bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of STK11, KEAP1, and KRAS mutations/co-mutations and associated clinical outcomes for patients newly diagnosed with metastatic non-small cell lung cancer.
Authors: Dabbous Firas , Wang Ching-Yu , Simmons Daniel , Huse Samuel , Jassim Rami 
Published: June 2023

e21186 Background: Data on the prevalence of emerging mutations /co-mutations (e.g., STK11, KRAS, and KEAP1) and associated clinical outcomes in metastatic non-small cell lung cancer (mNSCLC) patients are lacking therefore the objective of this study is to address these gaps in the current data. Methods: This study used the Flatiron clinico-genomic database and included newly diagnosed patients (≥18 years old) with stage IV NSCLC and known histology/PD-L1 status. Patients enrolled in clinical trials, with positive/missing EGFR or ALK, other malignancies, mixed histology, or without structured data within 90 days of diagnosis were excluded. The prevalence of STK11, KEAP1, KRAS mutations and co-mutations for each combination were evaluated in the overall study cohort and stratified by histology and PD-L1 status ( > or ≤1%). The overall survival (OS) from the date of diagnosis with stage IV was analyzed using Kaplan-Meier methods. Results: Of the 17,020 patients with NSCLC, 964 met the selection criteria and were included in the study. The prevalence of STK11, KEAP1, and KRAS is 18%, 15%, and 35%, respectively. With the exception of KRAS, the prevalence of all selected mutations and the co-mutations is higher in patients with PD-L1 negative and non-squamous NSCLC. The prevalence of KRAS is higher in patients with PD-L1 positive and non-squamous NSCLC (Table). The median OS was 10.1 months (95% CI, 8.6, 11.2) for the overall population, and 6.6 (5.7-8.3), 7.1 (5.8-8.8) and 9.9 (7.6-11.9) months in patients with STK11, KEAP1, and KRAS mutations, respectively. The median OS in patients with co-mutations ranges from 6.1 to 6.7 months. Conclusions: STK11, KEAP1, and KRAS mutations and co-mutations are common in mNSCLC patients. Current treatments, particularly in STK11, KEAP1, and co-mutation patients, are associated with poor OS. To address these harder to treat subgroups new treatment options or clinical trials should be considered. [Table: see text]
Examining molecular testing practices and targeted therapy use in advanced/metastatic non-small cell lung cancer (mNSCLC): A quality improvement initiative across ten community cancer centers.
Authors: Lopes Gilberto , Delcuze Bethany , Dewald Ilona , McKinnon Kelly E. , Carter Jeffrey D. , Heggen Cherilyn 
Published: June 2023

e21191 Background: A growing number of targeted therapy approvals for mNSCLC have dramatically increased requirements for molecular testing. Identifying and addressing real-world challenges mNSCLC care teams face due to resulting workflow shifts is essential to optimize patient outcomes. Methods: In March–September 2022, 126 health care professionals (HCPs) who treat NSCLC at 10 US community oncology clinics completed surveys assessing practice patterns, challenges, and confidence related to biomarker testing and targeted therapy use. HCPs (N = 105) participated in interdisciplinary audit and feedback (AF) sessions to examine clinical evidence and develop clinic-specific action plans to address identified gaps. Results: Participants represented the interprofessional NSCLC care team: medical oncologists (32%), pathologists (1%), radiation oncologists (1%), pulmonologists (2%), PCP/other physicians (5%), advanced practice professionals (22%), nurses (19%), and other HCPs (e.g. patient navigator, practice manager; [19%]). At the time of the program there were 9 NCCN-recommended biomarkers for mNSCLC. Less than half of HCPs reported regular testing for 4 of these biomarkers (Table 1). The majority of HCPs were somewhat (52%) or very/extremely (23%) likely to start treatment prior to receiving molecular testing results. Top reported barriers to integrating molecular diagnostics into routine practice were biopsy tissue availability/quality (45%) and determining whether to begin treatment prior to receipt of molecular testing results (43%). Gap-oriented clinic action plans aimed to improve communication between oncologists, pulmonologists, and pathologists to increase quality and efficiency of testing. A targeted therapy toolkit was developed with a panel of oncology and pathology experts and distributed to participants to address gaps in knowledge of testing practices and guidelines. HCP confidence in biomarker testing increased from 72% to 92% following the intervention. More HCPs correctly answered knowledge (43% pre-AF vs 61% post-AF) and competence (29% pre-AF vs 54% post-AF) questions following participation in the AF sessions. Conclusions: While molecular testing is critical for mNSCLC care, HCPs report sub-optimal rates of conducting testing prior to treatment and incorporating results into treatment planning. Here, we highlight an unmet need for improved interdisciplinary communication and coordination in mNSCLC care teams and an educational intervention strategy that can be used to improve HCP biomarker and targeted therapy use in mNSCLC. [Table: see text]
Osimertinib rechallenge in advanced EGFR non-small cell lung cancer patients.
Authors: Uy Natalie F. , Tratt Micah , Eaton Keith D. , Santana-Davila Rafael , Baik Christina S 
Published: June 2023

