Comparison of Conventional TNM and Novel TNMB Staging Systems for Non–Small Cell Lung Cancer

Haro, Greg J.; Sheu, Bonnie; Cook, Nancy R.; Woodard, Gavitt A.; Mann, Michael J.; Kratz, Johannes R.

doi:10.1001/jamanetworkopen.2019.17062

Cited by 16 publications

(16 citation statements)

References 15 publications

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“…In the recent past, efforts have been made to increase the inclusion of molecular markers in clinical staging of NSCLC. 51,52 Patients with localized stage disease do not receive routine molecular analysis, and current recommendations limit next-generation sequencing (NGS) testing to those with advanced-stage NSCLC. 53,54 This leads to low-resolution risk stratification and missing out of high-risk patients who would profit from different treatment modalities.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of TP53 and KEAP1 Mutations and Their Impact on Survival in Localized- and Advanced-Stage NSCLC

Saleh

Scheffler

Merkelbach‐Bruse

et al. 2022

Journal of Thoracic Oncology

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Introduction: TP53 and KEAP1 are frequently mutated in NSCLC, but their prognostic value is ambiguous, particularly in localized stage tumors.Methods: This retrospective cohort study included a total of 6297 patients with NSCLC who were diagnosed between November 1998 and February 2020. The primary end point was overall survival. Patients were diagnosed in a central pathology laboratory as part of the Network Genomic Medicine collaboration, encompassing more than 300 lung cancer-treating oncology centers in Germany. All patients underwent molecular testing, including targeted next-generation panel sequencing and in situ hybridization.Results: A total of 6297 patients with NSCLC were analyzed. In 1518 surgically treated patients (Union for International Cancer Control [UICC] I-IIIA), truncating TP53 mutations and KEAP1 mutations were independent negative prognostic markers in multivariable analysis (hazard ratio [HR] TP53truncating ¼ 1.43, 95% confidence interval [CI]: 1.07-1.91, p ¼ 0.015; HR KEAP1mut ¼ 1.68, 95% CI:1.24-2.26, p ¼ 0.001). Consistently, these mutations were associated with shorter disease-free survival. In 4779 patients with advanced-stage (UICC IIIB-IV) tumors, TP53 mutations did not predict outcome in univariable analysis. In contrast, KEAP1 mutations remained a negative prognostic factor (HR KEAP1mut ¼ 1.40, 95% CI: 1.23-1.61, p < 0.001) in patients with advanced-stage tumors. Furthermore, those with KEAP1mutant tumors with co-occurring TP53 missense mutations had longer overall survival than those with KEAP1-mutant tumors with wild-type or truncating TP53 mutations.Conclusions: This study found that TP53 and KEAP1 mutations were prognostic for localized and advanced-stage NSCLC. The increased relative hazard of harboring TP53 or KEAP1 mutations was comparable to an increase in one UICC stage. Our data suggest that molecular stratification on the basis of TP53 and KEAP1 mutation status should be implemented for localized and advanced-stage NSCLC to optimize and modify clinical decision-making.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of TP53 and KEAP1 Mutations and Their Impact on Survival in Localized- and Advanced-Stage NSCLC

Saleh

Scheffler

Merkelbach‐Bruse

et al. 2022

Journal of Thoracic Oncology

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“…Staging refinement using the 14-gene lung cancer assay It has been previously established that biological molecular signatures can refine prognosis in patients with other types of malignancies [45,46], though such molecular predictors have yet to be formally incorporated into the established TNM staging system for lung cancer [17,36]. The utilization of the 14-gene lung cancer assay as a complement to conventional staging has been evaluated, and it has been shown to improve survival predictions [47,48].…”

Section: A 14-gene Prognostic and Predictive Molecular Assay For Early-stage Nsclcmentioning

confidence: 99%

“…These findings demonstrate improved prognostic ability of the TNMB staging system in a way that has been difficult to attain with reorganization of conventional nonmolecular approaches alone. Following retrospective analysis, a prospective validation was performed [48]. In a prospective cohort study, 238 patients with stage I-IIIC nonsquamous NSCLC underwent surgical resection and prognostic assay evaluation at the time of cancer treatment at UCSF.…”

Section: A 14-gene Prognostic and Predictive Molecular Assay For Early-stage Nsclcmentioning

confidence: 99%

Improved Outcomes and Staging in Non-Small-Cell Lung Cancer Guided by A Molecular Assay

et al. 2021

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There remains a critical need for improved staging of non-small-cell lung cancer, as recurrence and mortality due to undetectable metastases at the time of surgery remain high even after complete resection of tumors currently categorized as ‘early stage.’ A 14-gene quantitative PCR-based expression profile has been extensively validated to better identify patients at high-risk of 5-year mortality after surgical resection than conventional staging – mortality that almost always results from previously undetectable metastases. Furthermore, prospective studies now suggest a predictive benefit in disease-free survival when the assay is used to guide adjuvant chemotherapy decisions in early-stage non-small-cell lung cancer patients.

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“…To predict which patients may recur after surgery, clinicians have traditionally grouped patients using the TNM (Tumor, Node, Metastasis) staging system 4 . Multiple groups, however, have identified molecular signatures that more accurately predict recurrence and mortality beyond conventional TNM staging 5 – 13 . These signatures are based on a variety of genetic, genomic, and epigenetic biomarkers prognostic of recurrence.…”

Section: Introductionmentioning

confidence: 99%

Genetic and immunologic features of recurrent stage I lung adenocarcinoma

Kratz

Tsui

et al. 2021

Sci Rep

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Although surgery for early-stage lung cancer offers the best chance of cure, recurrence still occurs between 30 and 50% of the time. Why patients frequently recur after complete resection of early-stage lung cancer remains unclear. Using a large cohort of stage I lung adenocarcinoma patients, distinct genetic, genomic, epigenetic, and immunologic profiles of recurrent tumors were analyzed using a novel recurrence classifier. To characterize the tumor immune microenvironment of recurrent stage I tumors, unique tumor-infiltrating immune population markers were identified using single cell RNA-seq on a separate cohort of patients undergoing stage I lung adenocarcinoma resection and applied to a large study cohort using digital cytometry. Recurrent stage I lung adenocarcinomas demonstrated higher mutation and lower methylation burden than non-recurrent tumors, as well as widespread activation of known cancer and cell cycle pathways. Simultaneously, recurrent tumors displayed downregulation of immune response pathways including antigen presentation and Th1/Th2 activation. Recurrent tumors were depleted in adaptive immune populations, and depletion of adaptive immune populations and low cytolytic activity were prognostic of stage I recurrence. Genomic instability and impaired adaptive immune responses are key features of stage I lung adenocarcinoma immunosurveillance escape and recurrence after surgery.

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Comparison of Conventional TNM and Novel TNMB Staging Systems for Non–Small Cell Lung Cancer

Cited by 16 publications

References 15 publications

Comprehensive Analysis of TP53 and KEAP1 Mutations and Their Impact on Survival in Localized- and Advanced-Stage NSCLC

Comprehensive Analysis of TP53 and KEAP1 Mutations and Their Impact on Survival in Localized- and Advanced-Stage NSCLC

Improved Outcomes and Staging in Non-Small-Cell Lung Cancer Guided by A Molecular Assay

Genetic and immunologic features of recurrent stage I lung adenocarcinoma

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