Early NSCLC Research Articles

P4.07F.01 Real World Characteristics and Distant Metastasis Free Survival of Patients with Early NSCLC Treated with Chemoimmunotherapy

P4.07F.01 Real World Characteristics and Distant Metastasis Free Survival of Patients with Early NSCLC Treated with Chemoimmunotherapy

The diagnostic value of serum exosomal miRNA-587 combined with hypersensitive C-reactive protein as noninvasive biomarker in early-stage non-small cell lung cancer

Abstract Objectives Lung cancer is a highly prevalent and life-threatening disease worldwide, with non-small cell lung cancer (NSLC) accounting for around 80 % of all cases. Exosomes contain important genetic information for humans that could be employed, especially for early screening of tumors. Accordingly, we aimed to use exosomal miRNA (ex-miRNA) in early NSCLC diagnosis. Methods The extracted ex-miRNAs were validated through transmission electron microscopy, particle size potentiometer, and western blot analyses. Microarray was used to verify ex-miRNAs, and 20 miRNAs were selected. Herein, we obtained 240 blood samples from NSCLC patients (101 in the early stage) and 234 from healthy donors. Our study deployed real-time fluorescence quantitative PCR (qRT-PCR) for detecting significantly down-regulated miR-587 expression. In addition, the hypersensitive C-reactive protein (Hs-CRP) levels were measured in patient samples. Results The results of calculating the area under the curve (AUC) revealed that the diagnostic efficiency of miR-587 and Hs-CRP were 0.771 and 0.863, respectively. Meanwhile, the combined diagnostic efficiency of both increased to 0.901. In patients with early NSCLC, the diagnostic efficiency of miR-587, Hs-CRP, and combined AUC were 0.726, 0.873, and 0.899, respectively. This indicates that the accuracy of early NSCLC diagnosis is very high. Finally, we combined miR-587 and Hs-CRP with CEA and NSE for NSCLC (AUC=0.956) and early-stage patients (AUC=0.921). Conclusions In this study, miR-587 and Hs-CRP have significant diagnostic efficiency for NSCLC, especially the combination of CEA and NSE that could indicate early NSCLC diagnosis.

Comparison of methods for cancer stem cell detection in prognosis of early stages NSCLC

BackgroundDespite advances in diagnosis and treatment in lung cancer, therapies still fail to improve patient management due to resistance mechanisms and relapses. As Cancer stem cells (CSCs) directly contribute to tumor growth and therapeutic resistance, their clinical detection represents a major challenge. However specific and additional CSC markers lack. Thus, our aim was to achieve selective detection of CSCs with specific glycan patterns and assess the CSCs burden to predict the risk of relapse in NSCLC tumors.MethodsThe lung CSCs detection and sorting with a lectin MIX were assessed and compared to CD133 in vitro. Then, its putative role as CSC biomarker was evaluated in vivo and its clinical significance on 221 NSCLC patients.ResultsWe showed a significant CSCs enrichment in the MIX+ sorted fraction compared to CD133+ cells and confirmed its high tumorigenic capacity. The MIX prognostic value on the overall survival from early stages patients was validated suggesting its potential for detecting CSCs directly linked to tumor aggressiveness.ConclusionThe MIX could be more relevant for detecting and sorting CSCs than CD133. Moreover, its prognosis value could enable clinicians to better classify early-stage patients at high risk of relapse in order to tailor therapeutic decisions.

Neoadjuvant and Adjuvant Treatments for Early Stage Resectable NSCLC: Consensus Recommendations From the International Association for the Study of Lung Cancer

Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the International Association for the Study of Lung Cancer commissioned a diverse multidisciplinary international expert panel to evaluate the current landscape and provide diagnostic, staging, and therapeutic recommendations for patients with rNSCLC, with particular emphasis on patients with American Joint Committee on Cancer-Union for International Cancer Control TNM eighth edition stages II and III disease. Using a team-based approach, we generated 19 recommendations, of which all but one achieved greater than 85% consensus among panel members. A public voting process was initiated, which successfully validated and provided qualitative nuance to our recommendations. Highlights include the following: (1) the critical importance of a multidisciplinary approach to the evaluation of patients with rNSCLC driven by shared clinical decision-making of a multispecialty team of expert providers; (2) biomarker testing for rNSCLC; (3) a preference for neoadjuvant chemoimmunotherapy for stage III rNSCLC; (4) equipoise regarding the optimal management of patients with stage II between upfront surgery followed by adjuvant therapy and neoadjuvant or perioperative strategies; and (5) the robust preference for adjuvant targeted therapy for patients with rNSCLC and sensitizing EGFR and ALK tumor alterations. Our primary goals were to provide practical recommendations sensitive to the global differences in biology and resources for patients with rNSCLC and to provide expert consensus guidance tailored to the individualized patient needs, goals, and preferences in their cancer care journey as these are areas where physicians must make daily clinical decisions in the absence of definitive data. These recommendations will continue to evolve as the treatment landscape for rNSCLC expands and more knowledge is acquired on the best therapeutic approach in specific patient and disease subgroups.

1538: AI tumor delineation for all breathing phases in early NSCLC

1538: AI tumor delineation for all breathing phases in early NSCLC

227P Sexual dimorphism in immune profile of early and advanced NSCLC

227P Sexual dimorphism in immune profile of early and advanced NSCLC

Validation of an Updated Algorithm to Identify Patients With Incident Non-Small Cell Lung Cancer in Administrative Claims Databases.

Real-world lung cancer data in administrative claims databases often lack staging information and specific diagnostic codes for lung cancer histology subtypes. This study updates and validates Turner's 2017 treatment-based algorithm using more recent claims and electronic health record (EHR) data. This study used Optum's deidentified Market Clarity Data of linked medical and pharmacy claims with EHR data. Eligible patients had an incident lung cancer diagnosis (January 2014-December 2020) and ≥one valid histology code for lung cancer 30 days before to 60 days after diagnosis. Histology and stage information from the EHR were used to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We evaluated the Turner algorithm using cohort 1 patients diagnosed between June 2014 and October 2015 (step 1) and between November 2015 and December 2020 after approval of immunotherapies (step 2). Next, we evaluated cohort 2 patients diagnosed between November 2015 and December 2020 using an updated algorithm incorporating the latest US treatment guidelines (step 3), and compared the results for cohort 2 (Turner algorithm, step 2 patients). Furthermore, an algorithm to determine early NSCLC (eNSCLC; stage I-III) versus metastatic or advanced/metastatic non-small cell lung cancer (stage IV) was evaluated among patients with available histology and stage information. A total of 5,012 patients were included (cohort 1, step 1: n = 406; cohort 1, step 2: n = 2,573; cohort 2, step 3: n = 2,744). The updated algorithm showed improved performance relative to the previous Turner algorithm for sensitivity (0.920-0.932), specificity (0.865-0.923), PPV (0.976-0.988), and NPV (0.640-0.673). The eNSCLC algorithm showed high specificity (0.874) and relatively low sensitivity (0.539). An updated treatment-based algorithm identifying patients with incident NSCLC was validated using EHR data and distinguished lung cancer subtypes in claims databases when EHR data were not available.

Tumoral and stromal hMENA isoforms impact tertiary lymphoid structure localization in lung cancer and predict immune checkpoint blockade response in patients with cancer

Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA11a linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response. Methods involved RNA-SEQ on NSCLC cells with depleted hMENA isoforms. A retrospective observational study assessed tissues from surgically treated N0 patients with NSCLC, using immunohistochemistry for tumoral and stromal hMENA isoforms, fibronectin, and TLS presence. ICB-treated patient tumors were analyzed using Nanostring nCounter and GeoMx spatial transcriptomics. Multiparametric flow cytometry characterized B cells and tissue-resident memory T cells (TRM). Survival and ICB response were estimated in the cohort and validated using bioinformatics pipelines in different datasets. Findings indicate that hMENA11a in NSCLC cells upregulates the TLS regulator LTβR, decreases fibronectin, and favors CXCL13 production by TRM. Conversely, hMENAΔv6 in CAFs inhibits LTβR-related NF-kB pathway, reduces CXCL13 secretion, and promotes fibronectin production. These patterns are validated in N0 NSCLC tumors, where hMENA11ahigh expression, CAF hMENAΔv6low, and stromal fibronectinlow are associated with intratumoral TLS, linked to memory B cells and predictive of longer survival. The hMENA isoform pattern, fibronectin, and LTβR expression broadly predict ICB response in tumors where TLS indicates an anti-tumor immune response. This study uncovers hMENA alternative splicing as an unexplored contributor to TLS-related Tumor Immune Microenvironment (TIME) and a promising biomarker for clinical outcomes and likely ICB responsiveness in N0 patients with NSCLC. This work is supported by AIRC (IG 19822), ACC (RCR-2019-23669120), CAL.HUB.RIA Ministero Salute PNRR-POS T4, "Ricerca Corrente" granted by the Italian Ministry of Health.

