Comparative Efficacy and Safety of Lorlatinib Versus Alectinib and Lorlatinib Versus Brigatinib for ALK-Positive Advanced/Metastatic NSCLC: Matching-Adjusted Indirect Comparisons.

INTRODUCTION: The comparative efficacy and safety of lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), versus second-generation ALK TKIs as a first-line treatment for ALK+ advanced/metastatic nonsmall cell lung cancer (NSCLC) remains uncertain as there are no head-to-head clinical trials. METHODS: Matching-adjusted indirect comparisons (MAICs) were conducted using phase III trial data demonstrating superior efficacy over crizotinib, a first-generation ALK TKI. MAICs were conducted to compare lorlatinib (CROWN) versus alectinib (ALEX and ALESIA) and brigatinib (ALTA-1L) with matching based on prespecified effect modifiers. Efficacy outcomes included progression-free survival (PFS), objective response (OR), and time to progression in the central nervous system (TTP-CNS). Safety outcomes included Grade ≥3 adverse events (AEs) and AEs leading to treatment discontinuation, dose reduction, or dose interruption. RESULTS: Lorlatinib was estimated to improve PFS compared to alectinib (ALEX) (HR: 0.54 [95% CI: 0.33, 0.88]) and brigatinib (ALTA-1L) (HR: 0.51 [95% CI: 0.31, 0.82]). Lorlatinib was estimated to improve TTP-CNS compared with brigatinib (HR: 0.19 [95% CI: 0.05, 0.71]). The estimated Grade ≥3 AE rate was higher with lorlatinib than with alectinib (RR: 1.48 [95% CI: 1.13, 1.94]); however, no differences were observed in other safety endpoints (ie, AEs leading to discontinuation, dose reduction, or interruption) or compared to brigatinib. CONCLUSION: Lorlatinib was estimated to have superior efficacy over first- and second-generation ALK-TKIs, but a higher rate of Grade ≥3 AEs compared to alectinib. These data support the use of lorlatinib as a first-line treatment for ALK+ advanced/metastatic NSCLC.

cost-effectiveness of aumolertinib as first-line treatment for EGFR-mutated advanced nonsmall-cell lung cancer.

Aim: To evaluate the cost-effectiveness of aumolertinib as the epidermal growth factor receptor-mutated advanced nonsmall-cell lung cancer first-line treatment from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the AENEAS trial. Only direct medical costs were considered in the model. Utilities were obtained from published literature. Sensitivity and scenario analyses were performed to explore the robustness of the model.Results: Compared with gefitinib, aumolertinib yielded an additional 0.941 expected life-years and 0.692 quality-adjusted life-years (QALYs), with an incremental cost of $18,855.55 over a 20-year time horizon. The incremental cost-effectiveness ratios were $20,051.67/life-year and $27,272.29/QALY, that below the willing-to-pay threshold of $38,223.34/QALY.Conclusion: Aumolertinib was a cost-effective alternative first-line treatment for patients with epidermal growth factor receptor-positive advanced nonsmall-cell lung cancer in China.

What is this article about? This study assesses the costs and health outcomes associated with aumolertinib therapy for Chinese patients diagnosed with advanced or metastatic nonsmall cell lung cancer (NSCLC). Aumolertinib therapy is a specific type of medication used to treat a certain type of lung cancer called nonsmall cell lung cancer. It is a newer treatment that targets certain genetic changes in the cancer cells.How was this done? The costs and treatment benefits were estimated using data from the AENEAS trial, provincial medical cost lists and previously published studies. A Markov model was developed to simulate disease progression. Provincial Medical Cost Lists are official lists maintained by different provincial governments in China that specify the drugs and their prices that are covered by the public healthcare system. A Markov Model is a mathematical tool used to predict how a disease might progress over time. It is like a simulation where the possible outcomes of the disease are analyzed, helping to understand the likely course of the disease and how different treatments might affect it.What were the results? The cost of treatment with aumolertinib for Chinese patients with advanced or metastatic NSCLC was considered to be acceptable based on the benefits it provides.What do the study results mean? The results suggest that aumolertinib is a cost-effective treatment for patients with advanced or metastatic NSCLC in China.

High-cost treatments for advanced lung cancer in Japan (Lung Cancer Study Group of the Japan Clinical Oncology Group).

