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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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248 hot topic(s) found with the query "Lung cancer"

The State of State Biomarker Testing Insurance Coverage Laws
(Posted: May 14, 2024 3PM)

From the article:" There has been a recent push for legislation mandating coverage of “biomarker testing” according to evidence that receipt of such testing can depend on race and ethnicity, age, geography, or site of care. A specific type of biomarker testing for cancer subtypes (ie, “tumor profiling”) is becoming particularly important because many newer cancer therapies target specific mutations (eg, EGFR in non–small cell lung cancer, KRAS in colorectal cancer). Although use of biomarker testing is increasing, barriers to access persist. Cost and lack of insurance coverage are common barriers to testing because insurance coverage varies across commercial payers, Medicare, and Medicaid."

Racial and ethnic disparities in genomic testing among lung cancer patients: a systematic review.
Clare Meernik et al. J Natl Cancer Inst 2024 2 (Posted: Feb 11, 2024 10AM)

From the abstract: "We conducted a systemic review to examine racial and ethnic disparities in the use of genomic testing among lung cancer patients in the U.S. Two comprehensive searches in PubMed, Embase, and Scopus were conducted (September 2022, May 2023). Original studies that assessed rates of genomic testing by race or ethnicity were included. A majority of studies, though not all, observed racial and ethnic disparities in the use of genomic testing among patients with lung cancer. Heterogeneity of study results throughout a period of changing clinical guidelines suggests that minoritized populations—Black patients in particular—have faced additional barriers to genomic testing."

Concurrent Circulating Tumor DNA and Tissue Genotyping-Ready for Prime Time?
Benjamin A Bleiberg et al. JAMA Netw Open 2024 1 (1) e2351679 (Posted: Jan 23, 2024 7AM)

From the article: "Cell-free circulating tumor DNA (ctDNA) is shed by tumor cells into the systemic circulation and, thanks to advancements in next-generation sequencing (NGS) technologies, affords the opportunity to noninvasively detect cancer-specific somatic variants. The use of ctDNA-based molecular genotyping for tumor profiling and identification of patients eligible for targeted therapies has been integrated into clinical practice for a variety of tumor types. The prime example of this is in non–small cell lung cancer (NSCLC), where identifying actionable variants via genomic profiling is essential to determining the appropriate standard of care for patients. "

Lung cancer in patients who have never smoked - an emerging disease.
Jaclyn LoPiccolo et al. Nat Rev Clin Oncol 2024 1 (Posted: Jan 11, 2024 7AM)

From the abstract: " New data have provided important insights into the molecular and genomic characteristics of LCINS, which are distinct from those of smoking-associated lung cancers and directly affect treatment decisions and outcomes. Herein, we review the emerging data regarding the aetiology and features of LCINS, particularly the genetic and environmental underpinnings of this disease as well as their implications for treatment. "

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.
John V Heymach et al. N Engl J Med 2023 10 (18) 1672-1684 (Posted: Nov 02, 2023 9AM)

From the abstract: "Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non–small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcome. 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). Perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. "

Emerging cancer risks in BRCA2 pathogenic germline variant carriers.
Patrick R Benusiglio et al. Eur J Hum Genet 2023 9 (Posted: Sep 28, 2023 11AM)

From the paper: "Carriers of pathogenic germline variants (PGV) in BRCA2 could soon be offered gastric cancer screening using gastroscopy. In the longer term, some might even take part in lung cancer screening programs. Indeed, while the risks of breast, ovarian, pancreatic and prostate cancer have been documented for years, recent data show an increased risk of gastric cancer, and suggest an association with lung cancer. This article focuses specifically on BRCA2, while sidelining its sister gene BRCA1, as evidence for a broad cancer spectrum is much stronger for the former."

Assessing a Polygenic Risk Score for Lung Cancer Susceptibility in Non-Hispanic White and Black Populations.
Matthew R Trendowski et al. Cancer Epidemiol Biomarkers Prev 2023 8 (Posted: Aug 15, 2023 2PM)

Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black populations in model development. Methods: We used a previously published lung cancer PRS based on 80 SNPs associated with lung cancer risk in the OncoArray cohort and validated in UK Biobank. The PRS was evaluated for association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of COPD, and the top five principal components for genetic ancestry.

Genetic Profiles Affect Smokers' Lung Cancer Risk
CN Martimez, Medscape, August 2023 (Posted: Aug 11, 2023 11AM)

Smokers with extreme phenotypes of high and low risk of developing tobacco-associated lung cancer have different genetic profiles, according to a multidisciplinary study conducted by specialists from the Cancer Center at the University of Navarra Clinic (CUN). The study was conducted using DNA from 133 heavy smokers who had not developed lung cancer at a mean age of 80 years, and from another 116 heavy smokers who had developed this type of cancer at a mean age of 50 years. This DNA was sequenced using next-generation techniques, and the results were analyzed using bioinformatics and artificial intelligence.

The Inflammatory Profile Correlates with COVID-19 Severity and Mortality in Cancer Patients
CE Budin et al, JPM, August 7, 2023 (Posted: Aug 08, 2023 8PM)

The correlation of the inflammatory profile with the severity of the disease in neoplastic patients with SARS-CoV-2 infection was addressed. A database of 1537 patients hospitalized in the pneumology department was analyzed. After applying the inclusion and exclusion criteria, 83 patients (67% males, 33% females) were included. Most of the analyzed patients were hospitalized with a moderate form of disease, explaining the significant percentage of 25% mortality. The frequency of the type of neoplasm was higher for lung cancer, followed by malignant colon tumor. We identified a significant association between the increased value of ferritin (p < 0.0001, OR = 22.31), fibrinogen (p = 0.009, OR = 13.41), and C-reactive protein (p = 0.01, OR = 7.65), respectively, and the level of severity of COVID-19.

Private Payer and Medicare Coverage Policies for Use of Circulating Tumor DNA Tests in Cancer Diagnostics and Treatment.
Michael P Douglas et al. J Natl Compr Canc Netw 2023 6 (6) 609-616.e4 (Posted: Jun 14, 2023 9AM)

71 of 1,066 total policies met study inclusion criteria, of which 57 were private policies and 14 were Medicare LCDs; 70% of private policies and 100% of Medicare LCDs covered at least one indication. Among 57 private policies, 89% specified a policy with coverage for ctDNA for initial treatment selection most common (69%). Of 40 policies addressing progression, coverage was provided 28% of the time, and of 20 policies addressing MRD, coverage was provided 65% of the time. Non-small cell lung cancer was the cancer type most frequently covered for initial treatment (47%) and progression (60%).

Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC
M Tsuboi et al, NEJM, June 4, 2023 (Posted: Jun 05, 2023 8AM)

In this planned final analysis of overall survival from the phase 3 ADAURA trial, adjuvant osimertinib resulted in significantly longer overall survival than placebo among patients with completely resected, EGFR-mutated, stage II to IIIA NSCLC as well as in the overall population (patients with stage IB to IIIA disease).

Adjuvant Treatments for Surgically Resected Non-Small Cell Lung Cancer Harboring EGFR Mutations: A Review.
Antonio Passaro et al. JAMA Oncol 2023 5 (Posted: May 12, 2023 6AM)

The use of adjuvant chemotherapy for stage IB-IIIA resected non–small cell lung cancer (NSCLC) has limited benefit for improving cure rates. The proportion of epidermal growth factor receptor (EGFR) alterations among patients with resected NSCLC is comparable to that observed in patients with advanced disease, and the use of EGFR tyrosine kinase inhibitors (TKIs) has been demonstrated to prolong disease-free survival (DFS). With recent approval of osimertinib in this context, a focus on the rapidly evolving scenario and future perspective in clinical practice is needed and was the aim of the current review.

High-resolution circulating tumor DNA testing predicts survival in metastatic lung cancer clinical trials.
et al. Nat Med 2023 4 (Posted: Apr 15, 2023 8AM)

Data from circulating tumor DNA (ctDNA) testing were generated for over 1,900 samples across at least 3 time points in a phase 3 clinical trial and used to build a machine learning model to predict patient survival. The model accurately identified patients with a high risk of disease recurrence and could provide a basis for assigning therapies in phase 1/2 clinical trials.

Molecular Marker Testing in Curable Non-Small Cell Lung Cancer-Practice Necessarily Precedes Data.
Charu Aggarwal et al. JAMA Oncol 2023 4 (Posted: Apr 15, 2023 8AM)

Over the past decade, the differentiation of advanced non–small cell lung cancer (NSCLC) into multiple subgroups defined by the presence or absence of driver sequence variations and tumor expression of programmed cell death ligand 1 (PD-L1) has transformed outcomes. Comprehensive molecular genotyping using next-generation sequencing is recommended during the initial workup of advanced NSCLC based on established improvement in survival and an overall reduction of toxic effects for many patients. Optimal molecular testing strategies in early-stage NSCLC, however, have yet to be defined.

Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.
Christopher Abbosh et al. Nature 2023 4 (Posted: Apr 14, 2023 7AM)

Landmark analyses of plasma samples collected within 120?days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome.

Prognostic Mutational Signatures of NSCLC Patients treated with chemotherapy, immunotherapy and chemoimmunotherapy.
Margaret R Smith et al. NPJ precision oncology 2023 3 (1) 34 (Posted: Mar 28, 2023 6AM)

Different types of therapy are currently being used to treat non-small cell lung cancer (NSCLC) depending on the stage of tumor and the presence of potentially druggable mutations. However, few biomarkers are available to guide clinicians in selecting the most effective therapy for all patients with various genetic backgrounds. To examine whether patients’ mutation profiles are associated with the response to a specific treatment, we collected comprehensive clinical characteristics and sequencing data from 524 patients with stage III and IV NSCLC.

Top advances of the year: Precision oncology.
Aakash Desai et al. Cancer 2023 3 (Posted: Mar 23, 2023 6AM)

In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.

Towards the molecular era of discriminating multiple lung cancers
Z Wang, Ebiomedicine, March 21, 2023 (Posted: Mar 22, 2023 7AM)

This review summarizes recent advances in the molecular identification of multiple lung cancers and compares various methods based on somatic mutations, chromosome alterations, microRNAs, and tumor microenvironment markers. The paper also discusses current challenges at the forefront of genomics-based discrimination, including the selection of detection technology, application of next-generation sequencing, and intratumoral heterogeneity.

A Comprehensive Analysis of Programmed Cell Death-Associated Genes for Tumor Microenvironment Evaluation Promotes Precise Immunotherapy in Patients with Lung Adenocarcinoma
Y Huang et al, J Per Med, March 7, 2023 (Posted: Mar 07, 2023 6PM)

We used LASSO algorithm and multiple-cox regression to establish a programmed cell death-associated gene prognostic model. Further, we explored whether this model could evaluate the sensitivity of patients to anti-PD-1/PD-L1. In total, 1342 patients were included. We constructed a programmed cell death model in TCGA cohorts, and the overall survival (OS) was significantly different between the high- and low-risk score groups (HR 2.70; 95% CI 1.94–3.75; p < 0.0001; 3-year OS AUC 0.71). Specifically, this model was associated with immunotherapy progression-free survival benefit in the validation cohort (HR 2.42; 95% CI 1.59–3.68; p = 0.015; 12-month AUC 0.87).

Rare molecular subtypes of lung cancer.
Guilherme Harada et al. Nature reviews. Clinical oncology 2023 2 (Posted: Feb 23, 2023 9AM)

Oncogenes that occur in =5% of non-small-cell lung cancers have been defined as ‘rare’; nonetheless, this frequency can correspond to a substantial number of patients diagnosed annually. Within rare oncogenes, less commonly identified alterations (such as HRAS, NRAS, RIT1, ARAF, RAF1 and MAP2K1 mutations, or ERBB family, LTK and RASGRF1 fusions) can share certain structural or oncogenic features with more commonly recognized alterations (such as KRAS, BRAF, MET and ERBB family mutations, or ALK, RET and ROS1 fusions). Over the past 5 years, a surge in the identification of rare-oncogene-driven lung cancers has challenged the boundaries of traditional clinical grade diagnostic assays and profiling algorithms.

Integration of artificial intelligence in lung cancer: Rise of the machine.
Colton Ladbury et al. Cell reports. Medicine 2023 2 100933 (Posted: Feb 05, 2023 11AM)

In lung cancer, several data points over a patient’s diagnostic and treatment course are relevant to optimizing outcomes in the form of precision medicine, and artificial intelligence (AI) provides the opportunity to use available data from molecular information to radiomics, in combination with patient and tumor characteristics, to help clinicians provide individualized care. In doing so, AI can help create models to identify cancer early in diagnosis and deliver tailored therapy on the basis of available information,

Persistent mutation burden drives sustained anti-tumor immune responses.
Noushin Niknafs et al. Nature medicine 2023 1 (Posted: Jan 27, 2023 7AM)

Tumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses in the context of immunotherapy. We evaluated mutations in regions of the genome that are unlikely to undergo loss in a pan-cancer analysis across 31 tumor types (n?=?9,242) and eight immunotherapy-treated cohorts of patients with non-small-cell lung cancer, melanoma, mesothelioma, and head and neck cancer (n?=?524). We discovered that mutations in single-copy regions and those present in multiple copies per cell constitute a persistent tumor mutation burden (pTMB) which is linked with therapeutic response to immune checkpoint blockade.

Variation in Use of Lung Cancer Targeted Therapies Across State Medicaid Programs, 2020-2021.
Thomas J Roberts et al. JAMA network open 2023 1 (1) e2252562 (Posted: Jan 26, 2023 6AM)

Does the use of targeted therapies for non–small cell lung cancer (NSCLC) vary across state Medicaid programs? This cross-sectional study found substantial variation in the use of targeted therapies for EGFR- and ALK-altered NSCLC across Medicaid programs, with evidence of underuse in 30 of 33 states. The observed variation was associated with Medicaid policies, oncologist density, and state gross domestic product per capita.

Testing for EGFR Variants in Pleural and Pericardial Effusion Cell-free DNA in Patients With Non-Small Cell Lung Cancer.
Lee Kirsty W C et al. JAMA oncology 2022 12 (Posted: Dec 31, 2022 6AM)

In this diagnostic study of 171 patients with advanced NSCLC and PE (104 tyrosine kinase inhibitor [TKI]–naive and 67 with acquired resistance to first- or second-generation EGFR-TKI therapy), PE-cfDNA had high sensitivity and specificity (both 97%) and better sensitivity (97% vs 74%) than plasma for the detection of sensitizing EGFR variants. Accuracy was lower for EGFR Thr790Met variant (T790M) detection, but T790M alteration was detected more frequently in PE-cfDNA (51%) than in PE cell block samples (25%).

Leveraging Artificial Intelligence to Improve Accuracy of Lung Cancer Screening
NCI Blog, December 16, 2022 Brand (Posted: Dec 19, 2022 10AM)

Artificial intelligence (AI) has been used to discriminate between normal and precancer/cancer in a number of settings. In the past decade, significant progress has been made in computer-aided detection and diagnosis, leading to several Food and Drug Administration (FDA)-approved types of software. Recent efforts are focused on deep learning, a subset of AI that uses artificial neural networks to learn from huge amounts of data. If the trained neural network out-performs human expert interpretation, it is poised to transform medical imaging and diagnostics.

Extracellular matrix profiles determine risk and prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma
AL Parker et al, Genome Medicine, November 21, 2022 (Posted: Nov 21, 2022 8AM)

Development of a Molecular Blood-Based Immune Signature Classifier as Biomarker for Risks Assessment in Lung Cancer Screening.
Fortunato Orazio et al. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2022 9 (11) 2020-2029 (Posted: Nov 13, 2022 6AM)

Monocytic myeloid-derived suppressor cell (MDSC), polymorphonuclear MDSC, intermediate monocytes and CD8+PD-1+ T cells distinguished patients with lung cancer from controls with AUCs values of 0.94/0.72/0.88 in the training, validation, and lung cancer specificity set, respectively. AUCs raised up to 1.00/0.84/0.92 in subgroup analysis considering only MSC-negative subjects. A 14-immune genes expression signature distinguished patients from controls with AUC values of 0.76 in the validation set and 0.83 in MSC-negative subjects.

Preliminary Experience of Liquid Biopsy in Lung Cancer Compared to Conventional Assessment: Light and Shadows
M Montella et al, J Per Med, November 12, 2022 (Posted: Nov 13, 2022 6AM)

We showed that, when a genetic mutation was detected in pathological examination, this was always detected by liquid biopsy, demonstrating a very high concordance rate of genomic testing between tissues and their corresponding mutations obtained by liquid biopsy, without cases of false-negative results. In addition, in our study, liquid biopsy highlighted 26 mutations, with the prevalence of ALK mutation in 96.6% of patients, supporting the idea that this approach could be an effective tool in cases with insufficient tumor tissue specimens or in cases where tissue specimens are not obtainable.

Circulating tumor DNA as a novel prognostic indicator
A Vivancos et al, Nature Medicine, November 10, 2022 (Posted: Nov 11, 2022 5PM)

Recent years have witnessed the development and clinical implementation of liquid biopsy as an alternative source of tumor-derived DNA when tumor tissue sampling is challenging, or biopsy not recommended. Management of non–small-cell lung cancer (NSCLC) has become the main clinical scenario for the application of liquid biopsy in advanced disease, given the large number of targetable driver alterations (EGFR, ALK, ROS1, BRAF, MET, NTRK and RET) and the often-limited quantity of tumor tissue.