1P Integrated data analysis within IMMUcan identifies prognostic features of early NSCLC

1P Integrated data analysis within IMMUcan identifies prognostic features of early NSCLC

Identification of exosome protein panels as predictive biomarkers for non-small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes.MethodsHere, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes.ResultsOur study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients.ConclusionsThese findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

EP07.04-18 Factors Associated with Postoperative Recurrence in Early NSCLC with EGFR Mutation: Analysis of Korean National Population Data

EP07.04-18 Factors Associated with Postoperative Recurrence in Early NSCLC with EGFR Mutation: Analysis of Korean National Population Data

P1.25-17 Stereotactic Ablative Body Radiotherapy for Early NSCLC: Changes in Pulmonary Function, Dyspnoea and Quality of Life

P1.25-17 Stereotactic Ablative Body Radiotherapy for Early NSCLC: Changes in Pulmonary Function, Dyspnoea and Quality of Life

Prise en charge des stades précoces : place des thérapies ciblées en périopératoire: Management of early stages: the role of peri-operative targeted therapies

Targeted therapies are the cornerstone of the treatment of NSCLC with oncogenic addiction. Their evaluation in early stages NSCLC is more recent and involves a different methodological approach. At present, the results relate exclusively to NSCLC with EGFR mutation. While previous studies failed to validate the efficacy of adjuvant EGFR inhibitors, the ADAURA study recently demonstrated a benefit in terms of disease-free survival and overall survival. These results modify the therapeutic algorithm for these patients, although the methodological limitations leave many questions unanswered.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Neoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in resectable non-small cell lung cancer

BackgroundNeoadjuvant immunotherapy, the focus of current research and treatment modality for long-term survival, has become one of the main options in supporting primary treatment interventions in early NSCLC. MethodsThis was a retrospective analysis of patients with locally resectable NSCLC who received the neoadjuvant drug pembrolizumab combined with chemotherapy and underwent surgical resection. Pathological responses, PFS and OS in the whole sample and subgroups were analyzed. ResultsOf the 61 patients included in this retrospective analysis, 31 (50.82%) achieved a pCR, and 38 (62.30%) obtained an MPR. Patients with a pCR had significantly higher OS than the non-pCR group (HR = 0.093, P = 0.0227); patients with an MPR also had significantly elevated OS compared with the non-MPR group (HR = 0.05357, P = 0.0169). Patients with lymph node metastasis after surgery had significantly reduced OS (HR = 0.01607, p = 0.0004) and PFS (HR = 0.08757, p = 0.0004) than those without lymph node metastasis. There was no significant difference in OS and PFS between squamous cell carcinomas (SCC) group and adenocarcinomas (AD) group. No significant differences in OS and PFS were found between patients administered 2 and 3 cycles of neoadjuvant therapy before surgery, between those administered ≤5 and > 5 cycles of adjuvant therapy post-surgery, and between patients with TPS <50% and ≥50% (all P > 0.05). ConclusionNeoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in non-small cell lung cancer is safe and tolerable. Both pCR and MPR were closely associated with OS and PFS, reflecting a good response of tumor tissues to drug therapy. Lymph node metastasis after surgery was a poor prognostic factor, reducing OS and PFS.

Liquid Biopsy in NSCLC: An Investigation with Multiple Clinical Implications.