BACKGROUND: The treatment of lung cancer has made dramatic progress in the past decade, but due to the high cost of drugs, the total pharmaceutical cost has been rising explosively. There are currently no data available in Japan on which regimens are used, to what extent they are used, and what their total cost is. METHODS: Sixty Japanese centers belonging to the Lung Cancer Study Group of the Japan Clinical Oncology Group were surveyed for information about the first-line treatment for advanced lung cancer in practice from July 2021 to June 2022. Three types of cancer were included: driver gene mutation-negative NSCLC, EGFR mutation-positive NSCLC, and extensive-stage small cell lung cancer (ES-SCLC). RESULTS: Recent treatment costs for ICIs or ICI plus chemotherapy were about 20-55 times higher than those for conventional chemotherapy. Of the 3738 patients with driver gene aberration-negative NSCLC, 2573 (68.8%) received treatments with monthly cost of 500 000 Japanese yen (JPY) or more; 2555 (68.4%) received ICI therapy. Of the 1486 patients with EGFR mutation-positive NSCLC, 1290 (86.8%) received treatments with a monthly cost of 500 000 JPY or more; 1207 (81.2%) received osimertinib. ICI treatments with a monthly cost of 500 000 JPY or more were administered to 607 (56.3%) of 1079 patients with ES-SCLC. Elderly NSCLC patients received slightly more high-cost treatment than younger patients. CONCLUSION: Recent treatments cost many times more than conventional chemotherapy. This study revealed that high-cost treatments were widely used in advanced lung cancer and some of high-cost treatments were used despite the lack of clear evidence. Physicians should pay attention to the cost of treatments they use.

Mutations Associated With High-Grade irAEs in NSCLC Patients Receiving Immunotherapies.

OBJECTIVES: Compared to low-grade irAEs, high-grade irAEs are more often dose-limiting and can alter the long-term treatment options for a patient. Predicting the incidence of high-grade irAEs would help with treatment selection and therapeutic drug monitoring. MATERIALS AND METHODS: We performed a retrospective study of 430 stage III and IV patients with non-small cell lung cancer (NSCLC) who received an immune checkpoint inhibitor (ICI), either with or without chemotherapy, at a single comprehensive cancer center from 2015 to 2022. The study team retrieved sequencing data and complete clinical information, including detailed irAEs medical records. Fisher's exact test was used to determine the association between mutations and the presence or absence of high-grade irAEs. Patients were analyzed separately based on tumor subtypes and sequencing platforms. RESULTS: High-grade and low-grade irAEs occurred in 15.2% and 46.2% of patients, respectively. Respiratory and gastrointestinal irAEs were the 2 most common irAEs. The distribution of patients with or without irAEs was similar between ICI and ICI+chemotherapy-treated patients. By analyzing the mutation data, we identified 5 genes (MYC, TEK, FANCA, FAM123B, and MET) with mutations that were correlated with an increased risk of high-grade irAEs. For the adenocarcinoma subtype, mutations in TEK, MYC, FGF19, RET, and MET were associated with high-grade irAEs; while for the squamous subtype, ERBB2 mutations were associated with high-grade irAEs. CONCLUSION: This study is the first to demonstrate that specific tumor mutations correlate with the incidence of high-grade irAEs in patients with NSCLC treated with an ICI, providing molecular guidance for treatment selection and drug monitoring.

Visualization of nonsmall-cell lung cancer by near-infrared fluorescence imaging with tumor-targeting peptide ABT-510.

Nonsmall-cell lung cancer (NSCLC) is the most frequent type of lung cancer, with early surgical treatment proving vital for prolonged patient survival. However, precise visualization of NSCLC remains a challenge due to limited molecular imaging probes, the unique anatomical structure of the lungs, and respiratory movement interference. In this study, we investigated the potential utility of CD36, which is highly expressed in NSCLC, as an imaging target. A selective and water-soluble fluorescent probe, MPA-ABT-510, was successfully constructed by coupling ABT-510 with MPA, a near-infrared (NIR) fluorescent dye. Molecular docking analysis shows that MPA-ABT-510 possesses strong binding affinity to the CD36 protein, with specific hydrogen bond interactions at defined amino acid residues. In vitro assays reveals that the fluorescein isothiocyanate-labeled peptide ABT-510 specifically binds to the CD36-high expressing NSCLC cell lines H1299 and A549. In vivo imaging verifies that the MPA-ABT-510 efficiently accumulates in the tumor site with a distinct fluorescent signal. Ex vivo imaging revealed that tumor-to-lung fluorescence ratios for subcutaneous and orthotopic H1299 mouse models were 7.19 ± 0.73 and 1.91 ± 0.42, respectively, while those for A549 mice were 5.53 ± 0.64 and 1.77 ± 0.41, respectively. Biodistribution analysis demonstrated efficient MPA-ABT-510 uptake in H1299 and A549 liver metastases models with tumor-to-liver fluorescence ratios of 2.47 ± 0.48 and 2.19 ± 0.22, respectively. High MPA-ABT-510 accumulation was evident in A549 intestinal metastases models, as evidenced by tumor-to-colorectal fluorescence ratios of 4.27 ± 0.11. MPA-ABT-510 exhibits superior imaging capabilities with minimal safety concerns, so it is a promising candidate for NSCLC surgical navigation.

