Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse.,Nature Medicine

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Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse.
Nature Medicine ( IF 58.7 ) Pub Date : 2019-10-07 , DOI: 10.1038/s41591-019-0593-1
Francesca Chemi _{1,

2} , Dominic G Rothwell ₁ , Nicholas McGranahan _{3,

4,

5} , Sakshi Gulati ₁ , Chris Abbosh ₄ , Simon P Pearce ₁ , Cong Zhou ₁ , Gareth A Wilson _{4,

5} , Mariam Jamal-Hanjani _{3,

4} , Nicolai Birkbak _{4,

5,

6} , Jackie Pierce ₁ , Chang Sik Kim ₁ , Saba Ferdous ₁ , Deborah J Burt ₁ , Daniel Slane-Tan ₁ , Fabio Gomes ₂ , David Moore ₄ , Rajesh Shah ₇ , Maise Al Bakir ₅ , Crispin Hiley _{3,

4} , Selvaraju Veeriah ₄ , Yvonne Summers ₈ , Philip Crosbie _{2,

8,

9} , Sophia Ward ₅ , Barbara Mesquita ₁ , Marek Dynowski ₁₀ , Dhruva Biswas ₅ , Jonathan Tugwood ₁ , Fiona Blackhall _{2,

8} , Crispin Miller ₁₁ , Allan Hackshaw ₄ , Ged Brady _{1,

2} , Charles Swanton _{3,

4,

5} , Caroline Dive _{1,

2} ,

Affiliation

Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.
Cancer Research UK Lung Cancer Centre of Excellence, The University of Manchester, Manchester, UK.
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
University College London Cancer Institute, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Department of Molecular Medicine, Aarhus University, Aarhus, Denmark.
Department of Thoracic Surgery, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Scientific Computing Core Facility, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.
RNA Biology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.

Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. 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 study3, 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.

中文翻译：

肿瘤切除和疾病复发前的肺静脉循环肿瘤细胞播散。

大约 50% 接受根治性手术的早期非小细胞肺癌 (NSCLC) 患者将在 5 年内复发1,2。手术时检测循环肿瘤细胞（CTC）可能是识别复发风险较高的患者的工具，建议对这些患者进行更频繁的监测。在这里，我们询问 CellSearch 在早期 NSCLC 手术切除时检测到的肺静脉 CTC（PV-CTC）是否代表导致随后疾病复发的亚克隆。在参加 TRACERx 研究的 100 名患者中，有 48% 的患者检测到 PV-CTC，它们与肺癌特异性复发相关，并且在根据肿瘤分期进行调整的多变量分析中仍然是复发的独立预测因子。在一项案例研究中，手术时收集的单个 PV-CTC 的基因组分析显示，与 10 个月后检测到的转移瘤 (91%) 相比，与原发肿瘤 (79%) 的突变重叠率更高，这表明早期播散的 PV-CTC 是造成这种情况的原因。疾病复发。 PV-CTC 计数和基因组分析共同强调了 PV-CTC 作为 NSCLC 术后复发早期预测因子的潜力。然而，PV-CTC 在预测复发方面的敏感性有限，表明需要使用更大的独立队列进行进一步研究，以确认和更好地定义 PV-CTC 在早期 NSCLC 中的潜在临床效用。

更新日期：2019-10-07

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