Outcome In Non-small Cell Lung Cancer Research Articles

Stage IIIA Non-Small Cell Lung Cancer Treatment and Outcomes: A Single Institution Retrospective Analysis.

Stage III non-small cell lung cancer (NSCLC) treatment remains challenging, with a multitude of treatment options available. We assessed Stage IIIA NSCLC outcomes by treatment received. We performed a single-institution retrospective review of NSCLC patients with Stage IIIA disease treated January 01, 2010-March 01, 2022. Demographics, treatments, outcomes, and failure patterns were collected. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Failure patterns were assessed for differences using chi-square analysis. Of 270 Stage III NSCLC patients, 134 had Stage IIIA disease with a median follow-up of 29.9 months and a median age of 66 years (IQR 60-75). 66 (49.3%) patients were male, and 105 (78.4%) were current/former smokers (with 30 median pack-years). Patients were treated with definitive radiation with/without chemotherapy (CRT; n = 77, 57.5%), surgery with neoadjuvant chemotherapy and/or radiation (Neoadj; n = 42, 31.3%), and surgery without neoadjuvant therapy (Surg; n = 15, 11.2%). Median PFS was 25.4 months (95% CI 12.5-42.6) for CRT, 22.6 months (95% CI 12.2-44.4) for Neoadj, and 22.8 months (95% CI 5.2-NA) for Surg with no significant intergroup difference (p = 0.99). Median OS was 57.0 months (95% CI 37.4-77.5) for CRT, 51.5 months (95% CI 36.7-65.5) for Neoadj, and 35.3 months (95% CI 16.8-NR) for Surg with no significant intergroup difference (p = 0.99). In this single institution retrospective study, we find no significant differences in PFS, OS, and failure patterns between patients with Stage IIIA NSCLC treated with definitive (chemo)radiation and surgery with or without neoadjuvant therapy. Further work in the immunotherapy era is needed.

Real‑world therapeutic strategies and survival outcomes in advanced HER2-mutant non-small cell lung cancer.

Limited information is available regarding the clinical features and outcomes of advanced human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) in Taiwan, despite expanding treatment options for this distinct subtype. The present study explored the clinical features and outcomes of HER2-mutant NSCLC in a real-world setting. Relevant data were collected from patients with advanced or recurrent HER2-mutant NSCLC who received systemic therapy between 2011 and 2021 and were followed up until 2022 at two medical centers in Taiwan. Clinical features, treatment responses, and survival-associated factors were analyzed. This study included 45 patients (median age: 59.7 [range: 41.3-78.7] years). A775_G776insYVMA was the most common NSCLC subtype (57.8%), followed by G778_P780dup (11.1%). Approximately 53.3% of the patients received first-line platinum-based chemotherapy (PC) alone, whereas 13.3% received PC combined with an immune checkpoint inhibitor (ICI). The median overall survival (OS) and progression-free survival (PFS) after first-line therapy were 25.8 and 4.4 months, respectively. The objective response rate was generally higher in patients receiving first-line PC + ICI than in those receiving PC alone (33.3% vs. 12.5%; p = 0.269). Furthermore, patients receiving PC + ICI had longer PFS than did those receiving PC alone (9.5 vs. 4.4 months; p = 0.131) and those receiving tyrosine kinase inhibitor/ICI monotherapy (9.5 vs. 0.5 months; p = 0.015). Compared with patients having other NSCLC subtypes, those carrying HER2 exon 20 insertion mutations had shorter median PFS (17.3 vs. 2.9 months; p = 0.043) and OS (not reached vs. 19 months; p = 0.031). This study highlights the clinical features and outcomes of advanced HER2-mutant NSCLC in Taiwan. PC + ICI may be more effective than other regimens as first-line therapy. The prognostic role of HER2 exon 20 insertion mutations warrants further investigation.

Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA

The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers. Proteomic alterations were analyzed using label-free shotgun and targeted LC–MS/MS. MS275 enhanced the sensitivity of A549 cells to pemetrexed, but only when administered following prior treatment with pemetrexed. Both HeLa (p53 negative) and A549 (p53 positive) showed robust activation of γH2AX upon treatment with this combination. Importantly, CRISPR/Cas9 knockout of the uracil-DNA glycosylase UNG did not affect γH2AX activation or sensitivity to pemetrexed. Proteomic analysis revealed that MS275 altered the expression of known pemetrexed targets, as well as several proteins involved in pyrimidine metabolism and DNA repair, which could potentiate pemetrexed cytotoxicity. Contrary to the conventional model of antifolate toxicity, which implicates futile cycles of uracil incorporation and excision in DNA, we propose that ribonucleotide incorporation in nuclear and mitochondrial DNA significantly contributes to the cytotoxicity of antifolates like pemetrexed, and likely also of fluorinated pyrimidine analogs. HDAC inhibition apparently exacerbates cytotoxicity of these agents by inhibiting error-free repair of misincorporated ribonucleotides in DNA. The potential of HDACis to modulate pyrimidine metabolism and DNA damage responses offers novel strategies for improving NSCLC outcomes.