Tissue biopsy is essential for NSCLC diagnosis and treatment management. Over the past decades, liquid biopsy has proven to be a powerful tool in clinical oncology, isolating tumor-derived entities from the blood. Liquid biopsy permits several advantages over tissue biopsy: it is non-invasive, and it should provide a better view of tumor heterogeneity, gene alterations, and clonal evolution. Consequentially, liquid biopsy has gained attention as a cancer biomarker tool, with growing clinical applications in NSCLC. In the era of precision medicine based on molecular typing, non-invasive genotyping methods became increasingly important due to the great number of oncogene drivers and the small tissue specimen often available. In our work, we comprehensively reviewed established and emerging applications of liquid biopsy in NSCLC. We made an excursus on laboratory analysis methods and the applications of liquid biopsy either in early or metastatic NSCLC disease settings. We deeply reviewed current data and future perspectives regarding screening, minimal residual disease, micrometastasis detection, and their implication in adjuvant and neoadjuvant therapy management. Moreover, we reviewed liquid biopsy diagnostic utility in the absence of tissue biopsy and its role in monitoring treatment response and emerging resistance in metastatic NSCLC treated with target therapy and immuno-therapy.

Contemporary biomarker testing rates in both early and advanced NSCLC: Results from the MYLUNG pragmatic study.

9109 Background: The MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) consortium pragmatic study aims to identify and overcome barriers to timely and appropriate biomarker testing in patients (pts) with NSCLC. We previously reported retrospective real-world testing rates for 5 biomarkers from 2018-2020 in metastatic pts. We now report results from the prospective observational phase, including additional biomarkers in pts with both early and advanced NSCLC. Methods: This was a prospective, non-interventional cohort study of newly diagnosed pts with early stage (ES), locally advanced (LA), or metastatic NSCLC (mNSCLC) between 12/2020 and 9/2022 and enrolled from 12 community practices (69 sites) across The US Oncology Network. The proportion of pts with test results for 9 biomarkers at time of protocol initiation were examined: ALK, BRAF, EGFR, ROS1, PD-L1, KRAS, MET, NTRK, and RET. Timing of tests, use of single vs multigene NGS testing, clinical and socioeconomic factors, and reasons for not testing were collected in real time. Results: Of 1002 pts screened, 987 were enrolled and analyzed. There were 405 stage IB-IIIC pts [n = 284 stage IB-IIIA (ES cohort); n = 121 stage IIIB-IIIC (LA cohort)] and 582 stage IV pts (mNSCLC cohort). Descriptions for ES and LA vs mNSCLC pts respectively include median age 68 vs 69 yrs, 49% vs 52% female, 83% vs 77% white, 58% vs 79% adenocarcinoma histology, 71% vs 68% ECOG 0-1, and 33% vs 30% high school education level. Testing rates for ES vs mNSCLC cohorts are shown in the table below: prior to treatment initiation, 64% of ES and 83% of mNSCLC pts had at least one biomarker result; and 37% of mNSCLC pts had results for all 9 biomarkers. NGS testing occurred in 37% and 57% of the ES and mNSCLC cohorts respectively. Reasons for not testing included: barriers to ordering (42%, 25%), insufficient tissue (18%, 18%), clinical deterioration/crisis (5%, 12%), and other reasons (37%, 49%), respectively. Conclusions: As more genomic alterations are identified in NSCLC, we observed that many pts do not get full genotyping prior to treatment, and biomarker testing remains of utmost importance. Further analyses by distinct stages (e.g. LA), histology, social determinants, utilization of targeted therapies, and other reasons for not testing will be performed. These data will be used to evaluate future prospective interventions for MYLUNG, to help improve comprehensive biomarker testing for NSCLC. [Table: see text]

Differential expression analysis of circRUNX1 in patients with early resected EGFR-mutant NSCLC.

