Lung Cancer最新文献

Purpose: Hematological toxicities (HTs) in lung cancer (LCa) may compromise the delivery of Radio-Chemotherapy (RTCT), and consequently affect the control of the disease. The aim of this study is to evaluate the association of Single nucleotide polymorphisms (SNPs) with HT.

Material/methods: In this prospective multicentre study, 264 patients with primary LCa treated with RTCT between 2012 and 2018 were included. Genotyping analysis was performed on DNA isolated from peripheral blood samples by real-time polymerase chain reaction (PCR) using TaqMan. HTs were scored using the Common Toxicity Criteria (CTCAE) version 5.0.

Results: An increased risk of HT ≥ grade 2 was observed in patients with the GG genotype of the SNP rs7459185 (HSPβ1) with a hazard ratio (HR) of 1.462 (95 %CI 1.054-2.029, p = 0.007). Similarly, those patients had an increased risk of overall HT ≥ grade 3 with a HR of 1.531 (95 %CI 1.016-2.30, p = 0.007). The patients with the GG genotype experienced an acute lymphopenia ≥ Grade 3 (HR 1.590 [95 %CI 1.004-2.517; p 0.045]) and acute anemia ≥ Grade 2 (HR 1.886 [95 %CI 1.060-3.356; p 0.032]), compared to the GC/CC genotypes.

Conclusion: Our findings show a relationship between the functional GG genotypic of the SNP rs7459185 (HSPβ1) and heightened risk the development of HT, including anemia and lymphopenia in patients with LCa. This genetic variant could be utilized as a predictive marker to tailor treatment intensity, contributing to the advancement of individualized therapeutic approaches.

Background: Molecular testing is recommended to patients with advanced non-small cell lung cancer (NSCLC) because those who receive targeted therapy have better prognosis than patients who don't. However, recent studies have raised concerns that first-line companion diagnostic testing at diagnosis may have lower detection rates than previously reported. Therefore, we sought to determine the utility of comprehensive genomic profiling (CGP) tests in NSCLC by analyzing a nation-wide database.

Methods: We searched the Center for Cancer Genomics and Advanced Therapeutics database and downloaded clinical and genomic data from 3,240 lung cancer cases registered from June 2019 to August 2023. Patients undergoing tissue tests and plasma tests were analyzed separately. NSCLC with previously known driver mutations and those without were further analyzed separately. All 3,240 lung cancer patients were analyzed for the presence of germline findings.

Results: We found that 25 % of patients who had negative companion diagnostic results tested positive for driver oncogene mutations with indications for approved inhibitors when they underwent tissue CGP tests. Tissue CGP tests had lower detection rates for gene fusions compared with gene mutations (93 % for mutations and 73 % for fusions, p < 0.001), and plasma CGP tests had lower detection rates for both mutations and fusions compared with tissue testing (69 % for mutations and 37 % for fusions, p < 0.001). Finally, presumed germline pathogenic variants were detected in 3.9-5.3 % of NSCLC patients.

Conclusion: NSCLC patients who tested negative for companion diagnostic tests benefited from CGP tests, especially with tissue-based panels. CGP tests detect germline findings in NSCLC patients at rates similar to previous reports.

The enhanced comprehension of the molecular pathways underpinning oncogenesis in non-small cell lung cancer (NSCLC) has led to the advancement of personalized treatment for individuals with actionable mutations using targeted therapies. The rearranged during transfection (RET) proto-oncogene, is critical in the embryonic development of various tissues, including renal, neural, and neuroendocrine tissue. RET fusions have been observed in approximately 1-2% of NSCLC cases. Targeted therapies for NSCLC with RET alterations have progressed significantly over the past decade. While multikinase inhibitors (MKIs) faced limitations in efficacy and tolerability, the introduction of selective RET inhibitors (SRIs) such as selpercatininb and pralsetinib has transformed patient outcomes, resulting in deep and durable responses. Ongoing clinical trials are exploring their potential benefits in the neoadjuvant and adjuvant setting. Early phase clinical trials endeavor to demonstrate next-generation selective RET inhibitors can effectively overcome SRI resistance mechanisms, offer improved safety profiles, and enhance patient outcomes.

Lung cancer is mostly a disease of aging with approximately half of newly diagnosed patients being 70 years or older. Treatment decisions in this population pose unique challenges because of their heterogeneity with regards to daily functioning, cognition, organ function, comorbidities and polypharmacy, their underrepresentation in clinical trials and the impact of treatment on patient-centered outcomes, particularly in frail patients. The advent of targeted therapies and immunotherapy has revolutionized the management of advanced non-small cell lung cancer (NSCLC). Molecular profiling has allowed for the identification of actionable genomic alterations and targeted therapies have become standard of care for oncogene-driven NSCLC, significantly improving prognosis and quality of life. However, the data on the efficacy and tolerability of these treatments in older patients remain sparse. This review, conducted by the International Society of Geriatric Oncology (SIOG) NSCLC task force, examines the available literature on the use of targeted therapies in patients aged 70 years or older with oncogene-driven NSCLC. The task force's expert recommendations aim to guide treatment decisions for older patients with oncogene driven NSCLC.