Effects of Tp53 Gene Mutations on the Survival of Non-Small Cell Lung Cancer (NSCLC); A Short Review.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Mutations within the TP53 gene represent critical molecular events in NSCLC, contributing to the tumorigenesis in the pulmonary epithelial tissues. TP53 is a widely researched prognostic indicator in NSCLC, and pathological investigations have revealed a weak to mild negative predictive effect for TP53. Mutated p53 protein may have some pro-oncogenic impact, and the variations may change tumor inhibitors into oncogenes. The diverse mutational spectrum of TP53 in NSCLC with different mutations is linked to varied treatment responses. In contrast, first-line chemotherapeutics to this progress are limited, however, randomized trials with new chemotherapeutics have shown significant survival benefits. This review highlighted the critical influence of TP53 gene mutations on pathological-sensitivity and overall survival outcomes in NSCLC. Further research is needed to explore TP53 mutation-specific pathways and their effects on NSCLC progression and treatment effectiveness.

Study Protocol of the Korean EGFR Registry: A Multicenter Prospective and Retrospective Cohort Study in Nonsmall Cell Lung Cancer Patients With EGFR Mutation.

The provision of treatment for epidermal growth factor receptor (EGFR)-mutated nonsmall cell lung cancer (NSCLC) patients has increased in Korea. However, multicenter studies on the clinicopathologic dataset and treatment outcomes, using a large-scale dataset, have not been conducted. The current study is a prospective and retrospective multicenter observational cohort study that registers all stages of EGFR-mutated NSCLC patients. The Korean EGFR Registry was designed to enroll 2000 patients with all stages of EGFR-mutated NSCLC from 40 university hospitals across Korea. This study, encompassing both retrospective and prospective cohorts, aims to analyze clinical characteristics, treatment modalities, and outcomes in these patients. Data collection will include patient demographics, smoking history, quality of life assessments, pathological data, and treatment outcomes, with follow-up until December 2026. The primary endpoint is disease-free survival in patients who have undergone radical therapy (surgery and radiotherapy) or progression-free survival in those receiving targeted therapy (first, second, and subsequent lines), chemotherapy (first and subsequent lines), combination therapy, and palliative/maintenance therapy according to stages of EGFR-mutated NSCLC. The study will explore the diagnostic methods for EGFR mutations, clinical outcomes based on treatment modalities, and metastatic patterns in EGFR-mutated NSCLC patients. Moreover, it will investigate various aspects, including the safety and efficacy of a new third-generation EGFR tyrosine kinase inhibitor (TKI), lazertinib, approved for both first- and second-line treatments. This study is expected to provide valuable insights into the epidemiology, risk factors, progression, and treatment outcomes of EGFR-mutated NSCLC in Korea. The Korean EGFR Registry will contribute significantly to the understanding of the complex dynamics of EGFR-mutated NSCLC, aiding in the development of more effective and personalized treatment strategies.

Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings.

Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy. This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery. Major pathological response (MPR, primary endpoint) was previously reported; here, we report 3-year disease-free survival (DFS), OS, and clinical characteristics of patients developing brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent measurement of immune markers. Of 30 enrolled patients, 29 were taken to the operating room. 26 underwent R0 resection, with 17 experiencing MPR (10 pCR). With a median follow-up of 39.5 months, the median OS was 55.8 months, and the median DFS was 34.5 months. Landmark OS at 36 months was 77%. Among 14 patients with recurrent disease, 6 patients had BM. Patients whose tumors had mutations in STK11 and KEAP1 did not have a significantly higher incidence of BM. Reduced copy number of STK11 and KEAP1, both residing on chromosome 19p, was observed in ~1/3 of tumors. Reduced CN of STK11 was significantly associated with worse pathological response and incidence of BM. Consistent with recent phase III studies, 3-year OS data with neoadjuvant atezolizumab+chemotherapy was associated with prolonged PFS and OS. Establishing associations between STK11 and KEAP1 genomic alterations and key clinical outcomes in early-stage NSCLC requires further study.

Prognostic value of immunotherapy in advanced NSCLC based on baseline and dynamic changes in HALP.

