Dataset Information

The evolution of non-small cell lung cancer metastases in TRACERx.

ABSTRACT: Metastatic disease is responsible for the majority of cancer-related deaths¹. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.

SUBMITTER: Al Bakir M

PROVIDER: S-EPMC10115651 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The evolution of non-small cell lung cancer metastases in TRACERx.

Al Bakir Maise M Huebner Ariana A Martínez-Ruiz Carlos C Grigoriadis Kristiana K Watkins Thomas B K TBK Pich Oriol O Moore David A DA Veeriah Selvaraju S Ward Sophia S Laycock Joanne J Johnson Diana D Rowan Andrew A Razaq Maryam M Akther Mita M Naceur-Lombardelli Cristina C Prymas Paulina P Toncheva Antonia A Hessey Sonya S Dietzen Michelle M Colliver Emma E Frankell Alexander M AM Bunkum Abigail A Lim Emilia L EL Karasaki Takahiro T Abbosh Christopher C Hiley Crispin T CT Hill Mark S MS Cook Daniel E DE Wilson Gareth A GA Salgado Roberto R Nye Emma E Stone Richard Kevin RK Fennell Dean A DA Price Gillian G Kerr Keith M KM Naidu Babu B Middleton Gary G Summers Yvonne Y Lindsay Colin R CR Blackhall Fiona H FH Cave Judith J Blyth Kevin G KG Nair Arjun A Ahmed Asia A Taylor Magali N MN Procter Alexander James AJ Falzon Mary M Lawrence David D Navani Neal N Thakrar Ricky M RM Janes Sam M SM Papadatos-Pastos Dionysis D Forster Martin D MD Lee Siow Ming SM Ahmad Tanya T Quezada Sergio A SA Peggs Karl S KS Van Loo Peter P Dive Caroline C Hackshaw Allan A Birkbak Nicolai J NJ Zaccaria Simone S Jamal-Hanjani Mariam M McGranahan Nicholas N Swanton Charles C

Nature 20230412 7957

Metastatic disease is responsible for the majority of cancer-related deaths<sup>1</sup>. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at ...[more]

PMID: 37046095

Similar Datasets

Project description:Background and objectiveBone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.MethodsAn online electronic search was performed on PubMed and Google Scholar of all English-language literature using combinations of the following keywords: bone metastases, non-small cell lung cancer, pathophysiology, skeletal related events, response to therapy, predictive factors, and immunotherapy. Bibliographies of identified papers were reviewed for additional articles of interest. Observational cohort, retrospective studies, randomized controlled trials (RCTs), meta-analyses, and review articles were examined for this review.Key content and findingsBone metastases in lung cancer patients remain a common occurrence, impacting morbidity, mortality, and quality of life. Patients with skeletal related events (SREs) have worse prognosis. There is data supporting use of bisphosphonates and/or denosumab, and these should be considered in all patients with bone metastases. Novel studies comparing the genomic alterations of skeletal metastases and primary tumors are needed. As therapy for patients with advanced disease evolves, more studies are needed to evaluate the interplay between immunotherapy and bone metastases, and in determining the response to treatment in bone.ConclusionsPredicting development and progression of bone metastases could allow earlier and targeted therapy in patients with bone metastases. Predicting and evaluating response to conventional chemotherapy and immune checkpoint inhibitors in NSCLC patients with bone metastases remains an unmet need and merits further study.

Dataset Information

The evolution of non-small cell lung cancer metastases in TRACERx.

Publications

The evolution of non-small cell lung cancer metastases in TRACERx.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets