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Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse

Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years . Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom... Full description

Journal Title: Nature medicine 2019-10, Vol.25 (10), p.1534-1539
Main Author: Chemi, Francesca
Other Authors: Rothwell, Dominic G , McGranahan, Nicholas , Gulati, Sakshi , Abbosh, Chris , Pearce, Simon P , Zhou, Cong , Wilson, Gareth A , Jamal-Hanjani, Mariam , Birkbak, Nicolai , Pierce, Jackie , Kim, Chang Sik , Ferdous, Saba , Burt, Deborah J , Slane-Tan, Daniel , Gomes, Fabio , Moore, David , Shah, Rajesh , Al Bakir, Maise , Hiley, Crispin , Veeriah, Selvaraju , Summers, Yvonne , Crosbie, Philip , Ward, Sophia , Mesquita, Barbara , Dynowski, Marek , Biswas, Dhruva , Tugwood, Jonathan , Blackhall, Fiona , Miller, Crispin , Hackshaw, Allan , Brady, Ged , Swanton, Charles , Dive, Caroline
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/31591595
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title: Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
format: Article
creator:
  • Chemi, Francesca
  • Rothwell, Dominic G
  • McGranahan, Nicholas
  • Gulati, Sakshi
  • Abbosh, Chris
  • Pearce, Simon P
  • Zhou, Cong
  • Wilson, Gareth A
  • Jamal-Hanjani, Mariam
  • Birkbak, Nicolai
  • Pierce, Jackie
  • Kim, Chang Sik
  • Ferdous, Saba
  • Burt, Deborah J
  • Slane-Tan, Daniel
  • Gomes, Fabio
  • Moore, David
  • Shah, Rajesh
  • Al Bakir, Maise
  • Hiley, Crispin
  • Veeriah, Selvaraju
  • Summers, Yvonne
  • Crosbie, Philip
  • Ward, Sophia
  • Mesquita, Barbara
  • Dynowski, Marek
  • Biswas, Dhruva
  • Tugwood, Jonathan
  • Blackhall, Fiona
  • Miller, Crispin
  • Hackshaw, Allan
  • Brady, Ged
  • Swanton, Charles
  • Dive, Caroline
subjects:
  • Adult
  • Aged
  • Aged, 80 and over
  • Article
  • Biomarkers, Tumor - genetics
  • Carcinoma, Non-Small-Cell Lung - diagnosis
  • Carcinoma, Non-Small-Cell Lung - genetics
  • Carcinoma, Non-Small-Cell Lung - pathology
  • Carcinoma, Non-Small-Cell Lung - surgery
  • Care and treatment
  • Diseases
  • Enumeration
  • Excision (Surgery)
  • Female
  • Gene Expression Regulation, Neoplastic - genetics
  • Genetic aspects
  • Genome, Human - genetics
  • Humans
  • Lung cancer
  • Lung cancer, Non-small cell
  • Male
  • Metastases
  • Middle Aged
  • Multivariate analysis
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local - diagnosis
  • Neoplasm Recurrence, Local - genetics
  • Neoplasm Recurrence, Local - pathology
  • Neoplasm Recurrence, Local - surgery
  • Neoplasm Staging
  • Neoplastic Cells, Circulating - pathology
  • Non-small cell lung carcinoma
  • Patients
  • Pulmonary Veins - pathology
  • Relapse
  • Research
  • Risk factors
  • Small cell lung carcinoma
  • Surgery
  • Surgical instruments
  • Tumor cells
  • Tumors
  • Usage
ispartof: Nature medicine, 2019-10, Vol.25 (10), p.1534-1539
description: Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years . Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study , were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titlePulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
creatorChemi, Francesca ; Rothwell, Dominic G ; McGranahan, Nicholas ; Gulati, Sakshi ; Abbosh, Chris ; Pearce, Simon P ; Zhou, Cong ; Wilson, Gareth A ; Jamal-Hanjani, Mariam ; Birkbak, Nicolai ; Pierce, Jackie ; Kim, Chang Sik ; Ferdous, Saba ; Burt, Deborah J ; Slane-Tan, Daniel ; Gomes, Fabio ; Moore, David ; Shah, Rajesh ; Al Bakir, Maise ; Hiley, Crispin ; Veeriah, Selvaraju ; Summers, Yvonne ; Crosbie, Philip ; Ward, Sophia ; Mesquita, Barbara ; Dynowski, Marek ; Biswas, Dhruva ; Tugwood, Jonathan ; Blackhall, Fiona ; Miller, Crispin ; Hackshaw, Allan ; Brady, Ged ; Swanton, Charles ; Dive, Caroline
creatorcontribChemi, Francesca ; Rothwell, Dominic G ; McGranahan, Nicholas ; Gulati, Sakshi ; Abbosh, Chris ; Pearce, Simon P ; Zhou, Cong ; Wilson, Gareth A ; Jamal-Hanjani, Mariam ; Birkbak, Nicolai ; Pierce, Jackie ; Kim, Chang Sik ; Ferdous, Saba ; Burt, Deborah J ; Slane-Tan, Daniel ; Gomes, Fabio ; Moore, David ; Shah, Rajesh ; Al Bakir, Maise ; Hiley, Crispin ; Veeriah, Selvaraju ; Summers, Yvonne ; Crosbie, Philip ; Ward, Sophia ; Mesquita, Barbara ; Dynowski, Marek ; Biswas, Dhruva ; Tugwood, Jonathan ; Blackhall, Fiona ; Miller, Crispin ; Hackshaw, Allan ; Brady, Ged ; Swanton, Charles ; Dive, Caroline ; TRACERx Consortium
descriptionApproximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years . Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study , were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
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subjectAdult ; Aged ; Aged, 80 and over ; Article ; Biomarkers, Tumor - genetics ; Carcinoma, Non-Small-Cell Lung - diagnosis ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - surgery ; Care and treatment ; Diseases ; Enumeration ; Excision (Surgery) ; Female ; Gene Expression Regulation, Neoplastic - genetics ; Genetic aspects ; Genome, Human - genetics ; Humans ; Lung cancer ; Lung cancer, Non-small cell ; Male ; Metastases ; Middle Aged ; Multivariate analysis ; Mutation ; Neoplasm Metastasis ; Neoplasm Recurrence, Local - diagnosis ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - pathology ; Neoplasm Recurrence, Local - surgery ; Neoplasm Staging ; Neoplastic Cells, Circulating - pathology ; Non-small cell lung carcinoma ; Patients ; Pulmonary Veins - pathology ; Relapse ; Research ; Risk factors ; Small cell lung carcinoma ; Surgery ; Surgical instruments ; Tumor cells ; Tumors ; Usage
ispartofNature medicine, 2019-10, Vol.25 (10), p.1534-1539
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1Rothwell, Dominic G
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8Jamal-Hanjani, Mariam
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20Veeriah, Selvaraju
21Summers, Yvonne
22Crosbie, Philip
23Ward, Sophia
24Mesquita, Barbara
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26Biswas, Dhruva
27Tugwood, Jonathan
28Blackhall, Fiona
29Miller, Crispin
30Hackshaw, Allan
31Brady, Ged
32Swanton, Charles
33Dive, Caroline
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0Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
1Nature medicine
addtitleNat Med
descriptionApproximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years . Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study , were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
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8Carcinoma, Non-Small-Cell Lung - surgery
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28Neoplasm Recurrence, Local - pathology
29Neoplasm Recurrence, Local - surgery
30Neoplasm Staging
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32Non-small cell lung carcinoma
33Patients
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titlePulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
authorChemi, Francesca ; Rothwell, Dominic G ; McGranahan, Nicholas ; Gulati, Sakshi ; Abbosh, Chris ; Pearce, Simon P ; Zhou, Cong ; Wilson, Gareth A ; Jamal-Hanjani, Mariam ; Birkbak, Nicolai ; Pierce, Jackie ; Kim, Chang Sik ; Ferdous, Saba ; Burt, Deborah J ; Slane-Tan, Daniel ; Gomes, Fabio ; Moore, David ; Shah, Rajesh ; Al Bakir, Maise ; Hiley, Crispin ; Veeriah, Selvaraju ; Summers, Yvonne ; Crosbie, Philip ; Ward, Sophia ; Mesquita, Barbara ; Dynowski, Marek ; Biswas, Dhruva ; Tugwood, Jonathan ; Blackhall, Fiona ; Miller, Crispin ; Hackshaw, Allan ; Brady, Ged ; Swanton, Charles ; Dive, Caroline
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39Surgery
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abstractApproximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years . Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study , were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
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