Immune checkpoint inhibitors (ICIs) enhance the tumor-killing ability of T-cells in non-small cell lung cancer (NSCLC), improving overall survival (OS) and revolutionizing treatment for advanced stages. However, challenges remain, such as low response rates and the lack of effective markers for selecting candidates. This study evaluated the impact of hemoglobin, albumin, and platelet (HALP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the efficacy of immunotherapy and survival outcomes in advanced NSCLC. Additionally, it aimed to develop a nomogram based on these parameters. Clinical and hematological data from NSCLC patients who received immunotherapy were analyzed. Efficacy was assessed using the immune Response Evaluation Criteria in Solid Tumors (iRECIST), and progression-free survival (PFS) and OS were evaluated. Prediction models incorporated baseline and post-treatment HALP, NLR, and PLR values. The 203 patients had a median follow-up of 16 months, a median PFS (mPFS) of seven months (6.0-8.0), while the median OS (mOS) was not reached (24.0-not available). Pretreatment PLR (PLR0) was associated with a higher disease control rate (DCR) (odds ratio [OR] = 0.258), while initial immunotherapy and NLR after four treatment cycles (NLR4C) significantly improved the objective response rate (ORR). Cox regression analysis showed that pretreatment HALP (HALP0), HALP after four cycles of treatment (HALP4C), and pretreatment NLR (NLR0) significantly impacted PFS. Additionally, HALP0, NLR0, and PLR after four treatment cycles (PLR4C) were associated with OS. The C-indices for PFS and OS were 0.823 and 0.878, respectively, indicating good predictive accuracy. HALP, NLR, and PLR at various time points effectively predicted immunotherapy response in advanced NSCLC patients, with low HALP combined with high NLR and PLR indicating a poor prognosis. These findings could serve as the basis for stratified randomized controlled trials (RCTs) in the future.

Abstract PR004: Brain penetrant allosteric EGFR inhibitors for NSCLC

Abstract Approximately 30-50% of Non-Small Cell Lung Cancer (NSCLC) patients already have CNS disease at time of diagnosis or else develop it during treatment, and there remains a need for better outcomes in these patients. The 3rd-generation covalent EGFR inhibitor osimertinib is an effective therapy for NSCLC patients, improving upon 1st-generation inhibitors gefitinib and erlotinib, and achieving enhanced brain penetration relative to those agents. However, the survival benefit relative to the 1st-generation inhibitors is observed primarily in patients with exon19 deletions rather than the L858R mutation. We developed a series of mutant-selective allosteric EGFR inhibitors that specifically target the L858R mutation (and subsequent resistance mutations), with high selectivity over wt EGFR and across the kinome. Early compounds including the isoindolinone JBJ-09-063 demonstrated good in vivo efficacy in mouse tumor models, despite limited bioavailability. Diversification and optimization of the chemistry, involving a scaffold hopping approach and the replacement of the thiazole amide with benzimidazole, delivered a set of compounds with promising potency and rodent PK. A subset of these achieved good brain exposure in mice and efficacy in an intracranial H1975 brain metastasis model. The mutant-selectivity and ability to co-bind with osimertinib makes an allosteric EGFR inhibitor an ideal partner for combination therapy, with the potential to deliver enhanced outcomes in L858R-driven NSCLC, especially for patients with CNS disease. Citation Format: David Scott, Courtney Cullis, Tyler Beyett, Frederic Feru, Thomas Gero, Krista Gipson, Praful Gokhalle, Nathanael Gray, David Heppner, Sampson Huang, Pasi Jänne, Sandeepraj Pusalkar, Michael Eck. Brain penetrant allosteric EGFR inhibitors for NSCLC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr PR004

The impact of extent of nodal involvement on Stage IIIA(N2) NSCLC outcomes

ObjectivesStage IIIA(N2) non-small cell lung cancer (NSCLC) treatment can depend on the extent of nodal involvement, with surgery considered for limited disease and definitive chemoradiation preferred for bulky or multi-station disease. Evidence to support management is limited. This study evaluated the impact of the extent of Stage IIIA(N2) nodal involvement on outcomes after surgery. MethodsPatients who underwent surgical resection of T1-2N2M0 NSCLC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004-2019 were stratified as having limited (1 positive node) versus more extensive (>1 positive node) nodal disease, and survival was evaluated with Kaplan-Meier and Cox analyses. ResultsOf the 6,933 patients identified surgical patients, 2,129 (30.7%) had limited nodal disease while 4,804 (69.3%) had more extensive nodal involvement. The limited nodal group had higher 5-year overall survival than the more extensive node group (39.3% vs 30.3%, p<0.001), and more extensive nodal involvement (Hazard Ratio 1.26, p<0.001) was independently associated with worse survival in Cox analysis. Surgical patients had a higher 5-year overall survival than 1,644 comparable N2 patients with extensive nodal involvement who received definitive chemoradiation (30.9% vs 18.9%, p<0.001). ConclusionsIncreasing nodal involvement is associated with worse survival for Stage IIIA(N2) NSCLC patients but select patients with more extensive nodal disease may still benefit from surgery compared to chemoradiation.