Disparity in checkpoint inhibitor utilization among commercially insured adult patients with metastatic lung cancer.
Li Meng et al. Journal of the National Cancer Institute 2022 11 (Posted: Nov 11, 2022 6AM)

We identified metastatic lung cancer patients diagnosed between 2015 and 2020 from a large nationwide commercial claims database. We analyzed the time from metastatic lung cancer diagnosis to ICI therapy using Cox proportional hazard models. We found that commercially insured patients with metastatic lung cancer who lived in counties with greater percentage of racialized population had slower initiation of ICI therapy after lung cancer diagnosis, despite greater density of oncologists in their neighborhood.

Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non-Small-Cell Lung Cancer.
Sadik Helen et al. JCO precision oncology 2022 10 e2200246 (Posted: Nov 01, 2022 2PM)

For every 1,000 patients in the study cohort, 497 (49.7%) are lost to precision oncology because of factors associated with getting biomarker test results. Among the 503 of 1,000 patients who did receive results from a biomarker test, 147 (29.2%) did not receive appropriate targeted treatments. Thus, approximately 64% of potentially eligible patients with aNSCLC are not benefiting from precision oncology therapies appropriate for their disease.

Molecular Profiling in Non-Squamous Non-Small Cell Lung Carcinoma: Towards a Switch to Next-Generation Sequencing Reflex Testing
N Pujol et al, J Per Med, October 8, 2022 (Posted: Oct 10, 2022 11AM)

The wide range of actionable molecular alterations in non-squamous non-small cell lung carcinoma (NS-NSCLC) and the multiplicity of mechanisms of resistance to treatment resulted in the need for repeated testing to establish an accurate molecular diagnosis, as well as to track disease evolution over time. In this review, we discuss recent developments in the molecular profiling of NS-NSCLC and how NGS addresses current needs, as well as how it can be implemented to address future challenges in the management of NS-NSCLC.

Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer
MM Tsyganov et al, J Per Medicine, October 4, 2022 (Posted: Oct 04, 2022 9AM)

MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33–65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96–3.98; p = 0.06) compared to the group of patients with chemotherapy.

Fibroblast subsets in non-small cell lung cancer: associations with survival, mutations, and immune features.
Pellinen Teijo et al. Journal of the National Cancer Institute 2022 9 (Posted: Sep 11, 2022 9AM)

Multi-marker-defined CAF subsets were identified through high-content spatial profiling. The robust associations of CAFs with driver mutations, immune features, and outcome suggest CAFs as essential factors in NSCLC progression and warrant further studies to explore their potential as biomarkers or therapeutic targets. This study also highlights mfIHC-based CAF profiling as a powerful tool for the discovery of clinically relevant CAF subsets.

Broad clinical manifestations of polygenic risk for coronary artery disease in the Women’s Health Initiative
SL Clarke et al, Comm Medicine, August 25, 2022 (Posted: Aug 26, 2022 8AM)

Polygenic risk for CAD is associated with a variety of biomarkers, clinical measurements, behaviors, and diagnoses related to traditional risk factors, as well as risk-enhancing factors. Analysis of adjudicated outcomes shows a graded association between atherosclerosis related outcomes, with the highest odds ratios being observed for the most severe manifestations of CAD. We find associations between increased polygenic risk for CAD and decreased risk for incident breast and lung cancer, with replication of the breast cancer finding in an external cohort.

The oral microbiome and lung cancer risk: An analysis of 3 prospective cohort studies
E Vogtman et al, JNCI, August 5, 2022 (Posted: Aug 06, 2022 6AM)

Previous studies suggested associations between the oral microbiome and lung cancer, but studies were predominantly cross-sectional and underpowered. Multiple oral microbial measures were prospectively associated with lung cancer risk in three US cohort studies with associations varying by smoking history and histologic subtype. The oral microbiome may offer new opportunities for lung cancer prevention.

Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
J Byun et al, Nature Genetics, August 1, 2022 (Posted: Aug 01, 2022 11AM)

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity.

Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity
YY Elamin et al, Cell, July 11, 2022 (Posted: Jul 11, 2022 11AM)

We report a phase II study of 50 advanced non-small cell lung cancer (NSCLC) patients with point mutations or insertions in EGFR exon 20 treated with poziotinib (NCT03066206). The study achieved its primary endpoint, with confirmed objective response rates (ORRs) of 32% and 31% by investigator and blinded independent review, respectively, with a median progression-free survival of 5.5 months.

When can we be confident of surgical cure with ctDNA?
Frankell Alexander et al. Nature reviews. Clinical oncology 2022 7 (Posted: Jul 10, 2022 2PM)

Tracking circulating tumour DNA (ctDNA) after surgery holds promise for patient management and therapeutic intervention in non-small-cell lung cancer (NSCLC). A recent study tracks ctDNA from 261 patients with stages I–III NSCLC and suggests that the likelihood of disease relapse decreases for high-risk stage II/III patients after 18 months without ctDNA detection.

Association of High Tumor Mutation Burden in Non-Small Cell Lung Cancers With Increased Immune Infiltration and Improved Clinical Outcomes of PD-L1 Blockade Across PD-L1 Expression Levels.
Ricciuti Biagio et al. JAMA oncology 2022 6 (Posted: Jun 18, 2022 10AM)

Is tumor mutation burden (TMB) associated with improved outcomes of programmed cell death–1 (PD-1)/programmed death ligand–1 (PD-L1) inhibition across PD-L1 expression levels in non–small cell lung cancer (NSCLC)? In this cohort study of 1552 patients with NSCLC, the group with high TMB had improved response rates and survival after receiving PD-1/PD-L1 inhibition therapy across PD-L1 expression subgroups compared with the group with low TMB. High TMB levels were associated with increased CD8-positive T-cell infiltration and distinct immune response gene expression signatures.

Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management
AJ Cooper et al, Nature Rev Clin Oncology, May 2022 (Posted: May 14, 2022 11AM)

The discoveries of EGFR mutations and ALK rearrangements as actionable oncogenic drivers in non-small-cell lung cancer (NSCLC) has propelled a biomarker-directed treatment paradigm for patients with advanced-stage disease. Numerous EGFR and ALK tyrosine kinase inhibitors (TKIs) with demonstrated efficacy in patients with EGFR-mutant and ALK-rearranged NSCLCs have been developed. In this Review, we discuss the development of third-generation EGFR and ALK inhibitors, predominant mechanisms of resistance, and approaches to tackling resistance in the clinic, ranging from novel fourth-generation TKIs to combination regimens and other investigational therapies.

Longitudinal COVID-19 vaccination-induced antibody responses and Omicron neutralization in patients with lung cancer
PC Mack et al, Cell, April 19 2022 (Posted: Apr 21, 2022 7AM)

A blood-based miRNA signature with prognostic value for overall survival in advanced stage non-small cell lung cancer treated with immunotherapy
T Rajakumar et al, NPJ Precision ONcology, March 31, 2022 (Posted: Apr 02, 2022 8AM)

We sought to identify peripheral blood biomarkers, predictive of response to immunotherapies against lung cancer, based on whole blood microRNA profiling. Using three well-characterized cohorts consisting of a total of 334 stage IV NSCLC patients, we have defined a 5 microRNA risk score (miRisk) that is predictive of overall survival following immunotherapy in training and independent validation (HR 2.40, 95% CI 1.37–4.19; P?<?0.01) cohorts.

Co-occurring genomic alterations and immunotherapy efficacy in NSCLC
F Zhang et al, NPJ Precision Oncology, January 18, 2022 (Posted: Jan 18, 2022 7AM)

We analyzed the data of 1745 NSCLCs and delineated the landscape of interaction effects of common co-mutations on ICI efficacy. Particularly in nonsquamous NSCLC, KRAS mutation remarkably interacted with its co-occurring mutations in TP53, STK11, PTPRD, RBM10, and ATM. Based on single mutation-based prediction models, adding interaction terms (referred to as inter-model) improved discriminative utilities in both training and validation sets. The scores of inter-models exhibited undifferentiated effectiveness regardless of tumor mutational burden.

A lepidic gene signature predicts patient prognosis and sensitivity to immunotherapy in lung adenocarcinoma
LT Nguyen et al, Genome Medicine, January 12, 2022 (Posted: Jan 12, 2022 8AM)

We found dramatic immunological differences among histological subtypes. Differential gene expression analysis showed that the lepidic and solid subtypes could be differentiated based on their gene expression patterns while the other subtypes shared similar gene expression patterns. Our results indicated that higher L-scores were associated with prolonged survival, and higher S-scores were associated with shortened survival. L-scores and S-scores were also correlated with global genomic features such as tumor mutation burdens and driver genomic events.

Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern.
R Varanpalanbil et al, MEDRXIV, January 4,2022 (Posted: Jan 05, 2022 8AM)

Overall survival for oncology drugs approved for genomic indications
A Haslam et al, EJC, January 2022 (Posted: Dec 23, 2021 10AM)

We found 53 drugs approved for 92 unique indications from 2006 to 2020. We found that 50 drugs (55%) approved for a genomic indication had a randomized study evaluating OS benefit, and of those, only 22 demonstrated an improvement in OS. Similarly, 52 drugs (57%) evaluated PFS benefit, and 51 of these studies demonstrated an improvement in PFS. Drugs approved for BRAF V600 melanoma demonstrated an improvement in OS more often than drugs approved for ALK non–small cell lung cancer. The median improvement in OS was 4.7 months.

Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes
SY Liu et al, Nature Comms, November 8, 2021 (Posted: Nov 08, 2021 7AM)

By comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups).

Association of Clinicopathologic and Molecular Tumor Features With Recurrence in Resected Early-Stage Epidermal Growth Factor Receptor–Positive Non–Small Cell Lung Cancer
JAMA Network Open, November 5,2021 (Posted: Nov 06, 2021 9AM)

In this cohort study including 723 patients with EGFR-positive or wildtype EGFR NSCLC, 2-year disease-free survival of patients with EGFR-positive NSCLC was 81% for stage IA, 78% for stage IB, 57% for stage II and 47% for stage IIIA; overall, 5-year disease-free survival among patients with stage IB to IIIA was 37%. Micropapillary subtype, CTNBB1 and RNHP1 were features associated with increased risk of recurrence.

Estimating Recurrence Risk in Resected Early-Stage Epidermal Growth Factor Receptor–Positive Non–Small Cell Lung Cancer
C D'Avella et al, JAMA Network Open, November 5, 2021 (Posted: Nov 06, 2021 9AM)

Over the past decade, the landscape of NSCLC treatment has changed dramatically to include the use of targeted agents in advanced disease. One of the biggest success stories has been targeted therapy in the EGFR-positive population, which has transformed a disease with previously short survival to a well-managed chronic disease that many patients may live with for years.

Single-cell RNA sequencing for the identification of early-stage lung cancer biomarkers from circulating blood
J Kim et al, NPJ Genomic Medicine, October 15, 2021 (Posted: Oct 16, 2021 7AM)

We performed single-cell RNA-sequencing (scRNA-seq) analysis using Fluidigm C1 systems to characterize human lung cancer transcriptomes at single-cell resolution. Validation of scRNA-seq differentially expressed genes (DEGs) through quantitative real time-polymerase chain reaction found a positive correlation in fold-change values between C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) compared with bulk-cell level in 34 primary lung adenocarcinomas (LUADs) from Stage I patients. Furthermore, we discovered an inverse correlation between chemokine mRNAs, miR-532-5p, and miR-1266-3p in early-stage primary LUADs. Specially, miR-532-5p was quantifiable in plasma from the corresponding LUADs. Collectively, we identified markers of early-stage lung cancer that were validated in primary lung tumors and circulating blood.

Genomic and evolutionary classification of lung cancer in never smokers
T Zhang et al, Nature Genetics, September 6, 2021 (Posted: Sep 07, 2021 6AM)

Whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers’ progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke.