Objectives: The 9th edition of the tumor-node-metastasis (TNM) staging system for lung cancer was proposed at the 2023 World Conference on Lung Cancer in Singapore. This study aimed to externally validate and compare the latest staging of small-cell lung cancer (SCLC).

Methods: Four hundred and eight patients with limited-stage SCLC were collected after lung resection from four centers. Survival curves by TNM stages were drawn using the Kaplan-Meier method and further compared by the Log-rank test. The Cox regression, receiver operating characteristics curves, area under the curve (AUC), Akaike information criterion (AIC), Bayesian information criterion (BIC), and Concordance index (C-index) were used in this study.

Results: In comparing IA vs. IIB, IIA vs. IIB, IIA vs. IIIA, IIA vs. IIIB, and IIIA vs. IIIB, the 9th edition had a better distinguishing ability than the eighth staging system (all p < 0.05). Besides, the 9th edition TNM staging had better predictive power and accuracy for the overall survival (OS) of SCLC patients over the 8th edition (AUC of 3-year OS: 0.680 vs. o.668; AIC: 4425.25 vs. 4444.52; BIC: 4493.44 vs. 4512.71; C-index: 0.637 [0.04] vs. 0.629 [0.039], p < 0.001).

Conclusions: Our external validation demonstrates that the ninth edition of pathological TNM staging for limited-stage SCLC is reasonable and valid based on a multicenter study. The ninth edition has better prognostic accuracy than the eighth edition.

Objectives: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies.

Methods: We conducted a retrospective cohort study of patients diagnosed with advanced EGFR-mutant NSCLC who started first-line treatment with either osimertinib or another EGFR TKI (afatinib, erlotinib, or gefitinib) at The Christie (Manchester, UK) from January 2014 to May 2023. Data were extracted from electronic health records, and survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models.

Results: We identified 119 patients treated with first-line osimertinib and 217 with other EGFR TKIs. In the whole population, median age was 69 years (IQR 59.8-77) and 67.3 % of the patients had an ECOG 0-1. With a median follow-up of 73.2 months (95 % CI 66.2-115.7) and 30.6 months (95 % CI 26.0-38.4) in the earlier-generation TKIs and the osimertinib groups, respectively, the median OS was comparable (16.6 vs 16.9 months; HR = 1, p = 0.97). Patients with uncommon EGFR mutations (n = 48; 14.3 %) had poorer survival compared to those with common mutations (HR = 1.664, p = 0.002). Amongst patients who received two treatment lines, those who received osimertinib after another TKI had a shorter OS than those who received osimertinib first-line followed by another line of therapy (HR = 2.062, p = 0.022).

Conclusion: First-line osimertinib showed comparable OS to earlier-generation EGFR TKIs for advanced EGFR-mutant NSCLC. Patients with uncommon EGFR mutations had a poorer survival. Further research is warranted to optimize treatment for patients with uncommon EGFR mutations and to explore the cost-effectiveness of different sequencing approaches.

Objectives: Delayed surgery is significantly associated with an increased risk of disease progression and adverse outcomes in lung cancer. Evidence is available on the variation in delayed surgical treatment among patients with Non-Small Cell Lung Cancer (NSCLC). However, the relative contribution of patient- and area-level risk factors to the geographic patterns of delayed surgery in patients with NSCLC is poorly understood. Therefore, we aimed to explore the geographic variation in delay to surgical treatment among patients with NSCLC.

Materials and methods: This study utilized data from the Victorian Lung Cancer Registry (VLCR) and the Australian Bureau of Statistics (ABS). A total of 3,088 patients with NSCLC who had undergone surgery were included. We applied a Bayesian spatial multilevel model incorporating spatially structured and unstructured random effects to examine patient and area-level risk factors associated with delays to surgical treatment. Model comparison was conducted using the Deviance Information Criterion (DIC).

Results: Over one-third (40.45 %) of NSCLC patients experienced delayed surgical treatment. Significant geographic variation in delayed surgical treatment among NSCLC patients across Local Government Areas (LGAs) was observed. Factors significantly associated with higher odds of delayed surgical treatment included clinical stage II (AOR = 1.56, 95 % CrI: 1.26-1.92), stage III (AOR = 1.90, 95 % CrI: 1.46-2.47), stage IV (AOR = 2.04, 95 % CrI: 1.15-3.61), treatment at inner regional hospitals (AOR = 2.86, 95 % CrI: 2.17-3.70), presence of comorbidities (AOR = 1.19, 95 % CrI: 1.02-1.40), and diagnosis during the COVID-19 pandemic (AOR = 1.32, 95 % CrI: 1.10-1.57).