Gut metatranscriptomics based de novo assembly reveals microbial signatures predicting immunotherapy outcomes in non-small cell lung cancer.

Advanced-stage non-small cell lung cancer (NSCLC) poses treatment challenges, with immune checkpoint inhibitors (ICIs) as the main therapy. Emerging evidence suggests the gut microbiome significantly influences ICI efficacy. This study explores the link between the gut microbiome and ICI outcomes in NSCLC patients, using metatranscriptomic (MTR) signatures. We utilized a de novo assembly-based MTR analysis on fecal samples from 29 NSCLC patients undergoing ICI therapy, segmented according to progression-free survival (PFS) into long (> 6months) and short (≤ 6months) PFS groups. Through RNA sequencing, we employed the Trinity pipeline for assembly, MMSeqs2 for taxonomic classification, DESeq2 for differential expression (DE) analysis. We constructed Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) machine learning (ML) algorithms and comprehensive microbial profiles. We detected no significant differences concerning alpha-diversity, but we revealed a biologically relevant separation between the two patient groups in beta-diversity. Actinomycetota was significantly overrepresented in patients with short PFS (vs long PFS, 36.7% vs. 5.4%, p < 0.001), as was Euryarchaeota (1.3% vs. 0.002%, p = 0.009), while Bacillota showed higher prevalence in the long PFS group (66.2% vs. 42.3%, p = 0.007), when comparing the abundance of corresponding RNA reads. Among the 120 significant DEGs identified, cluster analysis clearly separated a large set of genes more active in patients with short PFS and a smaller set of genes more active in long PFS patients. Protein Domain Families (PFAMs) were analyzed to identify pathways enriched in patient groups. Pathways related to DNA synthesis and Translesion were more enriched in short PFS patients, while metabolism-related pathways were more enriched in long PFS patients. E. coli-derived PFAMs dominated in patients with long PFS. RF, SVM and XGBoost ML models all confirmed the predictive power of our selected RNA-based microbial signature, with ROC AUCs all greater than 0.84. Multivariate Cox regression tested with clinical confounders PD-L1 expression and chemotherapy history underscored the influence of n = 6 key RNA biomarkers on PFS. According toML models specific gut microbiome MTR signatures' associate with ICI treated NSCLC outcomes. Specific gene clusters and taxa MTR gene expression might differentiate long vs shortPFS.

Validation of the Scottish Inflammatory Prognostic Score (SIPS) in NSCLC Patients Treated with First-Line Pembrolizumab.

The Scottish Inflammatory Prognostic Score (SIPS), combining albumin (≥/<35 g/L) and neutrophil count (≤/>7.5 × 109/L), has been identified as a prognostic biomarker for patients with non-small cell lung cancer (NSCLC) undergoing treatment with pembrolizumab monotherapy. We sought to validate this biomarker of systemic inflammation in an external cohort. Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% at an English cancer centre were identified. Pre-treatment clinicopathological characteristics and the SIPS were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) was examined. Among 257 patients evaluated, 56% (n = 144) were classified as SIPS 0, 36% (n = 93) as SIPS 1, and 8% (n = 20) as SIPS 2. Factors such as age, performance status (PS) and brain metastases presence were significantly correlated with SIPS categories. Multivariate analysis revealed that both SIPS and PD-L1 status were independently associated with PFS and OS. The combination of SIPS with either PS or PD-L1 expression enhanced the ability to detect patients with the most favourable or poorest survival. Our study confirms the prognostic significance of the SIPS in patients with advanced NSCLC treated with pembrolizumab in the context of high PD-L1 expression. SIPS offers a straightforward, clinically applicable approach to patient stratification, potentially guiding therapeutic decisions and enhancing outcomes in advanced NSCLC. Future research should focus on validating these findings in prospective studies and exploring the integration of SIPS into clinical practice, alongside other prognostic markers, to optimize treatment strategies.

Impact of Socioeconomic Deprivation on Care Quality and Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer in United States Veterans.