e21196 Background: Treatment after front line osimertinib (osi) for epidermal growth factor receptor (EGFR) mutated advanced non-small cell lung cancer (NSCLC) remains a clinical challenge. Interval chemotherapy after osi may eradicate clones responsible for EGFR tyrosine kinase (TKI) resistance, which may re-sensitize the tumor to EGFR inhibition. We describe outcomes of metastatic EGFR NSCLC patients who undergo osi rechallenge. Methods: NSCLC patients with confirmed EGFR mutation were retrospectively reviewed from a single institutional database from 1/2010-12/2022. We identified patients who received osi after interval therapy following initial osi progression. Patient characteristics and tumor type were collected via chart review. Response was determined using RECIST 1.1. Results: Seventeen patients with osi rechallenge after initial progression were identified. Median age at time of osi rechallenge was 62 yrs (range 42-73). Patients were predominantly female (n = 11, 65%), white (n = 9, 53%) and Asian (n = 8, 47%), never smokers (n = 13, 77%). Patients had either del19 mutation (n = 10, 59%) or L858R mutation (n = 7, 41%). Twelve patients (71%) received a 1st or 2nd generation EGFR TKI (erlotinib n = 10, afatinib n = 2) prior to initial osi; eight patients (47%) had confirmed T790M mutation. Eight patients (47%) had CNS metastases prior to osi rechallenge. Twelve patients (71%) had ECOG 0-1 at time of rechallenge. Patients had a median of 4 (range 2-5) lines of therapy prior to osi rechallenge. Median time between initial osi discontinuation and osi rechallenge was 13.8 months (range 3.2-50.7). In the interim, 17 patients (100%) received chemotherapy, 2 (12%) received immunotherapy monotherapy, 3 (18%) received antibody drug conjugate, and 1 (6%) received TKI. Sixteen patients had follow-up restaging CT scans; 1 died before restaging imaging was obtained. Two patients achieved partial response (PR) (13%), and 6 patients had stable disease (SD) as the best response (38%). Median duration of initial osi was 13.9 months (range 1.9-26.4), and median duration of osi rechallenge was 3.6 months (range 1.0-10.3). Patients who had PR/SD were on osi for 7.5 months (range 2.7-10.3). Ten (59%) patients received osi rechallenge for at least 3 months duration, and 6 (35%) received osi rechallenge for at least 6 months duration. Conclusions: Osi rechallenge is a potential option for advanced EGFR NSCLC patients to obtain disease control at later lines of therapy. Further research is needed to characterize mechanisms of targeted therapy resistance and better select patients who can benefit from EGFR TKI re-exposure.
Clinical outcomes of chemotherapy rechallenge in patients with metastatic non-small cell lung (NSCLC) who progressed on immunotherapy maintenance after front line platinum doublets and immunotherapy.
Authors: Wang Kaiwen , Fossella Frank V. , Negrao Marcelo Vailati , Cascone Tina , Gay Carl Michael , Le Xiuning , Vokes Natalie I , Bueno Hume Celyne , Hassan Amy Aida , Gibbons Don Lynn , Lee J. Jack , Heymach John , Zhang Jianjun 
Published: June 2023