Assessing Clinical Outcomes in a Data-Rich World—A Reality Check on Real-World Data
JC Wong et al, JAMA Internal Med, July 26, 2021 (Posted: Jul 27, 2021 7AM)

Observational data of any form must still be interpreted with caution. As the field of RWE continues to evolve and enable new applications, end point definition will play an important role. Real-world evidence encompasses clinical uses beyond regulatory approval, by building retrospective evidence to inform practice in knowledge gaps and develop hypotheses for future clinical trials.

Sotorasib for Lung Cancers with KRAS p.G12C Mutation.
Skoulidis Ferdinandos et al. The New England journal of medicine 2021 6 (25) 2371-2381 (Posted: Jun 24, 2021 6AM)

In this phase 2 trial, sotorasib therapy led to a durable clinical benefit without new safety signals in patients with previously treated KRAS p.G12C–mutated NSCLC.

FDA Approves First Targeted Therapy for Lung Cancer Mutation Previously Considered Resistant to Drug Therapy
FDA, May 28, 2021 (Posted: May 30, 2021 10AM)

KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer. Today’s approval represents a significant step towards a future where more patients will have a personalized treatment approach.”

Machine Learning for Early Lung Cancer Identification Using Routine Clinical and Laboratory Data.
Gould Michael K et al. American journal of respiratory and critical care medicine 2021 (Posted: Apr 09, 2021 10AM)

Most lung cancers are diagnosed at an advanced stage. Pre-symptomatic identification of high-risk individuals can prompt earlier intervention and improve long-term outcomes. To develop a model to predict a future diagnosis of lung cancer based on routine clinical and laboratory data, using machine-learning. We assembled 6,505 non-small cell lung cancer (NSCLC) cases and 189,597 contemporaneous controls and compared the accuracy of a novel machine-learning model to a modified version of the well-validated PLCOm2012 risk model.

Adherence to NCCN ALK testing guidelines for patients with advanced non-small cell lung cancer in US Community Medical Centers.
Bernicker Eric H et al. The oncologist 2021 (Posted: Apr 09, 2021 10AM)

We assessed adoption of testing recommendations for ALK rearrangements in a national database. While test utilization increased over the time period studied (2012-2019), there is still room for improvement. Efforts are needed to increase test utilization in under-tested groups, thus enabling eligible patients to benefit from novel lung cancer therapies.

Rare deleterious germline variants and risk of lung cancer
Y Liu et al, NPJ Genomic Medicine, February 19, 2021 (Posted: Feb 20, 2021 0PM)

Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls

A Genomic-Pathologic Annotated Risk Model to Predict Recurrence in Early-Stage Lung Adenocarcinoma.
Jones Gregory D et al. JAMA surgery 2021 Feb (2) e205601 (Posted: Feb 11, 2021 7AM)

This study shows that integration of tumor genomics and clinicopathologic features improves risk stratification and prediction of recurrence after surgical resection of early-stage LUAD. Improved identification of patients at risk for recurrence could enrich and enhance accrual to adjuvant therapy clinical trials.

Germline Whole-Exome Sequencing Reveals the Potential Role of Hereditary Predisposition and Therapeutic Implications in SCLC
ASCO Post, February 4, 2021 (Posted: Feb 07, 2021 7AM)

A new study shows that there may be an inherited predisposition for small cell lung cancer (SCLC). The findings lay the foundation for understanding the interaction between genotype and tobacco exposure in exacerbating SCLC risk, as well as potential therapeutic implications. Because tobacco is the dominant carcinogen, secondary causes of lung cancer are often diminished in perceived importance. SCLC is almost exclusively related to tobacco and comprises 15-20% of all lung cancers.

Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair–targeted therapies
C Tlemsani et al, Sci Trans Med, January 27, 2021 (Posted: Jan 28, 2021 8AM)

Small cell lung cancer (SCLC) is generally regarded as a smoker’s cancer. However, the genetic factors that affect susceptibility to SCLC have not been fully evaluated. The authors performed whole-exome sequencing on the germ lines of a cohort of participants with SCLC, finding that almost half the cohort carried deleterious variants in cancer-predisposing genes. Those with pathogenic germline variants had better response to platinum-based chemotherapy.

A Genomic-Pathologic Annotated Risk Model to Predict Recurrence in Early-Stage Lung Adenocarcinoma
GD Jones et al JAMA SUregery, December 23, 2020 (Posted: Dec 24, 2020 7AM)

In this observational study of 426 patients with LUAD, alterations in SMARCA4 and TP53 and fraction of genome altered were independently associated with relapse-free survival. By integrating genomic and clinicopathologic factors, this prediction model outperformed the TNM-based model (concordance probability estimate, 0.73 vs 0.61) for prediction of relapse-free survival and was externally validated using The Cancer Genome Atlas data set.

Artificial intelligence is improving the detection of lung cancer- Machine learning systems for early detection could save lives.
E Svoboda, Nature Outlook, November 18, 2020 (Posted: Nov 23, 2020 8AM)

Lung cancer is the deadliest cancer in the world — about 75% of those who have it die within five years of diagnosis. But when cancers are found early, the prognosis is much better. If tumors are small and confined to the lung, almost two-thirds of people survive for at least five years. The need for early detection has fueled the development of AI systems that can detect ever-smaller lung tumors.

How liquid biopsies allow smarter lung-cancer treatment- Technologies that count tumour cells in the blood promise to improve survival times.
B Placket, Nature Outlook, November 18, 2020 (Posted: Nov 23, 2020 8AM)

Researchers hope to use liquid biopsies that measure the concentration of CTCs in the blood to monitor the effects of treatment and warn of potential relapses. “I’ve been an oncologist for about 30 years and this is the most exciting time for lung cancer research in my career.”