Background: Socioeconomic deprivation has been associated with higher lung cancer risk and mortality in non-Veteran populations. However, the impact of socioeconomic deprivation on outcomes for non-small cell lung cancer (NSCLC) in an integrated and equal-access healthcare system, such as the Veterans Health Administration (VHA), remains unclear. Hence, we investigated the impact of area-level socioeconomic deprivation on access to care and postoperative outcomes for early-stage NSCLC in United States Veterans. Methods: We conducted a retrospective cohort study of patients with clinical stage I NSCLC receiving surgical treatment in the VHA between 1 October 2006 and 30 September 2016. A total of 9704 Veterans were included in the study and assigned an area deprivation index (ADI) score, a measure of socioeconomic deprivation incorporating multiple poverty, education, housing, and employment indicators. We used multivariable analyses to evaluate the relationship between ADI and postoperative outcomes as well as adherence to guideline-concordant care quality measures (QMs) for stage I NSCLC in the preoperative (positron emission tomography [PET] imaging, appropriate smoking management, pulmonary function testing [PFT], and timely surgery [≤12 weeks after diagnosis]) and postoperative periods (appropriate surveillance imaging, smoking management, and oncology referral). Results: Compared to Veterans with low socioeconomic deprivation (ADI ≤ 50), those residing in areas with high socioeconomic deprivation (ADI > 75) were less likely to have timely surgery (multivariable-adjusted odds ratio [aOR] 0.832, 95% confidence interval [CI] 0.732-0.945) and receive PET imaging (aOR 0.592, 95% CI 0.502-0.698) and PFT (aOR 0.816, 95% CI 0.694-0.959) prior to surgery. In the postoperative period, Veterans with high socioeconomic deprivation had an increased risk of 30-day readmission (aOR 1.380, 95% CI 1.103-1.726) and decreased odds of meeting all postoperative care QMs (aOR 0.856, 95% CI 0.750-0.978) compared to those with low socioeconomic deprivation. There was no association between ADI and overall survival (adjusted hazard ratio [aHR] 0.984, 95% CI 0.911-1.062) or cumulative incidence of cancer recurrence (aHR 1.047, 95% CI 0.930-1.179). Conclusions: Our results suggest that Veterans with high socioeconomic deprivation have suboptimal adherence to care QMs for stage I NSCLC yet do not have inferior long-term outcomes after curative-intent resection. Collectively, these findings demonstrate the efficacy of an integrated, equal-access healthcare system in mitigating disparities in lung cancer survival that are frequently present in other populations. Future VHA policies should continue to target increasing adherence to QMs and reducing postoperative readmission for socioeconomically disadvantaged Veterans with early-stage NSCLC.

Ultrasound‐Responsive Lipid Nanoparticles for Targeted Therapy and Controlled Drug Release in Non‐Small Cell Lung Cancer

AbstractMultifunctional drug delivery systems offer tremendous potential for improving antitumor efficacy, precise drug targeting, and controlled drug release in treating non‐small cell lung cancer (NSCLC). In this study, the study develops a novel tumor‐targeting ultrasound‐responsive lipid nanoparticle (TUSL) platform capable of responding to external stimulation, enabling precise drug delivery with controlled release at the tumor site while minimizing systemic exposure and side effects. The TUSL platform is designed to carry doxorubicin (DOX) and tetrandrine (TET), specifically for drug‐resistant NSCLC. The developed TUSL exhibits a nano sized spherical structure with a hydrodynamic size of 141.8 nm, accommodating anti‐cancer drugs with loading capacities of 3.8% and 6.2% for TET and DOX, respectively. TUSL is engineered to target the epidermal growth factor receptor (EGFR) while demonstrating an ultrasound‐triggered drug release profile. Through the generation of CO2 bubbles upon ultrasound stimulation, the TUSL enhances DOX and TET internalization into tumor cells. In tumor‐bearing mice, TUSL administration demonstrates a superior tumor accumulation with minimal off‐target toxicity. The combined treatment with DOX and TET within TUSL exhibits synergistic effects, effectively inhibiting the growth of drug‐resistant NSCLC tumors. These findings highlight the efficacy of the EGFR‐targeted TUSL formulation in overcoming drug resistance and enhancing therapeutic outcomes in NSCLC.

Combination Immunotherapy With Radiotherapy in Non-Small Cell Lung Cancer: A Review of Evidence.