8529 Background: In the ADAURA study, patients with stage IB-IIIA of resected EGFR mutated lung adenocarcinoma receiving adjuvant osimertinib had a 2-year survival of 89% versus 52% in the placebo group (p&lt;0.001), however, predictive markers of response and recurrence are still needed. Circular RNA (circRNA) is a type of RNA which forms a covalently closed continuous loop. Some circRNAs have been reported as essential for tumor cell proliferation through functions distinct from the canonical linear RNA. In this project, we studied circRNA expression levels in formalin-fixed paraffin-embedded (FFPE) lung tumor samples in order to explore potential biomarkers that could predict the benefit of adjuvant EGFR TKIs in EGFR-mutant NSCLC patients. Methods: FFPE tumor samples from patients with EGFR-mutant, stage I-IIIB NSCLC (n=79) were collected. RNA was purified using the High Pure FFPET RNA Isolation Kit (Qiagen) and quantified by Nanodrop 2000 (Thermo Scientific). A total of 250 ng of RNA were subjected to overnight hybridization and downstream nCounter processing (NanoString) following manufacturer’s instructions for our circRNA custom panel. Differential expression analysis was performed using Excel (Microsoft) and Prism GraphPad (Dotmatics) software. Results: Analysis of the 79 samples included in the study shown a cluster of 3 circRNAs significantly upregulated (p&lt;0.05 and &gt;2 fold-change) in EGFR mutation-positive NSCLC relapsing withing the 36 months after resection, including circRUNX1, circFUT8 and circAASDH. Disease-free survival (DFS) was significantly shorter for the subgroup of patients with high versus low circRUNX1 expression. Additional multivariate analysis identified circRUNX1 expression and tumor stage as the only statically significant prognostic factors (circRUNX1 hazard ratio = 4.480, confidence interval = 2.172-9.239, P &lt; 0.001; pathological stage hazard ratio = 2.237, confidence interval = 1.183- 4.231, P = 0.008). Conclusions: CircRUNX1 could be a novel biomarker to predict the benefit of adjuvant EGFR TKIs with regards to DFS in EGFR-mutant resected NSCLC patients.

Is there a role for first generation TKIs in adjuvant setting of EGFR mutated early NSCLC?

Is there a role for first generation TKIs in adjuvant setting of EGFR mutated early NSCLC?

Economic Burden of Recurrence Among Resected Medicare Patients With Early Stage NSCLC

IntroductionPatients with early NSCLC (eNSCLC) who experience recurrence are associated with worse survival outcomes, but the economic burden of recurrence is not well characterized. This study evaluated the incremental health care resource utilization and costs of recurrence in Medicare patients with resected eNSCLC. MethodsThis retrospective observational study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims. Eligible patients were 65 years and older with newly diagnosed NSCLC stages IB to IIIA (American Joint Committee on Cancer Staging Manual, seventh edition) and surgery between January 2010 and December 2017. Continuous enrollment criteria were applied to ensure appropriate data capture. Per patient per month (PPPM) health care resource utilization and all-cause direct costs were compared for patients with versus without recurrence, which was identified from claims data using diagnosis, procedure, or drug codes. Patients were matched (1:1) using exact matching on cancer stage and treatment, and propensity score matching on other characteristics. ResultsIn total, 2035 (44%) out of 4595 patients had evidence of recurrence. After matching, 1494 patients were included in each cohort. Patients with recurrence had a significantly higher number of inpatient visits (+0.25 PPPM), outpatient visits (+1.10 PPPM), physician services (+3.70 PPPM), and emergency department (ED) visits (+0.25 PPPM; all p < 0.001). The average follow-up PPPM cost in the recurrence cohort was U.S. dollars $7437 and $1118 in the no-recurrence cohort, resulting in a difference of $6319 PPPM (p < 0.001) with inpatient costs as the largest contributor. ConclusionsOn the basis of a real-world population, the recurrence among patients with resected eNSCLC is associated with increased health care resource utilization and costs.

OA14.06 T-Cell Dynamics in Response to Neoadjuvant Atezolizumab in Early NSCLC by Antigen Response and T-Cell Receptor Sequencing

The Phase II LCMC3 (NCT02927301) trial of neoadjuvant atezolizumab in early-stage NSCLC (primary efficacy population [patients with surgery, excluding EGFR/ALK alterations]) showed a 20% (29/143) major pathologic response (MPR, ≤10% viable tumor) rate. LCMC3 incorporated numerous biomarker analyses. We explored the impact of treatment on T-cell dynamics in the tumor and peripheral blood in association with pathologic response.