response rates (CR/PR per physician assessment) of 20%, 29% and 30%, respectively. Of the 13 pts (21%) without documented 1L tx, 7 died ≤3 mo from enrollment. Median OS was 14 mo overall, with differences found between key genomic subsets (Table). Conclusions: BFAST is the first study to identify KRAS G12C mut using blood-based NGS and describe the natural history, clinical characteristics and genomic landscape of this pt subset. Up to 21% of pts may not receive 1L tx. Pts with TP53 co-mut appear to have favorable outcomes, while those with STK11 and/or KEAP1 co-mut appear to have inferior outcomes vs pts without these mut. The lack of PD-L1 testing in many pts indicates a lack of tissue for comprehensive tissue testing, highlighting a potential benefit of blood-based detection of biomarkers, including KRAS G12C. Clinical trial information: NCT03178552. [Table: see text]
Clinical performance of artificial intelligence-powered annotation of tumor cell PD-L1 expression for treatment of immune-checkpoint inhibitor (ICI) in advanced non-small cell lung cancer (NSCLC).
Authors: Kim Hyojin , Choi Sangjoon , Kim Seokhwi , Aum Jaehong , Pereira Sergio , Park Seonwook , Ma Minuk , Shin Seunghwan , Paeng Kyunghyun , Yoo Donggeun , Jung Wonkyung , Ock Chan-Young , Lee Se-Hoon , Chung Jin-haeng , Choi Yoon-La , Mok Tony S. K. 
Published: June 2021

9026 Background: Programmed death ligand 1 (PD-L1) expression is the standard biomarker for first line ICI in advanced NSCLC. However, manual evaluation of tumor proportion score (TPS) by pathologists has practical limitations including intra/inter-observer bias, variation in subjectivity on area of interest and intensive labor. We developed an artificial intelligence (AI)-powered TPS analyzer, namely Lunit SCOPE PD-L1, for objective annotation of tumor cell PD-L1 expression for prediction of ICI response in advanced NSCLC. Methods: Lunit SCOPE PD-L1 was developed by a total of 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 whole-slide images (WSI) stained by 22C3 pharmDx immunohistochemistry. A After excluding the in-house control tissue regions, the WSI were divided into patches, from which a deep learning-based model detected the location and PD-L1 positivity of tumor cells. The patch-level cell predictions were aggregated for TPS estimation. Clinical performance of the model was validated in an external cohort of 430 NSCLC tumor slides from patients treated with ≥ ICI at Seoul National University Bundang Hospital and Samsung Medical Center. Independent control TPS annotation of this external validation cohort was performed by three pathologists, and their consensus TPS was calculated by mean value of such. Results: AI-model (Lunit SCOPE PD-L1) predicts PD-L1-positive tumor cell with the area under the curves of 0.889 and PD-L1-negative tumor cells with that of 0.809 at cell-level analysis. At WSI-level, significant positive correlation was observed between TPS by AI model and control TPS by pathologists (Spearman coefficient = 0.9247, P < 0.001). Concordance rate between AI-model and control TPS by pathologists according to expression level of PD-L1 ≥ 50%, 1-49%, and < 1% status was 85.7%, 89.3%, and 52.4%, respectively. Median progression-free survival (mPFS) according to TPS by AI model ≥ 1% vs. < 1% were 2.8 vs. 1.7 months (hazard ratio, HR, 0.52, 95% confidence interval, CI, 0.38-0.71, P < 0.001). In contrast, mPFS according to control TPS was 2.8 vs. 2.1 months (HR 0.70, 95% CI 0.55-0.91, P < 0.001). Forty out of 84 patients (47.6%) annotated as control TPS < 1% by pathologists were considered as TPS ≥ 1% by AI-model and mPFS of this subgroup was 2.7 months. Conclusions: PD-L1 expression by AI-model correlates with PD-L1 expression by pathologists. Clinical performance of AI-model in WSI-level is comparable with assessment by pathologists. The AI-model can accurately predict tumor response and progression-free survival of ICI in advanced NSCLC.