e21205 Background: Maintenance immunotherapy (IO) is commonly utilized in metastatic NSCLC patients (pts) who did not progress after initial treatment with platinum doublet and IO. Upon progression, docetaxel with or without ramucirumab remains the treatment of choice, which is associated with poor response and high toxicity. We explored the option of rechallenge of original chemotherapy agents in this patient population. Methods: We queried MD Anderson Cancer Center GEMINI database to perform a retrospective review in pts who received chemotherapy (chemo) rechallenge with or without IO after progression on or after IO maintenance from 03/2016 – 12/2022 at MD Anderson Cancer Center. We assessed clinical response and progression free survival (PFS) with initial triplet treatment and rechallenge with chemotherapy. Clinical response was defined as clinical benefit based on clinician’s radiographic and clinical assessment. PFS was defined as the time interval free of disease progression. Demographics and results were summarized with descriptive statistics. Results: 20 patients received chemo rechallenge with or without IO after progression on IO maintenance. Upon chemo rechallenge, 7 pts received pemetrexed; 10 pts (50%) received carboplatin and pemetrexed; 19 pt received chemo rechallenge with IO. Median duration of initial IO maintenance was 9.4 months. Median duration of chemo rechallenge was 5.2 months. 10 (50%) pts discontinued chemo due to progression after receiving chemo rechallenge; 2 (10%) pts discontinued chemo rechallenge due to toxicities; 3 (15%) pts remained on therapy at the data cutoff of 2/10/2023. Median PFS with initial triplet was 14.3 months. Median PFS with chemo rechallenge was 7.4 months, longer than the histological control of 3-5 months from docetaxel +/- ramucirumab. Conclusions: Our single center retrospective review demonstrated that chemo rechallenge after progression on IO maintenance post front-line chemo-IO therapy had good tolerability and reasonable PFS, which may offer a reasonable alternative option to docetaxel+/-ramucirumab. Future studies are needed to confirm this result using docetaxel +/- ramucirumab as a control. [Table: see text]
Prevalence of actionable oncogenic alterations (AGA) among patients with advanced (adv) non-squamous (NSQ) non-small cell lung cancer (NSCLC) by age, sex, and race in the United States (US).
Authors: Oskar Sabine , Zu Ke (Kirsten) , Arunachalam Ashwini , Kao Yu-Han , Chen Cai , Zhao Bin , Aggarwal Himani 
Published: June 2023

e21206 Background: Identification of AGA in NSCLC has improved the understanding of lung cancer pathogenesis and introduced targeted therapies directed against specific genomic alterations. Given the limited data on the prevalence of AGA by demographics, we evaluated prevalence of AGA by age at diagnosis (dx), sex, and race. Methods: A descriptive study used the US nationwide de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database. Eligible patients were adults with a dx of adv NSQ NSCLC from Jan-2016 to Sep-2020 who initiated a first line therapy. The prevalence of AGA for each age, sex, or race stratum was calculated. Results: The cohort included 3938 patients; 67.9% White, 52.9% female, and median age at dx was 68 y. Table 1 presents the prevalence of AGA. The prevalence of EGFR and BRAF V600E mutations increased with age at dx. ALK rearrangement and ROS1 fusion were more prevalent among patients < 50 y vs ≥50 y while MET exon 14 skipping mutation was more prevalent among patients ≥75 y vs < 75 y. EGFR and KRAS G12C mutations were more prevalent in female vs male. Compared to White or Black, Asians had a higher prevalence of EGFR mutations and lower prevalence of KRAS G12C. Conclusions: The prevalence of certain AGA among patients with adv NSCLC vary by demographics, which may contribute to disproportionate disease burden in certain strata. These results highlight the need to enhance diversity of clinical trial populations and ensure the disease burden across demographics in the general population are represented in clinical trials. [Table: see text]
High-confidence AI-based biomarker profiling for H&E slides to optimize pathology workflow in lung cancer.
Authors: Ofek Efrat , Haj Razan , Molchanov Yossef , Yacobi Rinat , Mayer Chen , Barliya Tilda , Gazy Inbal , Dvir Addie , Hayun Ido , Zalach Jonathan , Paz Yaacov Nurit , Peled Nir , Bar Jair , Barshack Iris 
Published: June 2023

e21207 Background: In recent years AI methodologies have been increasingly adopted in the oncology space as part of the clinical decision process. Our previous research has shown accurate detection of actionable biomarkers based on AI algorithms applied to Hematoxylin & Eosin (H&E) scanned slides. While investigating a wide actionable biomarker panel, this profiling process can also flag patients with no actionable biomarkers. In Non-Small Cell Lung Cancer (NSCLC), EGFR, ALK, and ROS1 are the most commonly tested actionable alterations and the primary exclusion criteria for immunotherapy. Here we present a novel AI-based solution that can accurately and almost instantaneously detects patients without the main actionable biomarkers from the H&E image alone, thus helping prioritize the pathology lab workflow and navigate patients to a faster and more optimal diagnosis route. Methods: A retrospective cohort of 435 NSCLC patients was collected from the Sheba Medical Center pathology department. All cases (from primary and metastatic sites) with documented results for EGFR mutations, ALK, and ROS1-fusions were included. Molecular profiling was based on Oncomine Comprehensive, Dx target, or Solid tumor DNA assays, with 4 cases also supported by the Idylla EGFR mutation test. Deidentified digital whole slide images (WSIs) were run using Imagene’s AI classifier and compared to the officially reported results. The classifier was generated using self-supervised algorithm, combined with multiple instance learning algorithms applied using untagged and tagged FFPE H&E scan (40x or 20x magnification) from Imagene’s internal database (including TCGA research network slides). A categorical prediction (positive/negative) inferred on the validation set by the combined AI classifier model. Results: The combined AI model for detecting EGFR, ALK and ROS1 actionable alteration resulted in 127 patients (29.4% of the cohort) reported with no EGFR actionable mutation, ALK, or ROS1 fusions. Only two patients (1.57% of the negatively detected patients) were found to be false negative ( EGFR: p.G719D and p.L858R), demonstrating 98.43% accuracy. Conclusions: Image-based molecular detection can serve as an accurate and fast detection method to be used in the clinical setting for monitoring and prioritizing current pathology workflow. Specifically, it can detect a major fraction of the non-targetable patients and optimize their diagnostic flow.
Impact of a pathologist-driven molecular testing protocol on veterans with non-small cell lung cancer.
Authors: Li Rui , Frias Kletecka M. Carmen , Shin Daniel Sanghoon 
Published: June 2023

e21209 Background: Precision medicine has shifted the paradigm of cancer treatment in the last two decades. Currently, with over ten targetable mutations in non-small cell lung cancer (NSCLC) and increasingly emerging biomarkers for immunotherapy, genomic testing is necessary for every NSCLC patient. However, this multiple biomarker-defined treatment approach is often compromised by many challenges including slow turnaround time (TAT), high rate of quantity not sufficient (QNS) resulting in inaccurate molecular testing or needs for second biopsy. These barriers lead to increased risk of developing medical complications from re-biopsy or treatment delay as well as additional social and financial support, which is not always available for veterans. A recent study reported that up a one third of veterans with NSCLC containing highly actionable mutations were not prescribed targeted treatment, among which, 25% of patients do not have a documented molecular testing results. Herein, we reported a pathologist-driven protocol to enhance the implement of molecular testing on guiding NSCLC treatment in veteran population. Methods: A pathologist-driven molecular testing protocol is applied West Los Angeles VA hospital since 2018. First, in preparation for diagnosis and molecular testing, tissue block will be cut in serial sections in the following priority: 2 slides for H&E, 4 slides for IHC, 2 slides for PD-L1 staining. An additional slide is made for quality control (QC) purpose before 10 additional slides are cut for molecular testing and 6 for FISH studies. The reminder of the tissue block will be cut in serial sections and preserved in a vial along with tissue shaved at initial block effacement. Every tissue block will be exhausted. Upon initial evaluation of H&E slides, the reviewing pathologist, independent of the treating oncologist, will order molecular testing including EGFR, ALK, ROS and BRAF by NGS if NSCLC is identified. PD-L1 IHC staining is also ordered automatically regardless of the histology. If a clinically actionable mutation is detected, a mutation notification is immediately sent via email by the molecular pathologist to alert the treating oncologist. Results: After implementing this protocol, we observed a decreased rate of QNS (~30% reduction) and subsequently the need for 2ndbiopsy dropped substantially. We also observed a faster TAT between initial cancer diagnosis (within 7 days) and the resulting of molecular testing to guide subsequent treatment. Conclusions: Refined tissue processing and pathologist driven ordering system can significantly impact initial management of patients with NSCLC as it reduces the rate of QNS and repeat biopsy/TAT. This protocol can be easily implemented in VA system or other community based healthcare system.
Real-world healthcare resource utilization amongst non-small cell lung cancer (NSCLC) patients tested with a host immune classifier (HIC).
Authors: Iams Wade Thomas , Le Kimberly , Princic Nicole , Marlin Taylor 
Published: June 2023