First-Line Lorlatinib or Crizotinib in Advanced ALK -Positive Lung Cancer.
Shaw Alice T et al. The New England journal of medicine 2020 Nov (21) 2018-2029 (Posted: Nov 19, 2020 11AM)

In an interim analysis of results among patients with previously untreated advanced ALK-positive NSCLC, those who received lorlatinib had significantly longer progression-free survival and a higher frequency of intracranial response than those who received crizotinib.

What Are the Risk Factors for Lung Cancer?
CDC, November 2020 Brand (Posted: Nov 18, 2020 10AM)

Your risk of lung cancer may be higher if your parents, brothers or sisters, or children have had lung cancer. This could be true because they also smoke, or they live or work in the same place where they are exposed to radon and other substances that can cause lung cancer.

Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44
AL Cummings et al, Nature Cancer, November 26, 2020 (Posted: Nov 17, 2020 8AM)

Improving lung cancer risk stratification leveraging whole transcriptome RNA sequencing and machine learning across multiple cohorts
Y Choi et al, Genome Medicine, October 2020 (Posted: Oct 24, 2020 10AM)

Bronchoscopy for suspected lung cancer has low diagnostic sensitivity, rendering many inconclusive results. The Bronchial Genomic Classifier (BGC) was developed to help with patient management by identifying those with low risk of lung cancer when bronchoscopy is inconclusive.

Deep Learning Using Chest Radiographs to Identify High-Risk Smokers for Lung Cancer Screening Computed Tomography: Development and Validation of a Prediction Model.
Lu Michael T et al. Annals of internal medicine 2020 Sep (Posted: Sep 03, 2020 7AM)

Lung cancer screening with chest computed tomography (CT) reduces lung cancer death. Eligibility criteria for screening with CT require detailed smoking information and miss many incident lung cancers. An automated deep-learning approach based on chest radiographs may identify more smokers at high risk for lung cancer who could benefit from screening.

Association of Cerebrospinal Fluid Tumor DNA Genotyping With Survival Among Patients With Lung Adenocarcinoma and Central Nervous System Metastases
YS Li et al, JAMA Network Open, August 4, 2020 (Posted: Aug 05, 2020 8AM)

Patients with a diagnosis of lung adenocarcinoma and CNS metastases experienced heterogeneous survival outcomes based on genetic profiling in cerebrospinal fluid. These data suggest that CSF might facilitate risk stratifying CNS metastases into appropriate outcomes and provide reference for further clinical study.

Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants.
Larsson Susanna C et al. PLoS medicine 2020 Jul (7) e1003178 (Posted: Jul 29, 2020 8AM)

Our findings support the well-established relationship between smoking and lung cancer and suggest that smoking may also be a risk factor for cancer of the head and neck, oesophagus, stomach, cervix, and bladder. We found no evidence supporting a relationship between alcohol consumption and overall or site-specific cancer risk.

The National Lung Matrix Trial of personalized therapy in lung cancer.
Middleton Gary et al. Nature 2020 Jul (Posted: Jul 17, 2020 10AM)

Despite pre-clinical data supporting the drug–biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke.

An umbrella approach to test lung cancer therapies
A Drilon et al, Nature News, July 15, 2020 (Posted: Jul 17, 2020 10AM)

A clinical trial has tested the use of gene-sequencing results for lung cancer to match patients to targeted therapies. Some paired treatments were a good fit, but others did not succeed, for reasons that will require further exploration.

Lung Adenocarcinoma (LUAD) Discoveries from two NCI Proteomics Consortia
NCI, July 9, 2020 Brand (Posted: Jul 10, 2020 6AM)

Advances in genomics have revealed new insights in the biology of LUAD, but comprehensive information about how various gene mutations lead to this disease is still lacking. Investigators addressed this challenge by adding comprehensive proteomics to genomics, or proteogenomics, to reveal an additional dimension of lung cancer biology.

Liquid biopsy for early stage lung cancer moves ever closer
C Rolfo et al, Nat Rev Clin Oncol, May 26, 2020 (Posted: May 27, 2020 9AM)

Lung cancer screening is currently based only on low-dose CT scans; however, novel, more accessible methods that might improve uptake and adherence are eagerly awaited. New liquid biopsy approaches promise to revolutionize cancer screening. Herein, we discuss the opportunities and challenges associated with two such novel assays.

Mendelian randomization applied to pharmaceutical use: the case of metformin and lung cancer.
Yarmolinsky James et al. International journal of epidemiology 2020 May (Posted: May 10, 2020 7AM)

Evaluating the Use of Circulating MicroRNA Profiles for Lung Cancer Detection in Symptomatic Patients
T Fehlmann et al, JAMA Oncology, March 5, 2020 (Posted: Mar 06, 2020 8AM)

This cohort study used genome-wide microRNA profiles from the blood samples of 3046 individuals to identify patients with lung cancer with 91.4% accuracy, 82.8% sensitivity, and 93.5% specificity. Meaning The findings of this study suggest that circulating microRNAs may be used in a liquid biopsy to complement imaging tests, sputum cytology, and biopsies

CT derived radiomic score for predicting the added benefit of adjuvant chemotherapy following surgery in stage I, II resectable non-small cell lung cancer: a retrospective multicohort study for outcome prediction
P Vaidya et al, Lancet Digital Health, February 13, 2020 (Posted: Feb 14, 2020 8AM)

Smoke signals in the DNA of normal lung cells
Nature News, January 30, 2020 (Posted: Jan 31, 2020 9AM)

Healthy cells in smokers’ lungs have a high burden of mutations, similar to the mutational profile of lung cancer. Surprisingly, ex-smokers’ lungs have a large fraction of healthy cells with nearly normal profiles.

Effect of Concurrent Chemoradiation With Celecoxib vs Concurrent Chemoradiation Alone on Survival Among Patients With Non–Small Cell Lung Cancer With and Without Cyclooxygenase 2 Genetic Variants- A Phase 2 Randomized Clinical Trial
N Bi et al, JAMA Network Open, December 18, 2019 (Posted: Dec 19, 2019 9AM)

Could selective cyclooxygenase 2 inhibition combined with standard concurrent chemoradiation therapy improve survival among patients with unresectable stage III non–small cell lung cancer?

