Towards the molecular era of discriminating multiple lung cancers

Wang, Ziyang; Yuan, Xiaoqiu; Jiang, Guanchao; Li, Yun; Yang, Fan; Wang, Jun

doi:10.1016/j.ebiom.2023.104508

Cited by 4 publications

(2 citation statements)

References 101 publications

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“…Incorrect discrimination of MLCs leads to improper treatment and thus should be avoided. Clinicopathology has laid the foundation for discriminating MPLC and IPM, with comprehensive histology assessment (CHA) (9) as the guideline recommendation(6, [10][11][12], nevertheless displaying insu ciency in certain cases with a sensitivity of 76-78% and a speci city of 47-74% (13,14). The advent of next-generation sequencing (NGS) revolutionized the discrimination of MLCs (5,(13)(14)(15)(16)) but lacking explicit protocol accessible for medical practitioners.…”

Section: Introductionmentioning

confidence: 99%

“…Clinicopathology has laid the foundation for discriminating MPLC and IPM, with comprehensive histology assessment (CHA) (9) as the guideline recommendation(6, [10][11][12], nevertheless displaying insu ciency in certain cases with a sensitivity of 76-78% and a speci city of 47-74% (13,14). The advent of next-generation sequencing (NGS) revolutionized the discrimination of MLCs (5,(13)(14)(15)(16)) but lacking explicit protocol accessible for medical practitioners. Limited studies tentatively pointed out the requirement of at least 100 genes to de ne clonal relatedness of MLCs with no validation (17).…”

Section: Introductionmentioning

confidence: 99%

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Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution

Wang,

Yuan,

Liu

et al. 2024

Preprint

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Background: Next-generation sequencing (NGS) can help differentiate multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), but remains vague in panel choice and clonal relatedness interpretation. Methods: First, cases with definite diagnosis of MPLC or IPM were simulatedusing the whole-exome sequencing (WES)data from 80 single lung cancer, samples from different tumors mimicking MPLC while those from the same tumor simulating IPM. Different panels were modeled by gene subsampling. Two interpretation methods of clonal relatedness were compared: counting the shared mutations (MoleA) versus probability calculation based on all the mutations (MoleB). We drew ROC curves for each panel and interpretation method with reference to the definite diagnosis, and selected the optimal combinations according to area under the ROC curve (AUCs) and inconclusive rate. Results: MoleB outperformed MoleA with all panels. The AUCs plateaued at high levels when applying NCCNplus MoleB (9 driver genes recommended by the National Comprehensive Cancer Network [NCCN] plus TP53) (AUC = 0.950±0.002) or pancancer MoleA (363-genes) (AUC = 0.792±0.004). Then the superiority of selected strategies was validated in two independent cohorts of multiple lung cancers. All NGS-based methodologies significantly separated the disease-free survival in the WES cohort (N = 42), and NCCNplus MoleB also successfully stratified the prognosis in the non-WES cohort (N = 94). Further phylogenetic analysis and timing of driver alterations revealed the evolutionary differences between MPLC and IPM. Conclusions: These findings have established the first modified panel and corresponding NGS-based procedures to discriminate multiple lung cancers (MLCs).

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution

Wang,

Yuan,

Liu

et al. 2024

Preprint

Self Cite

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Multiple primary lung cancer: Updates and perspectives

Wang,

Zhang,

Wang

et al. 2024

Intl Journal of Cancer

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Management of multiple primary lung cancer (MPLC) remains challenging, partly due to its increasing incidence, especially with the significant rise in cases of multiple lung nodules caused by low‐dose computed tomography screening. Moreover, the indefinite pathogenesis, diagnostic criteria, and treatment selection add to the complexity. In recent years, there have been continuous efforts to dissect the molecular characteristics of MPLC and explore new diagnostic approaches as well as treatment modalities, which will be reviewed here, with a focus on newly emerging evidence and future perspectives, hope to provide new insights into the management of MPLC and serve as inspiration for future research related to MPLC.

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From Morphology to Molecules: Advances in the Distinction of Multiple Primary Lung Cancers From Intrapulmonary Metastases in Non–Small Cell Lung Cancer

Olteanu,

Kern,

Kalson

et al. 2024

Advances in Anatomic Pathology

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The increasing incidence of multiple lung nodules underscores the need for precise differentiation between multiple primary lung cancers (MPLCs) and intrapulmonary metastases (IPMs). This distinction impacts patient prognosis and treatment strategies. The prevalence of multiple lung nodules, ranging from 19.7% to 55.5%, highlights the clinical significance of this challenge. Historically, the role of histopathology, particularly comprehensive histology assessment (CHA), has been pivotal in differentiating MPLCs and IPMs. However, CHA has significant limitations, resulting in a constant search for a better way to distinguish those lesions. The best strategy for delineating MPLCs from IPMs is a multidisciplinary approach combining clinical data, radiology, histology, and molecular methods. Histology provides architectural and cellular characteristics, radiology contributes anatomic context and lesion characterization, and molecular methods reveal molecular features critical for accurate differentiation. Incorporating clinical data further enhances diagnostic precision. This review presents current knowledge and current approaches to multiple lung tumors. It is clear that even with a combination of pathology, radiology, and molecular data, definitive classification of multifocal lung tumors is not always possible.

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Towards the molecular era of discriminating multiple lung cancers

Cited by 4 publications

References 101 publications

Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution

Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution

Multiple primary lung cancer: Updates and perspectives

From Morphology to Molecules: Advances in the Distinction of Multiple Primary Lung Cancers From Intrapulmonary Metastases in Non–Small Cell Lung Cancer

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