Predictive value of ENLIGHT-DP in patients with metastatic lung adenocarcinoma treated with immune checkpoint inhibitors and platinum chemotherapy directly from histopathology slides using inferred transcriptomics DOI Creative Commons
Johnathan Arnon, Gal Dinstag, Omer Tirosh

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e010132 - e010132

Published: Jan. 1, 2025

Introduction Immune checkpoint inhibitors (ICI) have improved outcomes in non-small cell lung cancer (NSCLC). Nevertheless, the clinical benefit of ICI as monotherapy or combination with chemotherapy remains widely varied and existing biomarkers limited predictive value. We present an analysis ENLIGHT-DP, a novel transcriptome-based biomarker directly from histopathology slides, patients adenocarcinoma (LUAD) treated platinum-based chemotherapy. Methods retrospectively scanned high-resolution H&E slides pretreatment tumor-tissue samples 50 metastatic LUAD first-line (46) without (4) applied our ENLIGHT-DP pipeline to generate, blinded manner, individual prediction score. predicts response targeted therapies given slide scans two steps: (1) predict messenger RNA expression using DeepPT, digital-pathology-based algorithm. (2) Use these values input ENLIGHT, platform that derived drug-specific networks gene expressions. then unblinded evaluated value comparison programmed death ligand (PD-L)-1 tumor mutational burden (TMB). Results is treatment receiver operating characteristic (ROC) area under curve (AUC) 0.69 (p=0.01) outperforms both TMB PD-L1 ROC AUC 0.52 0.46, respectively. Using predetermined binary cut-off (established on independent cohorts) for predicted respond ICI, achieves 100% positive (PPV) 44% sensitivity, superior PD-L1>50% (65% PPV 38% sensitivity) TMB-high (82% 26% sensitivity). was highly PD-L1<1% TMB-low outlier groups 0.88 0.80, respectively (p value<0.05). only this cohort significantly correlated progression-free survival (HR: 0.45, 95% CI: 0.2 0.99, p=0.048). Conclusion demonstrate application accurate chemotherapy, outperforming TMB, relying solely accessible slides. Further studies different types, bigger NSCLC cohorts are warranted.

Language: Английский

Advances and challenges in the treatment of lung cancer DOI Open Access
Yuting Li,

Bingshuo Yan,

Shiming He

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115891 - 115891

Published: Nov. 16, 2023

Lung cancer accounts for a relatively high proportion of malignant tumors. As the most prevalent type lung cancer, non-small cell (NSCLC) is characterized by morbidity and mortality. Presently, arsenal treatment strategies encompasses surgical resection, chemotherapy, targeted therapy radiotherapy. However, despite these options, prognosis remains distressingly poor with low 5-year survival rate. Therefore, it urgent to pursue paradigm shift in methodologies. In recent years, advent sophisticated biotechnologies interdisciplinary integration has provided innovative approaches cancer. This article reviews cutting-edge developments nano drug delivery system, molecular photothermal strategy, immunotherapy Overall, systematically summarizing critically analyzing latest progress current challenges we aim provide theoretical basis development novel drugs treatment, thus improve therapeutic outcomes patients.

Language: Английский

Citations

139
Pharmacogenomics: Driving Personalized Medicine DOI Creative Commons
Wolfgang Sadée, Daqing Wang, Katherine E. Hartmann

et al.

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 75(4), P. 789 - 814

Published: March 16, 2023

Abstract

Personalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool improve outcomes prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all "-omics" fields (e.g., proteomics, transcriptomics, metabolomics, metagenomics). This review summarizes basic principles relevant translation assessing pharmacogenomics' central role converging diverse elements of personalized medicine. We discuss genetic variations pharmacogenes (drug-metabolizing enzymes, drug transporters, receptors), their clinical relevance biomarkers, legacy decades research pharmacogenetics. All types including proteins, nucleic acids, viruses, cells, genes, irradiation, can benefit from genomics, expanding across Food Drug Administration approvals therapeutics involving biomarkers increase rapidly, demonstrating growing impact pharmacogenomics. A beacon for therapeutic approaches, molecularly targeted cancer therapies highlight trends discovery applications. To account human complexity, multicomponent biomarker panels genetic, personal, environmental factors guide diagnosis increasingly artificial intelligence cope extreme data complexities. However, application encounters substantial hurdles, such unknown validity ethnic groups, underlying bias care, real-world validation. address science technologies germane medicine, integrated economic, ethical, regulatory issues, providing insights current status future direction care.