Evidence That Established Lung Cancer Mortality Disparities in American Indians Are Not Due to Lung Cancer Genetic Testing and Targeted Therapy Disparities.
Begnaud Abbie et al. Clinical lung cancer 2019 Oct (Posted: Nov 26, 2019 9AM)

American Indians and Alaska Natives (AI/AN) continue to experience extreme lung cancer health disparities. In this Minnesota study, there was no significant difference in mutation testing in AI compared to non-AI controls at large health care systems. These data indicate that other factors are likely contributing to the higher mortality in this group.

Study Suggests Repurposed Drugs Might Treat Aggressive Lung Cancer
NIH Director's Blog, November 19, 2019 Brand (Posted: Nov 21, 2019 7AM)

Using gene-editing technology to conduct a systematic, large-scale search for druggable vulnerabilities in certain types of cancer cells grown in lab dishes, researchers recently identified a metabolic pathway that appears to play a key role in small cell lung cancer. What makes this news even more encouraging is drugs that block this pathway already exist.

Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer.
Hellmann Matthew D et al. The New England journal of medicine 2019 Nov (21) 2020-2031 (Posted: Nov 21, 2019 7AM)

First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up.

Appraising the causal relevance of DNA methylation for risk of lung cancer.
Battram Thomas et al. International journal of epidemiology 2019 Sep (Posted: Sep 26, 2019 8AM)

DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.

Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and Mortality in Patients With Non–Small Cell Lung Cancer
Y Chen et al, JAMA Network Open, September 20, 2019 (Posted: Sep 22, 2019 0PM)

In this multiple-cohort study, TP53 and ATM comutation sites were scattered throughout the genes analyzed. Comutation in TP53 and ATM was associated with a higher tumor mutation burden and better overall survival compared with sole mutations and no mutation.

Cancer Patients Have Limited Understanding of Genomic Test Results
Health Analytics, September 2019 (Posted: Sep 18, 2019 9AM)

A majority of patients with cancer don’t understand critical features of the genomic test results they receive when participating in clinical trials, according to a pilot study conducted under the Lung Cancer Master Protocol (Lung-MAP), the first lung cancer precision medicine trial supported by the National Cancer Institute (NCI).

Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone in Patients With Epidermal Growth Factor Receptor–Mutated Lung Adenocarcinoma
JAMA Oncology, September 5, 2019 (Posted: Sep 06, 2019 7AM)

In this phase 2 randomized clinical trial that included 139 patients, the addition of metformin to standard EGFR–tyrosine kinase inhibitors significantly improved both progression-free survival and overall survival.

Systemic Therapy for Locally Advanced and Metastatic Non–Small Cell Lung Cancer: A Review
KC Arbour et al, JAMA, August 27, 2019 (Posted: Aug 28, 2019 7AM)

Improved understanding of the biology and molecular subtypes of non–small cell lung cancer have led to more biomarker-directed therapies for patients with metastatic disease. These biomarker-directed therapies and newer empirical treatment regimens have improved overall survival for patients with metastatic non–small cell lung cancer.

Liquid biopsy-based single-cell metabolic phenotyping of lung cancer patients for informative diagnostics
Z Li et al, Nature Comms, August 26, 2019 (Posted: Aug 27, 2019 7AM)

Recent Advances in Lung Cancer Immunotherapy: Input of T-Cell Epitopes Associated With Impaired Peptide Processing.
Leclerc Marine et al. Frontiers in immunology 2019 1505 (Posted: Aug 01, 2019 8AM)

Association of Survival and Immune-Related Biomarkers With Immunotherapy in Patients With Non–Small Cell Lung Cancer A Meta-analysis and Individual Patient–Level Analysis
Y Yu et al, JAMA Network Open, July 10, 2019 (Posted: Jul 11, 2019 8AM)

In this meta analysis of more than 14,000 patients, integrated tumor microenvironment-based biomarkers was found to be an effective means to predict responsiveness to immunotherapy for patients with advanced non?small cell lung cancer.

Prediction of the 1-Year Risk of Incident Lung Cancer: Prospective Study Using Electronic Health Records from the State of Maine.
Wang Xiaofang et al. Journal of medical Internet research 2019 May 21(5) e13260 (Posted: May 22, 2019 8AM)

End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography
D Ardila et al, Nature Medicine, May 20, 2019 (Posted: May 20, 2019 11AM)

A.I. Took a Test to Detect Lung Cancer. It Got an A- Artificial intelligence may help doctors make more accurate readings of CT scans used to screen for lung cancer.
D Grady, NY Times, May 20, 2019 (Posted: May 20, 2019 11AM)

Association of Patient Characteristics and Tumor Genomics With Clinical Outcomes Among Patients With Non-Small Cell Lung Cancer Using a Clinicogenomic Database.
Singal Gaurav et al. JAMA 2019 Apr (14) 1391-1399 (Posted: Apr 10, 2019 7AM)

Atezolizumab Approved for Initial Treatment of Metastatic Lung Cancer
NCI, January 2019 Brand (Posted: Jan 29, 2019 7AM)

For Early-Stage Lung Cancer, Study Identifies Potential New Biomarker, Treatment Target
NCI, January 3, 2019 Brand (Posted: Jan 07, 2019 0AM)

Race, Poverty, and Initial Implementation of Precision Medicine for Lung Cancer.
Kehl Kenneth L et al. Journal of the National Cancer Institute 2018 Dec (Posted: Dec 30, 2018 9AM)

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities.
Eapen Mathew Suji et al. Drugs 2018 Nov (16) 1717-1740 (Posted: Nov 21, 2018 0PM)

Mutational monitoring of EGFR T790M in cfDNA for clinical outcome prediction in EGFR-mutant lung adenocarcinoma.
Su Kang-Yi et al. PloS one 2018 13(11) e0207001 (Posted: Nov 19, 2018 10AM)

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Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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