Conclusions: This study highlights the need to improve the treatment pathway for patients with NSCLC by reducing the time between diagnosis and surgery. Future targeted initiatives are essential to promote timely surgeries for NSCLC patients, especially in high-need areas.

Background: Manual extraction of real-world clinical data for research can be time-consuming and prone to error. We assessed the feasibility of using natural language processing (NLP), an AI technique, to automate data extraction for patients with advanced lung cancer (aLC). We assessed the external validity of our NLP-extracted data by comparing our findings to those reported in the literature.

Methods: Patients diagnosed with stage IIIB or IV lung cancer between January 2015 to December 2017 at Princess Margaret Cancer Centre who received at least one dose of systemic therapy were included. Their electronic health records were provided to Pentavere's NLP platform, DARWEN^TM, in March 2019. Descriptive statistics summarized baseline patient and cancer characteristics, molecular biomarkers, and first-line systemic therapies. Cox multivariate models were used to evaluate prognostic factors for advanced non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) cohort.

Result: NLP extracted clinical information (n = 333 patients) in a total of 8 hours, with only a few missing data for smoking status (n = 2), and Eastern Cooperative Oncology Group (ECOG) status (n = 5). Baseline patient and cancer characteristics summarized from NLP-extracted data were comparable to those in previous studies and population reports. For NSCLC patients, being male (HR 1.44, 95 % CI [1.04, 2.00]), having worse ECOG (1.48 [1.22, 1.81]), and having liver (2.24 [1.45, 3.46]), bone (2.09 [1.48, 2.96]), or lung metastases (2.54 [1.05, 2.26]) were associated with worse survival outcomes. For SCLC patients, having older age (HR 1.70 per 10 years, 95 % CI [1.10, 2.63]) and liver metastases (3.81 [1.61, 9.01]) were associated with worse survival outcomes.

Conclusion: Our study demonstrated that automated data extraction using NLP is feasible and time efficient. Additionally, the NLP-extracted data can be used to identify valid and useful clinical endpoints for research. NLP holds significant potential to accelerate the extraction of real-world data for future observational studies.

Introduction: MET amplification (METamp) can be a de novo or acquired resistance driver; however, the definition of METamp that best captures patients who may respond to targeted therapy remains debated. We explored the genomic landscape of METamp NSCLC including degree of amplification, co-drivers, amplicon size, and outcomes to MET inhibitors.

Methods: Hybrid-capture NGS-based genomic profiling from 88,547 tissue and 12,428 liquid NSCLC samples were queried for METamp (copy number (CN) ≥ ploidy + 4, or amplification ratio (AmpRatio; [CN/sample ploidy] ≥ 3). A nationwide de-identified real-world (rw) clinico-genomic database (CGDB) of NGS results linked to deidentified, electronic health record-derived clinical data was used to assess treatment and outcomes.

Results: Among 10,760 evaluable patients in CGDB, 362 (3.4%) had a METamp. In targeted therapy-naïve cases, MET AmpRatio negatively correlated with non-METex14 co-drivers (median 4.1 vs 2.9, p < 0.0001). MET AmpRatio was not significantly correlated with tumor mutational burden (p = 0.79) but was inversely correlated with amplicon size (p < 0.001). Among paired METamp tissue samples, 8/30 had METamp detected in liquid; higher tumor fraction and AmpRatio were associated with liquid detection. Among 39 METamp patients receiving MET inhibitors, longer median real-world progression free survival was observed with MET AmpRatio ≥ 3 vs < 3 (4.9 vs. 1.7mos, HR 0.53 [95 %CI:0.21-1.3]).

Conclusions: MET AmpRatio positively correlated with focal amplification and absence of co-drivers and trended with increased benefit from MET inhibitors. Further studies evaluatingcombinatorial data including MET AmpRatio, amplicon size and presence of other potential drivers, as predictive biomarkers for therapies targeting MET amplification in NSCLC are warranted.

The peri-operative management of non-small cell lung cancer (NSCLC) in earlier stage disease has seen significant advances in recent years with the incorporation of immune checkpoint inhibitors and targeted therapy. However, many unanswered questions and challenges remain, including the application of clinical trial data to routine clinical practice. Recognising the unique demographic profile of Asian patients with NSCLC and heterogeneous healthcare systems, the Asian Thoracic Oncology Research Group (ATORG) convened a consensus meeting in Singapore on 26 April 2024 to discuss relevant issues spanning diagnostic testing to post-neoadjuvant treatment considerations and future directions. An interdisciplinary group of 19 experts comprising medical oncologists, thoracic surgeons, radiation oncologists, pulmonologists and pathologists from Singapore, Hong Kong, Mainland China, Korea, Japan, Taiwan, India, Malaysia, Thailand, Vietnam and Australia met to discuss emerging data, identify existing gaps in clinical care and develop a multidisciplinary, multinational expert consensus statement on the peri-operative management of NSCLC tailored to the Asia-Pacific region.