Radiotherapy plays a fundamental role in the treatment of patients with all stages of non-small-cell lung cancer (NSCLC). The emergence of immune checkpoint inhibitors (ICIs) has transformed the standard of care in these patients. The use of ICIs is increasingly utilized in the definitive setting as an adjunct to chemoradiotherapy or surgery and remains a vital component in the treatment of metastatic disease. Despite improvements in patient survival, the use of immunotherapy as monotherapy has shown limited overall response rates with susceptibility to resistance. Radiotherapy has been identified as a viable option to enhance the response rate to ICI and improve outcomes in NSCLC. We queried the English PubMed database utilizing variably combined search items including "radiation," "chemoradiation," "immune checkpoint," "immunotherapy," "stereotactic body radiotherapy," and "non-small-cell lung". We additionally searched various acceptable alternative terms for similar keywords such as "radiotherapy" in place of "radiation." These results were subsequently curated for relevance and impact on current treatment paradigms. In this review, we discuss preclinical and clinical studies relating to combinatorial use of immunotherapy and radiation in NSCLC. These studies are presented in the context of early-stage, operable stage III, unresectable stage III, and metastatic disease. The majority of the data illustrate promising results regarding the additive or synergistic effects of radiation and immunotherapy with a suggestion that the timing of these treatment modalities is crucial to optimizing outcomes. While there is now evidence regarding the favorable interplay between radiation and immunotherapy in NSCLC, there remain multiple unanswered questions which are expected to be addressed in ongoing clinical trials.

Implementation of Liquid Biopsy in Non-Small-Cell Lung Cancer: An Ontario Perspective.

Lung cancer is the leading cause of cancer-related deaths in Canada, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Timely access to comprehensive molecular profiling is critical for selecting biomarker-matched targeted therapies, which lead to improved outcomes in advanced NSCLC. Tissue biopsy samples are the gold standard for molecular profiling; however, several challenges can prevent timely and complete molecular profiling from being performed, causing delays in treatment or suboptimal therapy selection. Liquid biopsy offers a minimally invasive method for molecular profiling by analyzing circulating tumour DNA (ctDNA) and RNA (cfRNA) in plasma, potentially overcoming these barriers. This paper discusses the outcomes of a multidisciplinary working group in Ontario, which proposed three eligibility criteria for liquid biopsy reimbursement: (1) insufficient tissue for complete testing or failed tissue biomarker testing; (2) suspected advanced NSCLC where tissue biopsy is not feasible; and (3) high-risk patients who may deteriorate before tissue results are available. The group also addressed considerations for assay selection, implementation, and economic impact. These discussions aim to inform reimbursement and implementation strategies for liquid biopsy in Ontario's public healthcare system, recognizing the need for ongoing evaluation as technology and evidence evolve.

Maximum standardized uptake value-to-tumor size ratio in fluorodeoxyglucose F18 positron emission tomography/computed tomography: a simple prognostic parameter for non-small cell lung cancer.

By correcting the effect of tumor size on metabolic activity, the maximum standardized uptake value-to-tumor size (SUVmax:tumor size) ratio on fluorodeoxyglucose F18 positron emission tomography (18F-FDG PET)/computed tomography (CT) scans can be a prognostic parameter of non-small cell lung cancer (NSCLC). The current study evaluates the prognostic value of SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans in patients with NSCLC. Furthermore, the SUVmax:tumor size ratio is compared with other established PET parameters. This study included 108 patients with NSCLC who underwent pretreatment 18F-FDG PET/CT scans and curative lung surgery. The associations between the SUVmax:tumor size ratio and other conventional PET parameters were investigated. The recurrence-free survival according to the SUVmax:tumor size ratio was also analyzed. In addition, the SUVmax:tumor size ratio was compared according to postoperative pathologic findings. In total, 72 (66.7%) of the 108 participants presented with adenocarcinoma (ADC). Nineteen (17.6%) patients experienced recurrence during a median follow-up period of 32.3 months. The median SUV max:tumor size ratio was 2.37 (1.23 for ADCs and 3.90 for other histologic types). The SUVmax:tumor size ratio was associated with SUVmax and mean SUV, as well as metabolic tumor volume and total lesion glycolysis. Patients with an SUVmax:tumor size ratio higher than the median had a worse recurrence outcome than those with an SUVmax:tumor size ratio lower than the median. Participants with ADC who presented with lymphovascular invasion had a higher SUVmax:tumor size ratio than those without. The presence of lymph node metastasis and advanced histologic grade were associated with a high SUVmax:tumor size ratio in patients with ADC. The SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans was associated with aggressive tumor behavior and poor outcome in NSCLCs, particularly ADC. The SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans has a prognostic value in patients with NSCLCs, especially ADC.

Artificial intelligence applications in personalizing lung cancer management: state of the art and future perspectives.