Human papillomavirus and Merkel cell polyomavirus in Korean patients with nonsmall cell lung cancer: Evaluation and genetic variability of the noncoding control region.

Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT-ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor-associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases.

Impact of Durvalumab on the Duration and Complexity of Corticosteroid Therapy for Pneumonitis After Chemoradiotherapy.

INTRODUCTION: It is unclear how the duration and tapering pattern of corticosteroid therapy for pneumonitis changed after the introduction of durvalumab consolidation therapy. METHODS: We retrospectively evaluated the medical records of patients diagnosed with nonsmall cell lung cancer who received chemoradiotherapy between January 2014 and December 2020. RESULTS: Data for 135 patients treated before durvalumab approval and 100 patients treated with durvalumab after its approval were analyzed. In both groups, more than 70% were male, with a median age of 66 y. Approximately 85% were smokers, and the most common tumor histology was adenocarcinoma. Most patients were treated with doses of 60 and 66 Gy (n = 127 [94%] vs. n = 95 [95%]). Among the patients treated with durvalumab, 57%, 38%, and 5% had grade 1, grade 2, and grade 3 pneumonitis; none had grade 4 or 5 pneumonitis. Patients treated with durvalumab exhibited a longer duration of corticosteroid therapy for pneumonitis (17 wk; range: 2-88 wk) than patients not treated with durvalumab (7 wk; range: 0.4-21 wk; P < 0.001). Pneumonitis relapse was more frequent in patients treated with durvalumab (n = 8; 23%) than in patients not treated with durvalumab (n = 2; 7%). Among the 8 patients treated with durvalumab, 2 had recurrent pneumonitis, 1 could not terminate corticosteroids. CONCLUSIONS: Our data show that durvalumab prolongs the duration of corticosteroid therapy and increases the complexity of corticosteroid tapering patterns. This study can help manage pneumonitis caused by immune checkpoint inhibitors and other drugs used after chemoradiotherapy in routine practice and clinical trials.

Nonsmall-cell lung cancer treatment: current status of drug repurposing and nanoparticle-based drug delivery systems.

Drug repurposing is the strategy of drug utilization for a treatment option other than the intended indications. This strategy has witnessed increased adoption over the past decades, especially within cancer nanomedicine. Cancer nanomedicine has been facilitated through nanoparticle-based (NP-based) delivery systems which can combat nonsmall-cell lung cancer (NSCLC) via recent advances in nanotechnology and apply its benefits to existing drugs. The repurposing of drugs, coupled with NP-based drug delivery systems, presents a promising avenue for achieving effective therapeutic solutions with accelerated outcomes. This review aims to present an overview of NSCLC treatments, with a specific focus on drug repurposing. It seeks to elucidate the latest advances in clinical studies and the utilization of NP-based drug delivery systems tailored for NSCLC treatment. First, the molecular mechanisms of Food and Drug Administration (FDA)-approved drugs for NSCLC, including ROS1 tyrosine kinase inhibitors (TKI) like repotrectinib, approved in November 2023, are detailed. Further, in vitro studies employing a combination strategy of drug repurposing and NP-based drug delivery systems as a treatment approach against NSCLC are listed. It includes the latest study on nanoparticle-based drug delivery systems loaded with repurposed drugs.

METTL5: A Potential Biomarker for Nonsmall Cell Lung Cancer That Promotes Cancer Cell Proliferation by Interacting with IGF2BP3.