Significance Statement

aims optimize care individual patients use predictive Pharmacogenomics drives guides development therapeutics. addresses large-scale repositories accelerating medical advances. The is discussed, along hurdles impeding broad implementation, context ethics, economics, affairs.

Language: Английский

Citations

84
Five-Year Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non–Small Cell Lung Cancer DOI Creative Commons
Samuel Rosner, Joshua E. Reuss, Marianna Zahurak

et al.

Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 29(4), P. 705 - 710

Published: Feb. 15, 2023

Neoadjuvant anti-PD-1 therapy has shown promise for resectable non-small cell lung cancer (NSCLC). We reported the first phase I/II trial of neoadjuvant nivolumab in NSCLC, finding it to be safe and feasible with encouraging major pathological responses (MPR). now present 5-year clinical outcomes from this trial, representing our knowledge, longest follow-up data any type.Two doses (3 mg/kg) were administered 4 weeks before surgery 21 patients Stage I-IIIA NSCLC. recurrence-free survival (RFS), overall (OS), associations MPR PD-L1, evaluated.With a median 63 months, RFS OS rates 60% 80%, respectively. The presence pre-treatment tumor PD-L1 positivity (TPS ≥1%) each trended toward favorable RFS; HR, 0.61 [95% confidence interval (CI), 0.15-2.44] 0.36 (95% CI, 0.07-1.85), At follow-up, 8 9 (89%) alive disease-free. There no cancer-related deaths among MPR. In contrast, 6/11 without experienced relapse, 3 died.Five-year NSCLC compare favorably historical outcomes. improved RFS, though definitive conclusions are limited by cohort size.

Language: Английский

Citations

49
Non-small-cell lung cancer DOI
Lizza Hendriks, Jordi Remón, C. Faivre‐Finn

et al.

Nature Reviews Disease Primers, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 26, 2024

Language: Английский

Citations

43
New promises and challenges in the treatment of advanced non-small-cell lung cancer DOI

May-Lucie Meyer,

Bailey G Fitzgerald,

Luís Paz-Ares

et al.

The Lancet, Journal Year: 2024, Volume and Issue: 404(10454), P. 803 - 822

Published: Aug. 1, 2024

Language: Английский

Citations

38
Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer DOI Creative Commons
Yue Zeng, Chunhong Hu, Yizheng Li

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(6), P. 1680 - 1688

Published: May 13, 2024

Abstract Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical have explored its relationship response to checkpoint inhibitors (ICIs). Here we report results from cohort 1 the prospective observational STRESS-LUNG study, which investigated association between and efficacy first-line treatment ICIs advanced non-small-cell lung was assessed Patient Health Questionnaire-9 Generalized Anxiety Disorder 7-item scale. The study included 227 111 (48.9%) exhibiting who presented (Patient score ≥5) anxiety (Generalized at baseline. On primary endpoint analysis, baseline exhibited a significantly shorter median progression-free survival compared those without (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 2.43, P = 0.002). secondary associated lower objective rate (46.8% 62.1%, odds 0.54, 0.022), reduced 2-year overall 46.5% 64.9% (hazard for death 1.82, 1.12 2.97, 0.016) detriments quality life. exploratory analysis indicated group showed elevated blood cortisol levels, adverse outcomes. This suggests there an worse outcomes cancer treated ICIs, highlighting potential significance addressing management. ClinicalTrials.gov registration: NCT05477979 .

Language: Английский

Citations

23
Programmed Death Ligand-1 and Tumor Mutation Burden Testing of Patients With Lung Cancer for Selection of Immune Checkpoint Inhibitor Therapies: Guideline From the College of American Pathologists, Association for Molecular Pathology, International Association for the Study of Lung Cancer, Pulmonary Pathology Society, and LUNGevity Foundation DOI Open Access
Lynette M. Sholl, Mark M. Awad, Upal Roy

et al.