e21210 Background: The HIC is a blood-based proteomic test that measures immune response in patients with NSCLC. The test stratifies patients into two groups, HIC-H and HIC-C which helps evaluate patient prognosis and response to treatment. While clinical validity of the HIC test has been published, no real-world studies have described healthcare resource utilization (HCRU) amongst patients who have been tested with the HIC. This claims analysis describes HCRU amongst patients with NSCLC tested with the HIC. Methods: MarketScan Commercial and Medicare Supplemental Databases linked to Biodesix data files of HIC test results were retrospectively queried to identify patients who were age 18 and older on index date (date of HIC testing), underwent a HIC proteomic test, were continuously enrolled in the MarketScan database for the 6-months before index (pre-index period) and one month post-index, and had at least one non-diagnostic medical claim of lung cancer during the pre-index period. Data utilized was between January 1, 2016 to June 30, 2021. HCRU was measured per patient per month (PPPM) during the pre-index and post-index period and compared between HIC-H and HIC-C cohorts. Results: Of the 328 included patients, 260 patients were HIC-H and 68 were HIC-C. On index, 178 patients had non-metastatic lung cancer and 150 patients had metastatic lung cancer. When examining HCRU in all patients prior to the HIC test, significantly more HIC-C patients had an outpatient visit with an oncologist (40% vs 27%, P < 0.05) or a primary care physician (71% vs 56%, P < 0.05). When assessing only patients with metastatic lung cancer prior to index, significantly more HIC-C patients had inpatient admissions (57% vs 37%, P < 0.05) and more outpatient visits with a primary care physician (73% vs 50%, P < 0.05). When examining HCRU in patients after the HIC test, metastatic patients had significantly more prescriptions (4.6 vs 3.6, P < 0.05). Metastatic HIC-H patients also had significantly more visits to the emergency room (64% vs 43%, P < 0.05). Conclusions: Patients who are identified as HIC-C tend to have higher HCRU earlier in their lung cancer diagnosis and treatment course (prior to HIC testing). In the post-index period, metastatic HIC-H patients had higher HCRU with respect to prescriptions and emergency visits. Other post-index HCRU metrics such as primary care utilization and inpatient admissions were similar among HIC-C and HIC-H patients. Earlier identification of HIC-C and HIC-H patients may help identify those most likely to benefit from additional health system navigation support.
Machine learning models based on radiomics features to predict treatment response, biomarker status, and bone metastasis in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).
Authors: Yu Jisang , Velichko Yury , Kim Hyeonseon , Gennaro Nicolò , Soliman Moataz , Kim Leeseul , Oh Youjin , Djunadi Trie Arni , Lee Jeeyeon , Chung Liam Il-Young , Yoon Sung Mi , Shah Zunairah , Yang Won Jun , Kim Hye Sung , Lee Yunjoo , Lee Soowon , Kang Daeun , Agrawal Rishi , Aouad Pascale , Chae Young Kwang 
Published: June 2023

e21217 Background: Radiomics can predict diagnosis, metastasis, actionable mutations and treatment response in NSCLC patients by analyzing the heterogeneity of tumors and its surrounding tissues from medical images. In this abstract, machine-learning models based on radiomic features, in patients with NSCLC, were established and evaluated. Methods: Patients with NSCLC and treated with ICIs were selected. Main tumor and peri-tumoral space were segmented on chest CT scans with contrast at the start of immunotherapy by four clinicians. Among 255 radiomic features were extracted using LIFEx software (IMIV/CEA, Orsay, France), the top 30 features with the highest Fleiss’ kappa coefficient were chosen. The Random Forest (RF) algorithm with mixed effects was utilized to develop models. We divided data into two groups as a training set (70%) and a validation set (30%) and conducted bootstrapping to evaluate the efficiency of the models. The performance of the models was determined by calculating the sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). Durable disease control, progression, clinical progression, EGFR mutations, bone metastasis was evaluated by each model. Durable disease control was defined as no progression of diseases for 24 weeks or more after initiation of ICIs according to RECIST 1.1. Progression was defined by RECIST 1.1 on the first follow-up CT. Clinical progression was defined when treatment was discontinued due to disease progression. Results: Total 102 patients were analyzed; 55 (53.9%) were female and 47 (46.1%) were male. The mean age at the start of ICI treatment was 65.6 [range: 22-89]. The multi-reader radiomics-based models predicts durable disease control, progression, clinical progression, EGFR mutation, and bone metastasis with a sensitivity of 0.700, 0.714, 0.286, 0.909, and 0.810, and specificity of 0.417, 0.444, 0.778, 0.200, and 0.222 respectively. The statistical values of the models are shown in the Table. Conclusions: The machine-learning models grounded on radiomics features has limited accuracy to prognosticate ICIs treatment outcome, EGFR mutations, and distant bone metastasis. Further studies with larger sample sizes are warranted. [Table: see text]