Objective: To examine if METTL5 promotes the proliferation of nonsmall cell lung cancer (NSCLC) cells by interacting with IGF2BP3. Methods: The expression patterns of METTL5 and IGF2BP3 in NSCLC tissues, their relationship with survival rate, and their correlation were analyzed using bioinformatics and clinical sample analyses. The effects of METTL5 overexpression and IGF2BP3 knockdown, as well as those of METTL5 knockdown and IGF2BP3 overexpression, on the proliferation of NSCLC cells were analyzed by transfecting appropriate constructs. The interaction between METTL5 and IGF2BP3 was verified using the co-immunoprecipitation (Co-IP) assay. The in vivo effects of METTL5 and IGF2BP3 on NSCLC growth were analyzed using the tumor-bearing nude mouse model. Results: METTL5 and IGF2BP3 expression levels were positively correlated and were associated with poor clinical prognosis. The METTL5 and IGF2BP3 expression levels were upregulated in the clinical NSCLC samples. IGF2BP3 expression did not affect METTL5 expression but was regulated by METTL5. IGF2BP3 overexpression mitigated the METTL5 knockdown-induced impaired cell proliferation. Meanwhile, IGF2BP3 knockdown suppressed METTL5-mediated NSCLC cell proliferation. The Co-IP assay results revealed the interaction between METTL5 and IGF2BP3 in NSCLC cells. IGF2BP3 knockdown suppressed tumor growth, whereas IGF2BP3 overexpression enhanced tumor volume and quality. Conclusion: METTL5 induces NSCLC cell proliferation by interacting with IGF2BP3. Thus, METTL5 is a potential biomarker and a therapeutic target for NSCLC.

5-Year Real-World Outcomes With Frontline Pembrolizumab Monotherapy in PD-L1 Expression ≥ 50% Advanced NSCLC.

BACKGROUND: In clinical trials, frontline pembrolizumab for advanced NSCLC has demonstrated durable, clinically meaningful, long-term survival benefits over chemotherapy. Our objective was to evaluate 5-year survival rates outside the idealized setting of clinical trials for advanced/metastatic NSCLC treated with frontline pembrolizumab monotherapy. METHODS: Using a nationwide, electronic health record-derived, deidentified database in the United States, we studied adult patients with advanced/metastatic NSCLC (unresectable stage IIIB/IIIC, or stage IV), with PD-L1 expression ≥ 50%, no documented EGFR, ALK, or ROS1 genomic alteration, and ECOG performance status of 0-1 initiating frontline pembrolizumab monotherapy from November 1, 2016, through March 31, 2020, excluding those in clinical trials. Kaplan-Meier was used to determine overall survival (OS). Data cutoff was May 31, 2023. RESULTS: A total of 804 patients were eligible for the study, including 404 women (50%); median age was 72 years (range, 38-85 years), with 310 patients (39%) ≥ 75 years old. Median follow-up time from pembrolizumab initiation to data cutoff was 60.5 months (range, 38.0-78.7). At data cutoff, 549 patients (68%) had died. Median OS was 19.2 months (95% CI, 16.6-21.4), and survival rate at 5 years was 25.1% (95% CI, 21.7-28.7). Overall, 266 patients (33%) received 1 or more subsequent regimens, most commonly an anti-PD-(L)1 agent (as monotherapy or combination therapy) or platinum-based chemotherapy. CONCLUSIONS: With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness, with survival outcomes consistent with those of pivotal clinical trials, for treating patients with advanced NSCLC with PD-L1 expression of ≥ 50% and no EGFR, ALK, or ROS1 genomic alteration.

Clinicopathological Features and Survival Outcomes of Resected Lung Adenosquamous Carcinoma: Results From a Nationwide Japanese Registry Data.

OBJECTIVES: The objective of this study was to clarify the clinicopathological features and prognostic factors of resected lung adenosquamous carcinoma (ASC) using a nationwide multi-institutional database. METHODS: We retrospectively reviewed the records of 15,542 patients who underwent complete R0 resection for ASC (n = 326), adenocarcinoma (AC, n = 11,820), or squamous cell carcinoma (SC, n = 3396) from a Japanese lung cancer registry in 2010. To reduce the selection bias, an inverse probability of treatment weighting (IPTW) method using a propensity score was implemented. RESULTS: The ASC group showed worse recurrence-free and overall survival (RFS and OS) than both the AC and SC groups (5-year OS: 57.5% in ASC, 83.9% in AC [< 0.001], and 62.3% in SC [P = .086]). In multivariate analyses, prognostic factors that affected OS for ASC included male, p-stage II-III, and postoperative complications within 30 days (grade ≥ 3 in the Clavien-Dindo classification). The sensitizing EGFR mutation was detected in 28 (21.5%) of 130 screened patients with ASC, but it did not affect either RFS, OS, or postrecurrence survival. Although more patients in the ASC group received adjuvant chemotherapy compared to the AC and SC groups, both multivariate and IPTW-adjusted analyses did not show positive impact of adjuvant chemotherapy on RFS and OS in ASC. CONCLUSIONS: In this nationwide registry study, lung ASC was more aggressive than both AC and SC. No apparent survival impact of conventional adjuvant chemotherapy prompted us to investigate novel adjuvant strategies to optimize survival outcomes.