Lung cancer is still a leading cause of cancer-related deaths worldwide. Vital to ameliorating patient survival rates are early detection, precise evaluation, and personalized treatments. Recent years have witnessed a profound transformation in the field, marked by intricate diagnostic processes and intricate therapeutic protocols that integrate diverse omics domains, heralding a paradigm shift towards personalized and preventive healthcare. This dynamic landscape has embraced the incorporation of advanced machine learning and deep learning techniques, particularly artificial intelligence (AI), into the realm of precision medicine. These groundbreaking innovations create fertile ground for the development of AI-based models adept at extracting valuable insights to inform clinical decisions, with the potential to quantitatively interpret patient data and impact overall patient outcomes significantly. In this comprehensive narrative review, a synthesis of various studies is presented, with a specific focus on three core areas aimed at providing clinicians with a practical understanding of AI-based technologies' potential applications in the diagnosis and management of non-small cell lung cancer (NSCLC). The emphasis is placed on methods for diagnosing malignancy in lung lesions, approaches to predicting histology and other pathological characteristics, and methods for predicting NSCLC gene mutations. The review culminates in a discussion of current trends and future perspectives within the domain of AI-based models, all directed toward enhancing patient care and outcomes in NSCLC. Furthermore, the review underscores the synthesis of diverse studies, accentuating AI applications in NSCLC diagnosis and management. It concludes with a forward-looking discussion on current trends and future perspectives, highlighting the LANTERN Study as a pioneering force set to elevate patient care and outcomes to unprecedented levels.

Cost-effectiveness Analysis of Tumor Treating Fields Therapy Combined With Immune Checkpoint Inhibitor in Metastatic Non-small-cell Lung Cancer

BackgroundThe LUNAR clinical trial revealed that incorporating Tumor Treating Fields (TTFields) therapy alongside immune checkpoint inhibitor (ICI) significantly prolonged the overall survival of patients with metastatic, platinum-resistant non-small-cell lung cancer (NSCLC). However, the cost of TTFields therapy is high and may further increase the financial burden for patients. Our research aims to evaluate the cost-effectiveness of TTFields therapy addition with ICI for metastatic NSCLC. MethodsWe constructed a Markov model to evaluate the healthcare costs associated with TTFields therapy combined with ICI for the treatment of advanced NSCLC. In this model, the clinical data utilized came from the LUNAR trial, while drug costs and health state utility values were extracted from public databases and relevant scholarly publications. The major outcomes incorporated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). ResultsCompared with ICI therapy alone, ICI combination with TTFields therapy resulted in 0.42 QALYs at the cost of $167,329, with an ICER of $398,402.38 per year. The calculated ICER surpassed the generally accepted US willingness-to-pay (WTP) threshold of 150,000 per QALY. One-way sensitivity analyses demonstrated that the utility of progression disease is the most influential factor, followed by the cost of TTFields therapy, the utility of progression-free survival, the cost of ICI, and the cost of adverse events in TTFields therapy combined with ICI. Only when the cost of TTFields therapy is reduced by approximately 80.48%, it would be cost-effective within the commonly accepted WTP threshold of $150,000/QALY. ConclusionsAccording to the US WTP, the combination of TTFields therapy with ICI does not currently represent a cost-effective strategy for metastatic NSCLC followed progression on platinum-resistant therapy. Considering its promising clinical outcomes for metastatic NSCLC, it is necessary to control the expenses of this therapeutic strategy in future applications.

Associations of Medicaid expansion with stage at diagnosis, timely initiation and receipt of guideline-concordant treatment, and survival among individuals newly diagnosed with non-small cell lung cancer.