Archives of Pathology & Laboratory Medicine, Journal Year: 2024, Volume and Issue: 148(7), P. 757 - 774

Published: April 16, 2024

Context.— Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to approval immune therapies for patients with non–small cell lung cancer. Certain checkpoint inhibitor require use companion diagnostics, but methodologic variability has uncertainty around test selection implementation practice. Objective.— To develop evidence-based guideline recommendations testing immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) tumor mutation burden (TMB), Design.— The College American Pathologists convened a panel experts cancer biomarker accordance standards trustworthy clinical practice guidelines established by National Academy Medicine. A systematic literature review was conducted address 8 key questions. Using Grading Recommendations Assessment, Development, Evaluation (GRADE) approach, were created from available evidence, certainty that judgments as defined GRADE Evidence Decision framework. Results.— Six recommendation statements developed. Conclusions.— This summarizes current hurdles associated PD-L1 expression TMB therapy advanced presents setting.

Language: Английский

Citations

17
Liquid biopsy for human cancer: cancer screening, monitoring, and treatment DOI Creative Commons
Hao Wang, Yi Zhang, Hao Zhang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(6)

Published: May 28, 2024

Currently, tumor treatment modalities such as immunotherapy and targeted therapy have more stringent requirements for obtaining growth information require accurate easy-to-operate detection methods. Compared with traditional tissue biopsy, liquid biopsy is a novel, minimally invasive, real-time tool detecting directly or indirectly released by tumors in human body fluids, which suitable the of new modalities. Liquid has not been widely used clinical practice, there are fewer reviews related applications. This review summarizes applications components (e.g., circulating cells, DNA, extracellular vesicles, etc.) tumorigenesis progression. includes development process techniques biopsies, early screening tumors, detection, guiding therapeutic strategies (liquid biopsy-based personalized medicine prediction response). Finally, current challenges future directions proposed. In sum, this will inspire researchers to use technology promote realization individualized therapy, improve efficacy provide better options patients.

Language: Английский

Citations

17
Immune checkpoint inhibitors in colorectal cancer: limitation and challenges DOI Creative Commons

Suying Yan,

Wanting Wang,

Zhiqiang Feng

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 11, 2024

Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions metastatic colorectal have yielded suboptimal results. ICIs can decrease tumor development by preventing tumor's immune evasion, presenting patients with new treatment alternative. The increased use of checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, demonstrated significant clinical effectiveness MSI-H CRC, whereas their efficacy is limited MSS. Acquired resistance still occur positive response to ICIs. This paper describes currently discusses mechanisms which acquired occurs, primarily related loss impaired presentation antigens, reduced IFN-λ cytokine or metabolic dysregulation, summarizes incidence adverse effects. We posit that future hinges upon advancement precise prediction biomarkers implementation combination therapies. study aims elucidate constraints associated foster targeted problem-solving approaches, thereby enhancing potential benefits more patients.

Language: Английский

Citations

12
A novel sub-regional radiomics model to predict immunotherapy response in non-small cell lung carcinoma DOI Creative Commons
Jie Peng,

Dan Zou,

Xudong Zhang

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 22, 2024

Abstract Background Identifying precise biomarkers of immunotherapy response for non-small cell lung carcinoma (NSCLC) before treatment is challenging. This study aimed to construct and investigate the potential performance a sub-regional radiomics model (SRRM) as novel tumor biomarker in predicting patients with NSCLC treated immune checkpoint inhibitors, test whether its predictive superior that conventional radiomics, mutational burden (TMB) score programmed death ligand-1 (PD-L1) expression. Methods We categorized 264 from retrospective databases two centers into training ( n = 159) validation 105) cohorts. Radiomic features were extracted three sub-regions region interest using K-means method. 1,896 each sub-region, resulting 5688 per sample. The least absolute shrinkage selection operator regression method was used select radiomic features. SRRM constructed validated support vector machine algorithm. next-generation sequencing classify cohorts high TMB (≥ 10 muts/Mb) low (< groups; immunohistochemistry performed assess PD-L1 expression formalin-fixed, paraffin-embedded sections, defined ≥ 50% cells being positive. Associations between progression-free survival (PFS) variant genes assessed. Results Eleven employed develop SRRM. areas under receiver operating characteristic curve (AUCs) proposed 0.90 (95% confidence interval [CI] 0.84−0.96) 0.86 CI 0.76−0.95) cohorts, respectively. (low vs. high; cutoff value 0.936) significantly associated PFS (hazard ratio [HR] 0.35 [0.24−0.50], P < 0.001) (HR 0.42 [0.26−0.67], A significant correlation H3C4 , PAX5 EGFR ) observed. In cohort, demonstrated higher AUC (0.86, than (0.66, 0.034) (0.54, 0.552). Conclusions had better expression, score. effectively stratified risk among receiving immunotherapy.

Language: Английский

Citations

9