Inaccurate Clinical Stage Is Common and Associated With Poor Survival in Patients With Lung Cancer.

INTRODUCTION: Clinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. METHODS: In this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. RESULTS: We identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both "understaging" (path > clinical) and "overstaging" (clinical > path) were associated with inferior survival. CONCLUSIONS: Inaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy.

Stereotactic Body Radiotherapy Reirradiation Is Safe in Patients With Lung Cancer With In-Field Enlarged Tumor Recurrence.

Introduction: Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for reirradiation. Materials and Methods: Fifteen patients with recurrent stage III lung cancer treated with stereotactic body radiotherapy (SABR) between October 2013 and December 2017 were retrospectively evaluated for local control as a first endpoint; overall survival, disease-free survival, and treatment-related toxicity were secondary endpoints. Results: The median age was 68 (IQR: 50-71) years, and the median tumor size was 3.3 cm (IQR: 3.0-4.5). The radiation field was all within the previous radiation (previous 80%-90% isodose line), and the median dose was 66 Gy/(2 Gy × 33 standard fractionation). For SABR, the median biologically effective dose at an α/ß ratio of 10 (BED10) was 60.0 Gy (IQR: 39.38-85.0) and given in 3 to 5 fractions. Three patients experienced grade 3 or 4 toxicity but none experienced grade 5. The median follow-up period was 14 (IQR: 10-23) months. The local control rate was found as 86.7% in the first year, 80% in the second year, and 80% in the third year. The median disease-free survival was 8 (IQR: 6-20) months and the median overall survival was 14 (IQR: 10-23) months. The rate of overall survival was 66.6% for the first year and 33.3% for the second and third years. The disease-free survival rate was 46.6% for the first year and 40% for the second and third years. Nine patients who received doses of BED10 ≥ 50 Gy developed no local recurrence (P = .044). Discussion: In local local-regional recurrence of lung cancer, radiosurgery as reirradiation can be used at doses of BED10 ≥ 50 Gy and above to provide local control for radical or palliative purposes. SABR is an important and relatively safe treatment option in such recurrences.

Enhancing the revelation of key genes and interaction networks in non-small cell lung cancer with major depressive disorder: A bioinformatics analysis.

Background and Aims: Lung cancer is ranked as the second most prevalent form of cancer worldwide. Nonsmall cell lung cancer (NSCLC) represents the predominant histological subtype. Research suggests that one-third of lung cancer patients also experiencing depression. Antidepressants play an indispensable role in the management of NSCLC. Despite significant advancements in treatment, lung cancer patients still face a high mortality rate. Major depressive disorder (MDD) and related antidepressants involved in treatment efficacy and prognosis of NSCLC. However, there has been a lack of screening and analysis regarding genes and networks associated with both NSCLC and MDD. Methods: To investigate the correlation between MDD and NSCLC, our discovery and validation analysis included four datasets from the Gene Expression Omnibus database from NSCLC or MDD. Differential gene expression (DEGs) analysis, GO and KEGG Pathway, and protein-protein interaction network analyzes to identify hub genes, networks, and associated observations link between MDD and NSCLC. Results: The analysis of two datasets yielded a total of 84 downregulated and 52 upregulated DEGs. Pathway enrichment analyzes indicated that co-upregulated genes were enriched in the regulation of positive regulation of cellular development, collagen-containing extracellular matrix (ECM), cytokine binding, and axon guidance. We identified 20 key genes, which were further analyzed using the MCODE plugin to identify two core subnetworks. The integration of functionally similar genes provided valuable insights into the potential involvement of these hub genes in diverse biological processes including angiogenesis humoral immune response regulation inflammatory response organization ECM network. Conclusion: We have identified a total of 136 DEGs that participate in multiple biological signaling pathways. A total of 20 hub genes have demonstrated robust associations, potentially indicating novel diagnostic and therapeutic targets for both diseases.