47 Background: Medicaid expansion under the Patient Protection and Affordable Care Act improved health insurance coverage among patients with cancer. Individuals with non-small cell lung cancer (NSCLC) may benefit from Medicaid expansion throughout the cancer control continuum. This study examined the associations of Medicaid expansion with stage at disease diagnosis, timely initiation and receipt of guideline-concordant treatment, and five-year overall survival among individuals with NSCLC. Methods: We identified individuals newly diagnosed at age 18-64 with stages I-IV first primary NSCLC between January 1, 2008 and December 31, 2019 in 50 states and Washington, D.C. from the National Cancer Database (n=332,368). We examined the associations of Medicaid expansion with (1) diagnosis stage, which was categorized into early (I&amp;II) and late (III&amp;IV); (2) timely initiation of guideline-concordant treatment within 30 days after cancer diagnosis (yes/no); (3) receipt of guideline-concordant treatment (yes/no) derived from the National Comprehensive Cancer Network cancer treatment guidelines; and (4) five-year overall survival. We applied a difference-in-differences (DD) approach to examine the changes in study outcomes associated with Medicaid expansion, controlling for key sociodemographic and clinical factors. Results: The percentage of early-stage diagnoses increased from 23.1% pre-expansion to 31.9% post-expansion in expansion states and from 22.3% to 29.5% in non-expansion states, translating to greater increase of 1.7 (95% confidence interval (CI): 0.3-3.1) percentage points (ppt) in expansion states after adjustment (Table). Medicaid expansion was also associated with greater increases in timely initiation of guideline-concordant care (DD: 1.6 (95% CI: 0.1-3.1) ppt) and five-year overall survival (DD: 1.3 (95% CI: 0.7-1.9) ppt). Conclusions: Medicaid expansion may improve access to NSCLC care and outcomes across the cancer control continuum, from early-stage diagnosis, treatment initiation, and overall survival. Association of Medicaid expansion and study outcomes among NSCLC patients. Expansion States Non-expansion States Pre-ME Post-ME Difference Pre-ME Post-ME Difference DD Adjusted DD Early-stage diagnosis 23.1 31.9 8.7 (7.4 to 10.1) 22.3 29.5 7.2 (6.2 to 10.1) 1.5 (-0.1 to 3.2) 1.7 (0.3 to 3.1) Timely initiation of guideline-concordant care 31.3 27.5 -3.9 (-5.3 to -2.4) 33.4 27.8 -5.6 (-6.24 to -2.4) 1.7 (0.1 to 3.3) 1.6 (0.1 to 3.1) Receipt of guideline-concordant care 65.2 68.2 2.9 (1.8 to 4.0) 62.9 66.4 3.5 (2.7 to 4.0) -0.6 (-2.0 to 0.8) -0.2 (-1.7 to 1.3) Five-year survival 21.3 34.8 13.5 (13.1 to 13.9) 18.6 30.2 11.6 (11.1 to 12.2) 1.9 (1.2 to 2.5) 1.3 (0.7 to 1.9) Abbreviation: ME, Medicaid expansion.

Association between patient medications and postoperative outcomes in early-stage non-small cell lung cancer.

Currently, there is no consensus on how to comprehensively assess comorbidities in lung cancer patients in the clinical setting. Prescription medications may be a preferred comorbidity assessment tool and provide a simple mechanism for predicting postoperative outcomes for lung cancer. We examined the relationship between prescription medications and postoperative outcomes for early-stage non-small cell lung cancer (NSCLC). We conducted a retrospective cohort study of patients with clinical stage I NSCLC who underwent surgical resection in the Veterans Health Administration (VHA) between 10/01/2006 and 09/30/2016. Details of all outpatient prescriptions filled by patients within the VHA system from 1-year up to 14 days before surgery were collected. Medications were categorized using the Anatomical Therapeutic Chemical (ATC) Level One classification system. We assessed the association of medications prescribed in the year prior to surgery with postoperative adverse events (composite of death or major complication) at 30 and 90 days following surgery and overall survival (OS). We included 9,741 veterans in the analysis. The median number of prescription medications filled in the year preceding surgery was 11 (interquartile range: 7-16). In multivariable-adjusted analyses, a higher number of prescription medications was associated with increased risk of 30-day [multivariable-adjusted odds ratio (aOR): 1.016; 95% confidence interval (CI): 1.007-1.026] and 90-day postoperative adverse events (aOR: 1.015; 95% CI: 1.006-1.024) and decreased OS (adjusted hazard ratio: 1.019; 95% CI: 1.014-1.023). Within a subgroup of patients with a high comorbidity burden (Charlson-Deyo Comorbidity Index score of 6-8), a higher number of prescription medications was also associated with reduced OS (P<0.001). Patients prescribed medications from the ATC respiratory system class had elevated risk of postoperative adverse events at 30 days (aOR: 1.255; 95% CI: 1.095-1.439) and 90 days (aOR: 1.254; 95% CI: 1.097-1.434) compared to patients without these prescription medications. Significantly increased odds for 90-day postoperative adverse events were observed with each additional prescription medication from the ATC respiratory (aOR: 1.057; 95% CI: 1.027-1.088) and nervous system (aOR: 1.035; 95% CI: 1.005-1.066) classes. The number of medications prescribed preoperatively is associated with short- and long-term postoperative outcomes for early-stage NSCLC, even when adjusting for several covariates including age and comorbidity burden. Patients prescribed a higher number of medications acting primarily on the respiratory and nervous systems are at elevated risk for postoperative adverse events after curative-intent resection. Prescription medications may be a reliable tool to assess comorbidities and perioperative risk for patients with NSCLC.