Efficacy of neoadjuvant chemotherapy combined with surgery in patients with nonsmall cell lung cancer: A meta-analysis.

INTRODUCTION: This meta-analysis sought to investigate the effect of neoadjuvant chemotherapy (NACT) combined with surgery in patients with nonsmall cell lung cancer (NSCLC). METHODS: With time span from January 2010 to December 2022, PubMed, Web of Science and Embase, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials on comparison between NACT combined with surgery and surgery alone in patients with NSCLC. Then a meta-analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 1511 studies were retrieved and 12 were finally included. Meta-analysis results showed that compared with surgery alone, a combination of NACT and surgery was associated with higher treatment response rate (odds ratio, OR = 2.459, 95% confidence interval, CI [1.785, 3.388], P < 0.001), 1-year survival rate (OR = 2.185, 95% CI [1.608, 2.970], P < 0.001), and 3-year survival rate (OR = 2.195, 95% CI [1.568, 3.073], P < 0.001) and lower levels of intraoperative blood loss (standardized mean difference, SMD = -0.932, 95% CI [-1.588, -0.275], P = 0.005) and length of hospital stay (SMD = -0.481, 95% CI [-0.933, -0.028], P = 0.037). CONCLUSION: NACT combined with surgery is superior to surgery alone in the treatment of NSCLC and can promote postoperative recovery. Collectively, such combination is a safe and effective treatment for patients with NSCLC.

The Role of Emphysema on Postoperative Prognosis in Early-Stage Nonsmall Cell Lung Cancer.

BACKGROUND: Emphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer. METHODS: A total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema. RESULTS: The emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age > 70 years (vs. < 70 years, hazard ratio 4.03, P < 0.001), and SUVmax > 1.8 (vs. ≤ 1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors. CONCLUSIONS: Early-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis.

Efficacy of cross-line anti-programmed death 1/programmed cell death-ligand 1 antibody in the treatment of advanced nonsmall cell lung cancer: A retrospective study.

Background and Aims: Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross-line ICIs therapy is effective in treating non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results: Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross-line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross-line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061-30.979), 31.643 (95% CI: 23.513-39.774), and 7.997 (95% CI: 3.746-12.247) months, respectively (p = 0.003). The median second progression-free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276-5.864), 3.530 (95% CI: 0.674-6.386), and 1.570 (95% CI: 0-4.091) months, respectively (p = 0.091). Conclusions: Cross-line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.

Prognostic and predictive biomarkers with therapeutic targets in nonsmall-cell lung cancer: A 2023 update on current development, evidence, and recommendation.

BACKGROUND: Since the publication of the original work in 2014, significant progress has been made in the characterization of genomic alterations that drive oncogenic addiction of nonsmall cell lung cancer (NSCLC) and how the immune system can leverage non-oncogenic pathways to modulate therapeutic outcomes. This update evaluates and validates the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in NSCLC. DATA SOURCES: We performed a literature search from January 2015 to October 2023 using the keywords non-small cell lung cancer, clinical practice guidelines, gene mutations, genomic assay, immune cancer therapy, circulating tumor DNA, predictive and prognostic biomarkers, and targeted therapies. STUDY SELECTION AND DATA EXTRACTION: We identified, reviewed, and evaluated relevant clinical trials, meta-analyses, seminal articles, and published clinical practice guidelines in the English language. DATA SYNTHESIS: Regulatory-approved targeted therapies include those somatic gene alterations of EGFR ("classic" mutations, exon 20 insertion, and rare EGFR mutations), ALK, ROS1, BRAF V600, RET, MET, NTRK, HER2, and KRAS G12C. Data for immunotherapy and circulating tumor DNA in next-generation sequencing are considered emerging, whereas the predictive role for PIK3CA gene mutation is insufficient. CONCLUSIONS: Advances in sequencing and other genomic technologies have led to identifying novel oncogenic drivers, novel resistance mechanisms, and co-occurring mutations that characterize NSCLC, creating further therapeutic opportunities. The benefits associated with immunotherapy in the perioperative setting hold initial promise, with their long-term results awaiting.

Comparison between next-generation sequencing and multiplex polymerase chain reaction assays for nonsmall-cell lung cancer molecular diagnosis.

PURPOSE: Genetic mutation detection has become an important step in nonsmall-cell lung cancer (NSCLC) treatment because of the increasing number of drugs that target genomic rearrangements. A multiplex test that can detect multiple gene mutations prior to treatment is thus necessary. Currently, either next-generation sequencing (NGS)-based or polymerase chain reaction (PCR)-based tests are used. We evaluated the performance of the Oncomine Dx Target Test (ODxTT), an NGS-based multiplex biomarker panel test, and the AmoyDx Pan Lung Cancer PCR Panel (AmoyDx PLC panel), a real-time PCR-based multiplex biomarker panel test. MATERIALS AND METHODS: Patients with histologically diagnosed NSCLC and a sufficient sample volume to simultaneously perform the AmoyDx PLC panel and ODxTT-M were included in the study. The success and detection rates of both tests were evaluated. RESULTS: Biopsies revealed 116 cases of malignancies, 100 of which were NSCLC. Of these, 59 met the inclusion criteria and were eligible for analysis. The success rates were 100% and 98% for AmoyDx PLC panel and ODxTT-M, respectively. Nine driver mutations were detected in 35.9% and 37.3% of AmoyDx PLC and ODxTT-M panels, respectively. EGFR mutations were detected in 14% and 12% of samples using the AmoyDx PLC panel and ODxTT-M, respectively. Of the 58 cases in which both NGS and AmoyDx PLC panels were successful, discordant results were observed in seven cases. These differences were mainly due to different sensitivities of the detection methods used and the gene variants targeted in each test. DISCUSSION: The AmoyDx PLC panel, a PCR-based multiplex diagnostic test, exhibits a high success rate. The frequency of the nine genes targeted for treatment detected by the AmoyDx PLC panel was comparable to the frequency of mutations detected by ODxTT-M. Clinicians should understand and use the AmoyDx PLC panel and ODxTT-M with respect to their respective performances and limitations.

Can cell-free DNA (cfDNA) in pleural lavage serve as a predictive and prognostic biomarker among surgically treated Stage I-III a nonsmall cell lung cancer (NSCLC)? A pilot study.

BACKGROUND AND OBJECTIVES: The role of cell-free DNA (cfDNA) in operable nonsmall cell lung cancer (NSCLC) is unclear. This study was aimed to evaluate the feasibility for identification of cfDNA in pleural lavage fluid and its correlation with plasma in resectable NSCLCs. METHODS: Consecutively resected NSCLCs were evaluated for cfDNA levels in preoperative plasma (PLS1), intraoperative pleural-lavage (PLV) and postoperative (at 1 month) plasma sample (PLS2). CfDNA was isolated and measured quantitatively by qPCR in a TaqMan probe-detection approach using the human ß-actin gene as the amplifying target. RESULTS: All (n = 34) except one were negative for malignant cells in PLV cytology. CfDNA could be isolated from all the three samples (PLS1, PLV, and PLS2) successfully in each patient. The median cfDNA levels in PLS1, PLV and PLS2 were 118 ng/mL (IQR 61-158), 167 ng/mL (IQR 59.9-179.9) and 103 ng/mL (IQR 66.5-125.4) respectively. The median follow-up was 34.1 months (IQR 25.2-41.6). A significant overall-survival (OS) and disease-free survival (DFS) were recorded for patients with cfDNA level cut-offs at 125, 170, and 100 ng/mL, respectively for PLS1, PLV, and PLS2. Patients with raised cfDNA in PLS1 (>125 ng/mL) and PLV (>170 ng/mL) had significantly poorer 2-year OS, p = 0.005 and p = 0.012, respectively. The hazards (OS) were also higher for those with raised cfDNA in PLV (HR = 5.779, 95% CI = 1.162-28.745, p = 0.032). PLV (>170 ng/mL) had increased pleural recurrences (p = 0.021) and correlated significantly with poorer DFS at 2-years (p = 0.001) with increased hazards (HR = 9.767, 95% CI = 2.098-45.451, p = 0.004). Multivariable analysis suggested higher cfDNA in PLV as a poor prognostic factor for both OS and DFS. CONCLUSIONS: Among patients with operable NSCLC, it is feasible to identify cfDNA in pleural lavage and correlate PLV cfDNA with pleural recurrences and outcomes.